Opiate Prescriptions at Discharge Are Not Associated with Early Readmissions in Acute Pancreatitis.

BACKGROUND: Early readmissions in acute pancreatitis (AP) are common. The impact of opiate prescriptions on readmissions is unknown. AIMS: To determine whether the prescription of opiates at hospital discharge and the dose prescribed are associated with early readmissions in AP. METHODS: Direct admissions from the Emergency Department (ED) for AP from September 1, 2013, to August 31, 2016 were identified. Opiate prescription was defined as a new prescription at discharge in an opiate-naïve patient. Early readmission was ED visit or hospitalization within 30 days for an AP-related reason. Multivariable logistic regression was performed, adjusted for age, Charlson Comorbidity Index, pancreatic necrosis, baseline opiate use, non-opiate analgesics, and pain score at discharge. RESULTS: A total of 318 AP patients were identified; the overall early readmission rate was 18%. One hundred and twenty-one (38%) were prescribed opiates at discharge, and 22% had an early readmission. One hundred and ninety-seven (62%) were not prescribed opiates, and 16% had an early readmission. Median opiate dose was 48 mg (24-h morphine equivalents). On multivariable analysis, neither the prescription of opiates (OR 1.2, 95% CI 0.6-2.4, p = 0.55) nor the dose of opiates (OR 0.99, 95% CI 0.99-1.00, p = 0.39) was associated with early readmission. In subset analysis of patients discharged with an opiate prescription, those on opiates at baseline were significantly more likely to have an early readmission (OR 4.19, 95% CI 1.04-16.94, p = 0.04). CONCLUSIONS: In AP patients, neither prescription of opiates at discharge nor prescribed dose was associated with early readmission. Patients on opiates at baseline discharged with an opiate prescription were more likely to have an early readmission.

Outcomes of Chronic Pancreatitis in the Emergency Department.

OBJECTIVES: Chronic pancreatitis (CP) is a debilitating chronic illness. We sought to assess the most common reasons patients with CP visit the Emergency Department (ED), the disposition of ED visit [admission, discharge, death], and evaluate predictors of admission and discharge. METHODS: Within the Health Care Utilization Project Nationwide Emergency Department Sample (NEDS), we focused on patients, 18 years and older, presenting to the emergency department with CP (ICD-9 code 577.1) (2006-2009). Model was fitted to predict the likelihood of admission. RESULTS: Overall, a weighted sample of 638,310 patients visits for CP were identified, of which 399,559 (62.6%) were admitted, 228,523 (35.8%) were discharged from the ED, 5572 (0.9%) discharged against medical advice, and 4656 (0.7%) had an unknown destination. Of those admitted, 4370 (0.7%) died during the hospital episode. The most associated diagnoses for ED visit were diabetes (28.8%), abdominal pain (25.4%), acute pancreatitis (22.5%), cardiac complication (11.1%), infection (10.1%), and dehydration (8.8%). Multivariable analyses revealed that older (OR = 1.02 P < 0.001), sicker patients (Charlson Comorbidity Index ≥ 3, OR = 2.28 P < 0.001), patients presenting with C. difficile colitis (OR = 23.85 P < 0.001), alcohol withdrawal (OR = 6.71 P < 0.001), and acute pancreatitis (OR = 6.46 P < 0.001) were associated with increased odds of hospitalization. CONCLUSIONS: In this national database, our study demonstrates that diabetes, followed by abdominal pain, acute pancreatitis and cardiac complication, were the most common diagnoses associated with ED visits in patients with chronic pancreatitis. Most patients were admitted following the ED visit. Although C. Difficile colitis was a rare associated diagnosis with an ED visit, it was the strongest predictor of admission.

Early Abdominal Imaging Remains Over-Utilized in Acute Pancreatitis.

