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Although emerging data evidences that EUS-guided needle-based confocal laser endomicroscopy (nCLE) accurately diagnoses pancreatic cystic lesions (PCLs), there are a lack of interobserver agreement (IOA) studies utilizing reference histopathological diagnosis and for specific PCL subtypes. Hence, we sought to assess the IOA, intra-observer reliability (IOR), and diagnostic performance of EUS-nCLE using a large cohort of patients with histopathological diagnosis amongst a broad panel of international observers.EUS-nCLE videos (n = 76) of subjects with PCLs [intraductal papillary mucinous neoplasm (IPMN), mucinous cystic neoplasm (MCN), serous cystadenoma (SCA), pseudocyst, and cystic-neuroendocrine tumors/solid pseudopapillary neoplasm (cystic-NET/SPN)], simulating clinical prevalence rates were obtained from 3 prospective studies. An international panel of 13 endosonographers with nCLE experience, blinded to all PCL data, evaluated the video library twice with a two-week washout for PCL differentiation (mucinous vs. non-mucinous) and subtype diagnosis.The IOA (κ = 0.82, 95% CI 0.77-0.87) and IOR (κ = 0.82, 95% CI 0.78-0.85) were "almost perfect" to differentiate mucinous vs. non-mucinous PCLs. For PCL subtype, IOA was highest for SCA (almost perfect; κ = 0.85), followed by IPMN (substantial, κ = 0.72), and cystic-NET/SPN (substantial, κ = 0.73). The IOA was moderate for MCN (κ = 0.47), and pseudocyst (κ = 0.57). Compared to histopathology, observers differentiated mucinous vs. non-mucinous PCLs with high accuracy (94.8%, 95% CI 93.3-96.1). For detecting specific PCLs subtypes, EUS-nCLE was highly accurate in diagnosing non-mucinous cysts (SCA: 98%; cystic-NET/SPN: 96%; pseudocyst: 96%) and slightly less accurate for mucinous lesions (IPMN: 86%; MCN: 84%).Diagnosis of PCLs by EUS-nCLE guided virtual biopsy is very accurate and reliable for the most prevalent pancreatic cysts in clinical practice.

Insulin resistance (IR) increases the risk of index colorectal cancer (CRC) development. Limited data exist on IR values, lifestyle, and anthropometric alterations of patients after CRC diagnosis, a population at high risk for CRC recurrence.This is a retrospective cohort study using the National Health and Nutrition Examination Survey (NHANES), 1999-2010. We identified patients with and without prior CRC above age 50. Our outcomes were lifestyle, anthropometric measures, and IR measured using the triglyceride to high-density lipoprotein ratio and the homeostasis model assessment IR.There were 146,841 patients with prior CRC and 26,979,507 without prior cancer (controls) in our cohort. Prior patients with CRC were significantly older than controls (75.8 vs 62.3, P0.01), however, there were no significant differences in gender, ethnicity, income, caloric intake, tobacco use or alcohol consumption between both groups. Multivariate analysis revealed no difference between prior patients with CRC and controls in triglyceride to high-density lipoprotein ratio (adjusted percentage change = -2.17; 95% CI: -27.96 to 18.43) or homeostasis model assessment IR (adjusted percentage change = -6.85; 95% CI: -35.74 to 15.90). Despite similar weight at age 25, prior CRC subjects had lower weights compared to controls (at time of NHANES survey, one and 10 years before survey and greatest weight). Furthermore prior CRC subjects gained less weight in the 10 years before survey.Patients with prior CRC above age 50 have no conclusive evidence of increased IR compared to non-CRC controls. This is possibly due to lesser weight gain in the peri-CRC diagnosis or treatment period. Future efforts should focus on alternate etiologies for the increased CRC recurrence in this high-risk group.

