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PROspective Evaluation of Chronic Pancreatitis for EpidEmiologic and Translational StuDies: Rationale and Study Design for PROCEED From the Consortium for the Study of Chronic Pancreatitis, Diabetes, and Pancreatic Cancer. Pancreas Yadav, D., Park, W. G., Fogel, E. L., Li, L., Chari, S. T., Feng, Z., Fisher, W. E., Forsmark, C. E., Jeon, C. Y., Habtezion, A., Hart, P. A., Hughes, S. J., Othman, M. O., Rinaudo, J. A., Pandol, S. J., Tirkes, T., Serrano, J., Srivastava, S., Van Den Eeden, S. K., Whitcomb, D. C., Topazian, M., Conwell, D. L. ; 47 (10): 1229?38
Abstract

Prospective Evaluation of Chronic Pancreatitis for Epidemiologic and Translational Studies (PROCEED) is the first prospective, observational cohort study of chronic pancreatitis (CP) in the United States. The primary goals of PROCEED are to define disease progression, test the predictive capability of candidate biomarkers, and develop a platform to conduct translational and mechanistic studies in CP. Using objective and consensus-driven criteria, PROCEED will enroll adults at different stages of CP-controls, suspected CP, and definite CP. In addition to collecting detailed information using structured case report forms and protocol-mandated evaluations at baseline and during follow-up, PROCEED will establish a linked biorepository of blood, urine, saliva, stool, pancreatic fluid, and pancreatic tissue. Enrollment for PROCEED began in June 2017. As of July 1, 2018, nine clinical centers of the Consortium for the Study of Chronic Pancreatitis, Diabetes, and Pancreatic Cancer are enrolling, and 350 subjects have completed baseline evaluation. In conclusion, PROCEED will provide the most accurate and reliable estimates to date on progression of CP. The established cohort and biorepository will facilitate numerous analyses, leading to new strategies for diagnosis, methods to monitor disease progression, and treatment of CP.

View details for PubMedID 30325862
Sticky Situation: Bleeding Duodenal Lymphangiectasias Treated with Lymphatic Glue Embolization. Digestive diseases and sciences Li, A. A., Raghu, P., Chen, A., Triadafilopoulos, G., Park, W. 2021
View details for DOI 10.1007/s10620-021-06898-3

View details for PubMedID 33638090
Quality metrics in the performance of EUS: a population-based observational cohort of the United States. Gastrointestinal endoscopy Huang, R. J., Barakat, M. T., Park, W., Banerjee, S. 2021
Abstract

There exist few data on the quality of endoscopic ultrasound (EUS) in the community setting. We characterized EUS performance at the individual facility level in 3 large American states, using need for repeat biopsy (NRB) as a metric for procedural failure, and rate of unplanned hospital encounter (UHE) as a metric for adverse event.We collected data on 76,614 EUS procedures performed at 166 facilities in California, Florida, and New York (2009-2014). The endpoints for the study were 7-day rate of UHE after EUS, and 30-day rate of NRB after EUS with fine-needle aspiration. Facility-level factors analyzed included annual procedure volume, urban/rural location, and free-standing status (facilities not attached to a larger hospital). Predictors for UHE and NRB were analyzed in both multivariable regression and nonparametric local regression.Facility volume did not predict risk for UHE. However, high facility volume protected against NRB (p-trend <0.001) even after adjustment for other facility-level factors. When regressing facility volume against risk for NRB in local regression, a join-point (inflection point) was identified at 97 procedures per annum. Once facilities reached this threshold volume, there appeared little additional protective effect of higher volume. Rural facility location (OR, 1.81; 95% CI, 1.36-2.40) and free-standing status (OR, 1.57; 95% CI, 1.16-2.13) also associated with NRB.Facility volume does not predict risk for adverse events after EUS. However, high facility volume is associated with decreased rates of technical failure (as assessed by NRB). These data provide one of the first descriptions of EUS practice in community settings and highlight opportunities to improve endoscopic quality nationally.

View details for DOI 10.1016/j.gie.2020.12.055

View details for PubMedID 33476611
Acute Pancreatitis and Diabetes Mellitus: A Review. The Korean journal of internal medicine Richardson, A., Park, W. G. 2020
Abstract

Diabetes following Acute Pancreatitis (AP) is becoming increasingly recognized. It is unclear what subtype of Diabetes Mellitus (DM) occurs; however, Type 3c diabetes mellitus (T3cDM) is gaining increasing recognition. T3cDM has differing pathophysiology than other subtypes of DM and therefore differing disease course and treatment. Current studies have examined the incidence and prevalence of DM following AP, and meta-analyses have shown around 15% develop DM at 1 year with an increasing proportion developing DM at 5 years. It has been observed that some patients have transient hyperglycemia following AP episode with a subset developing persistent impaired glucose metabolism; however, the exact timeline is not well defined. The data on risk factors for developing DM after AP is limited and mixed; however, it is likely that severity of AP may impact the propensity to develop DM. Screening guidelines have not been established following AP; however, screening 1- year post event will likely capture a sizable proportion of newly developed DM. The endocrine and exocrine pancreas are closely linked, and studies have found significant overlap in dysfunction of both after AP. Finally, there are some data to suggest that diabetes predisposes patients to structural changes in the pancreas and increased risk of developing AP.

View details for DOI 10.3904/kjim.2020.505

View details for PubMedID 33147904
Effects of processing conditions on stability of immune analytes in human blood. Scientific reports Gottfried-Blackmore, A., Rubin, S. J., Bai, L., Aluko, S., Yang, Y., Park, W., Habtezion, A. 2020; 10 (1): 17328
Abstract

Minimizing variability in collection and processing of human blood samples for research remains a challenge. Delaying plasma or serum isolation after phlebotomy (processing delay) can cause perturbations of numerous analytes. Thus, a comprehensive understanding of how processing delay affects major endpoints used in human immunology research is necessary. Therefore, we studied how processing delay affects commonly measured cytokines and immune cell populations. We hypothesized that short-term time delays inherent to human research in serum and plasma processing impact commonly studied immunological analytes. Blood from healthy donors was subjected to processing delays commonly encountered in sample collection, and then assayed by 62-plex Luminex panel, 40-parameter mass cytometry panel, and 540,000 transcript expression microarray. Variance for immunological analytes was estimated using each individual's baseline as a control. In general, short-term processing delay led to small changes in plasma and serum cytokines (range-10.8 to 43.5%), markers and frequencies of peripheral blood mononuclear cell phenotypes (range 0.19 to 3.54 fold), and whole blood gene expression (stable for>20K genes)-with several exceptions described herein. Importantly, we built an open-access web application allowing investigators to estimate the degree of variance expected from processing delay for measurements of interest based on the data reported here.

View details for DOI 10.1038/s41598-020-74274-8

View details for PubMedID 33060628
NEXT-GENERATION SEQUENCING OF PANCREATIC CYST FLUID IS BOTH SENSITIVE AND SPECIFIC FOR THE CLASSIFICATION OF NEOPLASTIC CYSTS AND THE DETECTION OF ADVANCED NEOPLASIA IN INTRADUCTAL PAPILLARY MUCINOUS NEOPLASMS: A PROSPECTIVE MULTI-INSTITUTIONAL STUDY Singhi, A., Nikiforova, M. N., McGrath, K., Brand, R., Kenneth, F., Das, R., Singh, H., Khalid, A., Chennat, J., Sarkaria, S., Park, W. G., Lennon, A., Klapman, J. B., Centeno, B. A., Nasr, J. Y., Kubiliun, N., Tavakkoli, A., Vanderveldt, H., DeWitt, J. M., Wallace, M. B., Slivka, A., Wald, A. I., Lee, K., Bartlett, D. L., Zeh, H. J., Polanco, P. M., Boone, B., Schmidt, C., Marsh, J., Zureikat, A. H., Paniccia, A. MOSBY-ELSEVIER. 2020: AB171
View details for Web of Science ID 000545678400337
The State of Mentorship and Pancreatic Research Among Trainees in Pancreatology: A Multinational Survey Study. Pancreas Tsen, A., Han, S., Moreau, C., Akshintala, V. S., Yazici, C., Archibugi, L., Hopson, P., Gougol, A., Jin, D., Paragomi, P., Kamal, A., Valverde-Lopez, F., Papachristou, G. I., Park, W. G., Lee, P. J., Collaborative Alliance for Pancreatic Education and Research 2020
Abstract

OBJECTIVES: The recent decrease seen in pancreatic research and young investigator involvement may reflect inadequate mentorship. This study aimed to describe the current state of mentorship in pancreatic research and evaluate how mentorship is associated with research productivity.METHODS: In this prospective study, a survey addressing mentorship and research was distributed to trainees worldwide. Survey responses were analyzed using descriptive statistics and logistic regression was used to describe the association between mentorship and trainee research productivity.RESULTS: A total of 137 trainees from 16 countries participated. Although two-thirds of trainees expressed interest in pancreatic research and had identified a mentor in the field, only 34.8% had published a manuscript. Barriers to pancreatic research included lack of research opportunities (58.3%), limited mentorship (23.3%), and inadequate institutional support (15%). Although having a single mentor was not associated with research productivity (odds ratio, 1.43; 95% confidence interval, 0.74-2.76), having a local mentor was significantly associated with publishing (odds ratio, 4.57; 95% confidence interval, 1.95-10.74).CONCLUSIONS: Although many trainees interested in pancreatology have access to a mentor, barriers including lack of research opportunities, mentorship, and institutional support hinder trainee productivity. Opportunities for mentorship, collaboration, and networking are needed.

View details for DOI 10.1097/MPA.0000000000001503

View details for PubMedID 32132515
Imaging-Based Subtypes of Pancreatic Ductal Adenocarcinoma Exhibit Differential Growth and Metabolic Patterns in the Pre-Diagnostic Period: Implications for Early Detection. Frontiers in oncology Zaid, M., Elganainy, D., Dogra, P., Dai, A., Widmann, L., Fernandes, P., Wang, Z., Pelaez, M. J., Ramirez, J. R., Singhi, A. D., Dasyam, A. K., Brand, R. E., Park, W. G., Rahmanuddin, S., Rosenthal, M. H., Wolpin, B. M., Khalaf, N., Goel, A., Von Hoff, D. D., Tamm, E. P., Maitra, A., Cristini, V., Koay, E. J. 2020; 10: 596931
Abstract

Background: Previously, we characterized subtypes of pancreatic ductal adenocarcinoma (PDAC) on computed-tomography (CT) scans, whereby conspicuous (high delta) PDAC tumors are more likely to have aggressive biology and poorer clinical outcomes compared to inconspicuous (low delta) tumors. Here, we hypothesized that these imaging-based subtypes would exhibit different growth-rates and distinctive metabolic effects in the period prior to PDAC diagnosis.Materials and methods: Retrospectively, we evaluated 55 patients who developed PDAC as a second primary cancer and underwent serial pre-diagnostic (T0) and diagnostic (T1) CT-scans. We scored the PDAC tumors into high and low delta on T1 and, serially, obtained the biaxial measurements of the pancreatic lesions (T0-T1). We used the Gompertz-function to model the growth-kinetics and estimate the tumor growth-rate constant (alpha) which was used for tumor binary classification, followed by cross-validation of the classifier accuracy. We used maximum-likelihood estimation to estimate initiation-time from a single cell (10-6 mm3) to a 10 mm3 tumor mass. Finally, we serially quantified the subcutaneous-abdominal-fat (SAF), visceral-abdominal-fat (VAF), and muscles volumes (cm3) on CT-scans, and recorded the change in blood glucose (BG) levels. T-test, likelihood-ratio, Cox proportional-hazards, and Kaplan-Meier were used for statistical analysis and p-value <0.05 was considered significant.Results: Compared to high delta tumors, low delta tumors had significantly slower average growth-rate constants (0.024 month-1 vs. 0.088 month-1, p<0.0001) and longer average initiation-times (14 years vs. 5 years, p<0.0001). alpha demonstrated high accuracy (area under the curve (AUC)=0.85) in classifying the tumors into high and low delta, with an optimal cut-off of 0.034 month-1. Leave-one-out-cross-validation showed 80% accuracy in predicting the delta-class (AUC=0.84). High delta tumors exhibited accelerated SAF, VAF, and muscle wasting (p <0.001), and BG disturbance (p<0.01) compared to low delta tumors. Patients with low delta tumors had better PDAC-specific progression-free survival (log-rank, p<0.0001), earlier stage tumors (p=0.005), and higher likelihood to receive resection after PDAC diagnosis (p=0.008), compared to those with high delta tumors.Conclusion: Imaging-based subtypes of PDAC exhibit distinct growth, metabolic, and clinical profiles during the pre-diagnostic period. Our results suggest that heterogeneous disease biology may be an important consideration in early detection strategies for PDAC.

View details for DOI 10.3389/fonc.2020.596931

View details for PubMedID 33344245
Novel rigidizing overtube for colonoscope stabilization and loop prevention (with video). Gastrointestinal endoscopy Wei, M. T., Hwang, J. H., Watson, R. R., Park, W., Friedland, S. 2020
Abstract

Loop formation can impede scope advancement, destabilize the tip and cause pain. Strategies to mitigate looping include torque-based reduction maneuvers, variable stiffness shafts and abdominal splinting. In some cases, these strategies are insufficient and there is need for novel instruments. Loop formation is of particular concern in colonoscopy, but it can also impact performance of other endoscopic procedures such as enteroscopy and altered-anatomy ERCP. In this case series we demonstrate the utility of a novel rigidizing overtube (Pathfinder, Neptune Medical, Burlingame, Calif, USA) in colonoscopy and other endoscopic procedures where loop management is critical.We describe our initial experience with the Pathfinder overtube in 29 patients. The overtube is 85 centimeters long and can accommodate a pediatric colonoscope. In its native state, the overtube is extremely flexible. Once the overtube is advanced to the desired location, application of a vacuum to the device causes the device to become 15 times stiffer. The endoscope can then be advanced through the overtube without loop formation in the region that the overtube traverses.The overtube was used in 29 patients to assist with difficult procedures. The patients were predominantly male (N=18; 62.1%), with median age 66 (interquartile range 57-72). One patient received an upper endoscopy (3.4%), 24 received colonoscopy (82.8%), and 4 received enteroscopy (13.8%). The overtube was used in 12 for incomplete colonoscopy (41.4%), 6 for depth (20.7%), and 11 for stability (37.9%). Colonoscopy was performed in the setting of screening (N=3), surveillance given polyp history (N=7), referrals for polyp removal (N=10), workup of iron deficiency anemia (N=2), and incomplete colonoscopy (N=1). The lower endoscopy cases had a median cecal intubation time of 5 minutes and had interquartile range (4.25 - 7 minutes). Enteroscopy was performed in 4 patients. (1) The distal 60 cm of the ileum was examined with a pediatric colonoscope to exclude ileitis. (2) The overtube was used to stabilize a 6 mm endoscope to traverse a tight Crohn's ileocolonic stricture. (3) Altered-anatomy ERCP was performed using an enteroscope through the overtube to reach a hepaticojejunostomy. (4) Upper enteroscopy was performed and the mid-jejunum was reached. We present 4 cases that demonstrate the use of the overtube. There were no adverse events.Initial experience with a novel rigidizing overtube suggests that this tool can be useful in colonoscopy and other endoscopic procedures that are affected by looping.