BACKGROUND: Early abdominal computed tomography (CT) or magnetic resonance (MR) imaging is common in acute pancreatitis (AP). Guidelines (2007-2013) indicate routine use is unwarranted. AIMS: To compare the frequency and evaluate the predictors of early CT/MR utilization for AP between September 2006-2007 (period A) and September 2014-2015 (period B). METHODS: AP patients presenting directly to a large academic emergency department were prospectively enrolled during each period. Cases requiring imaging to fulfill diagnostic criteria were excluded. Early CT/MR (within 24 h of presentation) utilization rates were compared using Fisher's exact test. Predictors of early imaging usage were assessed with multivariate logistic regression. RESULTS: The cohort included 96 AP cases in period A and 97 in period B. There were no significant differences in patient demographics, comorbidity scores, or AP severity. Period B cases manifested decreased rates of the systemic inflammatory response syndrome (SIRS) during the first 24 h of hospitalization (67% period A vs. 43% period B, p = 0.001). Independent predictors of early imaging included age >60 and SIRS or organ failure on day 1. No significant decrease in early CT/MR usage was observed from period A to B on both univariate (49% period A vs. 40% period B, p = 0.25) and multivariate (OR 1.0 for period B vs. A, 95% CI 0.5-1.9) analysis. CONCLUSIONS: In a comparison of imaging practices for AP, there was no significant decrease in early abdominal CT/MR utilization from 2007 to 2015. Quality improvement initiatives specifically targeting early imaging overuse are needed.

Diagnosis of Chronic Pancreatitis Incorporating Endosonographic Features, Demographics, and Behavioral Risk.

OBJECTIVES: Diagnosing chronic pancreatitis remains challenging. Endoscopic ultrasound (EUS) is utilized to evaluate pancreatic disease. Abnormal pancreas function test is considered the "nonhistologic" criterion standard for chronic pancreatitis. We derived a prediction model for abnormal endoscopic pancreatic function test (ePFT) by enriching EUS findings with patient demographic and pancreatitis behavioral risk characteristics. METHODS: Demographics, behavioral risk characteristics, EUS findings, and peak bicarbonate results were collected from patients evaluated for pancreatic disease. Abnormal ePFT was defined as peak bicarbonate of less than 75 mEq/L. We fit a logistic regression model and converted it to a risk score system. The risk score was validated using 1000 bootstrap simulations. RESULTS: A total of 176 patients were included; 61% were female with median age of 48 years (interquartile range, 38-57 years). Abnormal ePFT rate was 39.2% (69/176). Four variables formulated the risk score: alcohol or smoking status, number of parenchymal abnormalities, number of ductal abnormalities, and calcifications. Abnormal ePFT occurred in 10.7% with scores 4 or less versus 92.0% scoring 20 or greater. The model C-statistic was 0.78 (95% confidence interval, 0.71-0.85). CONCLUSIONS: Number of EUS pancreatic duct and parenchymal abnormalities, presence of calcification, and smoking/alcohol status were predictive of abnormal ePFT. This simple model has good discrimination for ePFT results.

Low progression of intraductal papillary mucinous neoplasms with worrisome features and high-risk stigmata undergoing non-operative management: a mid-term follow-up analysis.