Background and Aims Previous studies have validated EUS-guided needle-based confocal laser endomicroscopy (nCLE) diagnosis of intraductal papillary mucinous neoplasms (IPMNs). We sought to derive EUS-guided nCLE criteria for differentiating IPMNs with high-grade dysplasia/adenocarcinoma (HGD-Ca) from those with low/intermediate-grade dysplasia (LGD). Methods We performed a post hoc analysis of consecutive IPMNs with a definitive diagnosis from a prospective study evaluating EUS-guided nCLE in the diagnosis of pancreatic cysts. Three internal endosonographers reviewed all nCLE videos for the patients and identified potential discriminatory EUS-guided nCLE variables to differentiate HGD-Ca from LGD IPMNs (phase 1). Next, an interobserver agreement (IOA) analysis of variables from phase 1 was performed among 6 blinded external nCLE experts (phase 2). Last, 7 blinded nCLE-naive observers underwent training and quantified variables with the highest IOA from phase 2 using dedicated software (phase 3). Results Among 26 IPMNs (HGD-Ca in 16), the reference standard was surgical histopathology in 24 and cytology confirmation of metastatic liver lesions in 2 patients. EUS-guided nCLE characteristics of increased papillary epithelial “width” and “darkness” were the most sensitive variables (90%; 95% confidence interval [CI], 84%-94% and 91%; 95% CI, 85%-95%, respectively) and accurate (85%; 95% CI, 78%-90% and 84%; 95% CI, 77%-89%, respectively) with substantial (κ = 0.61; 95% CI, 0.51-0.71) and moderate (κ = 0.55; 95% CI, 0.45-0.65) IOAs for detecting HGD-Ca, respectively (phase 2). Logistic regression models were fit for the outcome of HGD-Ca as predictor variables (phase 3). For papillary width (cut-off ≥50 μm), the sensitivity, specificity, and area under the receiver operating characteristic curve (AUC) for detection of HGD-Ca were 87.5% (95% CI, 62%-99%), 100% (95% CI, 69%-100%), and 0.95, respectively. For papillary darkness (cut-off ≤90 pixel intensity), the sensitivity, specificity, and AUC for detection of HGD-Ca were 87.5% (95% CI, 62%-99%), 100% (95% CI, 69%-100%), and 0.90, respectively. Conclusions In this derivation study, quantification of papillary epithelial width and darkness identified HGD-Ca in IPMNs with high accuracy. These quantifiable variables can be used in multicenter studies for risk stratification of IPMNs. (Clinical trial registration number: NCT02516488.)

Endoscopic ultrasound (EUS) has been routinely utilized for the locoregional staging of esophageal cancer. One important aspect of clinical staging has been to stratify patients to treatment with neoadjuvant chemoradiation or primary surgical therapy. We hypothesized that EUS may have a limited impact on clinical decision making in patients with dysphagia and obstructing esophageal masses. This retrospective cohort study included all patients with esophageal adenocarcinoma undergoing esophageal EUS between July 2008 and September 2013. Dysplastic Barrett’s esophagus without invasive adenocarcinoma or incomplete staging was excluded. Patient demographics, endoscopic tumor characteristics, the presence of dysphagia, sonographic staging, and post-EUS therapy were recorded. Pathologic staging for patients who underwent primary surgical therapy was also recorded. Locally advanced disease was defined as at least T3 or N1, as these patients are typically treated with neoadjuvant therapy. Two hundred sixteen patients underwent EUS for esophageal adenocarcinoma, with 147 (68.1%) patients having symptoms of dysphagia on initial presentation. Patients with dysphagia were significantly more likely to have locally advanced disease on EUS than patients without dysphagia (p

The work-up of cystic lesions of the pancreas often involves endoscopic ultrasound (EUS) with fine needle aspiration (FNA). In addition to CEA and amylase measurement, fluid is routinely sent for cytologic examination. We evaluated the utility of cytologic findings in clinical decision-making.Records of patients who underwent EUS-guided pancreatic cyst aspiration were reviewed. Findings from axial imaging and EUS were compared to cyst fluid cytology as well as fluid amylase and CEA. All results were then compared to final diagnosis, determined by clinical analysis for those patients not resected, and surgical pathology report for those who underwent resection.A total of 167 patients were reviewed. Of 48 patients with suspicious findings on imaging, cytology yielded diagnostic information in 89.6 % of cases (43 patients). However, in the 119 patients where no suspicious components were revealed on imaging, fluid cytology yielded no significant diagnostic results in any case. In all cases where mucin was noted on cytologic review, thick fluid was also seen at the time of aspiration.In our cohort of patients with cystic pancreatic lesions, cytologic analysis of pancreatic cyst fluid yielded no diagnostic benefit over radiologic findings alone. In such cases where fluid is to be aspirated, specimens that would otherwise be sent for cytologic evaluation would be better served for other purposes, such as molecular analysis or banking for future research.

