Dhiraj Yadav

Trends in the epidemiology of the first attack of acute pancreatitis: a systematic review.

Objective: To systematically review trends in the epidemiology of the first attack of acute pancreatitis (AP) based on reported population-based studies. Methods: From Medline, we retrieved 18 full-length English language peer-reviewed original articles published from 1966 to June 2005 with population-based information on the epidemiology of first-attack AP. Trends over time were analyzed based on study- and country-specific data and the study site (UK vs non-UK). Results: Eight studies were from the UK and 10 from other European centers. An increase in the annual incidence per 100,000 for first-attack AP was reported in 10 of 12 studies with longitudinal data from 4 countries (UK, Sweden, Denmark, and Netherlands). The overall AP incidence seems to be higher in non-UK studies compared with that of UK, partly explained by a higher incidence of alcoholic pancreatitis in non-UK studies. A linear trend for increase in gallstone pancreatitis incidence over time was observed irrespective of the study site (UK or non-UK). The AP incidence and mortality increased with age. Gallstone pancreatitis was more common in female subjects, and alcoholic pancreatitis was more common in middle-aged male subjects. The AP case fatality (%) has decreased over time, but the overall population mortality rate per 100,000 has remained unchanged. Recurrence after the first attack is milder with a substantially lower mortality. Conclusions: The incidence of AP seems to be increasing. Differences in the incidence and etiology between and within countries reflect differences in the risk factor prevalence. Case-fatality rate, but not the population-based mortality rate, decreased over time.

Issues in hyperlipidemic pancreatitis.

Hypertriglyceridemia (HTG) is a rare cause of pancreatitis. Pancreatitis secondary to HTG, presents typically as an episode of acute pancreatitis (AP) or recurrent AP, rarely as chronic pancreatitis. A serum triglyceride (TG) level of more than 1,000 to 2,000 mg/dL in patients with type I, IV, or V hyperlipidemia (Fredricksons classification) is an identifiable risk factor. The typical clinical profile of hyperlipidemic pancreatitis (HLP) is a patient with a preexisting lipid abnormality along with the presence of a secondary factor (e.g., poorly controlled diabetes, alcohol use, or a medication) that can induce HTG. Less commonly, a patient with isolated hyperlipidemia (type V or I) without a precipitating factor presents with pancreatitis. Interestingly, serum pancreatic enzymes may be normal or only minimally elevated, even in the presence of severe pancreatitis diagnosed by imaging studies. The clinical course in HLP is not different from that of pancreatitis of other causes. Routine management of AP caused by hyperlipidemia should be similar to that of other causes. A thorough family history of lipid abnormalities should be obtained, and an attempt to identify secondary causes should be made. Reduction of TG levels to well below 1,000 mg/dL effectively prevents further episodes of pancreatitis. The mainstay of treatment includes dietary restriction of fat and lipid-lowering medications (mainly fibric acid derivatives). Experiences with plasmapheresis, lipid pheresis, and extracorporeal lipid elimination are limited.

Long-term outcomes of autoimmune pancreatitis: a multicentre, international analysis

Objective Autoimmune pancreatitis (AIP) is a treatable form of chronic pancreatitis that has been increasingly recognised over the last decade. We set out to better understand the current burden of AIP at several academic institutions diagnosed using the International Consensus Diagnostic Criteria, and to describe long-term outcomes, including organs involved, treatments, relapse frequency and long-term sequelae. Design 23 institutions from 10 different countries participated in this multinational analysis. A total of 1064 patients meeting the International Consensus Diagnostic Criteria for type 1 (n=978) or type 2 (n=86) AIP were included. Data regarding treatments, relapses and sequelae were obtained. Results The majority of patients with type 1 (99%) and type 2 (92%) AIP who were treated with steroids went into clinical remission. Most patients with jaundice required biliary stent placement (71% of type 1 and 77% of type 2 AIP). Relapses were more common in patients with type 1 (31%) versus type 2 AIP (9%, p<0.001), especially those with IgG4-related sclerosing cholangitis (56% vs 26%, p<0.001). Relapses typically occurred in the pancreas or biliary tree. Retreatment with steroids remained effective at inducing remission with or without alternative treatment, such as azathioprine. Pancreatic duct stones and cancer were uncommon sequelae in type 1 AIP and did not occur in type 2 AIP during the study period. Conclusions AIP is a global disease which uniformly displays a high response to steroid treatment and tendency to relapse in the pancreas and biliary tree. Potential long-term sequelae include pancreatic duct stones and malignancy, however they were uncommon during the study period and require additional follow-up. Additional studies investigating prevention and treatment of disease relapses are needed.

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 alcohol and smoking in pancreatitis.

Chronic alcohol use has been linked to chronic pancreatitis for over a century, but it has not been until the last decade that the role of alcohol in chronic pancreatitis has been elucidated in animals and, only in recent years, in human populations. Although a dose-dependent association between alcohol consumption and chronic pancreatitis may exist, a staistical association has been shown only with the consumption of ≥5 alcoholic drinks per day. Smoking also confers a strong, independent and dose-dependent risk of pancreatitis that may be additive or multiplicative when combined with alcohol. Alcohol increases the risk of acute pancreatitis in several ways and, most importantly, changes the immune response to injury. Genetic factors are also important and further studies are needed to clarify the role of gene–environment interactions in pancreatitis. In humans, aggressive interventional counseling against alcohol use may reduce the frequency of recurrent attacks of disease and smoking cessation may help to slow the progression of acute to chronic pancreatitis.

Incidence, Prevalence, and Survival of Chronic Pancreatitis: A Population-Based Study

OBJECTIVES:Population-based data on chronic pancreatitis (CP) in the United States are scarce. We determined incidence, prevalence, and survival of CP in Olmsted County, MN.METHODS:Using Mayo Clinic Rochesters Medical Diagnostic Index followed by a detailed chart review, we identified 106 incident CP cases from 1977 to 2006 (89 clinical cases, 17 diagnosed only at autopsy); CP was defined by previously published Mayo Clinic criteria. We calculated age- and sex-adjusted incidence (for each decade) and prevalence rate (1 January 2006) per 100,000 population (adjusted to 2000 US White population). We compared the observed survival rate for patients with expected survival for age- and sex-matched Minnesota White population.RESULTS:Median age at diagnosis of CP was 58 years, 56% were male, and 51% had alcoholic CP. The overall (clinical cases or diagnosed only at autopsy) age- and sex-adjusted incidence was 4.05/100,000 person-years (95% confidence interval (CI) 3.27–4.83). The incidence rate for clinical cases increased significantly from 2.94/100,000 during 1977–1986 to 4.35/100,000 person-years during 1997–2006 (P<0.05) because of an increase in the incidence of alcoholic CP. There were 51 prevalent CP cases on 1 January 2006 (57% male, 53% alcoholic). The age- and sex-adjusted prevalence rate per 100,000 population was 41.76 (95% CI 30.21–53.32). At last follow-up, 50 patients were alive. Survival among CP patients was significantly lower than age- and sex-specific expected survival in Minnesota White population (P<0.001).CONCLUSIONS:Incidence and prevalence of CP are low, and ∼50% are alcohol related. The incidence of CP cases diagnosed during life is increasing. Survival of CP patients is lower than in the Minnesota White population.

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 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.