Walter Park

All Publications

• Assessing the feasibility of handheld point-of-care ultrasound for pancreas visualization: A pilot study. Pancreas Lee, A. A., Antil, N., El Kaffas, A., Park, W. G. 2024

  View details for DOI 10.1097/MPA.0000000000002435

  View details for PubMedID 39626170

• Circulating biomarkers of macrophage activation in different stages of chronic pancreatitis: A pilot study. Pancreas Hagn-Meincke, R., Novovic, S., Hadi, A., Jensen, A. B., Drewes, A. M., Kraup, H., Frøkjær, J. B., Park, W. G., Jørgensen, P. L., Møller, H. J., Deleuran, B. W., Olesen, S. S. 2024

  Abstract

  Activation of type M2 macrophages has been implicated in the pathogenesis of chronic pancreatitis (CP). In a clinical pilot study, we investigated blood-based markers of macrophage activation at different stages of CP.We performed a cross-sectional analysis of prospectively collected plasma samples from healthy controls and patients with suspected or definitive CP according to the M-ANNHEIM criteria. Plasma concentrations of soluble CD163 (sCD163), soluble CD206 (sCD206), and monocyte chemoattractant protein-1 (MCP-1) were analyzed using enzyme-linked immunosorbent assays. Group and pairwise comparisons of analytes were performed using regression models and area under the receiver operating curves (AUC-ROC).In total, 73 subjects with CP (28 suspected CP and 45 definitive CP) and 40 controls were included. Compared to controls, the median plasma concentrations of sCD163 (p = 0.019) and sCD206 (p = 0.033) were elevated in patients with definitive CP. sCD206 was also elevated in patients with definitive CP (p = 0.042). ROC analysis revealed that the optimal sCD163 cutpoint to distinguish definitive CP from controls was 1.84 mg/ml (AUC-ROC 0.65; 95 % confidence interval [CI], 0.54-0.77). The optimal sCD206 cutpoint to distinguish definitive CP from controls was 0.24 mg/ml (AUC-ROC 0.66; 95 % CI 0.54-0.78). The analytes did not significantly discriminate patients with suspected CP from controls. MCP-1 concentrations showed no differences across subgroups.Our study demonstrates that subjects with definitive CP, sampled during a clinically quiescent phase, exhibited increased levels of sCD163 and sCD206. This indicates the presence of activated M2 macrophages in patients with CP at advanced, but not early, clinical stages.

  View details for DOI 10.1097/MPA.0000000000002443

  View details for PubMedID 39626186

• Pancreatitis pain quality changes at year 1 follow-up, but GP130 remains a biomarker for pain. Pancreatology : official journal of the International Association of Pancreatology (IAP) ... [et al.] Saloman, J. L., Jennings, K., Stello, K., Li, S., Evans Phillips, A., Hall, K., Fogel, E. L., Vege, S. S., Andersen, D. K., Fisher, W. E., Forsmark, C. E., Hart, P. A., Pandol, S. J., Park, W. G., Topazian, M. D., Van Den Eeden, S. K., Serrano, J., Conwell, D. L., Li, L., Yadav, D. 2024

  Abstract

  Debilitating abdominal pain is a common symptom affecting patients with chronic pancreatitis (CP). CP pain is dynamic due to multiple underlying mechanisms. The objective of this study was to 1) evaluate changes in pain phenotype at one year follow-up and 2) validate putative pain biomarkers in a prospective cohort study.The Neuropathic and Nociceptive PROMIS-PQ questionnaires were used to classify pain for participants with in the PROCEED study. Putative serum biomarkers were measured via immunoassay.At enrollment, 17.6 % (120/681) subjects with CP reported no pain in the previous year. Of those, 29 % experienced pain during the 1 yr follow-up whereas 18 % of those with pain prior to enrollment reported no pain during the 1 yr follow-up period. Of the 393 subjects with PROMIS-PQ data at enrollment, 212 also had follow-up data at 1 yr. Approximately half (53.3 %) of those individuals changed pain phenotype between baseline and follow-up. At 1 yr, serum TGFβ1 level was negatively correlated with nociceptive T-scores (p = 0.006). GP130 was significantly correlated with both nociceptive (p = 0.012) and neuropathic T-scores (p = 0.043) at 1 yr, which is consistent with the previously published findings.The positive association between TGFβ1 and pain is not maintained over time, suggesting it is a poor pain biomarker. However, serum GP130 is a consistent biomarker for mixed-type pain in CP. Preclinical studies show that targeting TGFβ1 or IL-6 (ligand for GP130) is sufficient to inhibit CP pain supporting further investigation of this as a potential therapeutic target.

  View details for DOI 10.1016/j.pan.2024.09.016

  View details for PubMedID 39322454

• Association of Serum Endocannabinoid Levels with Pancreatitis and Pancreatitis-Related Pain. Cannabis and cannabinoid research Goodman, M. T., Lombardi, C., Torrens, A., Bresee, C., Saloman, J. L., Li, L., Yang, Y., Fisher, W. E., Fogel, E. L., Forsmark, C. E., Conwell, D. L., Hart, P. A., Park, W. G., Topazian, M., Vege, S. S., Van Den Eeden, S. K., Bellin, M. D., Andersen, D. K., Serrano, J., Yadav, D., Pandol, S. J., Piomelli, D. 2024