Imaging patterns from endoscopic ultrasound (EUS)-guided needle-based confocal laser endomicroscopy (nCLE) have been associated with specific pancreatic cystic lesions (PCLs). We compared the accuracy of EUS with nCLE in differentiating mucinous from nonmucinous PCLs with that of measurement of carcinoembryonic antigen (CEA) and cytology analysis.We performed a prospective study of 144 consecutive patients with a suspected PCL (≥20 mm) who underwent EUS with fine-needle aspiration of pancreatic cysts from June 2015 through December 2018 at a single center; 65 patients underwent surgical resection. Surgical samples were analyzed by histology (reference standard). During EUS, the needle with the miniprobe was placed in the cyst, which was analyzed by nCLE. Fluid was aspirated and analyzed for level of CEA and by cytology. We compared the accuracy of nCLE in differentiating mucinous from nonmucinous lesions with that of measurement of CEA and cytology analysis.The mean size of dominant cysts was 36.4 ± 15.7 mm and the mean duration of nCLE imaging was 7.3 ± 2.8 min. Among the 65 subjects with surgically resected cysts analyzed histologically, 86.1% had at least 1 worrisome feature based on the 2012 Fukuoka criteria. Measurement of CEA and cytology analysis identified mucinous PCLs with 74% sensitivity, 61% specificity, and 71% accuracy. EUS with nCLE identified mucinous PCLs with 98% sensitivity, 94% specificity, and 97% accuracy. nCLE was more accurate in classifying mucinous vs nonmucinous cysts than the standard method (P.001). The overall incidence of postprocedure acute pancreatitis was 3.5% (5 of 144); all episodes were mild, based on the revised Atlanta criteria.In a prospective study, we found that analysis of cysts by nCLE identified mucinous cysts with greater accuracy than measurement of CEA and cytology analysis. EUS with nCLE can be used to differentiate mucinous from nonmucinous PCLs. ClincialTrials.gov no: NCT02516488.

Objective The aim of this study is to determine the diagnostic accuracy of preoperative evaluation to detect main pancreatic duct involvement in pancreatic cystic lesions thus differentiating mixed intraductal papillary mucinous neoplasm (IPMN) from branch duct (BD)-IPMN. Methods The pathology database of pancreatic resections from 2000 to 2014 was reviewed. Main pancreatic duct-IPMNs and IPMNs with intracystic mass/nodules were excluded. The preoperative test characteristics were analyzed using surgical histopathology as the "gold standard." Results Sixty BD-IPMNs and 23 mixed-IPMNs were identified. Mixed-IPMNs were larger (mean [standard deviation], 4.14 [2.9] vs 2.74 [1.9] mm; P = 0.03) and demonstrated frequent high-grade dysplasia/adenocarcinoma (43% vs 12%, P = 0.004) than BD-IPMNs. Endoscopic ultrasound (EUS) (sensitivity, 80%; specificity, 78%; accuracy, 79%) had the best diagnostic accuracy, whereas magnetic resonance imaging (MRI) (sensitivity, 83%; specificity, 63%; accuracy, 68%) had the highest sensitivity for the diagnosis of mixed-IPMN. A combination of EUS and MRI reached maximum sensitivity but with decreased accuracy (sensitivity, 100%; specificity, 64%; accuracy, 67%). The area under the curve for receiver operation curve was 0.71 whereas the optimal cyst size to detect main duct involvement was 3 cm. Conclusions For preoperative evaluation of pancreatic cystic lesions without evidence of intracystic nodules, a combination of MRI and EUS should be considered for improved detection of main duct involvement.

Objectives Diverticulitis in patients on immunosuppressant therapy has been associated with increased mortality, but there are no data for HIV-infected patients. Our aim was to compare the outcomes of hospitalizations for diverticulitis in patients with and without HIV infection. Methods Cross-sectional study of hospitalizations in the United States accessed through the Nationwide Inpatient Sample, Healthcare Cost and Utilization Project. Patients hospitalized for diverticulitis in 2007–2011 were included in the analysis. The primary outcomes of interest were mortality and surgical therapy rates. Patients from 2003 to 2011 were utilized to analyse trends in prevalence. Results There were 2375 patients with HIV infection hospitalized for diverticulitis and 1 160 391 patients without HIV infection hospitalized for diverticulitis from 2007 to 2011. The patients with HIV infection were younger and more likely to be male and nonwhite (P

OBJECTIVES Our objective was to delineate predictive factors differentiating groove pancreatitis (GP) from other lesions involving the head of the pancreas (HOP). METHODS A case-control study of patients older than 10 years was performed comparing patients with GP to those with other surgically resected HOP lesions. RESULTS Thirteen patients with GP (mean ± SD age, 51.9 ± 10.5 years; 11 males [84.6%]), all with a history of smoking (mean, 37.54 ± 17.8 pack-years), were identified. Twelve patients (92.3%) had a history of heavy alcohol drinking (heavy alcohol [EtOH]). The mean lesion size was 2.6 ± 1.1 cm, and the CA 19-9 was elevated (>37 IU/mL) in 5 patients (45.5%). The most common histopathologic condition was duodenal wall cyst with myofibroblastic proliferation and changes of chronic pancreatitis in the HOP.Univariate analysis revealed decreasing age, male sex, weight loss, nausea/vomiting, heavy EtOH, smoking, and a history of chronic pancreatitis were predictive of GP. A multivariate analysis among smokers demonstrated that weight loss (P = 0.006; odds ratio, 11.96; 95% confidence interval, 2.1-70.2), and heavy EtOH (P < 0.001; odds ratio, 82.2; 95% confidence interval, 9.16-738.1) were most predictive of GP. Compared to pancreatic adenocarcinoma (n = 183), weight loss and heavy EtOH remained predictive of GP. CONCLUSION Groove pancreatitis in the HOP is associated with a history of heavy EtOH and weight loss. In the absence of these symptoms, it is essential to rule out a malignant lesion.

