Adam Slivka

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.

Evaluation and Management of Autoimmune Pancreatitis: Experience at a Large US Center

OBJECTIVES:Autoimmune pancreatitis (AIP) is increasingly recognized as a form of chronic pancreatitis. Systematic evaluation and management of AIP in the United States is reported only from one center. Our aim was to review the evaluation and management of AIP at a large tertiary center.METHODS:We retrospectively reviewed information on demographics, clinical presentation, laboratory and imaging findings, extrapancreatic involvement, treatment response, and recurrence in 26 patients with AIP treated at the University of Pittsburgh Medical Center from 1998 to 2007.RESULTS:The median age at presentation was 62.5 years (range: 23–86), 65% were men, and 88% were Caucasians. The most common presentation included new-onset mild abdominal pain (65%), jaundice (62%), and weight loss (42%). Pancreatic mass, enlargement, or prominence on imaging was present in 85% of the patients. Serum IgG4 (immunoglobulin-4) was elevated (>140 mg/dl) in 44% (8/18) at presentation. The most common extrapancreatic finding was extrapancreatic/intrahepatic biliary strictures (35%). Peri-pancreatic vascular complications were noted in 23% of the patients. Six patients underwent partial or complete pancreatectomy. Partial or complete response was observed for initial steroid treatment in 19 patients and for methotrexate in 1 patient. Recurrences were common, especially in patients with extrapancreatic manifestations, and usually responded to a combination of steroids and azathioprine. Any one of the commonly used diagnostic criteria (Mayo Clinics HISORt criteria, the Japanese Pancreas Society criteria, Korean diagnostic criteria) was fulfilled in 85% of cases.CONCLUSIONS:In this second major US series, we confirm several findings previously reported in AIP. Our study highlights the presence of vascular complications in a subset of patients with AIP. The current diagnostic criteria may not identify all AIP patients.

The Role of Pancreatic Cyst Fluid Molecular Analysis in Predicting Cyst Pathology

BACKGROUND & AIMS Current methods to detect malignancy in mucinous cystic neoplasms of the pancreas remain inadequate. The role of detailed molecular analysis in this context was investigated. METHODS Endoscopic ultrasound-guided pancreatic cyst aspirates were prospectively collected during a period of 19 months and studied for cytology, carcinoembryonic antigen level, and molecular analysis. Molecular evaluation incorporated DNA quantification (amount and quality), k-ras point mutation, and broad panel tumor suppressor linked microsatellite marker allelic loss analysis by using fluorescent capillary electrophoresis. The sequence of mutation acquisition was also calculated on the basis of a clonal expansion model, and comparison was made to the final pathology. RESULTS Thirty-six cysts with confirmed histology were analyzed. There were 11 malignant, 15 premalignant, and 10 benign cysts. Malignant cysts could be differentiated from premalignant cysts on the basis of fluid carcinoembryonic antigen level (P=.034), DNA quality (P=.009), number of mutations (P=.002), and on the sequence of mutations acquired (P<.001). Early k-ras mutation followed by allelic loss was the most predictive of a malignant cyst (sensitivity, 91%; specificity, 93%). CONCLUSIONS Malignant cyst fluid contains adequate DNA to allow mutational analysis. A first hit k-ras mutation followed by allelic loss is most predictive of the presence of malignancy in a pancreatic cyst. This approach should serve as an ancillary tool to the conventional work-up of pancreatic cysts. Cumulative amount and timing of detectable mutational damage can assist in diagnosis and clinical management.

Brush cytology during ERCP for the diagnosis of biliary and pancreatic malignancies

Endoscopic retrograde cholangiopancreatography is a valuable tool in the diagnosis and management of pancreaticobiliary diseases. The diagnostic sensitivity of brush cytology is reported as between 18% and 70% for malignant bile duct or pancreatic duct strictures. We report our findings in 74 patients with pancreaticobiliary strictures who underwent ERCP. Brush cytology was performed on 55 bile duct specimens and 19 pancreatic duct specimens. No complications related to the procedure occurred; 4 specimens (5.4%) were unsatisfactory for interpretation. Strictures were benign in 22 patients (12 pancreatitis, 5 sclerosing cholangitis, 3 Mirizzi syndrome, and 2 papillitis) and malignant in 52 patients (29 pancreatic carcinoma, 10 cholangiocarcinoma, 6 metastatic disease, 4 pancreatic mucinous ductal ectasia, 1 ampullary carcinoma, and 2 non-functioning islet cell tumors). The nature of the stricture was confirmed by surgery, surgical biopsy, necropsy, or follow-up. The overall results for brush cytology were sensitivity 56.2%, specificity 100%, positive predictive value 100%, negative predictive value 51.2%, and accuracy 70%. Our results confirm the value, safety, and utility of obtaining cytologic specimens at the time of ERCP; confirmation was obtained in 65.5% of pancreatic carcinoma cases. Although a negative result does not exclude pancreaticobiliary malignancy, a positive result confirms this diagnosis.