  Abstract

  Background and Aims: This investigation examined the association of pancreatitis and pancreatitis-related pain with serum levels of two endocannabinoid molecules such as anandamide (AEA) and 2-arachidonoylglycerol (2-AG) and two paracannabinoid molecules such as oleoylethanolamide (OEA) and palmitoylethanolamide (PEA). Methods: A case-control study was conducted within the Prospective Evaluation of Chronic Pancreatitis for Epidemiological and Translational Studies, including participants with no pancreas disease (N = 56), chronic abdominal pain of suspected pancreatic origin or indeterminate chronic pancreatitis (CP) (N = 22), acute pancreatitis (N = 33), recurrent acute pancreatitis (N = 57), and definite CP (N = 63). Results: Circulating AEA concentrations were higher in women than in men (p = 0.0499), and PEA concentrations were higher in obese participants than those who were underweight/normal or overweight (p = 0.003). Asymptomatic controls with no pancreatic disease had significantly (p = 0.03) lower concentrations of AEA compared with all disease groups combined. The highest concentrations of AEA were observed in participants with acute pancreatitis, followed by those with recurrent acute pancreatitis, chronic abdominal pain/indeterminant CP, and definite CP. Participants with pancreatitis reporting abdominal pain in the past year had significantly (p = 0.04) higher concentrations of AEA compared with asymptomatic controls. Levels of 2-AG were significantly lower (p = 0.02) among participants reporting abdominal pain in the past week, and pain intensity was inversely associated with concentrations of 2-AG and OEA. Conclusions: Endocannabinoid levels may be associated with stage of pancreatitis, perhaps through activation of the CB1 receptor. Validation of our findings would support the investigation of novel therapeutics, including cannabinoid receptor-1 antagonists, in this patient population.

  View details for DOI 10.1089/can.2024.0079

  View details for PubMedID 39291350

• Reply to Vege. Gastroenterology Gardner, T. B., Park, W. G., Allen, P. J. 2024

  View details for DOI 10.1053/j.gastro.2024.09.015

  View details for PubMedID 39284556

• What's Behind it all: A Retrospective Cohort Study of Retrogastric Pancreatic Necrosis Management. Annals of surgery Harrison, J. M., Day, H., Arnow, K., Ngongoni, R. F., Joseph, A., Aldridge, T., Wheeler, K. J., DeLong, J. C., Bergquist, J. R., Worth, P. J., Dua, M. M., Friedland, S., Park, W., Eldika, S., Hwang, J. H., Visser, B. C. 2024

  Abstract

  To compare outcomes of laparoscopic transgastric necrosectomy (LTN) and direct endoscopic necrosectomy (DEN) in the management of retrogastric walled-off necrosis.Surgical and endoscopic transgastric approaches are used to manage retrogastric pancreatic necrosis. Studies comparing these treatment modalities are lacking but would influence contemporary practice patterns.LTN or DEN treated patients at Stanford University Hospital between 2011 and 2023 were identified. Cohort data included demographics, core pancreatitis care benchmarks, and clinical outcomes (total debridement time, new-onset endocrine and exocrine pancreatic insufficiency) as well as re-intervention, 30-day readmission, complication, and mortality rates. Long-term follow-up was also compared between intervention arms. Multivariable linear regression was used to assess the interaction between admission APACHE-II score and intervention on length of stay (LOS).106 patients (62% LTN, 38% DEN) were identified. Demographic and core pancreatitis benchmark data were similar between cohorts. 30-day readmission, complication, and mortality rates for surgical and endoscopic approaches were also similar: 23% vs. 25% (P = 0.98), 42% vs. 40% (P = 0.97), and 3% vs. 3% (P > 0.99). Median LTN total debridement time (minutes) was 131 vs. 134 for DEN, however, complete debridement was achieved with only 1 LTN compared to 3 DENs (P<0.01). While not statistically significant, LOS and unplanned intervention rates were less for LTN (8 vs. 10 days, P = 0.41 and 6% vs. 15%, P = 0.24). Multivariable analysis revealed a significant interaction between APACHE-II scores and LOS for LTN compared to DEN, which translated into a length of stay reduction for higher APACHE-II scoring patients (P = 0.02).LTN is a safe and efficient treatment modality for walled-off necrosis, and compared to DEN, can reduce the LOS in high APACHE-II score patients. While additional comparative research between the two intervention types is needed, this study supports a role for a surgical approach in the management of retrogastric pancreatic necrosis.

  View details for DOI 10.1097/SLA.0000000000006521

  View details for PubMedID 39225420

• Multiparametric MRI Scoring System of the Pancreas for the Diagnosis of Chronic Pancreatitis. Journal of magnetic resonance imaging : JMRI Tirkes, T., Yadav, D., Conwell, D. L., Zhao, X., Dasyam, A. K., Halappa, V. G., Patel, A., Shah, Z. K., Swensson, J., Takahashi, N., Venkatesh, S., Wachsman, A., Li, L., Jennings, K., Yang, Y., Hart, P. A., Pandol, S. J., Park, W. G., Vege, S. S., Topazian, M., Territo, P. R., Persohn, S. A., Andersen, D. K., Fogel, E. L. 2024