Background: Blockade of the vascular endothelial growth factor (VEGF) pathway shows evidence of activity in gastro-oesophageal (GE) and oesophageal cancer. We investigated the efficacy of sunitinib, a multikinase VEGF inhibitor, in patients with relapsed/refractory GE/oesophageal cancer. Methods: This was a single-stage Fleming phase II study. The primary end point was progression-free survival (PFS) at 24 weeks. If five or more patients out of a total of 25 were free of progressive disease at 24 weeks, sunitinib would be recommended for further study. Patients received sunitinib 37.5 mg orally daily and imaged every 6 weeks. Exploratory correlative analysis included serum growth factors, tumour gene expression and dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI). Results: Twenty-five evaluable patients participated in the study. Progression-free survival at 24 weeks was 8% (n=2 patients; confidence interval (CI): 95% 1.4–22.5%), and the duration of best response for the patients was 23 and 72 weeks. Ten patients (42%) had stable disease (SD) for >10 weeks. Overall response rate is 13%. Median PFS is 7 weeks (95% CI: 5.6–11.4 weeks) and the median overall survival is 17 weeks (95% CI: 8.9–25.3 weeks). Most common grade 3/4 toxicities included fatigue (24%), anaemia (20%) thrombocytopenia (16%), and leucopenia (16%). No patients discontinued therapy due to toxicity. Serum VEGF-A and -C levels, tumour complement factor B (CFB) gene expression, and DCE-MRI correlated with clinical benefit, defined as SD or better as best response. Conclusion: Sunitinib is well tolerated but only a select subgroup of patients benefited. Serum VEGF-A and -C may be early predictors of benefit. On this study, patients with clinical benefit from sunitinib had higher tumour CFB expression, and thus has identified CFB as a potential predictor for efficacy of anti-angiogenic therapy. These findings need validation from future prospective trials.

To evaluate national health care use and costs for pediatric acute pancreatitis.The Kids' Inpatient Database for 2006, 2009, and 2012 was queried for patients with a principal diagnosis of acute pancreatitis. Cases were grouped by age: preschool (5 years of age), school age (5-14 years of age), and adolescents (14 years of age).A total of 27 983 discharges for acute pancreatitis were found. The number of admissions increased with age: young n = 1279, middle n = 8012, and older n = 18 692. Duration of stay was highest in preschool children (median, 3.47 days; IQR, 2.01-7.35), compared with school age (median, 3.22 days; IQR, 1.81-5.63) and adolescents (median, 2.87 days; IQR, 1.61-4.81; P .001). The median cost of hospitalization varied with age: $6726 for preschoolers, $5400 for school-aged children, and $5889 for adolescents (P .001). Acute pancreatitis-associated diagnoses varied by age. The presence of gallstone pancreatitis, alcohol, and hypertriglyceridemia was more common among older children compared with younger children (P .001). There was an increasing trend in acute pancreatitis, chronic pancreatitis, and obesity for the 2 older age groups (P .001).Admission of children for acute pancreatitis constitutes a significant healthcare burden, with a rising number of admissions with age. However, the cost and duration of stay per admission are highest in young children.

Patients with metastatic colorectal cancer can develop jaundice from intrahepatic or extrahepatic causes. Currently, there is little data on the underlying causes and overall survival after onset of jaundice. The purpose of this study was to characterize the causes of jaundice and determine outcomes.Six hundred twenty-nine patients treated for metastatic colorectal cancer between 2004 and 2010 were retrospectively reviewed. Those developing jaundice were grouped as having intrahepatic or extrahepatic obstruction. Demographics, clinicopathologic, and outcome data were analyzed.Sixty-two patients with metastatic colorectal cancer developed jaundice. Intrahepatic biliary obstruction was most common, occurring in younger patients. Time from metastatic diagnosis to presentation of jaundice was similar between groups, as was the mean number of prior lines of chemotherapy. Biliary decompression was successful 41.7 % of the time and was attempted more commonly for extrahepatic causes. Median overall survival after onset of jaundice was 1.5 months and it was similar between groups, but improved to 9.6 months in patients who were able to receive further chemotherapy.Jaundice due to metastatic colorectal cancer is an ominous finding, representing aggressive tumor biology or exhaustion of therapies. Biliary decompression is often difficult and should only be pursued when additional treatment options are available.

