Satish Munigala

Increased Risk of Pancreatic Adenocarcinoma After Acute Pancreatitis

BACKGROUND & AIMS Acute pancreatitis (AP) is often the initial presentation of pancreatic cancer (pancreatic adenocarcinoma [PaCa]). We evaluated the risk of PaCa after AP. METHODS We performed a retrospective study of patients with AP who sought care in the Veterans Health Administration from 1998 through 2007. We excluded patients with pre-existing PaCa or recurrent AP and those who had the first episode of acute pancreatitis, from 1998 through 2000. RESULTS Of 495,504 patients with Veterans Health Administration inpatient and outpatient records, 5720 were diagnosed with AP (1.15%) and 710 were diagnosed with PaCa (0.14%), from 2000 through 2007. Seventy-six patients had AP within 2 years before being diagnosed with PaCa (10.7% of all patients with cancer diagnosed during that period). The risk for PaCa was greatest in the first year after AP (14.5 per 1000 patient-years) and then decreased rapidly. Risk for PaCa was negligible in patients <40 years old. The incidence of PaCa within the first year after AP was 7.69 per 1000 patient-years in fifth decade of life and reached 28.67 after the seventh decade. Time to diagnosis of PaCa after AP was ≤2 months for 34 patients, 3-12 months for 35 patients, 13-24 months for 7 patients, and >24 months for 10 patients. CONCLUSIONS A significant number of patients with PaCa initially present with AP; the diagnosis of cancer is often delayed by up to 2 years. We suggest that PaCa be routinely considered as a potential etiology of AP in patients ≥40 years old.

Patients with obstructive jaundice and biliary stricture ± mass lesion on imaging: prevalence of malignancy and potential role of EUS-FNA.

Background: In patients with obstructive jaundice and biliary stricture, the role of endoscopic ultrasound-guided fine-needle aspiration (EUS-FNA) is debated for fear of missing a potentially resectable pancreatobiliary malignancy (PBM). We evaluated the prevalence of (1) PBM; (2) lesions that do not require a potentially curative cancer surgery; and (3) potentially resectable PBMs in patients with false-negative diagnosis by EUS-FNA. Patients and Methods: This is a retrospective analysis of 342 patients who underwent EUS/EUS-FNA from 2002 to 2009 after presenting with obstructive jaundice and a biliary stricture. Of these, 170 patients had no definitive mass on computed tomography and 172 patients had definitive mass on computed tomography without evidence of unresectability. Final diagnosis was based on surgical pathology or definitive cytology and clinical follow-up of ≥12 months. Results: The mean age of patients (176 male) was 68.0±12.5 years. A final diagnosis of malignancy was made in only 248 patients (72.5%; 95% confidence interval, 67.7, 77.2). The overall accuracy of EUS-FNA for diagnosing malignancy was 92.4% (89.0, 94.8), with 91.5% sensitivity (87.1, 94.5) and 80.9% negative predictive value (72.0, 87.5). Among 21 patients with false-negative diagnosis, 8 had cholangiocarcinoma (2 resectable), 13 had pancreatic cancer (5 resectable). EUS-FNA provided information to potentially modify surgical management in 116 patients (33.9%; 95% confidence interval, 29.1, 39.0): 89 patients diagnosed as true negatives, 24 with distant malignant lymphadenopathy, and 3 with malignant lymphoma. Conclusions: In above-defined patient subset, the risk of missing resectable tumors by EUS-FNA has been exaggerated because of artifactually low negative predictive value resulting from a high pretest probability of PBM. The actual miss rate for resectable PBM by EUS-FNA is rather small and was 2% in present cohort. Information from EUS-FNA can potentially modify surgical management in up to one third of patients.

Prevalence of qacA/B Genes and Mupirocin Resistance Among Methicillin-Resistant Staphylococcus aureus (MRSA) Isolates in the Setting of Chlorhexidine Bathing Without Mupirocin

OBJECTIVE We aimed to determine the frequency of qacA/B chlorhexidine tolerance genes and high-level mupirocin resistance among MRSA isolates before and after the introduction of a chlorhexidine (CHG) daily bathing intervention in a surgical intensive care unit (SICU). DESIGN Retrospective cohort study (2005-2012) SETTING: A large tertiary-care center PATIENTS Patients admitted to SICU who had MRSA surveillance cultures of the anterior nares METHODS A random sample of banked MRSA anterior nares isolates recovered during (2005) and after (2006-2012) implementation of a daily CHG bathing protocol was examined for qacA/B genes and high-level mupirocin resistance. Staphylococcal cassette chromosome mec (SCCmec) typing was also performed. RESULTS Of the 504 randomly selected isolates (63 per year), 36 (7.1%) were qacA/B positive (+) and 35 (6.9%) were mupirocin resistant. Of these, 184 (36.5%) isolates were SCCmec type IV. There was a significant trend for increasing qacA/B (P=.02; highest prevalence, 16.9% in 2009 and 2010) and SCCmec type IV (P<.001; highest prevalence, 52.4% in 2012) during the study period. qacA/B(+) MRSA isolates were more likely to be mupirocin resistant (9 of 36 [25%] qacA/B(+) vs 26 of 468 [5.6%] qacA/B(-); P=.003). CONCLUSIONS A long-term, daily CHG bathing protocol was associated with a change in the frequency of qacA/B genes in MRSA isolates recovered from the anterior nares over an 8-year period. This change in the frequency of qacA/B genes is most likely due to patients in those years being exposed in prior admissions. Future studies need to further evaluate the implications of universal CHG daily bathing on MRSA qacA/B genes among hospitalized patients.

