Prospective, Multi-Institutional, Real-Time Next-Generation Sequencing of Pancreatic Cyst Fluid Reveals Diverse Genomic Alterations That Improve the Clinical Management of Pancreatic Cysts.

BACKGROUND & AIMS: Next-generation sequencing (NGS) of pancreatic cyst fluid is a useful adjunct in the assessment of patients with pancreatic cyst. However, previous studies have been retrospective or single institutional experiences. The aim of this study was to prospectively evaluate NGS on a multi-institutional cohort of patients with pancreatic cyst in real time. METHODS: The performance of a 22-gene NGS panel (PancreaSeq) was first retrospectively confirmed and then within a 2-year timeframe, PancreaSeq testing was prospectively used to evaluate endoscopic ultrasound-guided fine-needle aspiration pancreatic cyst fluid from 31 institutions. PancreaSeq results were correlated with endoscopic ultrasound findings, ancillary studies, current pancreatic cyst guidelines, follow-up, and expanded testing (Oncomine) of postoperative specimens. RESULTS: Among 1933 PCs prospectively tested, 1887 (98%) specimens from 1832 patients were satisfactory for PancreaSeq testing. Follow-up was available for 1216 (66%) patients (median, 23 months). Based on 251 (21%) patients with surgical pathology, mitogen-activated protein kinase/GNAS mutations had 90% sensitivity and 100% specificity for a mucinous cyst (positive predictive value [PPV], 100%; negative predictive value [NPV], 77%). On exclusion of low-level variants, the combination of mitogen-activated protein kinase/GNAS and TP53/SMAD4/CTNNB1/mammalian target of rapamycin alterations had 88% sensitivity and 98% specificity for advanced neoplasia (PPV, 97%; NPV, 93%). Inclusion of cytopathologic evaluation to PancreaSeq testing improved the sensitivity to 93% and maintained a high specificity of 95% (PPV, 92%; NPV, 95%). In comparison, other modalities and current pancreatic cyst guidelines, such as the American Gastroenterology Association and International Association of Pancreatology/Fukuoka guidelines, show inferior diagnostic performance. The sensitivities and specificities of VHL and MEN1/loss of heterozygosity alterations were 71% and 100% for serous cystadenomas (PPV, 100%; NPV, 98%), and 68% and 98% for pancreatic neuroendocrine tumors (PPV, 85%; NPV, 95%), respectively. On follow-up, serous cystadenomas with TP53/TERT mutations exhibited interval growth, whereas pancreatic neuroendocrine tumors with loss of heterozygosity of ≥3 genes tended to have distant metastasis. None of the 965 patients who did not undergo surgery developed malignancy. Postoperative Oncomine testing identified mucinous cysts with BRAF fusions and ERBB2 amplification, and advanced neoplasia with CDKN2A alterations. CONCLUSIONS: PancreaSeq was not only sensitive and specific for various pancreatic cyst types and advanced neoplasia arising from mucinous cysts, but also reveals the diversity of genomic alterations seen in pancreatic cysts and their clinical significance.

Safety, Efficacy and Clinical Utility of the 5.1mm EndoRotor Powered Debridement Catheter for Treatment of Walled-Off Pancreatic Necrosis.