Background and Aims EUS-guided needle-based confocal laser endomicroscopy (nCLE) characteristics of common types of pancreatic cystic lesions (PCLs) have been identified; however, surgical histopathology was available in a minority of cases. We sought to assess the performance characteristics of EUS nCLE for differentiating mucinous from non-mucinous PCLs in a larger series of patients with a definitive diagnosis. Methods Six endosonographers (nCLE experience >30 cases each) blinded to all clinical data, reviewed nCLE images of PCLs from 29 patients with surgical (n = 23) or clinical (n = 6) correlation. After 2 weeks, the assessors reviewed the same images in a different sequence. A tutorial on available and novel nCLE image patterns was provided before each review. The performance characteristics of nCLE and the κ statistic for interobserver agreement (IOA, 95% confidence interval [CI]), and intraobserver reliability (IOR, mean ± standard deviation [SD]) for identification of nCLE image patterns were calculated. Landis and Koch interpretation of κ values was used. Results A total of 29 (16 mucinous PCLs, 13 non-mucinous PCLs) nCLE patient videos were reviewed. The overall sensitivity, specificity, and accuracy for the diagnosis of mucinous PCLs were 95%, 94%, and 95%, respectively. The IOA and IOR (mean ± SD) were κ = 0.81 (almost perfect); 95% CI, 0.71-0.90; and κ = 0.86 ± 0.11 (almost perfect), respectively. The overall specificity, sensitivity, and accuracy for the diagnosis of serous cystadenomas (SCAs) were 99%, 98%, and 98%, respectively. The IOA and IOR (mean ± SD) for recognizing the characteristic image pattern of SCA were κ = 0.83 (almost perfect); 95% CI, 0.73-0.92; and κ = 0.85 ± 0.11 (almost perfect), respectively. Conclusions EUS-guided nCLE can provide virtual histology of PCLs with a high degree of accuracy and inter- and intraobserver agreement in differentiating mucinous versus non-mucinous PCLs. These preliminary results support larger multicenter studies to evaluate EUS nCLE. (Clinical trial registration number: NCT02516488.)

Left ventricular assist devices (LVADs) are being utilized for management of end-stage heart failure and require systemic anticoagulation. Gastrointestinal bleeding (GIB) is one of the most common adverse events following LVAD implantation. To investigate the impact of continuous-flow (CF) LVAD implants on outcomes of patients admitted with GIB. This is a cross-sectional study utilizing the Nationwide Inpatient Sample in the CF-LVAD era from 2010 to 2012. All adult admissions with a primary diagnosis of GIB were included. Among hospitalizations with GIB, patients with (cases) and without (controls) CF-LVAD implants were compared using univariate and multivariate analyses. The main outcome measurements were in-hospital mortality, length of stay, and hospitalization costs. Among 1,002,299 hospitalizations for GIB, 1112 (0.11%) patients had CF-LVADs. Bleeding angiodysplasia accounted for a majority of GIB in CF-LVAD patients (35.4% of 1112). Multivariate analysis adjusting for demographic, hospital and etiological differences, site of GIB, and patient comorbidities revealed that CF-LVADs were not adversely associated with mortality in GIB (OR 0.53, 95% CI 0.07–4.15). However, CF-LVADs independently accounted for prolonged hospitalization (3.5 days, 95% CI 2.6–4.6) and higher hospital charges ($37,032, 95% CI $7991–$66,074). In patients admitted with GIB, CF-LVAD implantation accounts for higher healthcare utilization, but is not adversely associated with mortality despite therapeutic anticoagulation, increased comorbidities, and comparatively delayed endoscopy. These findings are relevant as CF-LVADs are the dominant type of LVAD and are associated with increased risk of GIB compared to their predecessors.

Background and aims: Endoscopic ultrasound (EUS)-guided needle-based Confocal Laser Endomicroscopy (nCLE) characteristics of pancreatic cystic lesions (PCLs) have been identified in studies where the gold standard surgical histopathology was available in a minority of patients. There are diverging reports of interobserver agreement (IOA) and paucity of intraobserver reliability (IOR). Thus, we sought to validate current EUS-nCLE criteria of PCLs in a larger consecutive series of surgical patients. Methods: A retrospective analysis of patients who underwent EUS-nCLE at a single center was performed. For calculation of IOA (Fleiss’ kappa) and IOR (Cohen’s kappa), blinded nCLE-naïve observers (n = 6) reviewed nCLE videos of PCLs in two phases separated by a 2-week washout period. Results: EUS-nCLE was performed in 49 subjects, and a definitive diagnosis was available in 26 patients. The overall sensitivity, specificity, and accuracy for diagnosing a mucinous PCL were 94 %, 82 %, and 89 %, respectively. The IOA for differentiating mucinous vs. non-mucinous PCL was “substantial” (κ = 0.67, 95 %CI 0.57, 0.77). The mean (± standard deviation) IOR was “substantial” (κ = 0.78 ± 0.13) for diagnosing mucinous PCLs. Both the IOAs and mean IORs were “substantial” for detection of known nCLE image patterns of papillae/epithelial bands of mucinous PCLs (IOA κ = 0.63; IOR κ = 0.76 ± 0.11), bright particles on a dark background of pseudocysts (IOA κ = 0.71; IOR κ = 0.78 ± 0.12), and fern-pattern or superficial vascular network of serous cystadenomas (IOA κ = 0.62; IOR κ = 0.68 ± 0.20). Three (6.1 % of 49) patients developed post-fine needle aspiration (FNA) pancreatitis. Conclusion: Characteristic EUS-nCLE patterns can be consistently identified and improve the diagnostic accuracy of PCLs. These results support further investigations to optimize EUS-nCLE while minimizing adverse events. Study registration: NCT02516488