OBJECTIVE: To evaluate mid-term outcomes and predictors of survival in non-operated patients with pancreatic intraductal papillary mucinous neoplasms (IPMNs) with worrisome features or high-risk stigmata as defined by International Consensus Guidelines for IPMN. Reasons for non-surgical options were physicians' recommendation, patient personal choice or comorbidities precluding surgery. METHODS: In this retrospective, multicentre analysis, IPMNs were classified as branch duct (BD) and main duct (MD), the latter including mixed IPMNs. Univariate and multivariate analysis for overall survival (OS) and disease-specific survival (DSS) were obtained. RESULTS: Of 281 patients identified, 159 (57%) had BD-IPMNs and 122 (43%) had MD-IPMNs; 50 (18%) had high-risk stigmata and 231 (82%) had worrisome features. Median follow-up was 51 months. The 5-year OS and DSS for the entire cohort were 81% and 89.9%. An invasive pancreatic malignancy developed in 34 patients (12%); 31 had invasive IPMNs (11%) and 3 had IPMN-distinct pancreatic ductal adenocarcinoma (1%). Independent predictors of poor DSS in the entire cohort were age >70 years, atypical/malignant cyst fluid cytology, jaundice and MD >15 mm. Compared with MD-IPMNs, BD-IPMNs had significantly better 5-year OS (86% vs 74.1%, p=0.002) and DSS (97% vs 81.2%, p<0.0001). Patients with worrisome features had better 5-year DSS compared with those with high-risk stigmata (96.2% vs 60.2%, p<0.0001). CONCLUSIONS: In elderly patients with IPMNs that have worrisome features, the 5-year DSS is 96%, suggesting that conservative management is appropriate. By contrast, presence of high-risk stigmata is associated with a 40% risk of IPMN-related death, reinforcing that surgical resection should be offered to fit patients.

The Atlanta Classification, Revised Atlanta Classification, and Determinant-Based Classification of Acute Pancreatitis: Which Is Best at Stratifying Outcomes?

OBJECTIVES: To determine which classification is more accurate in stratifying severity. METHODS: The study used a retrospective analysis of a prospective acute pancreatitis database (June 2005-December 2007). Acute pancreatitis severity was stratified according to the Atlanta classification (AC) 1992, the revised Atlanta classification (RAC) 2012, and the determinant-based classification (DBC) 2012. Receiver operating characteristic analysis (area under the curve) compared the accuracy of each classification. Logistic regression identified predictors of mortality. RESULTS: 338 patients were analyzed: 13% had persistent organ failure (POF) (>48 hours), of whom 37% had multisystem POF, and 11% had pancreatic necrosis, of whom 19% had infected necrosis. Mortality was 4.1%. For predicting mortality (area under the curve), the RAC (0.91) and DBC (0.92) were comparable (P = 0.404); both outperformed the AC (0.81) (P < 0.001). For intensive care unit admission, the RAC (0.85) and DBC (0.85) were comparable (P = 0.949); both outperformed the AC (0.79) (P < 0.05). There were 2 patients in the critical category of the DBC. Multisystem POF was an independent predictor of mortality (odds ratio, 75.0; 95% confidence interval, 13.7-410.6; P < 0.001), whereas single-system POF, sterile necrosis, and infected necrosis were not. CONCLUSION: The RAC and DBC were generally comparable in stratifying severity. The paucity of patients in the critical category in the DBC limits its utility. Neither classification accounts for the impact of multisystem POF, which was the strongest predictor of mortality.

Randomized Noninferiority Trial Comparing Diagnostic Yield of Cytopathologist-guided versus 7 passes for EUS-FNA of Pancreatic Masses.

BACKGROUND AND AIM: To improve diagnostic yield of endoscopic ultrasound-guided fine needle aspiration (EUS-FNA) in solid pancreatic lesions, on-site cytology review has been recommended. Because this is not widely available throughout the world, the aim of this study was to compare the diagnostic yield of EUS-FNA performed with rapid on-site evaluation (ROSE) versus 7 FNA passes without ROSE in pancreatic masses. METHODS: In this multicenter randomized noninferiority trial, patients were randomized to ROSE versus 7 passes into a solid pancreatic mass. On the basis of the absolute difference in diagnostic yield with 7 passes versus cytopathologist-guidance, the noninferiority margin for the difference in diagnostic yield was defined as -15%. Definite diagnosis was defined to include positive for malignancy, neoplastic cells present, and negative for malignancy. RESULTS: A total of 142 patients were randomized with 73 in the cytopathologist arm and 69 in the 7 passes arm. Diagnostic yield for definite diagnosis was 78.3% with 7 passes and 78.1% with cytopathology guidance. With an absolute difference 0.2%, 95% CI -14.4 to 14.6, performing 7 passes was noninferior to cytopathologist-guided EUS-FNA. There was no significant difference in complications or time to perform FNA. A median of 5 passes were performed with ROSE. The median charge with onsite cytopathology was significantly greater than performing 7 passes [$1058 (958, 1445) versus $375 (275, 460), p<0.001]. CONCLUSIONS: The diagnostic yield for performing 7 passes during EUS-FNA into solid pancreatic masses is noninferior with lower charge compared to cytopathologist-guidance. This article is protected by copyright. All rights reserved.