  Abstract

  Ductal features alone may not offer high diagnostic sensitivity or most accurate disease severity of chronic pancreatitis (CP).Diagnose CP based on multiparametric MRI and MRCP features.Prospective.Between February 2019 and May 2021, 46 control (23 males, 49.3 ± 14.1 years), 45 suspected (20 males, 48.7 ± 12.5 years), and 46 definite (20 males, 53.7 ± 14.6 years) CP patients were enrolled at seven hospitals enrolled in the MINIMAP study. CP classification was based on imaging findings and clinical presentation.1.5 T. T1-weighted (T1W) spoiled gradient echo, T1 map with variable flip angle, dual-echo Dixon, secretin-enhanced MRCP before and after secretin infusion.Dual-echo fat fraction (FF), T1 relaxation time, extracellular volume (ECV), T1 signal intensity ratio of the pancreas to the spleen (T1 score), arterial-to-venous enhancement ratio (AVR), pancreatic tail diameter (PTD), pancreas volume, late gadolinium enhancement, pancreatic ductal elasticity (PDE), and duodenal filling grade of secretin-enhanced MRCP were measured.Logistic regression analysis generated CP-MRI and secretin-enhanced CP-SMRI scores. Receiver operating characteristics analysis was used to differentiate definite CP from control. Interobserver agreement was assessed using Lin's concordance correlation coefficient.Compared to control, definite CP cohort showed significantly higher dual-echo FF (7% vs. 11%), lower AVR (1.35 vs. 0.85), smaller PTD (2.5 cm vs. 1.95 cm), higher ECV (28% vs. 38%), and higher incidence of PDE loss (6.5% vs. 50%). With the cut-off of >2.5 CP-MRI score (dual-echo FF, AVR, and PTD) and CP-SMRI score (dual-echo FF, AVR, PTD, and PDE) had cross-validated area under the curves of 0.84 (sensitivity 87%, specificity 68%) and 0.86 (sensitivity 89%, specificity 67%), respectively. Interobserver agreement for both CP-MRI and CP-SMRI scores was 0.74.The CP-MRI and CP-SMRI scores yielded acceptable performance and interobserver agreement for the diagnosis of CP.1 TECHNICAL EFFICACY: Stage 2.

  View details for DOI 10.1002/jmri.29594

  View details for PubMedID 39225586

• Evaluation of Chronic Pancreatitis Prognosis Score in an American Cohort. Clinical and translational gastroenterology Park, S. K., Conwell, D. L., Hart, P. A., Li, S., Stello, K., Fogel, E. L., Fisher, W. E., Forsmark, C. E., Pandol, S. J., Park, W. G., Topazian, M., Serrano, J., Vege, S. S., Van Den Eeden, S. K., Li, L., Yadav, D., Saloman, J. L. 2024

  Abstract

  Chronic Pancreatitis Prognosis Score (COPPS) was developed to discriminate disease severity and predict risk for future hospitalizations. In this cohort study, we evaluated if COPPS predicts the likelihood of hospitalization(s) in an American cohort.The CPDPC consortium provided data and serum from subjects with chronic pancreatitis (N=279). COPPS was calculated with baseline data and stratified by severity (low, moderate, high). Primary endpoints included number and duration of hospitalizations during 12-month follow-up.The mean±SD COPPS was 8.4±1.6. COPPS correlated with all primary outcomes: hospitalizations for any reason (number: r=0.15, p=0.01; duration: r=0.16, p=0.01) and pancreas-related hospitalizations (number: r=0.15, p=0.02; duration: r=0.13, p=0.04). The severity distribution was 13.3% low, 66.0% moderate, and 20.8% high. 37.6% of subjects had ≥1 hospitalization(s) for any reason; 32.2% had ≥1 pancreas-related hospitalization(s). All primary outcomes were significantly different between severity groups: hospitalizations for any reason (number, p=0.004; duration, p=0.007) and pancreas-related hospitalizations (number, p=0.02; duration, p=0.04). The prevalence of continued drinking at follow-up (p=0.04) was higher in the low and moderate groups. The prevalence of anxiety at enrollment (p=0.02) and follow-up (p<0.05) was higher in the moderate and high groups.Statistically, COPPS significantly correlated with hospitalization outcomes, but the correlations were weaker than in previous studies, which may be related to the outpatient nature of the PROCEED cohort and lower prevalence of high severity disease. Studies in other prospective cohorts are needed to understand the full utility of COPPS as a potential tool for clinical risk assessment and intervention.

  View details for DOI 10.14309/ctg.0000000000000758

  View details for PubMedID 39137098

• Development of clinical screening tool for exocrine pancreatic insufficiency in patients with definite chronic pancreatitis. Pancreatology : official journal of the International Association of Pancreatology (IAP) ... [et al.] Othman, M. O., Forsmark, C., Yadav, D., Singh, V. K., Lara, L. F., Park, W., Zhang, Z., Yu, J., Kort, J. J. 2024

  Abstract

  BACKGROUND/OBJECTIVES: No simple, accurate diagnostic tests exist for exocrine pancreatic insufficiency (EPI), and EPI remains underdiagnosed in chronic pancreatitis (CP). We sought to develop a digital screening tool to assist clinicians to predict EPI in patients with definite CP.METHODS: This was a retrospective case-control study of patients with definite CP with/without EPI. Overall, 49 candidate predictor variables were utilized to train a Classification and Regression Tree (CART) model to rank all predictors and select a parsimonious set of predictors for EPI status. Five-fold cross-validation was used to assess generalizability, and the full CART model was compared with 4 additional predictive models. EPI misclassification rate (mRate) served as primary endpoint metric.RESULTS: 274 patients with definite CP from 6 pancreatitis centers across the United States were included, of which 58% had EPI based on predetermined criteria. The optimal CART decision tree included 10 variables. The mRate without/with 5-fold cross-validation of the CART was 0.153 (training error) and 0.314 (prediction error), and the area under the receiver operating characteristic curve was 0.889 and 0.682, respectively. Sensitivity and specificity without/with 5-fold cross-validation was 0.888/0.789 and 0.794/0.535, respectively. A trained second CART without pancreas imaging variables (n=6), yielded 8 variables. Training error/prediction error was 0.190/0.351; sensitivity was 0.869/0.650, and specificity was 0.728/0.649, each without/with 5-fold cross-validation.CONCLUSION: We developed two CART models that were integrated into one digital screening tool to assess for EPI in patients with definite CP and with two to six input variables needed for predicting EPI status.