BACKGROUND AND AIMS: Direct endoscopic necrosectomy (DEN) is a recommended strategy for treatment of walled-off-necrosis (WON). DEN uses a variety of devices including the EndoRotor (Interscope, Inc.) debridement catheter. Recently, a 5.1 mm EndoRotor with increased chamber size and rate of tissue removal was introduced. The aim of this study was to assess the efficacy and safety of this device. METHODS: A multi-center cohort study was conducted at eight institutions including patients who underwent DEN with the 5.1 mm EndoRotor. The primary outcome was the number of DEN sessions needed for WON resolution. Secondary outcomes included the average percent reduction in solid WON debris and decrease in WON area per session, total time spent performing EndoRotor therapy for WON resolution, and adverse events. RESULTS: 64 procedures in 41 patients were included. For patients in which the 5.1 mm EndoRotor catheter was the sole therapeutic modality, an average of 1.6 DEN sessions resulted in WON resolution with an average cumulative time of 85.5 minutes. Of the 21 procedures with data regarding percent of solid debris, the average reduction was 85% +/- 23% per session. Of the 19 procedures with data regarding WON area, the mean area significantly decreased from 97.6 +/- 72.0 cm2 to 27.1 +/- 35.5 cm2 (p<0.001) per session. Adverse events included two intra-procedural LAMS dislodgements managed endoscopically and three perforations none of which were related to EndoRotor. Bleeding was reported in seven cases, none required embolic or surgical therapy and two required blood transfusions. CONCLUSIONS: This is the first multi-center retrospective study to investigate the efficacy and safety of the 5.1 mm EndoRotor catheter for WON. Results from this study showed an average of 1.6 DEN sessions were needed to achieve WON resolution with an 85% single session reduction in solid debris and a 70% single session decrease in WON area with minimal adverse events.

Accuracy and agreement of a large panel of endosonographers for endomicroscopy-guided virtual biopsy of pancreatic cystic lesions.

BACKGROUND: 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. METHODS: 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. RESULTS: 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%). CONCLUSION: Diagnosis of PCLs by EUS-nCLE guided virtual biopsy is very accurate and reliable for the most prevalent pancreatic cysts in clinical practice.

Endoscopic Ultrasound-Guided Confocal Laser Endomicroscopy Increases Accuracy of Differentiation of Pancreatic Cystic Lesions.

BACKGROUND & AIMS: 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. METHODS: 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. RESULTS: 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. CONCLUSIONS: 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.

EUS-guided confocal laser endomicroscopy: prediction of dysplasia in intraductal papillary mucinous neoplasms (with video).

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-naïve 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.).

Acute Pancreatitis Admission Trends: A National Estimate through the Kids' Inpatient Database.

OBJECTIVES: To evaluate national health care use and costs for pediatric acute pancreatitis. STUDY DESIGN: 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). RESULTS: 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). CONCLUSION: 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.

Needle-based confocal laser endomicroscopy for the diagnosis of pancreatic cystic lesions: an international external interobserver and intraobserver study (with videos).

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.).

Routine staging with endoscopic ultrasound in patients with obstructing esophageal cancer and dysphagia rarely impacts treatment decisions.

BACKGROUND: 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. METHODS: 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. RESULTS: 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 < 0.0001). Additionally, 145 (67.1%) patients had a partially or completely obstructing mass on initial endoscopy, of which 136 (93.8%) were locally advanced (p < 0.0001 vs. non-obstructing lesions). CONCLUSIONS: An overwhelming majority of patients presenting with dysphagia and/or the presence of at least partially obstructing esophageal mass at the time of esophageal cancer diagnosis had an EUS that demonstrated at least locally advanced disease. The present study supports the hypothesis that EUS may be of limited benefit for management of esophageal cancer in patients with an obstructing mass and dysphagia.

Effects of Bariatric Surgery on Outcomes of Patients With Acute Pancreatitis.

BACKGROUND & AIMS: 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. METHODS: 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. RESULTS: 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). CONCLUSIONS: 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 Is Associated With Adverse Clinical Outcomes in Acute Pancreatitis: A Propensity-Matched Study.

OBJECTIVES: 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. METHODS: 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. RESULTS: 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%, P<0.001), 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; P<0.001), and higher hospitalization charges ($5,067; P<0.001). A propensity score-matched cohort analysis demonstrated that the primary outcomes, acute kidney failure (10.8 vs. 8.2%; P<0.001), respiratory failure (7.9 vs. 6.4%; P<0.001), and mortality (OR 1.6, 95% CI 1.2, 2.1) were more frequent in morbid obesity. CONCLUSIONS: 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.

Role of Endoscopic Ultrasound in the Evaluation of Pancreatic Cystic Neoplasms: A Concise Review.