Evaluation of Qualitative Magnetic Resonance Imaging Features for Diagnosis of Chronic Pancreatitis.

OBJECTIVES: The purpose of this study was to determine qualitative pancreatic magnetic resonance imaging (MRI) features that must be present to predict abnormal pancreatic secretory function in patients evaluated for chronic pancreatitis (CP). METHODS: The MRIs of study subjects were reviewed by 2 abdominal radiologists; qualitative parenchyma and ductal features were recorded. Endoscopic pancreatic function test (ePFT) results (reference standard) were classified as normal (peak pancreatic fluid bicarbonate [HCO3-] ≥75 meq/L) or abnormal (<75). Abnormal ePFT was further classified as mild/moderate (74-65) and marked deficiency (<65). Statistical analysis was performed to assess the association between MRI features and abnormal ePFT. RESULTS: The study cohort was composed of 93 subjects, mean age 49 years (range, 18-78 years), 65% females. Univariate analysis identified 9 qualitative MRI features significantly (P < 0.05) associated with abnormal pancreatic secretory function. Number of MRI features increases as peak pancreatic fluid [HCO3-] decreases (Pearson r = -0.629; P = 0.001). Receiver operating characteristic curve analysis determined that a threshold of 6 or more associated MRI features 64% sensitive and 94% specific for marked bicarbonate deficiency. CONCLUSIONS: Qualitative MRI parenchymal and ductal features are associated with CP. Presence of 6 or more features results in a higher specificity for the diagnosis of CP in advanced disease.

Lycopene in the prevention of renal cell cancer in the TSC2 mutant Eker rat model.

Renal cell carcinoma (RCC) is the most frequent upper urinary tract cancer in humans and accounts for 80-85% of malignant renal tumors. Eker rat represents a unique animal model to study RCC since these rats develop spontaneous renal tumors and leiomyoma, which may be due to tuberous sclerosis 2 (TSC2) mutation resulting in the activation of the mammalian target of rapamycin (mTOR) pathway. This study examines the role of a lycopene-rich diet in the development of RCC in the TSC2 mutant Eker rat model. Ten-week old female Eker rats (n=90) were assigned in equal numbers to receive 0, 100 or 200mg/kg of lycopene as part of their daily diet. After 18 months the rats were sacrificed and the kidneys were removed. Immunohistochemical staining with antibodies against mTOR, phospho-S6 and EGFR were performed, as well as hematoxylin-eosin staining for histologic examination of the tumors. Tumors were counted and measured in individual kidneys. Presence of tumor decreased from 94% in control animals to 65% in the experimental group, but the difference was not statistically significant (P<0.12). However, mean numbers of renal carcinomas were statistically significantly decreased in the lycopene-treated rats (P<0.008) when compared to untreated controls. In the lycopene group, tumor numbers decreased (P<0.002) and the numbers tended to decrease linearly (P<0.003) as supplemental lycopene increased from 0 to 200. Control rats fed only basal diet had a greater length of tumors (23.98 mm) than rats fed lycopene supplement groups (12.90 mm and 11.07 mm) (P<0.05). Moreover tumor length decreased (P<0.02) and tumor length tended to decrease linearly (P<0.03) as supplemental lycopene increased from 0 to 200mg/kg. All tumors showed strong staining with antibodies against mTOR, phospho-S6 and EGFR. In conclusion, dietary supplementation with lycopene attenuates the development of renal cell cancers in the predisposed TSC2 mutant Eker rat model. These results suggest that lycopene may play a role in the prevention of RCC.