  View details for DOI 10.1016/j.pan.2024.04.003

  View details for PubMedID 38693039

• Utilization of Pancreatic Endotherapy in Patients with Chronic Pancreatitis: Results From a Multicenter Cohort Study in the United States. Gastrointestinal endoscopy Han, S., Conwell, D. L., Easler, J. J., Yang, Y., Andersen, D. K., Fisher, W. E., Fogel, E. L., Forsmark, C., Hart, P. A., Hughes, S. J., Li, L., Pandol, S. J., Park, W. G., Serrano, J., Van Den Eeden, S. K., Vege, S. S., Yadav, D. 2024

  Abstract

  Although commonly used for treating complications of chronic pancreatitis (CP), data on the frequency and factors associated with the use of pancreatic endotherapy (PET) are limited. Our aim was to define the utilization and factors predictive for receiving PET in a well-characterized CP cohort.This is a cross-sectional analysis of data from PROCEED, a multicenter US cohort study of CP. PET modalities primarily consisted of ERCP. A treatment course was defined as the number of sessions performed for a specific indication. A repeat course was defined as PET >1 year after completion of the last course. Multivariable logistic regression identified predictive factors for receiving PET, and proportional rates model assessed risk factors for repeat PET.Of a total of 681 subjects, 238 (34.9%) received PET. Factors associated with receiving PET included female sex (OR: 1.26, 95% CI: 1.03-1.53), lower education (OR: 1.30, 95% CI: 1.04-1.62), income ≤ $50,000 per year (OR: 1.35, 95% CI: 1.07-1.71) and prior acute pancreatitis (AP) (OR: 1.74, 95% CI: 1.31, 2.32). 103/238 subjects (43.3%) underwent repeat PET at a median duration of 2 years with 23.1% receiving 2 courses, 9.7% receiving 3 courses, and 10.4% receiving 4+ courses.Nearly half of patients with CP who undergo PET received one or more repeat courses within 2-3 years. In addition to a prior history of AP, demographic and socioeconomic factors were associated with receiving PET.

  View details for DOI 10.1016/j.gie.2024.04.002

  View details for PubMedID 38583544

• Safety, Tolerability, and Dose-Limiting Toxicity of Lacosamide in Patients With Painful Chronic Pancreatitis: Protocol for a Phase 1 Clinical Trial to Determine Safety and Identify Side Effects. JMIR research protocols Fogel, E. L., Easler, J. J., Yuan, Y., Yadav, D., Conwell, D. L., Vege, S. S., Han, S. Y., Park, W., Patrick, V., White, F. A. 2024; 13: e50513

  Abstract

  BACKGROUND: Chronic abdominal pain is the hallmark symptom of chronic pancreatitis (CP), with 50% to 80% of patients seeking medical attention for pain control. Although several management options are available, outcomes are often disappointing, and opioids remain a mainstay of therapy. Opioid-induced hyperalgesia is a phenomenon resulting in dose escalation, which may occur partly because of the effects of opioids on voltage-gated sodium channels associated with pain. Preclinical observations demonstrate that the combination of an opioid and the antiseizure drug lacosamide diminishes opioid-induced hyperalgesia and improves pain control.OBJECTIVE: In this phase 1 trial, we aim to determine the safety, tolerability, and dose-limiting toxicity of adding lacosamide to opioids for the treatment of painful CP and assess the feasibility of performance of a pilot study of adding lacosamide to opioid therapy in patients with CP. As an exploratory aim, we will assess the efficacy of adding lacosamide to opioid therapy in patients with painful CP.METHODS: Using the Bayesian optimal interval design, we will conduct a dose-escalation trial of adding lacosamide to opioid therapy in patients with painful CP enrolled in cohorts of size 3. The initial dose will be 50 mg taken orally twice a day, followed by incremental increases to a maximum dose of 400 mg/day, with lacosamide administered for 7 days at each dose level. Adverse events will be documented according to Common Terminology Criteria for Adverse Events (version 5.0).RESULTS: As of December 2023, we have currently enrolled 6 participants. The minimum number of participants to be enrolled is 12 with a maximum of 24. We expect to publish the results by March 2025.CONCLUSIONS: This trial will test the feasibility of the study design and provide reassurance regarding the tolerability and safety of opioids in treating painful CP. It is anticipated that lacosamide will prove to be safe and well tolerated, supporting a subsequent phase 2 trial assessing the efficacy of lacosamide+opioid therapy in patients with painful CP, and that lacosamide combined with opiates will lower the opioid dose necessary for pain relief and improve the safety profile of opioid use in treating painful CP.TRIAL REGISTRATION: Clinicaltrials.gov NCT05603702; https://clinicaltrials.gov/study/NCT05603702.INTERNATIONAL REGISTERED REPORT IDENTIFIER (IRRID): PRR1-10.2196/50513.