View details for DOI 10.1016/j.gie.2020.07.054

View details for PubMedID 32739483
Management of patients with increased risk for familial pancreatic cancer: updated recommendations from the International Cancer of the Pancreas Screening (CAPS) Consortium. Gut Goggins, M., Overbeek, K. A., Brand, R., Syngal, S., Del Chiaro, M., Bartsch, D. K., Bassi, C., Carrato, A., Farrell, J., Fishman, E. K., Fockens, P., Gress, T. M., van Hooft, J. E., Hruban, R. H., Kastrinos, F., Klein, A., Lennon, A. M., Lucas, A., Park, W., Rustgi, A., Simeone, D., Stoffel, E., Vasen, H. F., Cahen, D. L., Canto, M. I., Bruno, M. 2020; 69 (1): 7?17
Abstract

The International Cancer of the Pancreas Screening Consortium met in 2018 to update its consensus recommendations for the management of individuals with increased risk of pancreatic cancer based on family history or germline mutation status (high-risk individuals).A modified Delphi approach was employed to reach consensus among a multidisciplinary group of experts who voted on consensus statements. Consensus was considered reached if ?75% agreed or disagreed.Consensus was reached on 55 statements. The main goals of surveillance (to identify high-grade dysplastic precursor lesions and T1N0M0 pancreatic cancer) remained unchanged. Experts agreed that for those with familial risk, surveillance should start no earlier than age 50 or 10 years earlier than the youngest relative with pancreatic cancer, but were split on whether to start at age 50 or 55. Germline ATM mutation carriers with one affected first-degree relative are now considered eligible for surveillance. Experts agreed that preferred surveillance tests are endoscopic ultrasound and MRI/magnetic retrograde cholangiopancreatography, but no consensus was reached on how to alternate these modalities. Annual surveillance is recommended in the absence of concerning lesions. Main areas of disagreement included if and how surveillance should be performed for hereditary pancreatitis, and the management of indeterminate lesions.Pancreatic surveillance is recommended for selected high-risk individuals to detect early pancreatic cancer and its high-grade precursors, but should be performed in a research setting by multidisciplinary teams in centres with appropriate expertise. Until more evidence supporting these recommendations is available, the benefits, risks and costs of surveillance of pancreatic surveillance need additional evaluation.

View details for DOI 10.1136/gutjnl-2019-319352

View details for PubMedID 31672839

View details for PubMedCentralID PMC7295005
Prevalence, risk factors and clinical outcomes of COVID-19 in patients with a history of pancreatitis in Northern California. Gut Gubatan, J., Levitte, S., Patel, A., Balabanis, T., Sharma, A., Jones, E., Lee, B., Manohar, M., Swaminathan, G., Park, W., Habtezion, A. 2020
View details for DOI 10.1136/gutjnl-2020-321772

View details for PubMedID 32493828
Unique circulating immune signatures for recurrent acute pancreatitis, chronic pancreatitis and pancreatic cancer: A pilot study of these conditions with and without diabetes. Pancreatology : official journal of the International Association of Pancreatology (IAP) ... [et al.] Park, W. G., Li, L., Appana, S., Wei, W., Stello, K., Andersen, D. K., Hughes, S. J., Whitcomb, D. C., Brand, R. E., Yadav, D., Habtezion, A., Consortium for the Study of Chronic Pancreatitis, D. 2019
Abstract

OBJECTIVE: This exploratory study seeks to identify distinct circulating immune signatures among patients having recurrent acute pancreatitis (RAP), chronic pancreatitis (CP), and pancreatic adenocarcinoma (PDAC).METHODS: A retrospective analysis of human serum samples from collaborating institutions of the Consortium for the Study of Chronic Pancreatitis, Diabetes, and Pancreatic Cancer (CPDPC) was performed. Samples came from the North American Pancreatitis Studies 2 (NAPS2) cohort and the Pancreatic Adenocarcinoma Gene Environment Risk Study (PAGER) and were analyzed using a 62-plex Luminex assay in a blinded fashion. Group and pairwise comparisons were performed to identify unique immune signature panels and to calculate diagnostic utility using area under the curve analysis.RESULTS: A total of 179 patients' samples were included: 41 controls, 40 CP, 78 PDAC and 20 RAP patients, of which 20 controls, 20 CP, and 58 PDAC patients had diabetes mellitus (DM). A unique immune signature panel could discriminate RAP, CP, and PDAC from controls with an AUC range from 0.77 to 0.86 (95% CI range: 0.64-0.94), RAP from CP, and CP from PDAC with an AUC of 0.77 (95% CI 0.64-0.90) and 0.76 (95% CI 0.67-0.86), respectively. Furthermore, an immune signature panel could also discriminate PDAC-DM from DM controls with an AUC of 0.96 (95% CI: 0.93-1.00) CONCLUSION: This study identifies unique immune analytes that may serve as novel diagnostic and predictive non-invasive biomarkers of RAP, CP, and PDAC. Further validation is warranted in prospective cohorts as developed by the CPDPC.

View details for DOI 10.1016/j.pan.2019.11.008

View details for PubMedID 31791885
Evaluation of integrin alphavbeta6 cystine knot PET tracers to detect cancer and idiopathic pulmonary fibrosis. Nature communications Kimura, R. H., Wang, L., Shen, B., Huo, L., Tummers, W., Filipp, F. V., Guo, H. H., Haywood, T., Abou-Elkacem, L., Baratto, L., Habte, F., Devulapally, R., Witney, T. H., Cheng, Y., Tikole, S., Chakraborti, S., Nix, J., Bonagura, C. A., Hatami, N., Mooney, J. J., Desai, T., Turner, S., Gaster, R. S., Otte, A., Visser, B. C., Poultsides, G. A., Norton, J., Park, W., Stolowitz, M., Lau, K., Yang, E., Natarajan, A., Ilovich, O., Srinivas, S., Srinivasan, A., Paulmurugan, R., Willmann, J., Chin, F. T., Cheng, Z., Iagaru, A., Li, F., Gambhir, S. S. 2019; 10 (1): 4673
Abstract

Advances in precision molecular imaging promise to transform our ability to detect, diagnose and treat disease. Here, we describe the engineering and validation of a new cystine knot peptide (knottin) that selectively recognizes human integrin alphavbeta6 with single-digit nanomolar affinity. We solve its 3D structure by NMR and x-ray crystallography and validate leads with 3 different radiolabels in pre-clinical models of cancer. We evaluate the lead tracer's safety, biodistribution and pharmacokinetics in healthy human volunteers, and show its ability to detect multiple cancers (pancreatic, cervical and lung) in patients at two study locations. Additionally, we demonstrate that the knottin PET tracers can also detect fibrotic lung disease in idiopathic pulmonary fibrosis patients. Our results indicate that these cystine knot PET tracers may have potential utility in multiple disease states that are associated with upregulation of integrin alphavbeta6.

View details for DOI 10.1038/s41467-019-11863-w

View details for PubMedID 31611594
Magnetic resonance imaging as a non-invasive method for the assessment of pancreatic fibrosis (MINIMAP): a comprehensive study design from the consortium for the study of chronic pancreatitis, diabetes, and pancreatic cancer ABDOMINAL RADIOLOGY Tirkes, T., Yadav, D., Conwell, D. L., Territo, P. R., Zhao, X., Venkatesh, S. K., Kolipaka, A., Li, L., Pisegna, J. R., Pandol, S. J., Park, W. G., Topazian, M., Serrano, J., Fogel, E. L., Consortium Study Chronic 2019; 44 (8): 2809?21
View details for DOI 10.1007/s00261-019-02049-5

View details for Web of Science ID 000473245000014
A multimodality test to guide the management of patients with a pancreatic cyst. Science translational medicine Springer, S., Masica, D. L., Dal Molin, M., Douville, C., Thoburn, C. J., Afsari, B., Li, L., Cohen, J. D., Thompson, E., Allen, P. J., Klimstra, D. S., Schattner, M. A., Schmidt, C. M., Yip-Schneider, M., Simpson, R. E., Fernandez-Del Castillo, C., Mino-Kenudson, M., Brugge, W., Brand, R. E., Singhi, A. D., Scarpa, A., Lawlor, R., Salvia, R., Zamboni, G., Hong, S., Hwang, D. W., Jang, J., Kwon, W., Swan, N., Geoghegan, J., Falconi, M., Crippa, S., Doglioni, C., Paulino, J., Schulick, R. D., Edil, B. H., Park, W., Yachida, S., Hijioka, S., van Hooft, J., He, J., Weiss, M. J., Burkhart, R., Makary, M., Canto, M. I., Goggins, M. G., Ptak, J., Dobbyn, L., Schaefer, J., Sillman, N., Popoli, M., Klein, A. P., Tomasetti, C., Karchin, R., Papadopoulos, N., Kinzler, K. W., Vogelstein, B., Wolfgang, C. L., Hruban, R. H., Lennon, A. M. 2019; 11 (501)
Abstract

Pancreatic cysts are common and often pose a management dilemma, because some cysts are precancerous, whereas others have little risk of developing into invasive cancers. We used supervised machine learning techniques to develop a comprehensive test, CompCyst, to guide the management of patients with pancreatic cysts. The test is based on selected clinical features, imaging characteristics, and cyst fluid genetic and biochemical markers. Using data from 436 patients with pancreatic cysts, we trained CompCyst to classify patients as those who required surgery, those who should be routinely monitored, and those who did not require further surveillance. We then tested CompCyst in an independent cohort of 426 patients, with histopathology used as the gold standard. We found that clinical management informed by the CompCyst test was more accurate than the management dictated by conventional clinical and imaging criteria alone. Application of the CompCyst test would have spared surgery in more than half of the patients who underwent unnecessary resection of their cysts. CompCyst therefore has the potential to reduce the patient morbidity and economic costs associated with current standard-of-care pancreatic cyst management practices.

View details for DOI 10.1126/scitranslmed.aav4772

View details for PubMedID 31316009
Novel Methylated DNA Markers Discriminate Advanced Neoplasia in Pancreatic Cysts: Marker Discovery, Tissue Validation, and Cyst Fluid Testing. The American journal of gastroenterology Majumder, S., Taylor, W. R., Yab, T. C., Berger, C. K., Dukek, B. A., Cao, X., Foote, P. H., Wu, C. W., Mahoney, D. W., Aslanian, H. R., Fernandez-Del Castillo, C., Doyle, L. A., Farrell, J. J., Fisher, W. E., Lee, L. S., Lee, Y. N., Park, W., Rodrigues, C., Gould Rothberg, B. E., Salem, R. R., Simeone, D. M., Urs, S., Van Buren, G., Smyrk, T. C., Allawi, H. T., Lidgard, G. P., Raimondo, M., Chari, S. T., Kendrick, M. L., Kisiel, J. B., Topazian, M. D., Ahlquist, D. A. 2019
Abstract

OBJECTIVES: Pancreatic cystic lesions (PCLs) may be precancerous. Those likely to harbor high-grade dysplasia (HGD) or pancreatic cancer (PC) are targets for surgical resection. Current algorithms to predict advanced neoplasia (HGD/PC) in PCLs lack diagnostic accuracy. In pancreatic tissue and cyst fluid (CF) from PCLs, we sought to identify and validate novel methylated DNA markers (MDMs) that discriminate HGD/PC from low-grade dysplasia (LGD) or no dysplasia (ND).METHODS: From an unbiased whole-methylome discovery approach using predefined selection criteria followed by multistep validation on case (HGD or PC) and control (ND or LGD) tissues, we identified discriminant MDMs. Top candidate MDMs were then assayed by quantitative methylation-specific polymerase chain reaction on archival CF from surgically resected PCLs.RESULTS: Of 25 discriminant MDMs identified in tissue, 13 were selected for validation in 134 CF samples (21 cases [8 HGD, 13 PC], 113 controls [45 ND, 68 LGD]). A tree-based algorithm using 2 CF-MDMs (TBX15, BMP3) achieved sensitivity and specificity above 90%. Discrimination was significantly better by this CF-MDM panel than by mutant KRAS or carcinoembryonic antigen, with areas under the receiver operating characteristic curve of 0.93 (95% confidence interval: 0.86-0.99), 0.71 (0.57-0.85), and 0.72 (0.60-0.84), respectively. Cutoffs for the MDM panel applied to an independent CF validation set (31 cases, 56 controls) yielded similarly high discrimination, areas under the receiver operating characteristic curve = 0.86 (95% confidence interval: 0.77-0.94, P = 0.2).DISCUSSION: Novel MDMs discovered and validated in tissue accurately identify PCLs harboring HGD/PC. A panel of 2 MDMs assayed in CF yielded results with potential to enhance current risk prediction algorithms. Prospective studies are indicated to optimize and further evaluate CF-MDMs for clinical use.

View details for DOI 10.14309/ajg.0000000000000284

View details for PubMedID 31306149
A Prospective Study to Establish a New-Onset Diabetes Cohort: From the Consortium for the Study of Chronic Pancreatitis, Diabetes, and Pancreatic Cancer. Pancreas Maitra, A., Sharma, A., Brand, R. E., Van Den Eeden, S. K., Fisher, W. E., Hart, P. A., Hughes, S. J., Mather, K. J., Pandol, S. J., Park, W. G., Feng, Z., Serrano, J., Rinaudo, J. A., Srivastava, S., Chari, S. T. ; 47 (10): 1244?48
Abstract

The National Cancer Institute and the National Institute for Diabetes and Digestive and Kidney Diseases initiated the Consortium for the Study of Chronic Pancreatitis, Diabetes, and Pancreatic Cancer (CPDPC) in 2015 (the CPDPC's origin, structure, governance, and research objectives are described in another article in this journal). One of the key objectives of CPDPC is to assemble a cohort of 10,000 subjects 50 years or older with new-onset diabetes, called the NOD cohort. Using a define, enrich, and find early detection approach, the aims of the NOD study are to (a) estimate the 3-year probability of pancreatic ductal adenocarcinoma (PDAC) in NOD (define), (b) establish a biobank of clinically annotated biospecimens from presymptomatic PDAC and control new-onset type 2 diabetes mellitus subjects, (c) conduct phase 3 validation studies of promising biomarkers for identification of incident PDAC in NOD patients (enrich), and (d) provide a platform for development of a future interventional screening protocol for early detection of PDAC in patients with NOD that incorporates imaging studies and/or clinical algorithms (find). It is expected that 85 to 100 incidences of PDAC will be diagnosed during the study period in this cohort of 10,000 patients.

