Koenraad J. Mortele

Frequent Detection of Pancreatic Lesions in Asymptomatic High-Risk Individuals

BACKGROUND & AIMS The risk of pancreatic cancer is increased in patients with a strong family history of pancreatic cancer or a predisposing germline mutation. Screening can detect curable, noninvasive pancreatic neoplasms, but the optimal imaging approach is not known. We determined the baseline prevalence and characteristics of pancreatic abnormalities using 3 imaging tests to screen asymptomatic, high-risk individuals (HRIs). METHODS We screened 225 asymptomatic adult HRIs at 5 academic US medical centers once, using computed tomography (CT), magnetic resonance imaging (MRI), and endoscopic ultrasonography (EUS). We compared results in a blinded, independent fashion. RESULTS Ninety-two of 216 HRIs (42%) were found to have at least 1 pancreatic mass (84 cystic, 3 solid) or a dilated pancreatic duct (n = 5) by any of the imaging modalities. Fifty-one of the 84 HRIs with a cyst (60.7%) had multiple lesions, typically small (mean, 0.55 cm; range, 2-39 mm), in multiple locations. The prevalence of pancreatic lesions increased with age; they were detected in 14% of subjects younger than 50 years old, 34% of subjects 50-59 years old, and 53% of subjects 60-69 years old (P < .0001). CT, MRI, and EUS detected a pancreatic abnormality in 11%, 33.3%, and 42.6% of the HRIs, respectively. Among these abnormalities, proven or suspected neoplasms were identified in 85 HRIs (82 intraductal papillary mucinous neoplasms and 3 pancreatic endocrine tumors). Three of 5 HRIs who underwent pancreatic resection had high-grade dysplasia in less than 3 cm intraductal papillary mucinous neoplasms and in multiple intraepithelial neoplasias. CONCLUSIONS Screening of asymptomatic HRIs frequently detects small pancreatic cysts, including curable, noninvasive high-grade neoplasms. EUS and MRI detect pancreatic lesions better than CT.

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.

A comparative evaluation of radiologic and clinical scoring systems in the early prediction of severity in acute pancreatitis.

OBJECTIVES:The early identification of clinically severe acute pancreatitis (AP) is critical for the triage and treatment of patients. The aim of this study was to compare the accuracy of computed tomography (CT) and clinical scoring systems for predicting the severity of AP on admission.METHODS:Demographic, clinical, and laboratory data of all consecutive patients with a primary diagnosis of AP during a two-and-half-year period was prospectively collected for this study. A retrospective analysis of the abdominal CT data was performed. Seven CT scoring systems (CT severity index (CTSI), modified CT severity index (MCTSI), pancreatic size index (PSI), extrapancreatic score (EP), ‘‘extrapancreatic inflammation on CT’’ score (EPIC), ‘‘mesenteric oedema and peritoneal fluid’’ score (MOP), and Balthazar grade) as well as two clinical scoring systems: Acute Physiology, Age, and Chronic Health Evaluation (APACHE)-II and Bedside Index for Severity in AP (BISAP) were comparatively evaluated with regard to their ability to predict the severity of AP on admission (first 24 h of hospitalization). Clinically severe AP was defined as one or more of the following: mortality, persistent organ failure and/or the presence of local pancreatic complications that require intervention. All CT scans were reviewed in consensus by two radiologists, each blinded to patient outcome. The accuracy of each imaging and clinical scoring system for predicting the severity of AP was assessed using receiver operating curve analysis.RESULTS:Of 346 consecutive episodes of AP, there were 159 (46%) episodes in 150 patients (84 men, 66 women; mean age, 54 years; age range, 21–91 years) who were evaluated with a contrast-enhanced CT scan (n=131 episodes) or an unenhanced CT scan (n=28 episodes) on the first day of admission. Clinically severe AP was diagnosed in 29/159 (18%) episodes; 9 (6%) patients died. Overall, the Balthazar grading system (any CT technique) and CTSI (contrast-enhanced CT only) demonstrated the highest accuracy among the CT scoring systems for predicting severity, but this was not statistically significant. There were no statistically significant differences between the predictive accuracies of CT and clinical scoring systems.CONCLUSIONS:The predictive accuracy of CT scoring systems for severity of AP is similar to clinical scoring systems. Hence, a CT on admission solely for severity assessment in AP is not recommended.

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.