Pancreatic cystic lesions are being discovered as incidental lesions during cross-sectional imaging studies of the abdomen with increasing frequency. Endoscopic ultrasound is an important diagnostic modality for managing pancreatic cystic lesions. There are various types of pancreatic cystic lesions, from benign to malignant. Endoscopic ultrasound has a multifactorial role in delineating the morphology of pancreatic cystic lesions, ranging from fluid and tissue acquisition for analysis-fine needle aspiration and through-the-needle biopsy, respectively-to advanced imaging techniques, such as contrast-harmonic mode endoscopic ultrasound and EUS-guided needle-based confocal laser endomicroscopy. In this review, we will summarize and provide an update on the specific role of EUS in the management of pancreatic cystic lesions.

Peribiliary cysts masquerading as choledocholithiasis.

Video 1The major papilla was cannulated with a sphincterotome over a straight wire. The polypoid saccular structures were identified by cholangioscopy.

Improving Pancreatic Cyst Management: Artificial Intelligence-Powered Prediction of Advanced Neoplasms through Endoscopic Ultrasound-Guided Confocal Endomicroscopy.

Despite the increasing rate of detection of incidental pancreatic cystic lesions (PCLs), current standard-of-care methods for their diagnosis and risk stratification remain inadequate. Intraductal papillary mucinous neoplasms (IPMNs) are the most prevalent PCLs. The existing modalities, including endoscopic ultrasound and cyst fluid analysis, only achieve accuracy rates of 65-75% in identifying carcinoma or high-grade dysplasia in IPMNs. Furthermore, surgical resection of PCLs reveals that up to half exhibit only low-grade dysplastic changes or benign neoplasms. To reduce unnecessary and high-risk pancreatic surgeries, more precise diagnostic techniques are necessary. A promising approach involves integrating existing data, such as clinical features, cyst morphology, and data from cyst fluid analysis, with confocal endomicroscopy and radiomics to enhance the prediction of advanced neoplasms in PCLs. Artificial intelligence and machine learning modalities can play a crucial role in achieving this goal. In this review, we explore current and future techniques to leverage these advanced technologies to improve diagnostic accuracy in the context of PCLs.

An unusual case of hematochezia: acute ischemic proctosigmoiditis.

Acute ischemia of the rectum is uncommon and usually occurs after aorto-iliac surgery. In this report, we present a case of acute ischemic proctosigmoiditis that developed from a brief episode of hypotension. An 85-year-old male presented to the emergency room with hypotension, mental confusion, and passage of maroon-colored stool. He was resuscitated and treated for presumed sepsis. Computerized tomography of the abdomen and pelvis displayed signs of acute inflammation of the distal colon and rectum. Endoscopic findings and microscopic examination of the rectal biopsy revealed changes consistent with acute ischemic proctosigmoiditis. An evaluation for infectious etiologies was negative. The patient's clinical condition improved over the next 24 h with supportive care. Involvement of the rectum is rare in ischemic colitis because of its abundant collateral blood supply. Acute ischemic proctosigmoiditis should be considered in the differential diagnosis of elderly patients with multiple co-morbidities presenting with hematochezia.

Insights into insulin resistance, lifestyle, and anthropometric measures of patients with prior colorectal cancer compared to controls: A National Health and Nutrition Examination Survey (NHANES) Study.

BACKGROUND: 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. METHODS: 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. RESULTS: 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, P < 0.01), 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. CONCLUSION: 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.

Diagnostic Accuracy of Preoperative Imaging for Differentiation of Branch Duct Versus Mixed Duct Intraductal Papillary Mucinous Neoplasms.

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.

The Work Productivity and Activity Impairment Questionnaire for Patients with Gastroesophageal Reflux Disease (WPAI-GERD): responsiveness to change and English language validation.

BACKGROUND: A validated productivity questionnaire, the Work Productivity and Activity Impairment questionnaire for Gastroesophageal Reflux Disease (WPAI-GERD), exists for Swedish patients with GERD. OBJECTIVE: To assess responsiveness to change of the WPAI-GERD and construct validity of the English language version. METHODS: 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. RESULTS: 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 (p < 0.001) for reduced work productivity (4.7 hours equivalent, p < 0.001). 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 (p < 0.001) 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. CONCLUSION: 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.