View details for PubMedID 30325864
Magnetic resonance imaging as a non-invasive method for the assessment of pancreatic fibrosis (MINIMAP): a comprehensive study design from the consortium for the study of chronic pancreatitis, diabetes, and pancreatic cancer. Abdominal radiology (New York) Tirkes, T., Yadav, D., Conwell, D. L., Territo, P. R., Zhao, X., Venkatesh, S. K., Kolipaka, A., Li, L., Pisegna, J. R., Pandol, S. J., Park, W. G., Topazian, M., Serrano, J., Fogel, E. L., Consortium for the Study of Chronic Pancreatitis, D. 2019
Abstract

Characteristic features of chronic pancreatitis (CP) may be absent on standard imaging studies. Quantitative Magnetic Resonance Imaging (MRI) techniques such as T1 mapping, extracellular volume (ECV) fraction, diffusion-weighted imaging (DWI) with apparent diffusion coefficient map (ADC), MR elastography (MRE), and T1-weighted signal intensity ratio (SIR) have shown promise for the diagnosis and grading severity of CP. However, radiologists still use the Cambridge classification which is based on traditional ductal imaging alone. There is an urgent need to develop new diagnostic criteria that incorporate both parenchymal and ductal features of CP seen by MRI/MRCP. Designed to fulfill this clinical need, we present the MINIMAP study, which was funded in September 2018 by the National Institutes of Health. This is a comprehensive quantitative MR imaging study which will be performed at multiple institutions in well-phenotyped CP patient cohorts. We hypothesize that quantitative MRI/MRCP features can serve as valuable non-invasive imaging biomarkers to detect and grade CP. We will evaluate the role of T1 relaxometry, ECV, T1-weighted gradient echo SIR, MRE, arteriovenous enhancement ratio, ADC, pancreas volume/atrophy, pancreatic fat fraction, ductal features, and pancreatic exocrine output following secretin stimulation in the assessment of CP. We will attempt to generate a multi-parametric pancreatic tissue fibrosis (PTF) scoring system. We anticipate that a quantitative scoring system may serve as a biomarker of pancreatic fibrosis; hence this imaging technique can be used in clinical practice as well as clinical trials to evaluate the efficacy of agents which may slow the progression or reverse measures of CP.

View details for PubMedID 31089778
Genetic Risk Score in Diabetes Associated With Chronic Pancreatitis Versus Type 2 Diabetes Mellitus. Clinical and translational gastroenterology Goodarzi, M. O., Nagpal, T., Greer, P., Cui, J., Chen, Y. I., Guo, X., Pankow, J. S., Rotter, J. I., Alkaade, S., Amann, S. T., Baillie, J., Banks, P. A., Brand, R. E., Conwell, D. L., Cote, G. A., Forsmark, C. E., Gardner, T. B., Gelrud, A., Guda, N., LaRusch, J., Lewis, M. D., Money, M. E., Muniraj, T., Papachristou, G. I., Romagnuolo, J., Sandhu, B. S., Sherman, S., Singh, V. K., Wilcox, C. M., Pandol, S. J., Park, W. G., Andersen, D. K., Bellin, M. D., Hart, P. A., Yadav, D., Whitcomb, D. C. 2019
Abstract

Diabetes mellitus (DM) is a complication of chronic pancreatitis (CP). Whether pancreatogenic diabetes associated with CP-DM represents a discrete pathophysiologic entity from type 2 DM (T2DM) remains uncertain. Addressing this question is needed for development of specific measures to manage CP-DM. We approached this question from a unique standpoint, hypothesizing that if CP-DM and T2DM are separate disorders, they should be genetically distinct. To test this hypothesis, we sought to determine whether a genetic risk score (GRS) based on validated single nucleotide polymorphisms for T2DM could distinguish between groups with CP-DM and T2DM.We used 60 T2DM single nucleotide polymorphisms to construct a weighted GRS in 1,613 subjects from the North American Pancreatitis Study 2 and 2,685 subjects from the Multi-Ethnic Study of Atherosclerosis, all of European origin.The mean GRS was identical between 321 subjects with CP-DM and 423 subjects with T2DM (66.53 vs 66.42, P = 0.95), and the GRS of both diabetic groups was significantly higher than that of nondiabetic controls (n = 3,554, P < 0.0001). Exploratory analyses attempting to enrich the CP-DM group for pancreatogenic diabetes, such as eliminating diabetes diagnosed before CP, requiring pancreas-specific comorbidities, or removing those with a family history of diabetes, did not improve the ability of the GRS to distinguish between CP-DM and T2DM.Recognizing that we lacked a gold standard to define CP-DM, our study suggests that CP-DM may be a subtype of T2DM, a notion that should be tested in future, large prospective studies.This is an open-access article distributed under the terms of the Creative Commons Attribution-Non Commercial-No Derivatives License 4.0 (CCBY-NC-ND), where it is permissible to download and share the work provided it is properly cited. The work cannot be changed in any way or used commercially without permission from the journal.

View details for DOI 10.14309/ctg.0000000000000057

View details for PubMedID 31232720
THE EFFECT OF THE DISTRIBUTION OF THE INVERSE GROWTH RATE ON PANCREATIC CANCER PROGRESSION Abu-El-Haija, L., Ivy, J. S., Park, W., IEEE IEEE. 2019: 1044?54
View details for Web of Science ID 000529791401001
Isolated pancreatic tail remnants after transgastric necrosectomy can be observed. The Journal of surgical research Dua, M. M., Jensen, C. W., Friedland, S., Worth, P. J., Poultsides, G. A., Norton, J. A., Park, W. G., Visser, B. C. 2018; 231: 109?15
Abstract

BACKGROUND: Severe necrotizing pancreatitis may result in midbody necrosis and ductal disruption leaving an isolated pancreatic tail. The purpose of this study was to characterize outcomes among patients with an isolated tail remnant who underwent transgastric drainage or necrosectomy (endoscopic or surgical) and determine the need for subsequent operative management.MATERIALS AND METHODS: Patients with necrotizing pancreatitis and retrogastric walled-off collections treated by surgical transgastric necrosectomy or endoscopic cystgastrostomy� necrosectomy between 2009 and 2017 were identified by a retrospective chart review. All available preprocedure and postprocedure imaging was reviewed for evidence of isolated distal pancreatic tail remnants.RESULTS: Seventy-four patients were included (40 surgical and 34 endoscopic). All the patients in the surgical group underwent laparoscopic transgastric necrosectomy; the endoscopic group consisted of 26 patients for pseudocyst drainage and eight patients for necrosectomy. A disconnected pancreatic tail was identified in 22 (29%) patients (13 laparoscopic and nine endoscopic). After the creation of the "cystgastrostomy," there were no external fistulas despite the viable tail. Of the 22 patients, four patients developed symptoms at a median of 23months (two, recurrent episodic pancreatitis; two, intractable pain). Two patients (both initially in endoscopic group) ultimately required distal pancreatectomy and splenectomy at 24 and 6months after index procedure.CONCLUSIONS: Patients with a walled-off retrogastric collection and an isolated viable tail are effectively managed by a transgastric approach. Despite this seemingly "unstable anatomy," the creation of an internal fistula via surgical or endoscopic "cystgastrostomy" avoids external fistulas/drains and the short-term necessity of surgical distal pancreatectomy. A very small subset requires intervention for late symptoms.

View details for PubMedID 30278917
A Prospective Study to Establish a New-Onset Diabetes Cohort: From the Consortium for the Study of Chronic Pancreatitis, Diabetes, and Pancreatic Cancer PANCREAS Maitra, A., Sharma, A., Brand, R. E., Van Den Eeden, S. K., Fisher, W. E., Hart, P. A., Hughes, S. J., Mather, K. J., Pandol, S. J., Park, W. G., Feng, Z., Serrano, J., Rinaudo, J. S., Srivastava, S., Chari, S. T., Consortium Study Chronic 2018; 47 (10): 1244?48
View details for DOI 10.1097/MPA.0000000000001169

View details for Web of Science ID 000449304600013
PROspective Evaluation of Chronic Pancreatitis for EpidEmiologic and Translational StuDies: Rationale and Study Design for PROCEED From the Consortium for the Study of Chronic Pancreatitis, Diabetes, and Pancreatic Cancer PANCREAS Yadav, D., Park, W. G., Fogel, E. L., Li, L., Chari, S. T., Feng, Z., Fisher, W. E., Forsmark, C. E., Jeon, C. Y., Habtezion, A., Hart, P. A., Hughes, S. J., Othman, M. O., Rinaudo, J. S., Pandol, S. J., Tirkes, T., Serrano, J., Srivastava, S., Van Den Eeden, S. K., Whitcomb, D. C., Topazian, M., Conwell, D. L., Consortium Study Chronic 2018; 47 (10): 1229?38
View details for DOI 10.1097/MPA.0000000000001170

View details for Web of Science ID 000449304600011
Reporting Standards for Chronic Pancreatitis by Using CT, MRI, and MR Cholangiopancreatography: The Consortium for the Study of Chronic Pancreatitis, Diabetes, and Pancreatic Cancer. Radiology Tirkes, T., Shah, Z. K., Takahashi, N., Grajo, J. R., Chang, S. T., Venkatesh, S. K., Conwell, D. L., Fogel, E. L., Park, W., Topazian, M., Yadav, D., Dasyam, A. K., Consortium for the Study of Chronic Pancreatitis, D. 2018: 181353
Abstract

Chronic pancreatitis is an inflammatory condition of the pancreas with clinical manifestations ranging from abdominal pain, acute pancreatitis, exocrine and/or endocrine dysfunction, and pancreatic cancer. There is a need for longitudinal studies in well-phenotyped patients to ascertain the utility of cross-sectional imaging findings of chronic pancreatitis for diagnosis and assessment of disease severity. CT and MR cholangiopancreatography are the most common cross-sectional imaging studies performed for the evaluation of chronic pancreatitis. Currently, there are no universal reporting standards for chronic pancreatitis. Several features of chronic pancreatitis are applied clinically, such as calcifications, parenchymal T1 signal changes, focal or diffuse gland atrophy, or irregular contour of the gland. Such findings have not been incorporated into standardized diagnostic criteria. There is also lack of consensus on quantification of disease severity in chronic pancreatitis, other than by using ductal features alone as described in the Cambridge classification. The Consortium for the Study of Chronic Pancreatitis, Diabetes, and Pancreatic Cancer (CPDPC) was established by the National Institute of Diabetes and Digestive and Kidney Diseases and the National Cancer Institute in 2015 to undertake collaborative studies on chronic pancreatitis, diabetes mellitus, and pancreatic adenocarcinoma. CPDPC investigators from the Adult Chronic Pancreatitis Working Group were tasked with development of a new consensus approach to reporting features of chronic pancreatitis aimed to standardize diagnosis and assessment of disease severity for clinical trials. This consensus statement presents and defines features of chronic pancreatitis along with recommended reporting metrics. � RSNA, 2018 Online supplemental material is available for this article. See also the editorial by Megibow in this issue.

View details for PubMedID 30325281
Chronic pancreatitis changes in high-risk individuals for pancreatic ductal adenocarcinoma. Gastrointestinal endoscopy Thiruvengadam, S. S., Chuang, J., Huang, R., Girotra, M., Park, W. G. 2018
Abstract

BACKGROUND AND AIMS: Pancreatic intraepithelial neoplasia is associated with chronic pancreatitis (CP) changes on EUS. The objective of this study was to determine whether CP changes were more common in high-risk individuals (HRIs) than in controls and whether these changes differed among higher-risk subsets of HRIs.METHODS: HRIs and controls were identified from an endoscopy database. HRIs were defined as having predisposing mutations or a family history (FH) of pancreatic ductal adenocarcinoma. HRIs were classified as vHRIs who met cancer of the pancreas screening (CAPS) criteria for high risk and mHRIs who did not. Multivariable logistic regression was used to adjust for confounders and CP risk factors.RESULTS: 65 HRIs (44 vHRIs, 21 mHRIs) and 118 controls were included. HRIs were included for FH (25), Lynch syndrome (5), Peutz-Jeghers syndrome (2), and mutations in BRCA1/2 (26), PALB2 (3), ATM (3), and CDKN2A (1). After adjustment for relevant variables, HRIs were 16 times more likely to exhibit 3 or more CP changes than controls (95% CI, 2.6-97.0; P = .003). HRIs were also more likely to have hypoechoic foci (OR, 8.0; 95% CI, 1.9-32.9; P = .004). vHRIs and mHRIs did not differ in frequency of three or more CP changes on EUS.CONCLUSIONS: HRIs were more likely to exhibit CP changes and hypoechoic foci on EUS compared with controls. HRIs with these findings may require closer surveillance. HRIs who did or did not meet CAPS criteria did not differ with regard to CP findings, supporting a more inclusive approach to screening.

View details for DOI 10.1016/j.gie.2018.08.029

View details for PubMedID 30145314
RISK OF POST-PROCEDURAL UNPLANNED HOSPITAL ENCOUNTERS FOLLOWING ENDOSCOPIC ULTRASOUND WITH FINE-NEEDLE ASPIRATION OF THE PANCREAS: A POPULATION-LEVEL, PROPENSITY-SCORE CONTROLLED COHORT STUDY Huang, R. J., Barakat, M. T., Park, W. G., Banerjee, S. MOSBY-ELSEVIER. 2018: AB107?AB108
View details for Web of Science ID 000434248200111
Pancreatic cyst fluid glucose: rapid, inexpensive, and accurate diagnosis of mucinous pancreatic cysts Carr, R. A., Yip-Schneider, M. T., Simpson, R. E., Dolejs, S., Schneider, J. G., Wu, H., Ceppa, E. P., Park, W., Schmidt, C. MOSBY-ELSEVIER. 2018: 600?605
Abstract

The most widely accepted biochemical test for preoperative differentiation of mucinous from benign, nonmucinous pancreatic cysts is cyst fluid carcinoembryonic antigen. However, the diagnostic accuracy of carcinoembryonic antigen ranges from 70% to 86%. Based on previous work, we hypothesize that pancreatic cyst fluid glucose may be an attractive alternative to carcinoembryonic antigen.Pancreatic cyst fluid was collected during endoscopic or operative intervention. Diagnoses were pathologically confirmed. Glucose and carcinoembryonic antigen were measured using a patient glucometer and automated analyzer/enzyme-linked immunosorbent assay. Sensitivity, specificity, accuracy, and receiver operator characteristic analyses were performed.Cyst fluid samples from 153 patients were evaluated (mucinous: 25 mucinous cystic neoplasms, 77 intraductal papillary mucinous neoplasms, 4 ductal adenocarcinomas; nonmucinous: 21 serous cystic neoplasms, 9 cystic neuroendocrine tumors, 14 pseudocysts, 3 solid pseudopapillary neoplasms). Median cyst fluid glucose was lower in mucinous versus nonmucinous cysts (19 vs 96?mg/dL; P?192?ng/mL was 58% sensitive, 96% specific, and 69% accurate. Area under the curve for glucose and CEA were similar at 0.91 and 0.92.Cyst fluid glucose has significant advantages over carcinoembryonic antigen and should be considered for use as a routine diagnostic test for pancreatic mucinous cysts.