  View details for DOI 10.2196/50513

  View details for PubMedID 38451604

• Diagnosis and Management of Pancreatic Cysts. Gastroenterology Gardner, T. B., Park, W. G., Allen, P. J. 2024

  View details for DOI 10.1053/j.gastro.2024.02.041

  View details for PubMedID 38442782

• Circulating immune signatures in chronic pancreatitis with and without preceding acute pancreatitis: A pilot study. Pancreatology : official journal of the International Association of Pancreatology (IAP) ... [et al.] Hagn-Meincke, R., Yadav, D., Andersen, D. K., Vege, S. S., Fogel, E. L., Serrano, J., Bellin, M. D., Topazian, M. D., Conwell, D. L., Li, L., Van Den Eeden, S. K., Drewes, A. M., Pandol, S. J., Forsmark, C. E., Fisher, W. E., Hart, P. A., Olesen, S. S., Park, W. G., Consortium for the Study of Chronic Pancreatitis, D. 2024

  Abstract

  OBJECTIVE: To investigate profiles of circulating immune signatures in healthy controls and chronic pancreatitis patients (CP) with and without a preceding history of acute pancreatitis (AP).METHODS: We performed a phase 1, cross-sectional analysis of prospectively collected serum samples from the PROspective Evaluation of Chronic Pancreatitis for EpidEmiologic and Translation StuDies (PROCEED) study. All samples were collected during a clinically quiescent phase. CP subjects were categorized into two subgroups based on preceding episode(s) of AP. Healthy controls were included for comparison. Blinded samples were analyzed using an 80-plex Luminex assay of cytokines, chemokines, and adhesion molecules. Group and pairwise comparisons of analytes were performed between the subgroups.RESULTS: In total, 133 patients with CP (111 with AP and 22 without AP) and 50 healthy controls were included. Among the 80 analytes studied, CP patients with a history of AP had significantly higher serum levels of pro-inflammatory cytokines (interleukin (IL)-6, IL-8, IL-1 receptor antagonist, IL-15) and chemokines (Cutaneous T-Cell Attracting Chemokine (CTACK), Monokine induced Gamma Interferon (MIG), Macrophage-derived Chemokine (MDC), Monocyte Chemoattractant Protein-1 (MCP-1)) compared to CP without preceding AP and controls. In contrast, CP patients without AP had immune profiles characterized by low systemic inflammation and downregulation of anti-inflammatory mediators, including IL-10.CONCLUSION: CP patients with a preceding history of AP have signs of systemic inflammatory activity even during a clinically quiescent phase. In contrast, CP patients without a history of AP have low systemic inflammatory activity. These findings suggest the presence of two immunologically diverse subtypes of CP.

  View details for DOI 10.1016/j.pan.2024.02.012

  View details for PubMedID 38461145

• Systemic Neutrophil Gelatinase-Associated Lipocalin Alterations in Chronic Pancreatitis: A Multicenter, Cross-Sectional Study. Clinical and translational gastroenterology Gumpper-Fedus, K., Chasser, K., Pita-Grisanti, V., Torok, M., Pfau, T., Mace, T. A., Cole, R. M., Belury, M. A., Culp, S., Hart, P. A., Krishna, S. G., Lara, L. F., Ramsey, M. L., Fisher, W., Fogel, E. L., Forsmark, C. E., Li, L., Pandol, S., Park, W. G., Serrano, J., Van Den Eeden, S. K., Vege, S. S., Yadav, D., Conwell, D. L., Cruz-Monserrate, Z. 2024

  Abstract

  Chronic pancreatitis (CP) is a progressive fibroinflammatory disorder lacking therapies and biomarkers. Neutrophil gelatinase-associated lipocalin (NGAL) is a proinflammatory cytokine elevated during inflammation that binds fatty acids (FAs) like linoleic acid. We hypothesized that systemic NGAL could serve as a biomarker for CP and, with FAs, provide insights into inflammatory and metabolic alterations.NGAL was measured by immunoassay and FA composition was measured by gas chromatography in plasma ( n = 171) from a multicenter study, including controls ( n = 50), acute and recurrent acute pancreatitis (AP/RAP) ( n = 71), and CP ( n = 50). Peripheral blood mononuclear cells (PBMCs) from controls ( n = 16), AP/RAP ( n = 17), and CP ( n = 15) were measured by CyTOF.Plasma NGAL was elevated in subjects with CP compared to controls (AUC = 0.777) or AP/RAP (AUC = 0.754) in univariate and multivariate analyses with sex, age, BMI, and smoking (control AUC = 0.874; AP/RAP AUC = 0.819). NGAL was elevated in CP and diabetes compared to CP without diabetes (p < 0.001). NGAL + PBMC populations distinguished CP from controls (AUC = 0.950) or AP/RAP (AUC = 0.941). Linoleic acid was lower while dihomo-γ-linolenic and adrenic acids were elevated in CP (p < 0.05). Linoleic acid was elevated in CP with diabetes compared to CP subjects without diabetes (p = 0. 0471).Elevated plasma NGAL and differences in NGAL + PBMCs indicate an immune response shift that may serve as biomarkers of CP. The potential interaction of FAs and NGAL levels provide insights into the metabolic pathophysiology and improve diagnostic classification of CP.