Choledocholithiasis describes the presence of a stone impacted in the common bile duct (CBD). It has a varied presentation, ranging from incidentally noted stones to potentially life-threatening cholangitis. When an obstructive stone is found, it usually requires removal, and there are multiple modalities to choose from including endoscopic retrograde cholangiopancreatography (ERCP) and laparoscopic bile duct exploration. The best initial imaging test is with transabdominal ultrasound, but this frequently shows only a dilated CBD and not an actual stone. This creates diagnostic challenges, as missing and not removing a CBD stone can lead to recurrent or new disease in the future. Fortunately, by combining laboratory data with imaging, individuals with disease can be risk-stratified for the presence of a CBD stone, which facilitates cost-effective evaluation and treatment. The timing of intervention is also significant, as data shows an association with worse outcomes in certain groups if intervention is delayed.

A validated productivity questionnaire, the Work Productivity and Activity Impairment questionnaire for Gastroesophageal Reflux Disease (WPAI-GERD), exists for Swedish patients with GERD.To assess responsiveness to change of the WPAI-GERD and construct validity of the English language version.We used the WPAI-GERD in a before-after treatment clinical study of Canadian GERD patients with moderate or severe symptoms treated with esomeprazole 40 mg once daily for 4 weeks. We measured productivity variables including GERD-specific absence from work, reduced productivity while at work and reduced productivity while carrying out regular daily activities other than work during the preceding week.The analysis included 217 patients, of whom 71% (n = 153) were employed. Before treatment, employed patients reported an average 0.9 hours of absence from work due to GERD and 14.0% reduced work productivity (5.8 hours equivalent) in the previous week, as well as 21.0% reduced productivity in daily activities (all patients). After treatment, the corresponding figures decreased to 0.3 hours, 3.0% (1.1 hours equivalent) and 4.9%, respectively. Thus, the improvement (difference from start of treatment) in productivity was 0.6 hours (p = 0.011) for absence from work and 11.0% units (p0.001) for reduced work productivity (4.7 hours equivalent, p0.001). This translated into an avoided loss of work productivity of 5.3 hours in total on a weekly basis per employed patient. In addition, a 16.1% unit (p0.001) improvement for reduced productivity in activities was observed. Cross-sectional correlation coefficients of WPAI variables with symptoms (range 0.04-0.63) and health-related quality of life (HR-QOL; range 0.02-0.65) supported cross-sectional construct validity. Corresponding change score correlations between WPAI variables and HR-QOL (range 0.05-0.56) supported longitudinal construct validity of the WPAI-GERD while low change score correlations between productivity variables and relevant symptoms (range 0.06-0.34) did not.The English version of the WPAI-GERD showed good cross-sectional construct validity, and results indicated that the WPAI-GERD is responsive to change. Although the results also indicated that longitudinal construct validity may be poor, the overall findings suggest that further study of the instrument remains warranted.

The prevalence of obesity and number of patients undergoing bariatric surgery are increasing. Obesity has adverse effects in patients with acute pancreatitis (AP). We investigated whether bariatric surgery affects outcomes of patients with AP.We performed a retrospective study, collecting data from the US Nationwide Inpatient Sample (2007-2011) on all adult inpatients (≥18 years) with a principal diagnosis of AP (n = 1,342,681). We compared primary clinical outcomes (mortality, acute kidney injury, and respiratory failure) and secondary outcomes related to healthcare resources (hospital stay and charges) among patient groups using univariate and multivariate analyses. We performed a propensity score-matched analysis to compare outcomes of patients with versus without bariatric surgery.Of patients admitted to the hospital with a principal diagnosis of AP, 14,332 (1.07%) had undergone bariatric surgery. The number of patients that underwent bariatric surgery doubled, from 1801 in 2007 to 3928 in 2011 (P.001). AP in patients that had undergone bariatric surgery was most frequently associated with gallstones. Multivariate analysis associated prior bariatric surgery with decreased mortality (odds ratio, 0.41; 95% confidence interval, 0.18-0.92), shorter duration of hospitalization (0.65 days shorter; P.001), and lower hospital charges ($3558 lower) than in patients with AP not receiving bariatric surgery (P.001). A propensity score-matched cohort analysis found that mortality and odds of acute kidney injury were similar between patients with versus without history of bariatric surgery, whereas respiratory failure was less frequent in patients who received bariatric surgery (1.34% vs 4.42%; P.001).Prior bariatric surgery in patients hospitalized with AP is not adversely associated with in-hospital mortality, development of organ failure, or healthcare resource use. Bariatric surgery may mitigate the obesity-associated adverse prognostication in AP. These observations are pertinent for future research, because the prevalence of obesity and AP-related hospitalizations is increasing.