View details for PubMedID 29241991
Endoscopic ultrasound guided fine-needle aspiration and biopsy of pancreatic cysts TECHNIQUES IN GASTROINTESTINAL ENDOSCOPY Girotra, M., Park, W. G. 2018; 20 (1): 39?45
View details for DOI 10.1016/j.tgie.2017.10.004

View details for Web of Science ID 000425848000008
Transgastric pancreatic necrosectomy-expedited return to prepancreatitis health JOURNAL OF SURGICAL RESEARCH Dua, M. M., Worhunsky, D. J., Malhotra, L., Park, W. G., Poultsides, G. A., Norton, J. A., Visser, B. C. 2017; 219: 11?17
Abstract

The best operative strategy for necrotizing pancreatitis remains controversial. Traditional surgical necrosectomy is associated with significant morbidity; endoscopic and percutaneous strategies require repeated interventions with prolonged hospitalizations. We have developed a transgastric approach to pancreatic necrosectomy to overcome the shortcomings of the other techniques described.Patients with necrotizing pancreatitis treated from 2009 to 2016 at an academic center were retrospectively reviewed. Open or laparoscopic transgastric necrosectomy was performed if the area of necrosis was walled-off and in a retrogastric position on cross-sectional imaging. Study endpoints included postoperative complications and mortality.Forty-six patients underwent transgastric necrosectomy (nine open and 37 laparoscopic). Median (interquartile range) preoperative Acute Physiologic and Chronic Health Evaluation II score was 6 (3-12). Seventy percent of patients had >30% necrosis on preoperative imaging; infected necrosis was present in 35%. Median total length of stay (LOS) was 6 (3-12) d. No patient required a second operative debridement; four patients (9%) had short-term postoperative percutaneous drainage for residual fluid collections. Median follow-up was 1�y; there were no fistula or wound complications. Six patients (13%) had postoperative bleeding; five patients received treatment by image-guided embolization. There was one death in the cohort.Transgastric pancreatic necrosectomy allows for effective debridement with a single definitive operation. When anatomically suitable, this operative strategy offers expedited recovery and avoids long-term morbidity associated with fistulas and prolonged drainage.

View details for PubMedID 29078869
Endoscopic Ultrasound and Related Technologies for the Diagnosis and Treatment of Pancreatic Disease - Research Gaps and Opportunities Summary of a National Institute of Diabetes and Digestive and Kidney Diseases Workshop PANCREAS Lee, L. S., Andersen, D. K., Ashida, R., Brugge, W. R., Canto, M. I., Chang, K. J., Chari, S. T., DeWitt, J., Hwang, J., Khashab, M. A., Kim, K., Levy, M. J., McGrath, K., Park, W. G., Singhi, A., Stevens, T., Thompson, C. C., Topazian, M. D., Wallace, M. B., Wani, S., Waxman, I., Yadav, D., Singh, V. K. 2017; 46 (10): 1242?50
Abstract

A workshop was sponsored by the National Institute of Diabetes and Digestive and Kidney Diseases to address the research gaps and opportunities in pancreatic endoscopic ultrasound (EUS). The event occurred on July 26, 2017 in 4 sessions: (1) benign pancreatic diseases, (2) high-risk pancreatic diseases, (3) diagnostic and therapeutics, and (4) new technologies. The current state of knowledge was reviewed, with identification of numerous gaps in knowledge and research needs. Common themes included the need for large multicenter consortia of various pancreatic diseases to facilitate meaningful research of these entities; to standardize EUS features of different pancreatic disorders, the technique of sampling pancreatic lesions, and the performance of various therapeutic EUS procedures; and to identify high-risk disease early at the cellular level before macroscopic disease develops. The need for specialized tools and accessories to enable the safe and effective performance of therapeutic EUS procedures also was discussed.

View details for PubMedID 28926412

View details for PubMedCentralID PMC5645254
Editors' Introduction to the Chronic Pancreatitis and Pancreatic Cysts Special Issue. Digestive diseases and sciences Park, W. G., Habtezion, A. 2017
View details for DOI 10.1007/s10620-017-4613-z

View details for PubMedID 28523572
Global protease activity profiling provides differential diagnosis of pancreatic cysts. Clinical cancer research : an official journal of the American Association for Cancer Research Ivry, S. L., Sharib, J. M., Dominguez, D. A., Roy, N., Hatcher, S. E., Yip-Schneider, M., Schmidt, C. M., Brand, R. E., Park, W. G., Hebrok, M., Kim, G., O'Donoghue, A. J., Kirkwood, K. S., Craik, C. S. 2017
Abstract

Purpose: Pancreatic cysts are estimated to be present in 2%-3% of the adult population. Unfortunately, current diagnostics do not accurately distinguish benign cysts from those that can progress into invasive cancer. Misregulated pericellular proteolysis is a hallmark of malignancy, and therefore, we used a global approach to discover protease activities that differentiate benign nonmucinous cysts from premalignant mucinous cysts.Experimental Design: We employed an unbiased and global protease profiling approach to discover protease activities in 23 cyst fluid samples. The distinguishing activities of select proteases was confirmed in 110 samples using specific fluorogenic substrates and required less than 5 ?L of cyst fluid.Results: We determined that the activities of the aspartyl proteases gastricsin and cathepsin E are highly increased in fluid from mucinous cysts. IHC analysis revealed that gastricsin expression was associated with regions of low-grade dysplasia, whereas cathepsin E expression was independent of dysplasia grade. Gastricsin activity differentiated mucinous from nonmucinous cysts with a specificity of 100% and a sensitivity of 93%, whereas cathepsin E activity was 92% specific and 70% sensitive. Gastricsin significantly outperformed the most widely used molecular biomarker, carcinoembryonic antigen (CEA), which demonstrated 94% specificity and 65% sensitivity. Combined analysis of gastricsin and CEA resulted in a near perfect classifier with 100% specificity and 98% sensitivity.Conclusions: Quantitation of gastricsin and cathepsin E activities accurately distinguished mucinous from nonmucinous pancreatic cysts and has the potential to replace current diagnostics for analysis of these highly prevalent lesions. Clin Cancer Res; 23(16); 4865-74. �2017 AACR.

View details for DOI 10.1158/1078-0432.CCR-16-2987

View details for PubMedID 28424202
Cholestyramine as a promising, strong anion exchange resin for direct capture of genetic biomarkers from raw pancreatic fluids BIOTECHNOLOGY AND BIOENGINEERING Hilmer, A. J., Jeffrey, R. B., Park, W. G., Khosla, C. 2017; 114 (4): 934-938
Abstract

The ability to capture cell-free DNA from the gastrointestinal tract, in a minimally invasive manner, could enhance our ability to diagnose gastrointestinal disease, or gain a better understanding of the spatial mapping of the intestinal microbiota. We, therefore, sought to identify a class of capture agents that could directly and efficiently sequester genetic material from intestinal fluids. As a particular case study, we examined the ability to capture DNA from pancreatic secretions, for potential application in enabling the sequestration of early, genetic biomarkers of pancreatic disease. We hypothesized that the cholestyramine series of strong cation exchange resins, which are FDA approved for the treatment of high cholesterol, may be capable of capturing DNA from pancreatic secretions. We identified a particular cholestyramine resin, DOWEX 1?�?2 100-200?mesh, which is able to efficiently capture and purify DNA from pancreatic fluid. Using only 200??L of pancreatic secretions, we are able to recover 247?�?182?ng of amplifiable human DNA, giving an estimated pancreatic fluid DNA content of 1.23?�?0.91?ng/?L. To our knowledge, this is the first demonstration of a material that can effectively capture and purify DNA directly from untreated pancreatic fluids. Thus, our approach could hold high utility for the in vivo capture of DNA and disease biomarkers if incorporated into an appropriate sampling device. Biotechnol. Bioeng. 2016;9999: 1-5. � 2016 Wiley Periodicals, Inc.

View details for DOI 10.1002/bit.26207

View details for Web of Science ID 000395650600022
Fukuoka and AGA Criteria Have Superior Diagnostic Accuracy for Advanced Cystic Neoplasms than Sendai Criteria. Digestive diseases and sciences Sighinolfi, M., Quan, S. Y., Lee, Y., Ibaseta, A., Pham, K., Dua, M. M., Poultsides, G. A., Visser, B. C., Norton, J. A., Park, W. G. 2017; 62 (3): 626-632
Abstract

The aim of this study was to compare the American Gastroenterological Association guidelines (AGA criteria), the 2012 (Fukuoka criteria), and 2006 (Sendai criteria) International Consensus Guidelines for the diagnosis of advanced pancreatic cystic neoplasms.All patients who underwent surgical resection of a pancreatic cyst from August 2007 through January 2016 were retrospectively analyzed at a single tertiary academic center. Relevant clinical and imaging variables along with pathology results were collected to determine appropriate classification for each guideline. Advanced pancreatic cystic neoplasms were defined by the presence of either high-grade dysplasia or cystic adenocarcinoma. Diagnostic accuracy was measured by ROC analysis.A total of 209 patients were included. Both the AGA and Fukuoka criteria had a higher diagnostic accuracy for advanced neoplastic cysts than the Sendai criteria: AGA ROC 0.76 (95% CI 0.69-0.81), Fukuoka ROC 0.78 (95% CI 0.74-0.82), and Sendai ROC 0.65 (95% CI 0.61-0.69) (p�<�0.0001). There was no difference between the Fukuoka and the AGA criteria. While the sensitivity was higher in the Fukuoka criteria compared to the AGA criteria (97.7 vs. 88.6%), the specificity was higher in the AGA criteria compared to the Fukuoka criteria (62.4 vs. 58.2%).In a surgical series of patients with pancreatic cysts, the AGA and Fukuoka criteria had superior diagnostic accuracy for advanced neoplastic cysts compared to the original Sendai criteria.

View details for DOI 10.1007/s10620-017-4460-y

View details for PubMedID 28116593
Telephone-Based Mindfulness Therapy Intervention for Patients with Chronic Pancreatitis. Digestive diseases and sciences Aivaliotis, V. I., Lee, Y., Zia, J., Wassef, W., Abramson, M., Park, W. 2017; 62 (2): 502-509
Abstract

Patients with chronic pancreatitis (CP) have substantially impaired quality of life (QOL) both physically and mentally. Mindfulness therapy is a form of treatment that has been shown to be beneficial in many medical conditions but has not been evaluated in the CP patient population.The aims of this study were (1) to test the feasibility and usability of a novel telephone-based mindfulness therapy service for patients with CP and (2) to determine whether there was any effect on CP quality of life.We recruited ten patients with suspected or confirmed CP and five controls who were asked to utilize our telephone-based mindfulness therapy service daily for 28�days. Feasibility of the service was defined as the fraction of subjects with a�?50% compliance rate. Usability was assessed using a System Usability Scale (SUS). QOL was evaluated using the SF-36 questionnaire and the Pancreatitis Quality of Life Instrument (PANQOLI). Paired t tests were used to compare the SF-36 and PANQOLI pre- and post-intervention.There was an overall compliance rate of 67%. The mean SUS score for all participants was 79.3, above the average published score of 68. Results showed a significant improvement in the SF-36 Mental Component Summary scores after 28�days of mindfulness therapy for patients with CP, t(9)�=�2.48, p�=�0.035. There was also a significant improvement in the mean total PANQOLI scores in CP patients, t(9)�=�2.41, p�=�0.04, most notably in the social domain.Our telephone-based mindfulness therapy service represents a feasible and easily usable treatment adjunct for patients with CP, which may provide benefit in QOL by improving mental health-related domains.

View details for DOI 10.1007/s10620-016-4389-6

View details for PubMedID 27933469
Acute pancreatitis patient registry to examine novel therapies in clinical experience (APPRENTICE): an international, multicenter consortium for the study of acute pancreatitis. Annals of gastroenterology : quarterly publication of the Hellenic Society of Gastroenterology Papachristou, G. I., Machicado, J. D., Stevens, T., Goenka, M. K., Ferreira, M., Gutierrez, S. C., Singh, V. K., Kamal, A., Gonzalez-Gonzalez, J. A., Pelaez-Luna, M., Gulla, A., Zarnescu, N. O., Triantafyllou, K., Barbu, S. T., Easler, J., Ocampo, C., Capurso, G., Archibugi, L., Cote, G. A., Lambiase, L., Kochhar, R., Chua, T., Tiwari, S. C., Nawaz, H., Park, W. G., de-Madaria, E., Lee, P. J., Wu, B. U., Greer, P. J., Dugum, M., Koutroumpakis, E., Akshintala, V., Gougol, A. 2017; 30 (1): 106?13
Abstract

We have established a multicenter international consortium to better understand the natural history of acute pancreatitis (AP) worldwide and to develop a platform for future randomized clinical trials.The AP patient registry to examine novel therapies in clinical experience (APPRENTICE) was formed in July 2014. Detailed web-based questionnaires were then developed to prospectively capture information on demographics, etiology, pancreatitis history, comorbidities, risk factors, severity biomarkers, severity indices, health-care utilization, management strategies, and outcomes of AP patients.Between November 2015 and September 2016, a total of 20 sites (8 in the United States, 5 in Europe, 3 in South America, 2 in Mexico and 2 in India) prospectively enrolled 509 AP patients. All data were entered into the REDCap (Research Electronic Data Capture) database by participating centers and systematically reviewed by the coordinating site (University of Pittsburgh). The approaches and methodology are described in detail, along with an interim report on the demographic results.APPRENTICE, an international collaboration of tertiary AP centers throughout the world, has demonstrated the feasibility of building a large, prospective, multicenter patient registry to study AP. Analysis of the collected data may provide a greater understanding of AP and APPRENTICE will serve as a future platform for randomized clinical trials.

View details for PubMedID 28042246

View details for PubMedCentralID PMC5198234
EUS and related technologies for the diagnosis and treatment of pancreatic disease: research gaps and opportunities-Summary of a National Institute of Diabetes and Digestive and Kidney Diseases workshop. Gastrointestinal endoscopy Lee, L. S., Andersen, D. K., Ashida, R., Brugge, W. R., Canto, M. I., Chang, K. J., Chari, S. T., DeWitt, J., Hwang, J. H., Khashab, M. A., Kim, K., Levy, M. J., McGrath, K., Park, W. G., Singhi, A., Stevens, T., Thompson, C. C., Topazian, M. D., Wallace, M. B., Wani, S., Waxman, I., Yadav, D., Singh, V. K. 2017; 86 (5): 768?78
Abstract

A workshop was sponsored by the National Institute of Diabetes and Digestive and Kidney Diseases to address the research gaps and opportunities in pancreatic EUS. The event occurred on July 26, 2017 in 4 sessions: (1) benign pancreatic diseases, (2) high-risk pancreatic diseases, (3) diagnostic and therapeutics, and (4) new technologies. The current state of knowledge was reviewed, with identification of numerous gaps in knowledge and research needs. Common themes included the need for large multicenter consortia of various pancreatic diseases to facilitate meaningful research of these entities; to standardize EUS features of different pancreatic disorders, the technique of sampling pancreatic lesions, and the performance of various therapeutic EUS procedures; and to identify high-risk disease early at the cellular level before macroscopic disease develops. The need for specialized tools and accessories to enable the safe and effective performance of therapeutic EUS procedures also was discussed.