Pancreatic ductal adenocarcinoma radiology reporting template: Consensus statement of the society of abdominal radiology and the american pancreatic association

Pancreatic ductal adenocarcinoma is an aggressive malignancy with a high mortality rate. Proper determination of the extent of disease on imaging studies at the time of staging is one of the most important steps in optimal patient management. Given the variability in expertise and definition of disease extent among different practitioners as well as frequent lack of complete reporting of pertinent imaging findings at radiologic examinations, adoption of a standardized template for radiology reporting, using universally accepted and agreed on terminology for solid pancreatic neoplasms, is needed. A consensus statement describing a standardized reporting template authored by a multi-institutional group of experts in pancreatic ductal adenocarcinoma that included radiologists, gastroenterologists, and hepatopancreatobiliary surgeons was developed under the joint sponsorship of the Society of Abdominal Radiologists and the American Pancreatic Association. Adoption of this standardized imaging reporting template should improve the decision-making process for the management of patients with pancreatic ductal adenocarcinoma by providing a complete, pertinent, and accurate reporting of disease staging to optimize treatment recommendations that can be offered to the patient. Standardization can also help to facilitate research and clinical trial design by using appropriate and consistent staging by means of resectability status, thus allowing for comparison of results among different institutions.

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.

MELD-XI score and cardiac mortality or transplantation in patients after Fontan surgery

Objective The Fontan operation is a staged palliation for complex congenital heart disease and single ventricle physiology. Perioperative survivors of the Fontan operation experience long-term cardiac complications, including death. Liver and renal dysfunction are reported in these patients and have a direct effect on morbidity and mortality. This study aims to investigate whether the Model for End-stage Liver Disease eXcluding INR score (function of creatinine and total bilirubin, MELD-XI) predicts risk for cardiac mortality or transplantation in patients with Fontan circulation. Design and setting Retrospective, single-centre study. Time of first evaluation was the time of the earliest available MELD-XI score measurement, and follow-up was terminated by a cardiac event or by the last clinical evaluation. Patients Patients surviving after Fontan surgery and evaluated at Boston Childrens Hospital between 1993 and 2008. Main outcome measure Composite endpoint of sudden death, death from congestive heart failure or cardiac transplantation. Results The MELD-XI score was calculated as MELD-XI=11.76(loge creatinine)+5.112(loge total bilirubin)+9.44. Ninety-six patients were included (52 male, median age 26 years). After a mean follow-up period of 5.7 years, 18 patients (19%) experienced the composite end point. Baseline MELD-XI score was independently and directly related to the incidence of the composite endpoint (HR for high MELD-XI score group of 7.76, 95% CI 2.05 to 29.33, p=0.008). Conclusions Fontan patients with a higher MELD-XI score have shorter freedom from sudden cardiac death, death from congestive heart failure and cardiac transplantation.

Renal Cell Carcinoma: T1 and T2 Signal Intensity Characteristics of Papillary and Clear Cell Types Correlated with Pathology

OBJECTIVE The objective of our study was to describe the T1 and T2 signal intensity characteristics of papillary renal cell carcinoma (RCC) and clear cell RCC with pathologic correlation. MATERIALS AND METHODS Of 539 RCCs, 49 tumors (21 papillary RCCs and 28 clear cell RCCs) in 45 patients were examined with MRI. Two radiologists retrospectively and independently assessed each tumors T1 and T2 signal intensity qualitatively and quantitatively (i.e., the signal intensity [SI] ratio [tumor SI / renal cortex SI]). Of the 49 tumors, 37 (76%) were assessed for pathology features including tumor architecture and the presence of hemosiderin, ferritin, necrosis, and fibrosis. MRI findings and pathology features were correlated. Statistical methods included summary statistics and Wilcoxons rank sum test for signal intensity, contingency tables for assessing reader agreement, concordance rate between the two readers with 95% CIs, and Fishers exact test for independence, all stratified by RCC type. RESULTS Papillary RCCs and clear cell RCCs had a similar appearance and signal intensity ratio on T1-weighted images. On T2-weighted images, most papillary RCCs were hypointense (reader 1, 13/21; reader 2, 14/21), with an average mean signal intensity ratio for both readers of 0.67 +/- 0.2, and none was hyperintense, whereas most clear cell RCCs were hyperintense (reader 1, 21/28; reader 2, 17/28), with an average mean signal intensity ratio for both readers of 1.41 +/- 0.4 (p < 0.05). A tumor T2 signal intensity ratio of < or = 0.66 had a specificity of 100% and sensitivity of 54% for papillary RCC. Most T2 hypointense tumors exhibited predominant papillary architecture; most T2 hyperintense tumors had a predominant nested architecture (p < 0.05). CONCLUSION On T2-weighted images, most papillary RCCs are hypointense and clear cell RCCs, hyperintense. The T2 hypointense appearance of papillary RCCs correlated with a predominant papillary architecture at pathology.