Diagnostic Performance of Endoscopic Ultrasound (EUS) for Non-Calcific Chronic Pancreatitis (NCCP) Based on Histopathology.

Objectives:Studies correlating endoscopic ultrasound (EUS) with histopathology for chronic pancreatitis (CP) are limited by small sample size, and/or inclusion of many patients without CP, limiting applicability to patients with painful CP. The aim of this study was to assess correlation of standard EUS features for CP with surgical histopathology in a large cohort of patients with non-calcific CP (NCCP).Methods:Adult patients undergoing total pancreatectomy and islet autotransplantation (TPIAT) for NCCP, between 2008 and 2013, with EUS <1 year before surgery. Histology from resected pancreas at the time of TPIAT (from head, body, and tail) was graded by a GI pathologist blinded to the EUS features. A fibrosis score (FS) ≥2 was abnormal, and FS≥6 was considered severe fibrosis. A multivariate regression analysis for the EUS features predicting fibrosis, after taking age, sex, smoking, and body mass index into consideration, was performed. A quantitative receiver operating characteristic (ROC) curve analysis was performed and Spearman rank correlation co-efficient (r) was calculated.Results:68 patients (56 females, mean±s.d. age-38.77±10.92) underwent TPIAT for NCCP with pre-operative EUS. ROC curve showed that four or more EUS features provided the best balance of sensitivity (61%), specificity (75%), and accuracy (63%). Although significant, correlation between standard EUS features and degree of fibrosis was poor (r=0.24, P<0.05). Multivariate regression analysis showed that main pancreatic duct irregularity was the only independent EUS feature (P=0.02) which predicted CP.Conclusions:Correlation between standard EUS features and histopathology is poor in NCCP. MPD irregularity is an independent predictor for NCCP.

Diagnostic Performance of Contrast-Enhanced MRI With Secretin-Stimulated MRCP for Non-Calcific Chronic Pancreatitis: A Comparison With Histopathology

OBJECTIVES:Diagnosis of non-calcific chronic pancreatitis (NCCP) in patients presenting with chronic abdominal pain is challenging and controversial. Contrast-enhanced magnetic resonance imaging (MRI) with secretin-stimulated MRCP (sMRCP) offers a safe and noninvasive modality to diagnose mild CP, but its findings have not been correlated with histopathology. We aimed to assess the correlation of a spectrum of MRI/sMRCP findings with surgical histopathology in a cohort of NCCP patients undergoing total pancreatectomy with islet autotransplantation (TPIAT).METHODS:Adult patients undergoing TPIAT for NCCP between 2008 and 2013 were identified from our institution’s surgery database and were included if they had MRI/sMRCP within a year before surgery. Histology was obtained from resected pancreas at the time of TPIAT by wedge biopsy of head, body, and tail, and was graded by a gastrointestinal pathologist who was blinded to the imaging features. A fibrosis score (FS) of 2 or more was considered as abnormal, with FS ≥6 as severe fibrosis. A multivariate regression analysis was performed for MRI features predicting fibrosis, after taking age, sex, smoking, alcohol, and body mass index (BMI) into consideration. A quantitative receiver operating characteristic (ROC) curve analysis was performed and Spearman rank correlation coefficient (r) was calculated.RESULTS:Fifty-seven patients (females=49, males=8) with NCCP and MRI/sMRCP were identified. ROC curve analysis showed that two or more MRI/sMRCP features provided the best balance of sensitivity (65%), specificity (89%), and accuracy (68%) to differentiate abnormal (FS≥2) from normal pancreatic tissue. Two or more features provided the best cutoff (sensitivity 88%, specificity 78%) for predicting severe fibrosis (FS≥6). There was a significant correlation between the number of features and severity of fibrosis (r=0.6, P<0.0001). A linear regression after taking age, smoking, and BMI into consideration showed that main pancreatic duct irregularity, T1-weighted signal intensity ratio between pancreas and paraspinal muscle, and duodenal filling after secretin injection to be significant independent predictors of fibrosis.CONCLUSIONS:A strong correlation exists between MRI/sMRCP findings and histopathology of NCCP.