View details for PubMedID 28941651
How to Be an Advocate for Your Profession and Your Practice. Clinical gastroenterology and hepatology : the official clinical practice journal of the American Gastroenterological Association Park, W. G. 2017; 15 (10): 1489?91
View details for PubMedID 28923572
Cholestyramine as a promising, strong anion exchange resin for direct capture of genetic biomarkers from raw pancreatic fluids. Biotechnology and bioengineering Hilmer, A. J., Jeffrey, R. B., Park, W. G., Khosla, C. 2016
Abstract

The ability to capture cell-free DNA from the gastrointestinal tract, in a minimally invasive manner, could enhance our ability to diagnose gastrointestinal disease, or gain a better understanding of the spatial mapping of the intestinal microbiota. We, therefore, sought to identify a class of capture agents that could directly and efficiently sequester genetic material from intestinal fluids. As a particular case study, we examined the ability to capture DNA from pancreatic secretions, for potential application in enabling the sequestration of early, genetic biomarkers of pancreatic disease. We hypothesized that the cholestyramine series of strong cation exchange resins, which are FDA approved for the treatment of high cholesterol, may be capable of capturing DNA from pancreatic secretions. We identified a particular cholestyramine resin, DOWEX 1?�?2 100-200?mesh, which is able to efficiently capture and purify DNA from pancreatic fluid. Using only 200??L of pancreatic secretions, we are able to recover 247?�?182?ng of amplifiable human DNA, giving an estimated pancreatic fluid DNA content of 1.23?�?0.91?ng/?L. To our knowledge, this is the first demonstration of a material that can effectively capture and purify DNA directly from untreated pancreatic fluids. Thus, our approach could hold high utility for the in vivo capture of DNA and disease biomarkers if incorporated into an appropriate sampling device. Biotechnol. Bioeng. 2016;9999: 1-5. � 2016 Wiley Periodicals, Inc.

View details for DOI 10.1002/bit.26207

View details for PubMedID 27800600
Aryl Hydrocarbon Receptor Ligands in Cigarette Smoke Induce Production of Interleukin-22 to Promote Pancreatic Fibrosis in Models of Chronic Pancreatitis. Gastroenterology Xue, J., Zhao, Q., Sharma, V., Nguyen, L. P., Lee, Y. N., Pham, K. L., Edderkaoui, M., Pandol, S. J., Park, W., Habtezion, A. 2016
Abstract

Cigarette smoke has been identified as an independent risk factor for chronic pancreatitis (CP). Little is known about the mechanisms by which smoking promotes development of CP. We assessed the effects of aryl hydrocarbon receptor (AhR) ligands found in cigarette smoke on immune cell activation in humans and pancreatic fibrosis in animal models of�CP.We obtained serum samples from patients with CP treated at Stanford University hospital and healthy individuals (controls) and isolated CD4(+) T cells. Levels of�interleukin-22 (IL22) were measured by enzyme-linked immunosorbent assay and smoking histories were collected. T�cells from healthy nonsmokers and smokers were stimulated�and incubated with AhR agonists (2,3,7,8-tetrachlorodibenzo-p-dioxin or benzo[a]pyrene) or antagonists and analyzed by flow cytometry. Mice were given intraperitoneal injections of caerulein or saline, with or without lipopolysaccharide, to induce CP. Some mice were given intraperitoneal injections of AhR agonists at the start of caerulein injection, with or without an antibody against IL22 (anti-IL22) starting 2 weeks after the first caerulein injection, or recombinant mouse IL22 or vehicle (control) intraperitoneally 4 weeks after the first caerulein injection. Mice were exposed to normal air or cigarette smoke for 6 h/d for 7 weeks and expression of AhR gene targets was measured. Pancreata were collected from all mice and analyzed by histology and quantitative reverse transcription polymerase chain reaction. Pancreatic stellate cells and T cells were isolated and studied using immunoblot, immunofluorescence, flow cytometry, and enzyme-linked immunosorbent analyses.Mice given AhR agonists developed more severe pancreatic fibrosis (based on decreased pancreas size, histology, and increased expression of fibrosis-associated genes) than mice not given agonists after caerulein injection. In mice given saline instead of caerulein, AhR ligands did not induce fibrosis. Pancreatic T cells from mice given AhR agonists and caerulein were activated and expressed IL22, but not IL17 or interferon gamma. Human T cells exposed to AhR agonists up-regulated expression of IL22. In mice given anti-IL22, pancreatic fibrosis did not progress, whereas mice given recombinant IL22 had a smaller pancreas and increased fibrosis. Pancreatic stellate cells isolated from mouse and human pancreata expressed the IL22 receptor IL22RA1. Incubation of the pancreatic stellate cells with IL22 induced their expression of the extracellular matrix genes fibronectin 1 and collagen type I ?1 chain, but not ?2 smooth muscle actin or transforming growth factor-?. Serum samples from smokers had significantly higher levels of IL22 than those from nonsmokers.AhR ligands found in cigarette smoke increase the severity of pancreatic fibrosis in mouse models of pancreatitis via up-regulation of IL22. This pathway might be targeted for treatment of CP and serve as a biomarker of disease.

View details for DOI 10.1053/j.gastro.2016.09.064

View details for PubMedID 27769811
Clinical chronic pancreatitis CURRENT OPINION IN GASTROENTEROLOGY Park, W. G. 2016; 32 (5): 415-421
View details for DOI 10.1097/MOG.0000000000000293

View details for Web of Science ID 000382428500011
Neuroendocrine tumors of the pancreas: Degree of cystic component predicts prognosis. Surgery Cloyd, J. M., Kopecky, K. E., Norton, J. A., Kunz, P. L., Fisher, G. A., Visser, B. C., Dua, M. M., Park, W. G., Poultsides, G. A. 2016; 160 (3): 708-713
Abstract

Although most pancreatic neuroendocrine tumors are solid, approximately 10% are cystic. Some studies have suggested that cystic pancreatic neuroendocrine tumors are associated with a more favorable prognosis.A retrospective review of all patients with pancreatic neuroendocrine tumors who underwent operative resection between 1999 and 2014 at a single academic medical center was performed. Based on cross-sectional imaging performed before operation, pancreatic neuroendocrine tumors were classified according to the size of the cystic component relative to the total tumor size: purely cystic (100%), mostly cystic (?50%), mostly solid (<50%), and purely solid (0%). Clinicopathologic characteristics and recurrence-free survival were assessed between groups.In the study, 214 patients met inclusion criteria: 8 with purely cystic tumors, 7 with mostly cystic tumors, 15 with mostly solid tumors, and 184 with purely solid tumors. The groups differed in�terms of tumor size (1.5��0.5, 3.0��1.7, 3.7��2.6, and 4.0��3.5�cm), lymph node positivity (0%,�0%, 26.7%, and 34.2%), intermediate or high grade (0%, 16.7%, 20.0%, and 31.0%), synchronous liver metastases (0%, 14.3%, 20.0%, and 26.6%) and need for pancreaticoduodenectomy (0%, 0%, 6.7%, and 25.0%), respectively. No cases of purely cystic pancreatic neuroendocrine tumors were associated with synchronous liver or lymph node metastasis, intermediate/high grade, recurrence, or death due to disease. Among patients presenting without metastatic disease, 10-year recurrence-free survival was 100% in patients with purely and mostly cystic tumors versus 53.0% in�patients with purely and mostly solid tumors; however, this difference did not reach statistical significance.Pancreatic neuroendocrine tumors demonstrate a spectrum of biologic behavior with an increasing cystic component being associated with more favorable clinicopathologic features and prognosis. Purely cystic pancreatic neuroendocrine tumors may represent 1 subset that can be safely observed without immediate resection.

View details for DOI 10.1016/j.surg.2016.04.005

View details for PubMedID 27216830
Pancreatitis Quality of Life Instrument: A Psychometric Evaluation AMERICAN JOURNAL OF GASTROENTEROLOGY Wassef, W., DeWitt, J., Mcgreevy, K., Wilcox, M., Whitcomb, D., Yadav, D., Amann, S., Mishra, G., Alkaade, S., Romagnuolo, J., Stevens, T., Vargo, J., Gardner, T., Singh, V., Park, W., Hartigan, C., Barton, B., Bova, C. 2016; 111 (8): 1177-1186
Abstract

Chronic pancreatitis is a significant medical problem that impacts a large number of patients worldwide. In 2014, we developed a disease-specific instrument for the evaluation of quality of life in this group of patients: pancreatitis quality of life instrument (PANQOLI). The goal of this study was to evaluate its psychometric properties: its reliability and its construct validity.This is a cross-sectional multi-center study that involved 12 pancreatic disease centers. Patients who met the inclusion/exclusion criteria for chronic pancreatitis were invited to participate. Those who accepted were asked to complete seven questionnaires/instruments. Only patients who completed the PANQOLI were included in the study. Its reliability and its construct validity were tested.A total of 159 patients completed the PANQOLI and were included in the study. They had a mean age of 49.03, 49% were male, and 84% were Caucasian. Six of the 24 items on the scale were removed because of lack of inter-item correlation, redundancy, or lack of correlation to quality of life issues. The final 18-item scale had excellent reliability (Cronbach's alpha coefficient: 0.914) and excellent construct validity with good correlation to generic quality of life instruments (SF-12 and EORTC QLQ-C30/QLQ-PAN26) and lack of correlation to non-quality of life instruments (MAST and DAST). Through exploratory factor analysis, the PANQOLI was found to consist of four subscales: emotional function scale, role function scale, physical function scale, and "self-worth" scale.PANQOLI is the first disease-specific instrument to be developed and validated for the evaluation of quality of life in chronic pancreatitis patients. It has a unique subscale for "self-worth" that differentiates it from other generic instruments. Studies are currently under way to evaluate its use in other populations not included in this study.

View details for DOI 10.1038/ajg.2016.225

View details for Web of Science ID 000384720000020

View details for PubMedID 27296943
Pancreatitis Quality of Life Instrument: A Psychometric Evaluation AMERICAN JOURNAL OF GASTROENTEROLOGY Wassef, W., DeWitt, J., Mcgreevy, K., Wilcox, M., Whitcomb, D., Yadav, D., Amann, S., Mishra, G., Alkaade, S., Romagnuolo, J., Stevens, T., Vargo, J., Gardner, T., Singh, V., Park, W., Hartigan, C., Barton, B., Bova, C. 2016; 111 (8): 1177-1186
Abstract

Chronic pancreatitis is a significant medical problem that impacts a large number of patients worldwide. In 2014, we developed a disease-specific instrument for the evaluation of quality of life in this group of patients: pancreatitis quality of life instrument (PANQOLI). The goal of this study was to evaluate its psychometric properties: its reliability and its construct validity.This is a cross-sectional multi-center study that involved 12 pancreatic disease centers. Patients who met the inclusion/exclusion criteria for chronic pancreatitis were invited to participate. Those who accepted were asked to complete seven questionnaires/instruments. Only patients who completed the PANQOLI were included in the study. Its reliability and its construct validity were tested.A total of 159 patients completed the PANQOLI and were included in the study. They had a mean age of 49.03, 49% were male, and 84% were Caucasian. Six of the 24 items on the scale were removed because of lack of inter-item correlation, redundancy, or lack of correlation to quality of life issues. The final 18-item scale had excellent reliability (Cronbach's alpha coefficient: 0.914) and excellent construct validity with good correlation to generic quality of life instruments (SF-12 and EORTC QLQ-C30/QLQ-PAN26) and lack of correlation to non-quality of life instruments (MAST and DAST). Through exploratory factor analysis, the PANQOLI was found to consist of four subscales: emotional function scale, role function scale, physical function scale, and "self-worth" scale.PANQOLI is the first disease-specific instrument to be developed and validated for the evaluation of quality of life in chronic pancreatitis patients. It has a unique subscale for "self-worth" that differentiates it from other generic instruments. Studies are currently under way to evaluate its use in other populations not included in this study.

View details for DOI 10.1038/ajg.2016.225

View details for Web of Science ID 000384720000020

View details for PubMedID 27296943
Clinical chronic pancreatitis. Current opinion in gastroenterology Park, W. G. 2016
Abstract

To summarize observations in clinical chronic pancreatitis in the past year.A predisposing genetic mutation was identified in 67% of cases of pediatric chronic pancreatitis. A novel susceptibility gene involving a hybrid allele is associated with idiopathic chronic pancreatitis. ABO blood type B and FUT2 nonsecretor status is associated with asymptomatic hyperlipasemia and chronic pancreatitis. Alcohol consumption impairs cystic fibrosis transmembrane conductance regulator (CFTR) activity leading to decreased bicarbonate secretion and patients with susceptible CFTR mutations can develop clinical pancreatitis. Computed tomography imaging findings in chronic pancreatitis correlate poorly with pain patterns. Endoscopic ultrasound features correlate poorly with fibrosis. Circulating epithelial cells are present in chronic pancreatitis patients but not healthy volunteers. Surgery is superior to endoscopic treatment in providing durable pain relief (>5 years). Repetitive pancreatic duct stent placements and chronic narcotic use are preoperative predictors of poor outcome after total pancreatectomy with islet cell auto transplantation.Novel genetic mutations for idiopathic chronic pancreatitis are being identified. Alcohol impairs CFTR activity and may explain a mechanism for pancreatitis. Current imaging modalities correlate poorly with clinical pain presentation and fibrosis in chronic pancreatitis. Novel imaging modalities are needed. As total pancreatectomy with islet cell auto transplantation grows, rigorous outcomes analysis is needed to drive patient selection.

View details for PubMedID 27341355
Severe acute pancreatitis in the community: confusion reigns JOURNAL OF SURGICAL RESEARCH Dua, M. M., Worhunsky, D. J., Tran, T. B., Rumma, R. T., Poultsides, G. A., Norton, J. A., Park, W. G., Visser, B. C. 2015; 199 (1): 44-50
Abstract

The management of acute pancreatitis (AP) has evolved through enhanced understanding of the disease. Despite several evidence-based practice guidelines for AP, our hypothesis is that many hospitals still use historical treatments rather than adhere to the current guidelines, which have demonstrated shorter hospital stays, decreased infectious complications, decreased morbidity, and decreased mortality.Seventy-eight patients transferred to our institution with AP from 2010-2014 were retrospectively studied to compare pretransfer versus posttransfer adherence to current practice guidelines. Primary measures included use of antibiotics (abx), enteral nutrition, drainage of asymptomatic pseudocysts, and interventions for necrosis in the early phase (<4�wk).Pretransfer, abx were given to 51 patients; however, posttransfer, abx were discontinued in 33 patients and started in 6 patients within 24�h of admission (pretransfer versus posttransfer abx, 51 versus 24, P�<�0.001). Empiric abx for AP were used in 36 patients pretransfer versus 9 patients posttransfer (P�<�0.001). Patients were initially nil per os or on total parenteral nutrition in 89%; this was reduced to 17% within 72�h by starting a diet or enteric feeds (pretransfer versus posttransfer feeding, 9 versus 65 patients, P�<�0.001). Fifteen transfer patients had pseudocysts that were believed to "require drainage"; five patients received intervention but >4�wk from initial episode of AP. Pretransfer, five patients had pancreatic debridement in the early phase, which resulted in prolonged postoperative length of stay compared with eight patients requiring debridement, which were delayed (early versus late, 56 versus 16�d, P�<�0.05).There is still great confusion in the treatment of AP in community hospitals. Primary principles in the care of these patients are not routinely followed despite established guidelines. Increased dissemination is required to prevent lengthy hospitalizations and long-term morbidity.