Computed tomography features of nonalcoholic steatohepatitis with histopathologic correlation

Objective: This study was conducted to describe the computed tomography (CT) features of nonalcoholic steatohepatitis (NASH) and to evaluate if the CT features could be used to diagnose and stage NASH. Methods: From 1994 until 2004, pathology records revealed 68 patients with NASH. Of these, 12 patients underwent CT scans before (n = 6), on the same day as (n = 3), or after (n = 3) a liver biopsy. Using the same database, 9 patients with steatosis alone evaluated with a CT scan before (n = 2), on the same day as (n = 3), or after (n = 4) the liver biopsy were selected as a control group. Two radiologists measured liver attenuation (compared with spleen) and assessed the pattern of steatosis, craniocaudal liver span, caudate-to-right lobe ratio, preportal space distance, and presence of porta hepatis lymph nodes and ascites. Biopsy specimens were assessed by a pathologist, and the degree of necroinflammatory activity, steatosis, and fibrosis was determined. Histopathologic and CT findings were compared between patients with NASH and patients with steatosis alone using the Mann-Whitney U test and Fisher exact test. Results: In patients with NASH, the mean liver-to-spleen attenuation ratio was 0.66 (range: 0.1-1.1). Steatosis was diffuse (n = 9), geographic or nonlobar (n = 2), or diffuse with an area of focal sparing (n = 1). The liver craniocaudal span varied from 17.5 to 25.5 cm (mean = 21.4 cm), and hepatomegaly was present in 11 (91.7%) patients. The caudate-to-right-lobe ratio (mean = 0.43) and preportal space (mean = 4.5 mm) were normal in all cases. Porta hepatis lymph nodes were present in 7 (58.3%) patients; their mean dimensions were 16 mm × 11 mm. Ascites was absent in all patients. On histopathology, the degree of necroinflammatory activity was mild (n = 9), moderate (n = 1), or severe (n = 2). The degree of steatosis was 33% to 66% (n = 5) or >67% (n = 7). All but 3 patients had fibrosis; 6 had focal nonbridging fibrosis, 1 had multifocal nonbridging fibrosis, and 2 had bridging fibrosis. There was a significant correlation between the degree of steatosis on pathologic examination and the liver-to-spleen attenuation ratio on CT (P = 0.048). The severity of inflammation and stage of fibrosis on pathologic examination did not correlate with the CT features. Among patients with steatosis alone, the mean liver-to-spleen attenuation ratio was 0.80 (range: 0.3-1.2); the craniocaudal liver span varied from 12 to 20 cm (mean = 16 cm); hepatomegaly was present in 2 (22.2%) patients; the caudate-to-right lobe ratio was normal in all patients, with a mean of 0.36 (range: 0.22-0.47); the preportal space distance was enlarged in 2 cases (mean = 7.5 mm, range: 1-16 mm); porta hepatis lymph nodes were present in 7 (77.8%) patients, and their mean dimensions were 11 mm × 8 mm (large axis range: 6-19 mm, short axis range: 4-14 mm); and no patient had ascites. There was a significant difference in the craniocaudal liver span between patients with NASH (mean = 21 cm) and patients with steatosis (mean = 16 cm) (P < 0.05). The caudate-to-right-lobe ratio was also significantly different between patients with NASH (mean = 0.43) and patients with steatosis (mean = 0.36) (P < 0.05). There were no significant differences in liver-to-spleen attenuation ratios, measurements of preportal space, or the presence of porta hepatic lymph nodes. Conclusion: The CT features of NASH include steatosis, hepatomegaly, and porta hepatis lymph nodes, and the liver-to-spleen attenuation ratio correlated with the degree of steatosis on histopathology. Patients with NASH had a greater liver span and increased caudate-to-right-lobe-ratio compared with patients with steatosis alone.

Pancreatic Ductal Adenocarcinoma Radiology Reporting Template: Consensus Statement of the Society of Abdominal Radiology and the American Pancreatic Association

Pancreatic ductal adenocarcinoma is an aggressive malignancy with a high mortality rate. Proper determination of the extent of disease on imaging studies at the time of staging is one of the most important steps in optimal patient management. Given the variability in expertise and definition of disease extent among different practitioners as well as frequent lack of complete reporting of pertinent imaging findings at radiologic examinations, adoption of a standardized template for radiology reporting, using universally accepted and agreed on terminology for solid pancreatic neoplasms, is needed. A consensus statement describing a standardized reporting template authored by a multi-institutional group of experts in pancreatic ductal adenocarcinoma that included radiologists, gastroenterologists, and hepatopancreatobiliary surgeons was developed under the joint sponsorship of the Society of Abdominal Radiologists and the American Pancreatic Association. Adoption of this standardized imaging reporting template should improve the decision-making process for the management of patients with pancreatic ductal adenocarcinoma by providing a complete, pertinent, and accurate reporting of disease staging to optimize treatment recommendations that can be offered to the patient. Standardization can also help to facilitate research and clinical trial design by using appropriate and consistent staging by means of resectability status, thus allowing for comparison of results among different institutions.