Pancreatic juice prostaglandin e2 concentrations are elevated in chronic pancreatitis and improve detection of early disease.

OBJECTIVES: Chronic pancreatitis (CP) may be difficult to diagnose in early stages. We aimed to measure pancreatic juice (PJ) prostaglandin E2 (PGE2) concentrations to determine whether they are elevated in CP and improve diagnosis of early disease. METHODS: We measured PJ PGE2 in 10 patients with established CP, 25 patients who met criteria for "minimal change" chronic pancreatitis (MCCP), and 10 normal control participants. RESULTS: Median PJ PGE2 was elevated in CP (307 pg/ml, IQR (249-362)) and MCCP (568 pg/ml, (418-854)) compared with normal controls (104 pg/ml, (68-206)) (P≤ 0.001). Area under receiving operator curve (AUROC) for diagnosis of CP and MCCP was 0.9 and 0.62, respectively, for PJ bicarbonate concentration alone; AUROC was 1.0 and 0.94 for the combination of PJ bicarbonate and PGE2 concentrations. CONCLUSIONS: PJ PGE2 appears to be a biomarker for CP and is elevated in both established and "minimal change" chronic pancreatitis.

Differential expression of GNAS and KRAS mutations in pancreatic cysts.

CONTEXT: KRAS mutations play an important role in pancreatic cancer. GNAS mutations were discovered in intraductal papillary mucinous neoplasms (IPMN). OBJECTIVES: Our aim was to identify the frequency of KRAS and GNAS mutations in pancreatic cystic neoplasms and pancreatic ductal adenocarcinoma (PDAC). METHODS: Sixty-eight surgically resected formalin fixed, paraffin embedded pancreatic specimens were analyzed, including: 1) benign (20 serous cystadenoma (SCA)), 2) pre-malignant (10 mucinous cystic neoplasm (MCN), 10 branch duct intraductal papillary mucinous neoplasm (BD-IPMN), 9 main duct IPMN (MD-IPMN)), 3) malignant (19 PDAC). Total nucleic acid extraction was performed. KRAS codon 12/13 and GNAS codon 201 mutations were interrogated via targeted sequencing using the Ion Torrent's Personal Genome Machine (PGM). RESULTS: Mean age of 68 patients was 61.9±8.4 with 72% female. KRAS and GNAS mutations were more common in PDAC and IPMN. KRAS mutations predominated in PDAC compared to pancreatic cysts (16/19, 84% versus 10/49, 20%; P<0.001). GNAS mutations were more common in IPMN compared to non-IPMN lesions (8/19, 42% versus 2/49, 4%; P=0.0003). No GNAS mutations were detected in PDAC and MCN while 2 SCA carried GNAS mutations. Double mutations with KRAS and GNAS were only present in IPMN (5/19 versus 0/30 SCA and MCN, P=0.006). CONCLUSIONS: KRAS and GNAS mutations were more common in PDAC and IPMN with KRAS mutations primarily in PDAC and GNAS mutations more frequent in IPMN. No GNAS mutations occurred in MCN and double mutations were only present in IPMN.

A population-based assessment of the burden of acute pancreatitis in the United States.