View details for DOI 10.1016/j.jss.2015.04.054

View details for PubMedID 25972313
Cyst Fluid Glucose is Rapidly Feasible and Accurate in Diagnosing Mucinous Pancreatic Cysts. American journal of gastroenterology Zikos, T., Pham, K., Bowen, R., Chen, A. M., Banerjee, S., Friedland, S., Dua, M. M., Norton, J. A., Poultsides, G. A., Visser, B. C., Park, W. G. 2015; 110 (6): 909-914
Abstract

Better diagnostic tools are needed to differentiate pancreatic cyst subtypes. A previous metabolomic study showed cyst fluid glucose as a potential marker to differentiate mucinous from non-mucinous pancreatic cysts. This study seeks to validate these earlier findings using a standard laboratory glucose assay, a glucometer, and a glucose reagent strip.Using an IRB-approved prospectively collected bio-repository, 65 pancreatic cyst fluid samples (42 mucinous and 23 non-mucinous) with histological correlation were analyzed.Median laboratory glucose, glucometer glucose, and percent reagent strip positive were lower in mucinous vs. non-mucinous cysts (P<0.0001 for all comparisons). Laboratory glucose<50?mg/dl had a sensitivity of 95% and a specificity of 57% (LR+ 2.19, LR- 0.08). Glucometer glucose<50?mg/dl had a sensitivity of 88% and a specificity of 78% (LR+ 4.05, LR- 0.15). Reagent strip glucose had a sensitivity of 81% and a specificity of 74% (LR+ 3.10, LR- 0.26). CEA had a sensitivity of 77% and a specificity of 83% (LR+ 4.67, LR- 0.27). The combination of having either a glucometer glucose<50?mg/dl or a CEA level>192 had a sensitivity of 100% but a low specificity of 33% (LR+ 1.50, LR- 0.00).Glucose, whether measured by a laboratory assay, a glucometer, or a reagent strip, is significantly lower in mucinous cysts compared with non-mucinous pancreatic cysts.

View details for DOI 10.1038/ajg.2015.148

View details for PubMedID 25986360
Predictive Factors for Surgery Among Patients with Pancreatic Cysts in the Absence of High-Risk Features for Malignancy JOURNAL OF GASTROINTESTINAL SURGERY Quan, S. Y., Visser, B. C., Poultsides, G. A., Norton, J. A., Chen, A. M., Banerjee, S., Friedland, S., Park, W. G. 2015; 19 (6): 1101-1105
Abstract

Without a reliable biopsy technique for pancreatic cysts, consensus-based guidelines are used to guide surgical utilization. The primary objective of this study was to characterize the proportion of operations performed outside of these guidelines.A 5-year retrospective review between July 1, 2007, and June 30, 2012, was performed of consecutive patients seen at a single tertiary medical center for a pancreatic cyst. Manual chart review for relevant clinical variables and cyst characteristics was performed.During this period, 148 patients underwent surgery, and of these, 23 (16 %) patients had no high-risk criteria by the 2006 Sendai criteria. None of these harbored high-grade dysplastic or cancerous lesions. A high cyst carcinoembryonic antigen (CEA) level (35 %), patient anxiety (26 %), and physician concern (22 %) were explicit reasons to proceed to surgery. An elevated cyst CEA level >192 ng/ml was the most significant predictor (OR 5.14 (95 % confidence interval (CI) 1.47-18.0) for surgery without high-risk criteria.A high cyst CEA level was significantly associated with the decision to operate outside of consensus-based guidelines. The misuse of cyst CEA in the management of pancreatic cysts negatively impacts patient anxiety, increases physician uncertainty, and leads to surgery with minimal benefit.

View details for DOI 10.1007/s11605-015-2786-3

View details for PubMedID 25749855
Non-MalIg(G4)nant Biliary Obstruction: When the Pill Is Mightier than the Knife DIGESTIVE DISEASES AND SCIENCES Dua, M. M., Qadan, M., Lutchman, G. A., Park, W. G., Triadafilopoulos, G., Visser, B. C. 2015; 60 (5): 1178-1182
View details for DOI 10.1007/s10620-014-3329-6

View details for PubMedID 25138904
Short turn radius colonoscope in an anatomical model: Retroflexed withdrawal and detection of hidden polyps. World journal of gastroenterology Mcgill, S. K., Kothari, S., Friedland, S., Chen, A., Park, W. G., Banerjee, S. 2015; 21 (2): 593-599
Abstract

To evaluate the new RetroView? colonoscope and compare its ability to detect simulated polyps "hidden" behind colonic folds with that of a conventional colonoscope, utilizing anatomic colon models.Three anatomic colon models were prepared, with twelve simulated polyps "hidden" behind haustral folds and five placed in easily viewed locations in each model. Five blinded endoscopists examined two colon models in random order with the conventional or RetroView? colonoscope, utilizing standard withdrawal technique. The third colon model was then examined with the RetroView? colonoscope withdrawn initially in retroflexion and then in standard withdrawal. Polyp detection rates during standard and retroflexed withdrawal of the conventional and RetroView? colonoscopes were determined. Polyp detection rates for combined standard and retroflexed withdrawal (combination withdrawal) with the RetroView? colonoscope were also determined.For hidden polyps, retroflexed withdrawal using the RetroView? colonoscope detected more polyps than the conventional colonoscope in standard withdrawal (85% vs 12%, P = 0.0001). For hidden polyps, combination withdrawal with the RetroView? colonoscope detected more polyps than the conventional colonoscope in standard withdrawal (93% vs 12%, P ? 0.0001). The RetroView? colonoscope in "combination withdrawal" was superior to other methods in detecting all (hidden + easily visible) polyps, with successful detection of 80 of 85 polyps (94%) compared to 28 (32%) polyps detected by the conventional colonoscope in standard withdrawal (P < 0.0001) and 67 (79%) polyps detected by the RetroView? colonoscope in retroflexed withdrawal alone (P < 0.01). Continuous withdrawal of the colonoscope through the colon model while retroflexed was achieved by all endoscopists. In a post-test survey, four out of five colonoscopists reported that manipulation of the colonoscope was easy or very easy.In simulated testing, the RetroView? colonoscope increased detection of hidden polyps. Combining standard withdrawal with retroflexed withdrawal may become the new paradigm for "complete screening colonoscopy".

View details for DOI 10.3748/wjg.v21.i2.593

View details for PubMedID 25593483

View details for PubMedCentralID PMC4294171
Systematic Review of Pancreatic Cyst Fluid Biomarkers: The Path Forward. Clinical and translational gastroenterology Thiruvengadam, N., Park, W. G. 2015; 6
Abstract

There is significant research interest in developing and validating novel pancreatic cyst-fluid biomarkers given the increasing recognition of the prevalence of pancreatic cysts and their associated malignant potential. Although current international consensus guidelines are helpful, they fail to diagnose with certainty the cyst type and the level of epithelial dysplasia. They also fall short in predicting the future likelihood of malignant transformation. A systematic review was performed with the objective of summarizing cyst-fluid-based biomarkers that have been published in the medical literature over the past 10 years and characterizing the current quality of evidence. Our review demonstrates that there is an increasing interest in this topic with several different and innovative approaches including DNA, RNA, proteomic, and metabolomics profiling. Further techniques to improve upon cytological yield have also been studied. Besides identifying potentially useful clinical biomarkers, these empiric approaches have provided further insight into their pathogenesis. The level of evidence for the vast majority of these studies, however, is limited to retrospective early validation studies. The path forward will be to select out the most promising biomarkers and develop multicenter consortiums capable of capturing adequate sample sizes with appropriate study designs.

View details for DOI 10.1038/ctg.2015.17

View details for PubMedID 26065716
Pharmacologic therapy for acute pancreatitis WORLD JOURNAL OF GASTROENTEROLOGY Kambhampati, S., Park, W., Habtezion, A. 2014; 20 (45): 16868-16880
Abstract

While conservative management such as fluid, bowel rest, and antibiotics is the mainstay of current acute pancreatitis management, there is a lot of promise in pharmacologic therapies that target various aspects of the pathogenesis of pancreatitis. Extensive review of preclinical studies, which include assessment of therapies such as anti-secretory agents, protease inhibitors, anti-inflammatory agents, and anti-oxidants are discussed. Many of these studies have shown therapeutic benefit and improved survival in experimental models. Based on available preclinical studies, we discuss potential novel targeted pharmacologic approaches that may offer promise in the treatment of acute pancreatitis. To date a variety of clinical studies have assessed the translational potential of animal model effective experimental therapies and have shown either failure or mixed results in human studies. Despite these discouraging clinical studies, there is a great clinical need and there exist several preclinical effective therapies that await investigation in patients. Better understanding of acute pancreatitis pathophysiology and lessons learned from past clinical studies are likely to offer a great foundation upon which to expand future therapies in acute pancreatitis.

View details for DOI 10.3748/wjg.v20.i45.16868

View details for Web of Science ID 000346050700007

View details for PubMedCentralID PMC4258556
Pharmacologic therapy for acute pancreatitis. World journal of gastroenterology Kambhampati, S., Park, W., Habtezion, A. 2014; 20 (45): 16868-16880
Abstract

While conservative management such as fluid, bowel rest, and antibiotics is the mainstay of current acute pancreatitis management, there is a lot of promise in pharmacologic therapies that target various aspects of the pathogenesis of pancreatitis. Extensive review of preclinical studies, which include assessment of therapies such as anti-secretory agents, protease inhibitors, anti-inflammatory agents, and anti-oxidants are discussed. Many of these studies have shown therapeutic benefit and improved survival in experimental models. Based on available preclinical studies, we discuss potential novel targeted pharmacologic approaches that may offer promise in the treatment of acute pancreatitis. To date a variety of clinical studies have assessed the translational potential of animal model effective experimental therapies and have shown either failure or mixed results in human studies. Despite these discouraging clinical studies, there is a great clinical need and there exist several preclinical effective therapies that await investigation in patients. Better understanding of acute pancreatitis pathophysiology and lessons learned from past clinical studies are likely to offer a great foundation upon which to expand future therapies in acute pancreatitis.

View details for DOI 10.3748/wjg.v20.i45.16868

View details for PubMedID 25493000
Laparoscopic Transgastric Necrosectomy for the Management of Pancreatic Necrosis JOURNAL OF THE AMERICAN COLLEGE OF SURGEONS Worhunsky, D. J., Qadan, M., Dua, M. M., Park, W. G., Poultsides, G. A., Norton, J. A., Visser, B. C. 2014; 219 (4): 735-743
Abstract

Traditional open necrosectomy for pancreatic necrosis is associated with significant morbidity and mortality. Although minimally invasive techniques have been described and offer some promise, each has considerable limitations. This study assesses the safety and effectiveness of laparoscopic transgastric necrosectomy (LTN), a novel technique for the management of necrotizing pancreatitis.Between 2009 and 2013, patients with retrogastric pancreatic necrosis requiring debridement were evaluated for LTN. Debridement was performed via a laparoscopic transgastric approach using 2 to 3 ports and the wide cystgastrostomy left open. Patient demographics, disease severity, operative characteristics, and outcomes were collected and analyzed.Twenty-one patients (13 men, median age 54 years; interquartile range [IQR] 46 to 62 years) underwent LTN during the study period. The duration between pancreatitis onset and debridement was 65 days (IQR 53 to 124 years). Indications for operation included infection (7 patients) and persistent unwellness (14 patients). Median duration of LTN was 170 minutes (IQR 136 to 199 minutes); there were no conversions. Control of the necrosis was achieved via the single procedure in 19 of 21 patients. Median postoperative hospital stay was 5 days (IQR 3 to 14 days) and the majority (71%) of patients experienced no (n = 9) or only minor postoperative complications (n = 6) by Clavien-Dindo grade. Complications of Clavien-Dindo grade 3 or higher developed in 6 patients, including 1 death (5%). With a median follow-up of 11 months (IQR 7 to 22 months), none of the patients required additional operative debridement or had pancreatic/enteric fistulae or wound complications develop.Laparoscopic transgastric necrosectomy is a novel, minimally invasive technique for the management of pancreatic necrosis that allows for debridement in a single operation. When feasible, LTN can reduce the morbidity associated with traditional open necrosectomy and avoid the limitations of other minimally invasive approaches.

View details for DOI 10.1016/j.jamcollsurg.2014.04.012

View details for Web of Science ID 000342422500018
Laparoscopic transgastric necrosectomy for the management of pancreatic necrosis. Journal of the American College of Surgeons Worhunsky, D. J., Qadan, M., Dua, M. M., Park, W. G., Poultsides, G. A., Norton, J. A., Visser, B. C. 2014; 219 (4): 735-743
Abstract

Traditional open necrosectomy for pancreatic necrosis is associated with significant morbidity and mortality. Although minimally invasive techniques have been described and offer some promise, each has considerable limitations. This study assesses the safety and effectiveness of laparoscopic transgastric necrosectomy (LTN), a novel technique for the management of necrotizing pancreatitis.Between 2009 and 2013, patients with retrogastric pancreatic necrosis requiring debridement were evaluated for LTN. Debridement was performed via a laparoscopic transgastric approach using 2 to 3 ports and the wide cystgastrostomy left open. Patient demographics, disease severity, operative characteristics, and outcomes were collected and analyzed.Twenty-one patients (13 men, median age 54 years; interquartile range [IQR] 46 to 62 years) underwent LTN during the study period. The duration between pancreatitis onset and debridement was 65 days (IQR 53 to 124 years). Indications for operation included infection (7 patients) and persistent unwellness (14 patients). Median duration of LTN was 170 minutes (IQR 136 to 199 minutes); there were no conversions. Control of the necrosis was achieved via the single procedure in 19 of 21 patients. Median postoperative hospital stay was 5 days (IQR 3 to 14 days) and the majority (71%) of patients experienced no (n = 9) or only minor postoperative complications (n = 6) by Clavien-Dindo grade. Complications of Clavien-Dindo grade 3 or higher developed in 6 patients, including 1 death (5%). With a median follow-up of 11 months (IQR 7 to 22 months), none of the patients required additional operative debridement or had pancreatic/enteric fistulae or wound complications develop.Laparoscopic transgastric necrosectomy is a novel, minimally invasive technique for the management of pancreatic necrosis that allows for debridement in a single operation. When feasible, LTN can reduce the morbidity associated with traditional open necrosectomy and avoid the limitations of other minimally invasive approaches.