Efficacy and safety of therapeutic ERCP in patients with cirrhosis: a large multicenter study.

BACKGROUND AND AIMS Patients with cirrhosis may be less than optimal candidates for ERCP because of underlying ascites, coagulopathy, encephalopathy, and other problems. Although the risks of surgery in patients with cirrhosis are well known, few data are available regarding ERCP in patients with cirrhosis. We performed a retrospective, multicenter study of ERCP in patients with cirrhosis to evaluate outcomes, efficacy, and safety. METHODS Multicenter retrospective study. RESULTS A total of 538 ERCP procedures were performed on 328 patients with cirrhosis. A total of 229 patients had Child-Pugh (CP) class A, 229 patients had CP class B, and 80 patients had CP class C. Thrombocytopenia and coagulopathy were corrected before ERCP. The 30-day, procedure-related adverse events included post-ERCP pancreatitis (n = 25, 4.6%: 21 mild, 3 moderate, 1 severe), hemorrhage (n = 6, 1.1%), cholangitis (n = 15, 2.8%), perforation (n = 2, 0.4%), aspiration pneumonia (n = 5, 0.9%), bile leakage (n = 1, 0.2%), cholecystitis (n = 1, 0.2%), and death (n = 1, 0.2%). There was a higher incidence of adverse events in patients with CP class B and C disease when compared with those with CP class A disease (11.4%, 11.3%, and 6.1%, respectively; P = .048). There was no correlation between the risk of significant hemorrhage and the presence of coagulopathy or CP class, even in those who underwent a sphincterotomy. The presence of poorly controlled encephalopathy correlated with a higher overall adverse event rate (P = .003). Sub-analysis revealed that patients without primary sclerosing cholangitis had a significantly higher overall rate of adverse events, pancreatitis, bleeding, and cardiopulmonary adverse events after ERCP when compared with those with primary sclerosing cholangitis. CONCLUSIONS Our study was performed on a large series of patients with cirrhosis undergoing ERCP. Overall, the adverse events seen in patients with cirrhosis are similar to those seen in the general population of patients undergoing ERCP, although patients with CP classes B and C have higher adverse event rates compared with those with CP class A. Patients with cirrhosis without primary sclerosing cholangitis had significantly greater adverse event rates when compared with patients with primary sclerosing cholangitis.

Heavy Smoking Is Associated With Lower Age at First Episode of Acute Pancreatitis and a Higher Risk of Recurrence.

Objective There is limited data on cigarette smoking and the risk of acute pancreatitis (AP). We evaluated the influence of cigarette smoking on AP risk and clinical presentation in a large cohort of Veterans Administration (VA) patients. Methods Retrospective study of VA patients from 1998 to 2007. Exclusion criteria included (1) history of chronic pancreatitis (n = 3222) or gallstones (n = 14,574) and (2) age younger than 15 years (n = 270). A 2-year washout period was used to exclude patients with pre-existing recurrent AP. Results The study included 484,624 patients. From 2001 to 2007, a total of 6799 (1.4%) patients had AP. Alcohol (risk ratio, 4.20) and smoking (risk ratio, 1.78) were independent significant risk factors of AP on multiple regression analysis. Smoking increased the risk of AP in both nonalcoholics (0.57% vs 1.1%) and alcoholics (2.6% vs 4.1%). Smoking was associated with younger mean age at first episode of AP and higher likelihood of recurrent AP (≥4 episodes) in both nonalcoholics and alcoholics. The interval between recurrent episodes was not altered by alcohol or smoking. Conclusions In a large cohort of VA patients, smoking is an independent risk factor for AP and augmented the effect of alcohol on the risk, age of onset, and recurrence of AP.

Case-fatality from acute pancreatitis is decreasing but its population mortality shows little change

BACKGROUND/OBJECTIVES The reasons for changing epidemiology of acute pancreatitis (AP) are poorly defined. We hypothesized that trends for severity, case-fatality and population mortality from AP will provide an insight into the rising burden of AP in the population. We evaluated trends in the hospitalizations, case-fatality, severity and population mortality related to AP in the US population. STUDY We used the National Hospital Discharge Survey to calculate age, sex and race standardized hospitalizations of and case-fatality rates for AP, and Vital Statistics to calculate AP-related population mortality from 1983 to 2010, using 2010 US census as the reference. RESULTS Number of discharges per 100,000 population with primary diagnosis of AP increased 2 times from 42.4 (95% CI 38.2-46.5) during 1983-1986 to 85.4 (95% CI 62.8-108.1) during 2007-2010. During corresponding intervals, case-fatality from AP decreased 62% from 2.02% (95% CI 2.01-2.04) to 0.79% (95% CI 0.78-0.80), but population mortality per million population due to AP as primary cause remained stable from 9.28 (95% CI 8.94-9.62) to 9.91 (95% CI 9.56-10.26), and from AP as any cause decreased significantly (but only 12%) from 20.87 (95% CI 20.36-21.38) to 18.48 (95% CI 18.00-18.96). Prevalence of severe AP increased from 5% (95% CI 4.95-5.05%) during 1991-1994 to 9.78% (95% CI 9.73-9.83%) during 2007-2010. CONCLUSION An increasing prevalence of severe disease suggests true population increase to be an important contributor to the rising incidence of AP. A lack of proportional increase in population mortality suggests the impact of medical advances in the evaluation and management of AP.