Morbid obesity may adversely affect the clinical course of acute pancreatitis (AP); however, there are no inpatient, population-based studies assessing the impact of morbid obesity on AP-related outcomes. We sought to evaluate the impact of morbid obesity on AP-related clinical outcomes and health-care utilization.The Nationwide Inpatient Sample (2007-2011) was reviewed to identify all adult inpatients (≥18 years) with a principal diagnosis of AP. The primary clinical outcomes (mortality, renal failure, and respiratory failure) and secondary resource outcomes (length of stay and hospital charges) were analyzed using univariate and multivariate comparisons. Propensity score-matched analysis was performed to compare the outcomes in patients with and without morbid obesity.Morbid obesity was associated with 3.9% (52,297/1,330,302) of all AP admissions. Whereas the mortality rate decreased overall (0.97%→0.83%, P0.001), it remained unchanged in those with morbid obesity (1.02%→1.07%, P=1.0). Multivariate analysis revealed that morbid obesity was associated with increased mortality (odds ratio (OR) 1.6; 95% confidence interval (CI) 1.3, 1.9), prolonged hospitalization (0.4 days; P0.001), and higher hospitalization charges ($5,067; P0.001). A propensity score-matched cohort analysis demonstrated that the primary outcomes, acute kidney failure (10.8 vs. 8.2%; P0.001), respiratory failure (7.9 vs. 6.4%; P0.001), and mortality (OR 1.6, 95% CI 1.2, 2.1) were more frequent in morbid obesity.Morbid obesity negatively influences inpatient hospitalization and is associated with adverse clinical outcomes, including mortality, organ failure, and health-care resource utilization. These observations and the increasing global prevalence of obesity justify ongoing efforts to understand the role of obesity-induced inflammation in the pathogenesis and management of AP.

Background: Given the implicated role of proximal serrated polyps (PSP) in the development of interval colon cancer, it is important to investigate if proximal serrated polyp detection rate (PSPDR) correlates with adenoma detection rate (ADR) and the factors that are associated with higher detection rates. Methods: We performed a retrospective review of medical records of average-risk patients who underwent a screening colonoscopy at a tertiary care academic center. A total of 851 screening colonoscopies were analyzed. Results: Gastroenterologists (n=22) performed the 851 colonoscopies. In univariable logistic regression, endsocopists with a mean WT ≥11 minutes had a higher odds of detecting a PSP compared to endoscopists with a mean withdrawal time WT

Background: A number of studies compared the quality, efficacy and tolerability of oral sodium phosphate (NaP) and polyethylene glycol (PEG)-based solutions in preparation for colonoscopy. The primary aim of this study was to explore whether endoscopists can be effectively blinded to the type of bowel preparation. Methods: We recruited 3 experienced endoscopists and 57 outpatients (18–65 years old) undergoing colonoscopy. We randomized eligible patients to receive one of the two bowel preparations. Endoscopists who performed the tests were blinded to the type of preparation, and made their best judgment on the type and quality of the bowel preparation. Results: Forty-five patients completed the study. The overall correct estimation of the type of bowel preparation was 60.0% (95% CI; 45.5%, 73.0%). The cleansing quality did not differ between the two preparations. Patients found oral NaP solution much easier to take (81.8% versus 36.4%; P =0.005) and the PEG-based group tended to have more nausea or vomiting. 47.6% of patients in the PEG group indicated they would prefer to try another bowel preparation in the future compared to 4.5% in the oral NaP group ( P =0.002). We stopped the study after an interim analysis indicating that more than 600 patients would be required to detect statistically significant differences in the primary aim. Conclusion: Our findings suggest that blinding of endoscopists in clinical trials comparing oral NaP to PEG had a relatively low likelihood of bias. The study also suggests that oral NaP is easier to take and more tolerable than PEG without impairing cleansing quality.