  View details for DOI 10.14309/ctg.0000000000000686

  View details for PubMedID 38284831

• Circulating immune signatures across clinical stages of chronic pancreatitis: a pilot study. European journal of gastroenterology & hepatology Hagn-Meincke, R., Hart, P. A., Andersen, D. K., Vege, S. S., Fogel, E. L., Serrano, J., Bellin, M. D., Topazian, M. D., Conwell, D. L., Li, L., Van Den Eeden, S. K., Drewes, A. M., Pandol, S. J., Forsmark, C. E., Fisher, W. E., Yadav, D., Olesen, S. S., Park, W. G. 2023

  Abstract

  This pilot study seeks to identify serum immune signatures across clinical stages of patients with chronic pancreatitis (CP).We performed a cross-sectional analysis of prospectively collected serum samples from the PROspective Evaluation of Chronic Pancreatitis for EpidEmiologic and Translation StuDies-study. CP subjects were categorised into three clinical stages based on the presence/absence of metabolic complications: (1) CP with no diabetes and exocrine pancreatic dysfunction (EPD), (2) CP with either diabetes or EPD, and (3) CP with diabetes and EPD. Blinded samples were analysed using an 80-plex Luminex assay of cytokines/chemokines/adhesion molecules. Group and pairwise comparisons were performed to characterise immune signatures across CP subgroups.A total of 135 CP subjects (evenly distributed between clinical stages) and 50 controls were studied. Interleukin-6 (IL-6), interleukin-8 (IL-8), and soluble intercellular adhesion molecule 1 (sICAM-1) were significantly elevated in CP subjects compared to controls. The levels of IL-6 and IL-8 increased with advancing disease stages, with the highest levels observed in CP with diabetes and EPD (clinical stage 3). Furthermore, hepatocyte growth factor and macrophage-derived chemokine were significantly increased in clinical stage 3 compared to controls.Our study reveals a progressive elevation in pro-inflammatory cytokines and chemokines with advancing clinical stages of CP. These findings indicate potential targets for the development of disease-modifying interventions.

  View details for DOI 10.1097/MEG.0000000000002691

  View details for PubMedID 38047728

• ePancrelipase for the Treatment of Exocrine Pancreatic Insufficiency Due to Chronic Pancreatitis: Rationale and Methodology of a Prospective, Observational, Multicenter, Cohort Study Othman, M. O., Kort, J., Lara, L., Gonda, T., Kothari, D., Trikudanathan, G., Park, W., Li, M., Harb, D. LIPPINCOTT WILLIAMS & WILKINS. 2023: S14

  View details for Web of Science ID 001091849300018

• Long-Term Outcomes of ERCP in the Management of Chronic Pancreatitis Over a 10-year Period at a Tertiary Care Center Emelogu, I. K., Brooks, C. G., Deliwala, S., Calderon, L. F., Abraham, F. O., Kumar, V., Willingham, F., Keilin, S., Patel, V., Orr, J., Park, W., Chawla, S. LIPPINCOTT WILLIAMS & WILKINS. 2023: S106

  View details for Web of Science ID 001091849300132

• Serum Biomarkers of Nociceptive and Neuropathic Pain in Chronic Pancreatitis. The journal of pain Saloman, J. L., Li, Y., Stello, K., Li, W., Li, S., Phillips, A. E., Hall, K., Fogel, E. L., Vege, S. S., Li, L., Andersen, D. K., Fisher, W. E., Forsmark, C. E., Hart, P. A., Pandol, S. J., Park, W. G., Topazian, M. D., Van Den Eeden, S. K., Serrano, J., Conwell, D. L., Yadav, D. 2023

  Abstract

  Debilitating abdominal pain is a common symptom affecting most patients with chronic pancreatitis (CP). There are multiple underlying mechanisms that contribute to pain which makes successful treatment difficult. The identification of biomarkers for subtypes of pain could provide viable targets for non-opioid interventions and the development of mechanistic approaches to pain management in CP. Nineteen inflammation- and nociception-associated proteins were measured in serum collected from 358 subjects with definite CP enrolled in PROspective Evaluation of Chronic Pancreatitis for EpidEmiologic and Translational StuDies (PROCEED), a prospective observational study of pancreatitis in US adult subjects. First, serum levels of putative biomarkers were compared between CP subjects with and without pain. Only PDGF-B stood out, with levels significantly higher in the CP pain group as compared to subjects with no pain. Subjects with pain were then stratified into four pain subtypes (Neuropathic, Nociceptive, Mixed and Unclassified). A comparison of putative biomarker concentration among five groups (No pain and 4 pain subtypes), identified unique proteins that were correlated with pain subtypes. Serum TGFβ1 level was significantly higher in the Nociceptive Pain group compared to the No Pain group, suggesting that TGFβ1 may be a biomarker for Nociceptive pain. The Neuropathic pain only group was too small to detect statistical differences. However, GP130, a co-receptor for IL-6, was significantly higher in the Mixed pain group compared to the groups lacking a neuropathic pain component. These data suggest that GP130 may be a biomarker for Neuropathic pain in CP. PERSPECTIVE: Serum TGFβ1 and GP130 may be biomarkers for nociceptive and neuropathic CP pain, respectively. Preclinical data suggest inhibiting TGFβ1 or GP130 reduces CP pain in rodent models, indicating that additional translational and clinical studies may be warranted to develop a precision medicine approach to the management of pain in CP.