Chronic Pancreatitis and Fracture: A Retrospective, Population-Based Veterans Administration Study.

Objectives There is increasing evidence that chronic pancreatitis (CP) is a risk factor for osteoporotic fracture, but data on males with CP and fracture prevalence are sparse. We determined the association of sex and age using a large Veterans Administration database. Methods This was a retrospective analysis (1998–2007). Patients with CP (International Classification of Diseases code 577.1) and control subjects (without CP) were identified after exclusions and fracture prevalence (vertebral, hip, and wrist) were recorded. Results 453,912 Veterans Administration patients were identified (control subjects: 450,655 and patients with CP: 3257). Mean ages of control subjects and CP were 53.6 and 54.2 years (P < 0.014). Patients with CP had higher odds ratios of total fractures (2.35; 95% confidence interval [CI], 2.00–2.77), vertebral fracture 2.11 (95% CI, 1.44–3.01), hip fracture 3.49 (95% CI, 2.78–4.38), and wrist fracture 1.68 (95% CI, 1.29–2.18) when compared with control subjects. After adjusting for age group and etiology, patients with CP had increased odds of total fractures, vertebral fractures, and hip fractures (P < 0.05). Conclusions In this male-predominate Veterans Administration study, patients with CP were at increased risk of osteoporotic fractures. The risk was higher for hip fracture (>3 times) in patients with CP compared with control subjects. All patients with CP older than 45 years, irrespective of sex, should be screened for bone mineral density loss.

529 Esophageal Contraction Wave Abnormalities on High Resolution Manometry (HRM) Not Meeting Chicago Classification Criteria: Are They Clinically Relevant?

Introduction: The subjective perception of solid bolus hold up during swallowing is a common reason for referral for manometric investigation, yet standardmeasures of esophageal function relate poorly to patient perception and a large proportion of patients with dysphagia demonstrate no apparent abnormality on routine diagnostic testing for esophageal dysfunction. The utility of combined esophageal pressure-impedance recording has been recently enhanced by automated impedance manometry pressure-flow analysis (AIM analysis) and newmetrics have been conceived that better describe the interactions between bolus transport and pressure generation. In this study we undertook to assess whether these new esophageal pressure-flow metrics were altered when subjects perceived solid bolus hold up. Methods: Esophageal high-resolution pressure-impedance recordings of 5ml/10ml liquid/viscous swallows and 2cm/4cm solid swallows from 20 control subjects (29-73 years) were analysed. Two solid state pressure(P)/impedance(Z) catheter configurations were used; 32 1cm P/16 2cm Z (Sandhill Scientific) and 36 1cm P/18 2cm Z (Given Imaging). Bolus flow resistance, the relationship between bolus compression and bolus flow timing, was assessed using the pressure flow index (PFI) (Myers et al Neurogastro. Mot. 2012; Nguyen et al Neurogastro. Mot. 2012). Heightened perception of bolus hold up was assessed on a swallow by swallow basis using a 6 point scale (1 = no perception, 2 = awareness of bolus transit, 3-6 = bolus hold up). Results: On a swallow by swallow analysis, heightened perception of solid boluses (swallows with scores 3+) was associated with a higher PFI (distal esophagus Odds Ratio for score 3+ 1.001 [1.000 1.002], p = 0.021). A significant correlation was observed between the maximum subject reported perception score and the average PFI for solids (distal esophagus Pearsons r = 0.690, p,0.001). Grouping of subjects in relation to bolus perception revealed that the PFI was elevated for solids and viscous boluses, but not liquids, in subjects reporting bolus hold up (Figure). Esophageal peak pressures and iso-contour defect size were not significantly related to bolus perception. Conclusion: We report novel findings in relation to mechanical factors during bolus transport that may enhance bolus perception. This study shows that heightened perception of a swallowed bolus relates to subtle differences in flow resistance, which suggests higher levels of muscle tension during the transition phase from a bolus-containing to a lumen-occluded esophageal segment.