Michael R. O'Connell

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.

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.

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.

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.

Smoking is underrecognized as a risk factor for chronic pancreatitis

Background/Aims: Smoking is an established risk factor for chronic pancreatitis (CP). We sought to identify how often and in which CP patients physicians consider smoking to be a risk factor. Methods: We analyzed data on CP patients and controls prospectively enrolled from 19 US centers in the North American Pancreatitis Study-2. We noted each subject’s self-reported smoking status and quantified the amount and duration of smoking. We noted whether the enrolling physician (gastroenterologist with specific interest in pancreatology) classified alcohol as the etiology for CP and selected smoking as a risk factor. Results: Among 382/535 (71.4%) CP patients who were self-reported ever smokers, physicians cited smoking as a risk factor in only 173/382 (45.3%). Physicians cited smoking as a risk factor more often among current smokers, when classifying alcohol as CP etiology, and with higher amount and duration of smoking. We observed a wide variability in physician decision to cite smoking as a risk factor. Multivariable regression analysis however confirmed that the association of CP with smoking was independent of physician decision to cite smoking as a risk factor. Conclusions: Physicians often underrecognize smoking as a CP risk factor. Efforts are needed to raise awareness of the association between smoking and CP.

Use and perceived effectiveness of non-analgesic medical therapies for chronic pancreatitis in the United States

Aliment Pharmacol Ther 2011; 33: 149–159

Hospitalizations and testing in gastroparesis

Background and Aim:  Gastroparesis significantly impairs the quality of life in affected individuals and may lead to repeat hospitalizations due to refractory symptoms. We hypothesized that pain is a key reason for emergency encounters and diagnostic testing.

Hospitalizations for Chronic Pancreatitis in Allegheny County, Pennsylvania, USA

Background/Aims: Population-based estimates for chronic pancreatitis (CP) are scarce. We determined incident CP hospitalization rates and the risk of pancreatitis-related readmissions in Allegheny County, Pennsylvania, USA. Methods: We used Pennsylvania Health Care Cost Containment Council (PHC4) dataset to identify all unique White and Black Allegheny County residents with incident hospitalization for CP from years 1996–2005. We noted presence of alcoholism codes (from one year before index hospitalization until last contact) and pancreatitis-related readmissions until the third quarter of 2007. Age-, sex-, and race-adjusted (to US 2000 population) rates/100,000 were calculated. Results: 988 unique County residents with incident hospitalization for CP were identified. Of these, 37.6% also received alcoholism codes. Overall hospitalization rate was 7.75/100,000 (95% CI 7.26–8.24), which remained stable throughout the study period. Patients with alcoholism codes were significantly younger (47.2 vs. 58.0 years), more likely to be male (71.4 vs. 36.6%), and Black (38.5 vs. 17.7%). Hospitalization rates were significantly higher (2.4-fold) in Blacks (vs. Whites), particularly for those with alcoholism codes. During follow-up (median 45 months), pancreatitis-related readmissions were common, significantly more so for patients with alcoholism codes. Conclusions: CP hospitalization rates over a one-decade period were stable. Readmissions were highest among patients with a diagnosis of alcoholism.

TNF-alpha gene (TNFA) variants increase risk for multi-organ dysfunction syndrome (MODS) in acute pancreatitis

BACKGROUND/OBJECTIVES Acute pancreatitis (AP) is a complex inflammatory syndrome with unpredictable progression to systemic inflammation and multi-organ dysfunction syndrome (MODS). Tumor necrosis factor alpha (TNF-α) is a cytokine that may link inflammation to the systemic inflammatory response syndrome (SIRS), which usually precedes MODS. Small genetic cohort studies of the TNFA promoter in AP produced ambiguous results. We performed a comprehensive evaluation of TNFA promoter variants to assess both susceptibility to AP and risk of progression to MODS. METHODS We prospectively ascertained 401 controls and 211 patients with AP that were assessed for persistent SIRS (>48 h) and MODS. MODS was defined as failure of ≥2 organ systems (cardiovascular, pulmonary, and/or renal) persisting more than 48 h. Subjects were genotyped by DNA sequencing and analyzed for SNPs at -1031 C/T (rs1799964), -863 A/C (rs1800630), -857 C/T (rs1799724), -308 A/G (rs1800629), and -238 A/G (rs361525). RESULTS Twenty-three of 211 AP patients (11%) developed MODS. TNFA promoter variants were not associated with susceptibility to AP, but progression to MODS was associated with the minor allele at -1031C (56.5% vs. 32.4% P = 0.022, OR: 2.7; 95%CI: 1.12-6.51) and -863A (43.5% vs. 21.8% P = 0.022, OR: 2.76; 95%CI: 1.12-6.74). CONCLUSION TNFA promoter variants do not alter susceptibility to AP, but rather the TNF-α expression-enhancing -1031C and -863A alleles significantly increased the risk of AP progression to MODS. These data, within the context of previous studies, clarify the risk of specific genetic variants in TNFA and therefore the role of TNF-α in the overall AP syndrome.

ABO blood group and chronic pancreatitis risk in the NAPS2 cohort.

Objectives: A risk association has been observed between non-O blood groups and pancreatic adenocarcinoma. Chronic pancreatitis also increases risk for pancreatic cancer, raising questions as to whether non-O blood groups are a risk for chronic pancreatitis and whether the pathophysiologic pathways are linked. Our goal was to determine whether ABO blood group may affect the risk of chronic pancreatitis. Methods: The study cohort included chronic pancreatitis patients (n = 499) and healthy controls (n = 631) from the North American Pancreatitis Study 2 study. Genotyping was performed using Sequenom assay of rs8176746 A/C and rs505922 C/T to classify participants into ABO blood groups. Results: O blood group was nonsignificantly more common among cases (44.7% vs 42.0%; P = 0.36), particularly among cases with alcohol-related chronic pancreatitis (49.3% vs 42%; P = 0.060). Alcoholic patients without coexisting high-risk PRSS1, CFTR, or SPINK1 variants had a significant overrepresentation of O blood type when compared with controls (odds ratio, 1.54; 95% confidence interval, 1.09-2.17; P = 0.01). Conclusions: A, B, and AB blood groups were not associated with a greater likelihood of having chronic pancreatitis and may decrease the risk of chronic pancreatitis in individuals who are very heavy drinkers. These results suggest that the mechanism linking non-O blood type with pancreatic pathology is specific to carcinogenesis.