View details for DOI 10.1016/j.jamcollsurg.2014.04.012

View details for PubMedID 25158913
Getting the dead out: modern treatment strategies for necrotizing pancreatitis. Digestive diseases and sciences Dua, M. M., Worhunsky, D. J., Amin, S., Louie, J. D., Park, W. G., Triadafilopoulos, G., Visser, B. C. 2014; 59 (9): 2069-2075
View details for DOI 10.1007/s10620-014-3153-z

View details for PubMedID 24748229
Gastrointestinal stromal tumor: an unusual cause of gastrointestinal bleeding. Digestive diseases and sciences Wong, R. J., Longacre, T. A., Poultsides, G., Park, W., Rothenberg, M. E. 2013; 58 (11): 3112-3116
View details for DOI 10.1007/s10620-013-2678-x

View details for PubMedID 23633157
Metabolomic-derived novel cyst fluid biomarkers for pancreatic cysts: glucose and kynurenine. Gastrointestinal endoscopy Park, W. G., Wu, M., Bowen, R., Zheng, M., Fitch, W. L., Pai, R. K., Wodziak, D., Visser, B. C., Poultsides, G. A., Norton, J. A., Banerjee, S., Chen, A. M., Friedland, S., Scott, B. A., Pasricha, P. J., Lowe, A. W., Peltz, G. 2013; 78 (2): 295-302 e2
Abstract

BACKGROUND: Better pancreatic cyst fluid biomarkers are needed. OBJECTIVE: To determine whether metabolomic profiling of pancreatic cyst fluid would yield clinically useful cyst fluid biomarkers. DESIGN: Retrospective study. SETTING: Tertiary-care referral center. PATIENTS: Two independent cohorts of patients (n�= 26 and n�= 19) with histologically defined pancreatic cysts. INTERVENTION: Exploratory analysis for differentially expressed metabolites between (1) nonmucinous and mucinous cysts and (2) malignant and premalignant cysts was performed in the first cohort. With the second cohort, a validation analysis of promising identified metabolites was performed. MAIN OUTCOME MEASUREMENTS: Identification of differentially expressed metabolites between clinically relevant cyst categories and their diagnostic performance (receiver operating characteristic [ROC] curve). RESULTS: Two metabolites had diagnostic significance-glucose and kynurenine. Metabolomic abundances for both were significantly lower in mucinous cysts compared with nonmucinous cysts in both cohorts (glucose first cohort P�= .002, validation P�= .006; and kynurenine first cohort P�= .002, validation P�= .002). The ROC curve for glucose was 0.92 (95% confidence interval [CI], 0.81-1.00) and 0.88 (95% CI, 0.72-1.00) in the first and validation cohorts, respectively. The ROC for kynurenine was 0.94 (95% CI, 0.81-1.00) and 0.92 (95% CI, 0.76-1.00) in the first and validation cohorts, respectively. Neither could differentiate premalignant from malignant cysts. Glucose and kynurenine levels were significantly elevated for serous cystadenomas in both cohorts. LIMITATIONS: Small sample sizes. CONCLUSION: Metabolomic profiling identified glucose and kynurenine to have potential clinical utility for differentiating mucinous from nonmucinous pancreatic cysts. These markers also may diagnose serous cystadenomas.

View details for DOI 10.1016/j.gie.2013.02.037

View details for PubMedID 23566642
Metabolomic-derived novel cyst fluid biomarkers for pancreatic cysts: glucose and kynurenine GASTROINTESTINAL ENDOSCOPY Park, W. G., Wu, M., Bowen, R., Zheng, M., Fitch, W. L., Pai, R. K., Wodziak, D., Visser, B. C., Poultsides, G. A., Norton, J. A., Banerjee, S., Chen, A. M., Friedland, S., Scott, B. A., Pasricha, P. J., Lowe, A. W., Peltz, G. 2013; 78 (2): 295-?
Abstract

BACKGROUND: Better pancreatic cyst fluid biomarkers are needed. OBJECTIVE: To determine whether metabolomic profiling of pancreatic cyst fluid would yield clinically useful cyst fluid biomarkers. DESIGN: Retrospective study. SETTING: Tertiary-care referral center. PATIENTS: Two independent cohorts of patients (n�= 26 and n�= 19) with histologically defined pancreatic cysts. INTERVENTION: Exploratory analysis for differentially expressed metabolites between (1) nonmucinous and mucinous cysts and (2) malignant and premalignant cysts was performed in the first cohort. With the second cohort, a validation analysis of promising identified metabolites was performed. MAIN OUTCOME MEASUREMENTS: Identification of differentially expressed metabolites between clinically relevant cyst categories and their diagnostic performance (receiver operating characteristic [ROC] curve). RESULTS: Two metabolites had diagnostic significance-glucose and kynurenine. Metabolomic abundances for both were significantly lower in mucinous cysts compared with nonmucinous cysts in both cohorts (glucose first cohort P�= .002, validation P�= .006; and kynurenine first cohort P�= .002, validation P�= .002). The ROC curve for glucose was 0.92 (95% confidence interval [CI], 0.81-1.00) and 0.88 (95% CI, 0.72-1.00) in the first and validation cohorts, respectively. The ROC for kynurenine was 0.94 (95% CI, 0.81-1.00) and 0.92 (95% CI, 0.76-1.00) in the first and validation cohorts, respectively. Neither could differentiate premalignant from malignant cysts. Glucose and kynurenine levels were significantly elevated for serous cystadenomas in both cohorts. LIMITATIONS: Small sample sizes. CONCLUSION: Metabolomic profiling identified glucose and kynurenine to have potential clinical utility for differentiating mucinous from nonmucinous pancreatic cysts. These markers also may diagnose serous cystadenomas.

View details for DOI 10.1016/j.gie.2013.02.037

View details for Web of Science ID 000321825200015

View details for PubMedID 23566642
The Epidemiology of Idiopathic Acute Pancreatitis, Analysis of the Nationwide Inpatient Sample From 1998 to 2007 PANCREAS Chen, Y., Zak, Y., Hernandez-Boussard, T., Park, W., Visser, B. C. 2013; 42 (1): 1-5
Abstract

The study aimed to better define the epidemiology of idiopathic acute pancreatitis (IAP).We identified admissions with primary diagnosis of acute pancreatitis (AP) in Nationwide Inpatient Sample between 1998 and 2007. Idiopathic AP was defined as all cases after excluding International Classification of Diseases, Ninth Revision, codes for other causes of AP (including biliary, alcoholic, trauma, iatrogenic, hyperparathyroidism, hyperlipidemia, etc).Among the primary admissions for AP, 26.9% had biliary pancreatitis, 25.1% alcoholic, and 36.5% idiopathic. Idiopathic AP had estimated 81,8025 admissions with a mean hospitalization of 5.6 days. Patients with IAP accounted for almost half of the fatalities among the cases of AP (48.2%) and had a higher mortality rate than both patients with biliary pancreatitis and patients with alcoholic pancreatitis (1.9%, 1.5%, and 1.0%, respectively, P < 0.01). Forty-six percent of patients with biliary pancreatitis underwent cholecystectomy during the index hospitalization, compared with 0.42% of patients with IAP. Patients with IAP had a demographic distribution similar to that of patients with biliary AP (female predominant and older), which was distinct from patients with alcoholic pancreatitis (male predominant and younger). There was a gradual but steady decrease in the incidence of IAP, from 41% in 1998 to 30% in 2007.Despite improving diagnostics, IAP remains a common clinical problem with a significant mortality. Standardization of the clinical management of these patients warrants further investigation.

View details for DOI 10.1097/MPA.0b013e3182572d3a

View details for PubMedID 22750972
How to value technological innovation: a proposal for determining relative clinical value. Gastroenterology Ladabaum, U., Brill, J. V., Sonnenberg, A., Shaheen, N. J., Inadomi, J., Wilcox, C. M., Park, W. G., Hur, C., Pasricha, P. J. 2013; 144 (1): 5-8
View details for DOI 10.1053/j.gastro.2012.11.006

View details for PubMedID 23153872
Diagnostic Utility of Metabolomic-Derived Biomarkers for Pancreatic Cysts Park, W. G., Wu, M., Bowen, R., Zheng, M., Fitch, W. L., Pai, R. K., Wodziak, D., Visser, B. C., Poultsides, G. A., NORTON, J. A., Banerjee, S., Chen, A. M., Friedland, S., Pasricha, P. J., Lowe, A. W., Peltz, G. LIPPINCOTT WILLIAMS & WILKINS. 2012: 1394?94
View details for Web of Science ID 000310360500241
Pancreatic Neuroendocrine Tumors: Radiographic Calcifications Correlate with Grade and Metastasis ANNALS OF SURGICAL ONCOLOGY Poultsides, G. A., Huang, L. C., Chen, Y., Visser, B. C., Pai, R. K., Jeffrey, R. B., Park, W. G., Chen, A. M., Kunz, P. L., Fisher, G. A., Norton, J. A. 2012; 19 (7): 2295-2303
Abstract

Studies to identify preoperative prognostic variables for pancreatic neuroendocrine tumor (PNET) have been inconclusive. Specifically, the prevalence and prognostic significance of radiographic calcifications in these tumors remains unclear.From 1998 to 2009, a total of 110 patients with well-differentiated PNET underwent surgical resection at our institution. Synchronous liver metastases present in 31 patients (28%) were addressed surgically with curative intent. Patients with high-grade PNET were excluded. The presence of calcifications in the primary tumor on preoperative computed tomography was recorded and correlated with clinicopathologic variables and overall survival.Calcifications were present in 16% of patients and were more common in gastrinomas and glucagonomas (50%), but never encountered in insulinomas. Calcified tumors were larger (median size 4.5 vs. 2.3 cm, P=0.04) and more commonly associated with lymph node metastasis (75 vs. 35%, P=0.01), synchronous liver metastasis (62 vs. 21%, P<0.01), and intermediate tumor grade (80 vs. 31%, P<0.01). On multivariate analysis of factors available preoperatively, calcifications (P=0.01) and size (P<0.01) remained independent predictors of lymph node metastasis. Overall survival after resection was significantly worse in the presence of synchronous liver metastasis (5-year, 64 vs. 86%, P=0.04), but not in the presence of radiographic calcifications.Calcifications on preoperative computed tomography correlate with intermediate grade and lymph node metastasis in well-differentiated PNET. This information is available preoperatively and supports the routine dissection of regional lymph nodes through formal pancreatectomy rather than enucleation in calcified PNET.

View details for DOI 10.1245/s10434-012-2305-7

View details for PubMedID 22396008
Endoscopic mucosal resection with an over-the-counter hyaluronate preparation GASTROINTESTINAL ENDOSCOPY Friedland, S., Kothari, S., Chen, A., Park, W., Banerjee, S. 2012; 75 (5): 1040-1044
Abstract

Hyaluronic acid (HA) provides a long-lasting and distinct mucosal elevation for EMR, but expense and inconvenience have limited its adoption.To evaluate the safety and efficacy of an over-the-counter 0.15% HA preparation for EMR.Retrospective study.Veterans Administration Hospital and university hospital.30 patients with a total of 32 colonic lesions and 1 duodenal lesion.EMR by using HA.En bloc resection rate and complications.EMR was successful in all cases. En bloc resection was achieved in 26 of the 28 lesions up to 25 mm in diameter. Two lesions, both with fibrosis from prior attempted resection, had trace residual tissue necessitating cauterization with argon plasma. Five lesions measuring 30 mm to 60 mm all required piecemeal resection. There was one complication, a postpolypectomy bleed.Small number of patients and retrospective design.EMR may be performed safely and effectively by using an inexpensive, over-the-counter 0.15% HA preparation. Further studies are needed to verify the results of this study and to compare the safety and efficacy of this HA preparation with saline solution.

View details for DOI 10.1016/j.gie.2012.01.010

View details for Web of Science ID 000303277400016

View details for PubMedID 22381528
Comparison of EUS-Guided Pancreas Biopsy Techniques Using the Procore (TM) Needle 53rd Annual Meeting of the Society-for-Surgery-of-the-Alimentary-Tract (SSAT) / Digestive Disease Week (DDW) / Meeting of the Pancreas-Club Kothari, S., Chen, A. M., Pai, R., Friedland, S., Park, W. G., Banerjee, S. MOSBY-ELSEVIER. 2012: 145?45
View details for Web of Science ID 000304328000131
A New Colonoscope With a Short Turn Radius Allowing Full Withdrawal in Complete Retroflexion Improves Detection of Simulated Polyps Hidden Behind Folds and Flexures in Anatomic Colon Models 53rd Annual Meeting of the Society-for-Surgery-of-the-Alimentary-Tract (SSAT) / Digestive Disease Week (DDW) / Meeting of the Pancreas-Club Mcgill, S. K., Kothari, S., Friedland, S., Chen, A. M., Park, W. G., Pasricha, P. J., Banerjee, S. MOSBY-ELSEVIER. 2012: 215?15
View details for Web of Science ID 000304328001116
Radiation Exposure to Patients During ERCP Is Significantly Higher With Low Volume Endoscopists 53rd Annual Meeting of the Society-for-Surgery-of-the-Alimentary-Tract (SSAT) / Digestive Disease Week (DDW) / Meeting of the Pancreas-Club Kothari, S., Liao, C., Friedland, S., Chen, A. M., Park, W., Banerjee, S. MOSBY-ELSEVIER. 2012: 140?41
View details for Web of Science ID 000304328000119
Is EGD Necessary in Patients With Positive Fecal Occult Blood Test and Negative Colonoscopy? 53rd Annual Meeting of the Society-for-Surgery-of-the-Alimentary-Tract (SSAT) / Digestive Disease Week (DDW) / Meeting of the Pancreas-Club Kothari, S., Liao, C., Friedland, S., Chen, A. M., Park, W., Banerjee, S. MOSBY-ELSEVIER. 2012: 139?40
View details for Web of Science ID 000304328000117
Endoscopic Mucosal Resection Using an Inexpensive Over the Counter Hyaluronate Preparation 53rd Annual Meeting of the Society-for-Surgery-of-the-Alimentary-Tract (SSAT) / Digestive Disease Week (DDW) / Meeting of the Pancreas-Club Kothari, S., Banerjee, S., Chen, A. M., Park, W., Friedland, S. MOSBY-ELSEVIER. 2012: 344?45
View details for Web of Science ID 000304328001497
Diagnostic accuracy of cyst fluid amphiregulin in pancreatic cysts BMC GASTROENTEROLOGY Tun, M. T., Pai, R. K., Kwok, S., Dong, A., Gupta, A., Visser, B. C., Norton, J. A., Poultsides, G. A., Banerjee, S., Van Dam, J., Chen, A. M., Friedland, S., Scott, B. A., Verma, R., Lowe, A. W., Park, W. G. 2012; 12
Abstract

Accurate tests to diagnose adenocarcinoma and high-grade dysplasia among mucinous pancreatic cysts are clinically needed. This study evaluated the diagnostic utility of amphiregulin (AREG) as a pancreatic cyst fluid biomarker to differentiate non-mucinous, benign mucinous, and malignant mucinous cysts.A single-center retrospective study to evaluate AREG levels in pancreatic cyst fluid by ELISA from 33 patients with a histological gold standard was performed.Among the cyst fluid samples, the median (IQR) AREG levels for non-mucinous (n = 6), benign mucinous (n = 15), and cancerous cysts (n = 15) were 85 pg/ml (47-168), 63 pg/ml (30-847), and 986 pg/ml (417-3160), respectively. A significant difference between benign mucinous and malignant mucinous cysts was observed (p = 0.025). AREG levels greater than 300 pg/ml possessed a diagnostic accuracy for cancer or high-grade dysplasia of 78% (sensitivity 83%, specificity 73%).Cyst fluid AREG levels are significantly higher in cancerous and high-grade dysplastic cysts compared to benign mucinous cysts. Thus AREG exhibits potential clinical utility in the evaluation of pancreatic cysts.