Single-operator cholangioscopy in patients requiring evaluation of bile duct disease or therapy of biliary stones (with videos)

BACKGROUND The feasibility of single-operator cholangioscopy (SOC) for biliary diagnostic and therapeutic procedures was previously reported. OBJECTIVE To confirm the utility of SOC in more widespread clinical use. DESIGN Prospective clinical cohort study. SETTING Fifteen endoscopy referral centers in the United States and Europe. PATIENTS Two hundred ninety-seven patients requiring evaluation of bile duct disease or biliary stone therapy. INTERVENTIONS SOC examination and, as indicated, SOC-directed stone therapy or forceps biopsy. MAIN OUTCOME MEASUREMENTS Procedural success defined as ability to (1) visualize target lesions and, if indicated, collect biopsy specimens adequate for histological evaluation or (2) visualize biliary stones and initiate fragmentation and removal. RESULTS The overall procedure success rate was 89% (95% CI, 84%-92%). Adequate tissue for histological examination was secured in 88% of 140 patients who underwent biopsy. Overall sensitivity in diagnosing malignancy was 78% for SOC visual impression and 49% for SOC-directed biopsy. Sensitivity was higher (84% and 66%, respectively) for intrinsic bile duct malignancies. Diagnostic SOC procedures altered clinical management in 64% of patients. Procedure success was achieved in 92% of 66 patients with stones and complete stone clearance during the study SOC session in 71%. The incidence of serious procedure-related adverse events was 7.5% for diagnostic SOC and 6.1% for SOC-directed stone therapy. LIMITATIONS The study was observational in design with no control group. CONCLUSIONS Evaluation of bile duct disease and biliary stone therapy can be safely performed with a high success rate by using the SOC system.

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.

Alcohol and Smoking as Risk Factors in an Epidemiology Study of Patients With Chronic Pancreatitis

BACKGROUND & AIMS Alcohol has been implicated in the development of chronic pancreatitis (CP) in 60%-90% of patients, although percentages in the United States are unknown. We investigated the epidemiology of alcohol-related CP at tertiary US referral centers. METHODS We studied data from CP patients (n = 539) and controls (n = 695) enrolled in the North American Pancreatitis Study-2 from 2000 to 2006 at 20 US referral centers. CP was defined by definitive evidence from imaging or histologic analyses. Subjects and physicians each completed a study questionnaire. Using physician-assigned diagnoses, patients were assigned to an etiology group: alcohol (with/without other diagnoses), nonalcohol (any etiology of CP from other than alcohol), or idiopathic (no etiology identified). RESULTS The distribution of patients among etiology groups was: alcohol (44.5%), nonalcohol (26.9%), and idiopathic (28.6%). Physicians identified alcohol as the etiology more frequently in men (59.4% men vs 28.1% women), but nonalcohol (18% men vs 36.7% women) and idiopathic etiologies (22.6% men vs 35.2% women) more often in women (P < .01 for all comparisons). Nonalcohol etiologies were equally divided among obstructive, genetic, and other causes. Compared with controls, patients with idiopathic CP were more likely to have ever smoked (58.6% vs 49.7%, P < .05) or have a history of chronic renal disease or failure (5.2% vs 1.2%, P < .01). In multivariate analyses, smoking (ever, current, and amount) was independently associated with idiopathic CP. CONCLUSIONS The frequency of alcohol-related CP at tertiary US referral centers is lower than expected. Idiopathic CP and nonalcohol etiologies represent a large subgroup, particularly among women. Smoking is an independent risk factor for idiopathic CP.

Comparison of laparoscopic versus open repair of paraesophageal hernia

BACKGROUND Recent reports suggest that laparoscopic paraesophageal hernia repair (LPHR) is feasible, but no direct comparisons with the standard open paraesophageal hernia repair (OPHR) have been reported. The purpose of this study was to compare the short-term outcome of LPHR versus OPHR at a single institution. METHODS The operative and postoperative courses of 95 consecutive patients undergoing open or laparoscopic repair of a paraesophageal hernia (PEH) were retrospectively reviewed, and outcomes of LPHR versus OPHR were compared. RESULTS PEH was associated with advanced age and significant comorbidity. Although the operative time was increased for LPHR, there was a significant reduction in blood loss, intensive care unit stay, ileus, hospital stay, and overall morbidity associated with LPHR compared with OPHR. CONCLUSIONS PEH is associated with significant comorbidity that increases the operative risk. Short-term outcomes for LPHR are superior to OPHR, suggesting that the laparoscopic approach is the preferred approach to paraesophageal hernia repair.

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.

Type of pain, pain-associated complications, quality of life, disability and resource utilisation in chronic pancreatitis: a prospective cohort study

Objective To compare patients with chronic pancreatitis (CP) with constant pain patterns to patients with CP with intermittent pain patterns. Methods This was a prospective cohort study conducted at 20 tertiary medical centers in the USA comprising 540 subjects with CP. Patients with CP were asked to identify their pain from five pain patterns (A–E) defined by the temporal nature (intermittent or constant) and the severity of the pain (mild, moderate or severe). Pain pattern types were compared with respect to a variety of demographic, quality of life (QOL) and clinical parameters. Rates of disability were the primary outcome. Secondary outcomes included: use of pain medications, days lost from school or work, hospitalisations (preceding year and lifetime) and QOL as measured using the Short Form-12 (SF-12) questionnaire. Results Of the 540 CP patients, 414 patients (77%) self-identified with a particular pain pattern and were analysed. Patients with constant pain, regardless of severity, had higher rates of disability, hospitalisation and pain medication use than patients with intermittent pain. Patients with constant pain had lower QOL (by SF-12) compared with patients who had intermittent pain. Additionally, patients with constant pain were more likely to have alcohol as the aetiology for their pancreatitis. There was no association between the duration of the disease and the quality or severity of the pain. Conclusions This is the largest study ever conducted of pain in CP. These findings suggest that the temporal nature of pain is a more important determinant of health-related QOL and healthcare utilisation than pain severity. In contrast to previous studies, the pain associated with CP was not found to change in quality over time. These results have important implications for improving our understanding of the mechanisms underlying pain in CP and for the goals of future treatments and interventions.