OBJECTIVES: The aim of this study is to investigate the incidence and mortality of emergency department (ED) visits in the United States attributed to acute pancreatitis (AP) and quantify predictors of admission and mortality. METHODS: Using the nationwide ED sample, all ED visits between 2006 and 2009 for AP were extracted. Multivariable analyses were fitted for prediction of admission and mortality. RESULTS: A weighted sample of 1,224,121 patient visits with AP was captured. Of those, 75.4% resulted in admission and 0.7% died. Between 2006 and 2009, the incidence of AP ED visits increased from 9.9 to 10.6 per 10,000 person-years. Patients were more likely to be admitted if sicker (Charlson Comorbidity Index score ≥ 3; OR, 6.48; P < 0.001) and if the etiology of pancreatitis was alcoholic versus biliary (OR, 2.20; P < 0.001). They were more likely to die if sicker (Charlson Comorbidity Index score ≥ 3; OR, 1.51; P < 0.001) and covered with Medicare or Medicaid versus private insurance (OR, 1.40; P < 0.001 and OR, 1.45; P < 0.001, respectively). CONCLUSIONS: Emergency department visits for AP represent a significant burden on US health care. Although mortality is lower than previously reported, significant disparities exist in patients presenting with AP with regard to admission and mortality rates. Further investigations are needed to assess these disparities.

Investigating MicroRNA Expression Profiles in Pancreatic Cystic Neoplasms.

OBJECTIVES: Current diagnostic tools for pancreatic cysts fail to reliably differentiate mucinous from nonmucinous cysts. Reliable biomarkers are needed. MicroRNAs (miRNA) may offer insights into pancreatic cysts. Our aims were to (1) identify miRNAs that distinguish benign from both premalignant cysts and malignant pancreatic lesions using formalin-fixed, paraffin-embedded (FFPE) pathology specimens; (2) identify miRNAs that distinguish mucinous cystic neoplasm (MCN) from branch duct-intraductal papillary mucinous neoplasm (BD-IPMN). METHODS: A total of 69 FFPE pancreatic specimens were identified: (1) benign (20 serous cystadenoma (SCA)), (2) premalignant (10 MCN, 10 BD-IPMN, 10 main duct IPMN (MD-IPMN)), and (3) malignant (19 pancreatic ductal adenocarcinoma (PDAC)). Total nucleic acid extraction was performed followed by miRNA expression profiling of 378 miRNAs interrogated using TaqMan MicroRNA Arrays Pool A and verification of candidate miRNAs. Bioinformatics was used to generate classifiers. RESULTS: MiRNA profiling of 69 FFPE specimens yielded 35 differentially expressed miRNA candidates. Four different 4-miRNA panels differentiated among the lesions: one panel separated SCA from MCN, BD-IPMN, MD-IPMN, and PDAC with sensitivity 85% (62, 97), specificity 100% (93, 100), a second panel distinguished MCN from SCA, BD-IPMN, MD-IPMN, and PDAC with sensitivity and specificity 100% (100, 100), a third panel differentiated PDAC from IPMN with sensitivity 95% (76, 100) and specificity 85% (72, 96), and the final panel diagnosed MCN from BD-IPMN with sensitivity and specificity approaching 100%. CONCLUSIONS: MiRNA profiling of surgical pathology specimens differentiates serous cystadenoma from both premalignant pancreatic cystic neoplasms and PDAC and MCN from BD-IPMN.

Cigarette smoking impairs pancreatic duct cell bicarbonate secretion.