  View details for DOI 10.1016/j.jpain.2023.07.006

  View details for PubMedID 37451493

• Diagnosis of chronic pancreatitis using semi-quantitative MRI features of the pancreatic parenchyma: results from the multi-institutional MINIMAP study. Abdominal radiology (New York) Tirkes, T., Yadav, D., Conwell, D. L., Territo, P. R., Zhao, X., Persohn, S. A., Dasyam, A. K., Shah, Z. K., Venkatesh, S. K., Takahashi, N., Wachsman, A., Li, L., Li, Y., Pandol, S. J., Park, W. G., Vege, S. S., Hart, P. A., Topazian, M., Andersen, D. K., Fogel, E. L. 2023

  Abstract

  To determine the diagnostic performance of parenchymal MRI features differentiating CP from controls.This prospective study performed abdominal MRI scans at seven institutions, using 1.5 T Siemens and GE scanners, in 50 control and 51 definite CP participants, from February 2019 to May 2021. MRI parameters included the T1-weighted signal intensity ratio of the pancreas (T1 score), arterial-to-venous enhancement ratio (AVR) during venous and delayed phases, pancreas volume, and diameter. We evaluated the diagnostic performance of these parameters individually and two semi-quantitative MRI scores derived using logistic regression: SQ-MRI Model A (T1 score, AVR venous, and tail diameter) and Model B (T1 score, AVR venous, and volume).When compared to controls, CP participants showed a significantly lower mean T1 score (1.11 vs. 1.29), AVR venous (0.86 vs. 1.45), AVR delayed (1.07 vs. 1.57), volume (54.97 vs. 80.00 ml), and diameter of the head (2.05 vs. 2.39 cm), body (2.25 vs. 2.58 cm), and tail (1.98 vs. 2.51 cm) (p < 0.05 for all). AUCs for these individual MR parameters ranged from 0.66 to 0.79, while AUCs for the SQ-MRI scores were 0.82 and 0.81 for Model A (T1 score, AVR venous, and tail diameter) and Model B (T1 score, AVR venous, and volume), respectively. After propensity-matching adjustments for covariates, AUCs for Models A and B of the SQ-MRI scores increased to 0.92 and 0.93, respectively.Semi-quantitative parameters of the pancreatic parenchyma, including T1 score, enhancement ratio, pancreas volume, diameter and multi-parametric models combining these parameters are helpful in diagnosis of CP. Longitudinal analyses including more extensive population are warranted to develop new diagnostic criteria for CP.

  View details for DOI 10.1007/s00261-023-04000-1

  View details for PubMedID 37436452

  View details for PubMedCentralID 1432589

• Association of Chronic Pancreatitis Pain Features With Physical, Mental, and Social Health CLINICAL GASTROENTEROLOGY AND HEPATOLOGY Yadav, D., Askew, R. L., Palermo, T., Li, L., Andersen, D. K., Chen, M., Fisher, W. E., Fogel, E. L., Forsmark, C. E., Hart, P. A., Othman, M. O., Pandol, S. J., Park, W. G., Topazian, M. D., Van Den Eeden, S. K., Vege, S., Yang, Y., Serrano, J., Conwell, D. L., behalf Consortium Study 2023; 21 (7): 1781-+

  View details for DOI 10.1016/j.cgh.2022.09.026

  View details for Web of Science ID 001034448100001

• Pancreatic Cyst Fluid Analysis. Gastrointestinal endoscopy clinics of North America Siddappa, P. K., Park, W. G. 2023; 33 (3): 599-612

  Abstract

  Pancreatic cyst fluid analysis can help diagnose pancreatic cyst type and the risk of high-grade dysplasia and cancer. Recent evidence from molecular analysis of cyst fluid has revolutionized the field with multiple markers showing promise in accurate diagnosis and prognostication of pancreatic cysts. The availability of multi-analyte panels has great potential for more accurate prediction of cancer.

  View details for DOI 10.1016/j.giec.2023.03.006

  View details for PubMedID 37245938

• A COMBINED DNA/RNA-BASED NEXT-GENERATION SEQUENCING PLATFORM TO IMPROVE THE CLASSIFICATION OF PANCREATIC CYSTS AND EARLY DETECTION OF PANCREATIC CANCER ARISING FROM PANCREATIC CYSTS Nikiforova, M., Wald, A., Spagnolo, D., Melan, M., Grupillo, M., Lai, Y., Brand, R., Lennon, A., Mcgrath, K., Park, W., Pfau, P., Kubiliun, N., Dewitt, J., Easler, J., Dam, A., Mok, S., Wallace, M., Kumbhari, V., Boone, B., Marsh, J., Thakkar, S., Fairley, K., Afghani, E., Bhat, Y., Ramrakhiani, S., Nasr, J., Skef, W., Thiruvengadam, N., Khalid, A., Fasanella, K., Chennat, J., Das, R., Singh, H., Sarkaria, S., Slivka, A., Gabbert, C., Sawas, T., Tielleman, T., Vanderveldt, H., Tavakkoli, A., Smith, L., Smith, K., Bell, P., Hruban, R., Paniccia, A., Zureikat, A., Lee, K., Zeh, H., Minter, R., He, J., Nikiforov, Y., Singhi, A. MOSBY-ELSEVIER. 2023: AB784

  View details for Web of Science ID 001038022801630

• BURDEN OF PANCREATIC ENDOTHERAPY AND ITS ASSOCIATIONS IN PATIENTS WITH CHRONIC PANCREATITIS: RESULTS FROM A LARGE MULTICENTER COHORT Han, S., Conwell, D., Easler, J., Yang, Y., Andersen, D., Fisher, W., Fogel, E., Forsmark, C., Hart, P., Li, L., Pandol, S., Park, W., Serrano, J., Van Den Eeden, S., Vege, S., Yadav, D. MOSBY-ELSEVIER. 2023: AB644

  View details for Web of Science ID 001038022801411

• BURDEN OF PANCREATIC ENDOTHERAPY AND ITS ASSOCIATIONS IN PATIENTS WITH CHRONIC PANCREATITIS: RESULTS FROM A LARGE MULTICENTER COHORT Han, S., Conwell, D., Easler, J., Yang, Y., Andersen, D., Fisher, W., Fogel, E., Forsmark, C., Hart, P., Li, L., Pandol, S., Park, W., Serrano, J., Van den Eeden, S., Vege, S., Yadav, D. MOSBY-ELSEVIER. 2023: AB683-AB684