Background and objective Readers of randomized controlled trials (RCTs) commonly assume that what was not reported did not occur. We undertook an observational study to determine whether concealment of randomization or blinding was used in RCTs that failed to report these bias-reducing strategies. Methods We recorded the reporting of concealment of randomization and blinding in 105 RCTs. We subsequently contacted the authors and determined if they had used these methodological safeguards. Results We successfully obtained data from 98 authors. The authors in the full-text publications of these 98 RCTs failed to report the presence or absence of concealment of randomization in 55%, and the blinding status of participants in 26%, health care providers in 64%, data collectors in 84%, outcome assessors in 83%, and data analysts in 96%. In direct contact, authors frequently reported concealing randomization (96%; 95% confidence interval CI = 87–100%), blinding participants (20%; 95% CI = 7–41%), blinding health care providers (65%; 95% CI = 52–77%), blinding data collectors (65%; 95% CI = 53–75%), blinding outcome assessors (79%; 95% CI = 69–87%), and blinding data analysts (50%; 95% CI = 40–60%), despite not reporting the use of these methodological safeguards in their publications. Conclusions Readers should not assume that bias-reducing procedures not reported in an RCT did not occur.

Summary Background : The accuracy of physicians’ assessment of the severity of gastro-oesophageal reflux disease is unclear. Aim : To correlate physician and patient assessment of gastro-oesophageal reflux disease severity and its response to treatment. Methods : Adult uninvestigated gastro-oesophageal reflux disease patients (n = 217) completed symptom and health-related quality of life questionnaires at baseline and after treatment with esomeprazole 40 mg p.o. daily. Pearson coefficients quantified correlations between physician assessments and patient responses. Results : At baseline, the strongest correlations were heartburn severity (0.31), overall symptom severity (0.44) and a domain of the quality of life in reflux and dyspepsia questionnaire (0.31) (P

Background: Despite recommendations that patients rating their own health using utility and preference measures such as the feeling thermometer (FT) and standard gamble (SG) should also rate hypothetical marker states, little evidence supports marker state use. We evaluated whether the administration of marker states improves measurement properties of the FT and SG. Methods: We randomized 217 patients with gastroesophageal reflux disease to complete the FT (self-administered) and SG with marker states (FT +/SG+, n = 112) or without marker states (FT-/SG-, n = 105) before and after 4 weeks of treatment with a proton pump inhibitor, esomeprazole. Patients also completed other health-related quality of life instruments. Results: The use of marker states did not influence baseline utility scores (FT+ 0.66, FT- 0.68; SG+ 0.77, SG- 0.78, on a scale from 0 [dead] to 1.0 [full health]). Improvement after therapy was 0.21 in FT+ and 0.15 in FT- (both P < 0.001; difference between FT+ and FT- = 0.06, P = 0.02). Improvement in SG+ was 0.07 (P < 0.001) and 0.06 in SG- (P = 0.003) (difference between SG+ and SG- = 0.01, P = 0.63). Correlations with other health-related quality of life scores were generally stronger, with some statistically significant differences in correlations, for FT+ compared with FT-, but tended to be weaker for SG+ compared with SG-. Conclusion: The administration of marker states improved the responsiveness and validity of the FT but not of the SG. Decisions about administering marker states should depend on whether the FT and SG is of primary interest and the importance of optimal validity and responsiveness relative to competing objectives such as efficiency.

3612 Background: The RAS/RAF/MEK signal transduction pathway is critical to the development of colorectal cancer, and tumors harboring KRAS, NRAS, and BRAF mutations were shown to be resistant to radiation. Thus, we conducted a phase I study of trametinib, a potent MEK1/2 inhibitor, in combination with CRT in patients with LARC. Methods: Phase I trial for patients with Stage II/III rectal cancers with a 3+3 design, and an expansion cohort of 12 patients at the maximum tolerated dose (MTD). Trametinib is given orally at 3 dose levels: 0.5mg, 1mg, and 2mg (Mon-Fri). CRT regimen is infusional 5-flourouracil (5FU) 225mg/m2/day (Mon-Fri) and daily fractions of 1.8 Gy (total 50.4Gy). There is a 5-day trametinib lead-in followed by trametinib and CRT. Six to 10 weeks after completion of CRT, patients then proceed to their surgery and adjuvant therapy. The primary endpoint is to identify the MTD and recommended phase 2 dose of trametinib with CRT. Immunohistochemistry staining for phosphorylated –ERK (pERK) and genomic profiling is performed on the tumor samples. Results: Enrollment is complete at all dose levels with18 patients, and 15 patients evaluable for toxicity and response as of Feb 6. One dose-limiting toxicity of diarrhea was observed at the 2mg dose. Grade 3 and most common toxicities are shown in Table 1. No grade 4/5 toxicities have been observed. At 2mg dose level, 3/9 (33%) patients had pathological complete response (pCR) and 2/9 (22%) had a near pCR. Correlative studies confirm decrease in pERK levels with increasing doses of trametinib. Correlation of genomic mutational status with toxicity, response, and outcomes is being analyzed. Conclusions: The combination of trametinib with 5FU CRT is tolerable with promising preliminary activity. Final results will be presented at the meeting. Toxicities. Clinical trial information: NCT01740648. [Table: see text]