OBJECTIVE: To compare pancreatic duct cell function in smokers (current and past) and never smokers by measurement of secretin-stimulated peak bicarbonate concentration ([HCO3-]) in endoscopic collected pancreatic fluid (PF). METHODS: This retrospective study was cross-sectional in design, recording demographic information (age, gender, etc.), smoking status (former, current, never), alcohol intake, clinical data (imaging, endoscopy), and laboratory results (peak PF [HCO3-]) from subjects evaluated for pancreatic disease at a tertiary pancreas center. Univariate and multivariate statistical analysis (SAS Version 9.2, Cary, NC, USA) was performed to assess the relationship between cigarette smoking and secretin-stimulated pancreatic fluid bicarbonate concentration. RESULTS: A total of 131 subjects underwent pancreatic fluid collection (endoscopic pancreatic function test, ePFT) for bicarbonate analysis: 25.2% (33 out of 131) past smokers, 31.3% (41 out of 131) current smokers, and 43.5% (57 out of 131) were never smokers. Measures of Association: The mean peak PF [HCO3-] in never smokers (81.3 ± 18.5 mEq/L) was statistically higher (indicating better duct cell function) when compared to past smokers (66.8 ± 24.7 mEq/L, P=0.005) and current smokers (70.0 ± 20.2 mEq/L, P=0.005). However, the mean peak [HCO3-] in past smokers was not statistically different from that in current smokers (P=0.575), and therefore, the two smoking groups were combined to form a single "smokers cohort". When compared to the never smokers, the smokers cohort was older (P=0.037) and had a greater proportion of subjects with definite chronic pancreatitis imaging (P=0.010), alcohol consumption ≥20 g/day (P=0.012), and abnormal peak PF [HCO3-] (P<0.001). Risk-Based Estimates: Cigarette smoking (risk ratio, RR: 2.2, 95% CI: 1.3-3.5; P<0.001), diagnosis of definite chronic pancreatitis imaging (RR: 2.2, 95% CI: 1.6-3.2; P<0.001) and alcohol consumption ≥20 g/day (RR: 1.6, 95% CI: 1.1-2.4; P=0.033) were all associated with low mean peak PF [HCO3-] (indicating duct cell secretory dysfunction). Multivariate Analysis: Smoking (odds ratio, OR: 3.8, 95% CI: 1.6-9.1; P=0.003) and definite chronic pancreatitis imaging (OR: 5.7, 95% CI: 2.2-14.8; P<0.001) were determined to be independent predictors of low peak PF [HCO3-], controlling for age, gender, and alcohol intake. Furthermore there was no interaction between smoking status and alcohol intake in predicting duct cell dysfunction (P=0.571). CONCLUSION: Measurement of pancreatic fluid bicarbonate in smokers reveals that cigarette smoking (past and current) is an independent risk factor for pancreatic duct cell secretory dysfunction (low PF [HCO3-]). Furthermore, the risk of duct cell dysfunction in subjects who smoked was approximately twice the risk (RR: 2.2) in never smokers. Further in depth, translational research approaches to pancreatic fluid analysis may help unravel mechanisms of cigarette smoking induced pancreatic duct cell injury.

Interdisciplinary management of cystic neoplasms of the pancreas.

Cystic neoplasms of the pancreas are increasingly recognized due to the frequent use of abdominal imaging. It is reported that up to 20% of abdominal cross-sectional scans identify incidental asymptomatic pancreatic cysts. Proper characterization of pancreatic cystic neoplasms is important not only to recognize premalignant lesions that will require surgical resection, but also to allow nonoperative management of many cystic lesions that will not require resection with its inherent morbidity. Though reliable biomarkers are lacking, a wide spectrum of diagnostic modalities are available to evaluate pancreatic cystic neoplasms, including radiologic, endoscopic, laboratory, and pathologic analysis. An interdisciplinary approach to management of these lesions which incorporates recent, specialty-specific advances in the medical literature is herein suggested.

Inflammatory protein profiling of pancreatic cyst fluid using EUS-FNA in tandem with cytokine microarray differentiates between branch duct IPMN and inflammatory cysts.