View details for DOI 10.1186/1471-230X-12-15

View details for PubMedID 22333441
Adult Intestinal Malrotation: When Things Turn the Wrong Way DIGESTIVE DISEASES AND SCIENCES Palmer, O. P., Rhee, H. H., Park, W. G., Visser, B. C. 2012; 57 (2): 284-287
View details for DOI 10.1007/s10620-011-1818-4

View details for PubMedID 21805171
Goff Trans-pancreatic Septotomy Is an Effective and Safe Biliary Cannulation Technique for Patients Who Fail Standard Biliary Cannulation 76th Annual Scientific Meeting of the American-College-of-Gastroenterology Liao, C., Park, W., Chen, A., Friedland, S., Banerjee, S. NATURE PUBLISHING GROUP. 2011: S56?S56
View details for Web of Science ID 000299772000140
Colloid Carcinoma of the Pancreas DIGESTIVE DISEASES AND SCIENCES Plerhoples, T. A., Ahdoot, M., DiMaio, M. A., Pai, R. K., Park, W. G., Poultsides, G. A. 2011; 56 (5): 1295-1298
View details for DOI 10.1007/s10620-011-1573-6

View details for Web of Science ID 000289899200008

View details for PubMedID 21253833
Screening for pancreatic cancer: what can cyst fluid analysis tell us? F1000 medicine reports Park, W. G. 2011; 3: 3-?
Abstract

Pancreatic cysts are increasingly recognized as a dilemma in clinical practice because of their uncertain risk of malignancy. Because diagnosis by cytology is insensitive, current guidelines suggest using radiographic and clinical criteria to determine the appropriateness of surgery or surveillance, although this is far from perfect. Several cyst fluid biomarkers have been reported to aid diagnosis, and to date, carcinoembryonic antigen is the most accurate in detecting potentially cancerous mucinous cysts, but not in detecting malignant cysts. Recent studies have highlighted novel cyst fluid biomarkers based on DNA analysis, protein expression profiling, and secreted proteins that, if validated, may improve diagnosis and management.

View details for DOI 10.3410/M3-3

View details for PubMedID 21399760

View details for PubMedCentralID PMC3042313
Diagnostic Performance of Cyst Fluid Carcinoembryonic Antigen and Amylase in Histologically Confirmed Pancreatic Cysts PANCREAS Park, W. G., Mascarenhas, R., Palaez-Luna, M., Smyrk, T. C., O'Kane, D., Clain, J. E., Levy, M. J., Pearson, R. K., Petersen, B. T., Topazian, M. D., Vege, S. S., Chari, S. T. 2011; 40 (1): 42-45
Abstract

The objective of this study was to evaluate and validate cyst fluid carcinoembyronic antigen (CEA) and amylase in differentiating (1) nonmucinous from mucinous pancreatic cystic lesions (PCLs), (2) benign mucinous from malignant mucinous PCLs, and (3) pseudocysts from nonpseudocysts (amylase only).A retrospective analysis of patients with histologically confirmed PCLs from February 1996 to April 2007 was performed. Cyst fluid CEA (n=124) and/or amylase (n=91) were measured and correlated to cyst type.Carcinoembyronic antigen levels (P=0.0001), but not amylase, were higher in mucinous versus nonmucinous cysts. The sensitivity, specificity, and diagnostic accuracy of CEA 200 ng/mL or greater for the diagnosis of mucinous PCLs were 60%, 93%, and 72%, respectively. Carcinoembyronic antigen levels did not differentiate benign from malignant mucinous cysts. Whereas amylase levels were higher in pseudocysts than nonpseudocysts (P=0.009), 54% of noninflammatory PCLs had a level greater than 250 IU/L, including mucinous cystic neoplasms (median, 6800 IU/L; interquartile range, 70-25,295 IU/L). Malignant mucinous cysts had lower amylase levels than benign mucinous cysts (P=0.0008).Cyst fluid CEA and amylase levels are suggestive but not diagnostic in differentiating PCLs. Unlike CEA, amylase may help differentiate benign from malignant mucinous cysts. Novel biomarkers are needed.

View details for DOI 10.1097/MPA.0b013e3181f69f36

View details for Web of Science ID 000285375900009

View details for PubMedID 20966811

View details for PubMedCentralID PMC3005131
EUS-guided gold fiducial insertion for image-guided radiation therapy of pancreatic cancer: 50 successful cases without fluoroscopy GASTROINTESTINAL ENDOSCOPY Park, W. G., Yan, B. M., Schellenberg, D., Kim, J., Chang, D. T., Koong, A., Patalano, C., Van Dam, J. 2010; 71 (3): 513-518
Abstract

Image-guided radiation therapy (IGRT) accurately delivers a high dose of potentially tumoricidal radiation to its target while sparing adjacent healthy tissue. Application of IGRT to unresectable pancreatic cancer requires the use of fiducials to track the precise location of the tumor. Fiducial markers have been successfully placed endoscopically.To determine the feasibility of EUS-guided gold fiducial placement for IGRT.Prospective case series.Tertiary medical center.Consecutively referred patients with locally advanced unresectable pancreatic adenocarcinoma for EUS-guided insertion of gold fiducials from December 2006 to February 2009.Under only EUS guidance, fiducial markers were deployed into or near the tumor by using a 19-gauge needle. In most cases, a sterile water injection technique was used to insert the fiducials. Fluoroscopy was not used in any case.Successful placement of an adequate number of fiducials to proceed with IGRT as determined by CT.Fifty-seven consecutive patients were included. Fifty cases (88%) were successful. Of the cases in which fiducial placement was attempted and follow-up was adequate, 94% (50 of 53) of cases were successful.Single-center, nonrandomized study.EUS-guided fine-needle insertion was safe and effective in delivering gold fiducial markers for image-guided radiation therapy. Fluoroscopy was not required for successful fiducial placement.

View details for DOI 10.1016/j.gie.2009.10.030

View details for PubMedID 20189509
Management of Pancreatic Cystic Neoplasms: Decision-Making with Limited Information PANCREATOLOGY Park, W. G., Chari, S. T. 2010; 10 (2-3): 142-143
View details for DOI 10.1159/000276894

View details for Web of Science ID 000279583200006

View details for PubMedID 20460945
Election year fever? Voting on EUS criteria for chronic pancreatitis GASTROINTESTINAL ENDOSCOPY Park, W. G., Van Dam, J. 2009; 69 (7): 1262-1263
View details for DOI 10.1016/j.gie.2008.09.024

View details for Web of Science ID 000266800000009

View details for PubMedID 19481648
Painless Jaundice and Bilaterally Enlarged Sub-mandibular Glands in an Elderly Man DIGESTIVE DISEASES AND SCIENCES Park, W. G., Pai, R., Ro, K., Lowe, A. W. 2009; 54 (3): 488-490
View details for DOI 10.1007/s10620-008-0627-x

View details for Web of Science ID 000262970400005

View details for PubMedID 19034648
Prevalence of nonpolypoid (flat and depressed) colorectal neoplasms in asymptomatic and symptomatic adults JAMA-JOURNAL OF THE AMERICAN MEDICAL ASSOCIATION Soetikno, R. M., Kaltenbach, T., Rouse, R. V., Park, W., Maheshwari, A., Sato, T., Matsui, S., Friedland, S. 2008; 299 (9): 1027-1035
Abstract

Colorectal cancer is the second leading cause of cancer death in the United States. Prevention has focused on the detection and removal of polypoid neoplasms. Data are limited on the significance of nonpolypoid colorectal neoplasms (NP-CRNs).To determine the prevalence of NP-CRNs in a veterans hospital population and to characterize their association with colorectal cancer.Cross-sectional study at a veterans hospital in California with 1819 patients undergoing elective colonoscopy from July 2003 to June 2004.Endoscopic appearance, location, size, histology, and depth of invasion of neoplasms.The overall prevalence of NP-CRNs was 9.35% (95% confidence interval [95% CI], 8.05%-10.78%; n = 170). The prevalence of NP-CRNs in the subpopulations for screening, surveillance, and symptoms was 5.84% (95% CI, 4.13%-8.00%; n = 36), 15.44% (95% CI, 12.76%-18.44%; n = 101), and 6.01% (95% CI, 4.17%-8.34%; n = 33), respectively. The overall prevalence of NP-CRNs with in situ or submucosal invasive carcinoma was 0.82% (95% CI, 0.46%-1.36%; n = 15); in the screening population, the prevalence was 0.32% (95% CI, 0.04%-1.17%; n = 2). Overall, NP-CRNs were more likely to contain carcinoma (odds ratio, 9.78; 95% CI, 3.93-24.4) than polypoid lesions, irrespective of the size. The positive size-adjusted association of NP-CRNs with in situ or submucosal invasive carcinoma was also observed in subpopulations for screening (odds ratio, 2.01; 95% CI, 0.27-15.3) and surveillance (odds ratio, 63.7; 95% CI, 9.41-431). The depressed type had the highest risk (33%). Nonpolypoid colorectal neoplasms containing carcinoma were smaller in diameter as compared with the polypoid ones (mean [SD] diameter, 15.9 [10.2] mm vs 19.2 [9.6] mm, respectively). The procedure times did not change appreciably as compared with historical controls.In this group of veteran patients, NP-CRNs were relatively common lesions diagnosed during routine colonoscopy and had a greater association with carcinoma compared with polypoid neoplasms, irrespective of size.

View details for Web of Science ID 000253644800020

View details for PubMedID 18319413
Injection therapies for variceal bleeding disorders of the GI tract GASTROINTESTINAL ENDOSCOPY Park, W. G., Yeh, R. W., Triadafilopoulos, G. 2008; 67 (2): 313-323
View details for DOI 10.1016/j.gie.2007.09.052

View details for Web of Science ID 000253368100023

View details for PubMedID 18226695
Injection therapies for nonvariceal bleeding disorders of the GI tract GASTROINTESTINAL ENDOSCOPY Park, W. G., Neh, R. W., Triadafilopoulos, G. 2007; 66 (2): 343-354
View details for DOI 10.1016/j.gie.2006.11.019

View details for Web of Science ID 000248678700024

View details for PubMedID 17643711
Diagnosis and treatment of chronic hepatitis B: an update. Minerva gastroenterologica e dietologica Morgan, M., Park, W., Keeffe, E. B. 2007; 53 (1): 25-41
Abstract

The diagnosis of chronic hepatitis B virus (HBV) infection is made using a combination of serological, virologic, biochemical, and histologic markers. The natural history of HBV infection can be divided into four phases: immune tolerance, immune clearance (HBeAg-positive chronic hepatitis B), inactive HBsAg carrier, and reactivation (HBeAg-negative chronic hepatitis B). Patients in the immune clearance and reactivation phases, with elevated alanine aminotransferase (ALT) and HBV DNA levels, are candidates for antiviral therapy. The primary goal of therapy for chronic hepatitis B is suppression of viral replication, which has been shown to reduce hepatic necroinflammation and retard progression of hepatic fibrosis. Long-term suppression of serum HBV DNA is likely to reduce progression to cirrhosis and hepatic decompensation and decrease the risk of hepatocellular carcinoma. Current antiviral therapy for chronic hepatitis B includes interferon alfa, peginterferon alfa-2a, lamivudine, adefovir, entecavir, and telbivudine. In patients with HBeAg-positive chronic hepatitis B, antiviral treatment is indicated when the serum HBV DNA level is = or > 10(5) copies/mL (20,000 IU/mL) and the ALT level is elevated. For HBeAg-negative patients, the threshold for initiation of therapy is lower, i.e., a serum HBV DNA level = or > 10(4) copies/mL (2,000 IU/mL) in association with an elevated ALT level. The presence of at least moderate necroinflammation and the presence of fibrosis on liver biopsy, which is optional and not mandatory before therapy, may be useful in supporting the decision to initiate therapy, particularly in patients with normal ALT levels. While undergoing therapy, patients require monitoring every 3 to 6 months to ensure compliance and to test for the development of resistance if an oral agent is used. Issues that remain controversial or need to be studied further are the necessity of a baseline liver biopsy, the HBV DNA and ALT thresholds for initiation of therapy, the optimal duration of antiviral therapy, selection of one agent over another, and the role of combination therapy.

View details for PubMedID 17415343
Giant gastric ulcers in chronic spinal cord injury patients DIGESTIVE ENDOSCOPY Park, W. G., Rouse, R. V., Kahng, L. S., Bastidas, J. A., Meinke, L., Soetikno, R. M. 2007; 19 (1): 36-39
View details for DOI 10.1111/j.1443-1661.2007.00666.x

View details for Web of Science ID 000253940100008
Diagnosis and treatment of chronic hepatitis B. Minerva gastroenterologica e dietologica Park, W., Keeffe, E. B. 2004; 50 (4): 289-303
Abstract

The diagnosis of chronic hepatitis B virus (HBV) infection is made using a combination of serological, virological, biochemical, and histological markers. The natural history of HBV infection can be divided into 3 phases: immune tolerant, immune active with chronic hepatitis B, and inactive carrier; patients in the immune active phase are candidates for antiviral therapy. The primary goal of therapy for chronic hepatitis B is suppression of viral replication, which has been shown to reduce hepatic necroinflammation and retard progression of hepatic fibrosis. Long-term suppression of serum HBV DNA is likely to reduce progression to cirrhosis and hepatic decompensation and may also decrease the risk of hepatocellular carcinoma. Current antiviral therapy for chronic hepatitis B includes interferon alpha, lamivudine and adefovir, with recent studies demonstrating good safety and efficacy of peginterferon and other nucleoside analogues that will soon become additional treatment options. In patients with HBeAg-positive chronic hepatitis B, antiviral treatment is indicated when the serum HBV DNA level is = or >10(5) copies/mL and the alanine aminotransferase (ALT) level is elevated, particularly greater than 2 times the upper limits of normal. For HBeAg-negative patients, the threshold for initiation of therapy is a HBV DNA level = or >10(4) in association with an elevated ALT level. The presence of at least moderate necroinflammation and the presence of fibrosis on liver biopsy, which is optional and not mandatory before therapy, may be useful in supporting the decision to initiate therapy. While undergoing therapy, patients require monitoring every 3 to 6 months to ensure compliance and to test for the development of resistance if an oral agent is used. Issues that remain controversial or need to be studied further are the necessity of a baseline liver biopsy, the HBV DNA and ALT thresholds for initiation of therapy, the optimal duration of antiviral therapy, selection of one agent over another, and the role of combination therapy.

View details for PubMedID 15788985

Walter�Park

Associate Professor of Medicine (Gastroenterology and Hepatology) at the Stanford University Medical Center

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