BACKGROUND: Diagnosis of pancreatic cystic neoplasms remains problematic. We hypothesize that inflammatory mediator proteins in pancreatic cyst fluid can differentiate branch duct intraductal papillary mucinous neoplasms (BD-IPMNs) and pancreatic inflammatory cysts. We aim to 1) detect inflammatory mediator proteins (IMPs) using a multiplexed IMP-targeted microarray in pancreatic cyst fluid obtained during endoscopic ultrasound fine needle aspiration (EUS-FNA) and 2) compare IMP profiles in pancreatic cyst fluid from BD-IPMNs and inflammatory cysts. Pancreatic cyst fluid from ten patients (5 BD-IPMN and 5 inflammatory cysts) was obtained by EUS-FNA and analyzed directly with a multiplexed microarray assay to determine concentrations of 89 IMPs. Statistical analysis was performed using non-parametric methods. RESULTS: Eighty-three of the 89 assayed IMPs were detected in at least one of the 10 patient samples. Seven IMPs were detected in BD-IPMN but not inflammatory cysts, while eleven IMPs were identified in inflammatory cysts but not BD-IPMN. Notably, granulocyte-macrophage colony-stimulating factor (GM-CSF) expression was present in all five inflammatory cyst samples. Hepatocyte growth factor (HGF) was present in significantly higher concentrations in inflammatory cysts compared to BD-IPMN. CONCLUSION: Our exploratory analysis reveals that GM-CSF and HGF in EUS-FNA-collected pancreatic cyst fluid can distinguish between BD-IPMN and inflammatory cyst. Coupling microarray molecular techniques to EUS-FNA may represent a major step forward to our understanding complex pancreatic disease.

Anchoring depth electrodes for bedside removal: a "break-away" suturing technique for intracranial monitoring.

BACKGROUND: Intracranial depth electrodes for epilepsy are easily dislodged during long-term monitoring unless adequately anchored, but a technique is not available that is both secure and allows easy explantation without reopening the incision. OBJECTIVE: To describe a convenient and inexpensive method for anchoring depth electrodes that prevents migration and incidental pullout while allowing electrode removal at the bedside. METHODS: An easily breakable suture (eg, MONOCRYL) is tied around both the depth electrode and a heavy nylon suture and anchored to a hole at the edge of the burr hole; the tails of both are tunneled together percutaneously. The "break-away" MONOCRYL suture effectively anchors the electrode for as long as needed. At the completion of the intracranial electroencephalography session, the 2 tails of the nylon suture are pulled to break their encompassing MONOCRYL anchor suture, thus freeing the depth electrode for easy removal. RESULTS: The break-away depth electrode anchoring technique was used for 438 electrodes in 68 patients, followed by explantation of these and associated strip electrodes without reopening the incision. Only 1 electrode (0.2%) migrated spontaneously, and 3 depth electrodes (0.7%) fractured in 2 patients (2.9%) on explantation, necessitating open surgery to remove them in 1 of the patients (1.5%). CONCLUSION: An easy and inexpensive anchoring configuration for depth electrodes is described that provides an effective and safe means of securing the electrodes while allowing easy explantation at the bedside.

Differentiating Branch Duct and Mixed IPMN in Endoscopically Collected Pancreatic Cyst Fluid via Cytokine Analysis.

Background. Differentiating branch duct from mixed intraductal papillary mucinous neoplasm (BD-IPMN) is problematic, but clinically important as mixed IPMNs are managed surgically, while some BD-IPMN may be followed. Inflammatory mediator proteins (IMPs) have been implicated in acute and chronic inflammatory and malignant pancreatic diseases. Aim. To compare IMP profile of pancreatic cyst fluid collected endoscopically from BD-IPMN and mixed IPMN. Methods. Pancreatic cyst fluid from ten patients (5 BD-IPMN and 5 mixed IPMN) was collected by endoscopic ultrasound-guided fine needle aspiration or endoscopic retrograde cholangiopancreatography. Concentrations of 89 IMPs in these samples were determined using a multiplexed bead-based microarray protein assay and compared between BD-IPMN and mixed IPMN. Results. Eighty-six of 89 IMPs were detected in at least one of the 10 samples. Fourteen IMPs were detected only in mixed IPMN, while none were only in BD-IPMN. Of these, TGF-ß1 was most prevalent, present in 3 of 5 mixed IPMNs. Seventy-two IMPs were detected in both BD-IPMN and mixed IPMNs. Of these, only G-CSF (P < 0.05) was present in higher concentrations in mixed IPMNs. Conclusion. TGF-ß1 and G-CSF detected in endoscopically collected pancreatic cyst fluid are potential diagnostic biomarkers capable of distinguishing mixed IPMN from BD-IPMN.