  View details for Web of Science ID 001038022801477

• A Combined DNA/RNA-based Next-Generation Sequencing Platform to Improve the Classification of Pancreatic Cysts and Early Detection of Pancreatic Cancer Arising from Pancreatic Cysts. Annals of surgery Nikiforova, M. N., Wald, A. I., Spagnolo, D. M., Melan, M. A., Grupillo, M., Lai, Y., Brand, R. E., O'Broin-Lennon, A. M., McGrath, K., Park, W. G., Pfau, P. R., Polanco, P. M., Kubiliun, N., DeWitt, J., Easler, J. J., Dam, A., Mok, S. R., Wallace, M. B., Kumbhari, V., Boone, B. A., Marsh, W., Thakkar, S., Fairley, K. J., Afghani, E., Bhat, Y., Ramrakhiani, S., Nasr, J., Skef, W., Thiruvengadam, N. R., Khalid, A., Fasanella, K., Chennat, J., Das, R., Singh, H., Sarkaria, S., Slivka, A., Gabbert, C., Sawas, T., Tielleman, T., Vanderveldt, H. D., Tavakkoli, A., Smith, L. M., Smith, K., Bell, P. D., Hruban, R. H., Paniccia, A., Zureikat, A., Lee, K. K., Ongchin, M., Zeh, H., Minter, R., He, J., Nikiforov, Y. E., Singhi, A. D. 2023

  Abstract

  OBJECTIVE: We report the development and validation of a combined DNA/RNA next-generation sequencing (NGS) platform to improve the evaluation of pancreatic cysts.BACKGROUND AND AIMS: Despite a multidisciplinary approach, pancreatic cyst classification, such as a cystic precursor neoplasm, and the detection of high-grade dysplasia and early adenocarcinoma (advanced neoplasia) can be challenging. Next-generation sequencing of preoperative pancreatic cyst fluid improves the clinical evaluation of pancreatic cysts, but the recent identification of novel genomic alterations necessitates the creation of a comprehensive panel and the development of a genomic classifier to integrate the complex molecular results.METHODS: An updated and unique 74-gene DNA/RNA-targeted NGS panel (PancreaSeq Genomic Classifier) was created to evaluate 5 classes of genomic alterations to include gene fusions and gene expression. Further, CEA mRNA (CEACAM5) was integrated into the assay using RT-qPCR. Separate multi-institutional cohorts for training (n=108) and validation (n=77) were tested, and diagnostic performance was compared to clinical, imaging, cytopathologic, and guideline data.RESULTS: Upon creation of a genomic classifier system, PancreaSeq GC yielded a 95% sensitivity and 100% specificity for a cystic precursor neoplasm, and the sensitivity and specificity for advanced neoplasia was 82% and 100%, respectively. Associated symptoms, cyst size, duct dilatation, a mural nodule, increasing cyst size, and malignant cytopathology had lower sensitivities (41-59%) and lower specificities (56-96%) for advanced neoplasia. This test also increased the sensitivity of current pancreatic cyst guidelines (IAP/Fukuoka and AGA) by >10% and maintained their inherent specificity.CONCLUSIONS: Combined DNA/RNA NGS was not only accurate in predicting pancreatic cyst type and advanced neoplasia, but also improved the sensitivity of current pancreatic cyst guidelines.

  View details for DOI 10.1097/SLA.0000000000005904

  View details for PubMedID 37212422

• Distinct serum immune profiles define the spectrum of acute and chronic pancreatitis from the multi-center PROCEED study. Gastroenterology Lee, B., Jones, E. K., Manohar, M., Li, L., Yadav, D., Conwell, D. L., Hart, P. A., Vege, S. S., Fogel, E. L., Serrano, J., Andersen, D., Bellin, M. D., Topazian, M., Van Den Eeden, S. K., Pandol, S. J., Forsmark, C., Fisher, W. E., Park, W. G., Husain, S. Z., Habtezion, A. 2023

  Abstract

  Pancreatitis is a disease continuum, starting with acute pancreatitis (AP) and, in some cases, progressing to recurrent acute pancreatitis (RAP) and chronic pancreatitis (CP). Currently, there are no approved therapies or early diagnostic or prognostic biomarkers for pancreatitis. The current study aimed to examine whether patient serum immune profiling could identify non-invasive biomarkers and provide mechanistic insight into the disease continuum of pancreatitis.Using Olink immunoassay, we assessed the protein levels of 92 immune markers in serum samples from participants enrolled in the PROCEED study of the CPDPC consortium. Samples (n=231) were obtained from subjects without the pancreatic disease (n=56) and those with chronic abdominal pain (CAP) (n=24), AP (n=38), RAP (n=56), and CP (n=57).Thirty-three immune markers differentiated the combined pancreatitis groups from controls. Immune markers related to IL-17 signaling distinguished CP from AP and RAP. Similarly, the serum level of IL-17A and CCL20 differentiated CP from CAP, suggesting the involvement of Th17 cells in CP pathogenesis. The receiver operator characteristic (ROC) curve with two immune markers (IL-17A and ST1A1) could differentiate CP from CAP (optimistic AUC=0.78). Macrophage classical activation pathway elevated along the continuum of pancreatitis, suggesting an accumulation of proinflammatory signals over disease progression. Several immune markers were associated with smoking, alcohol, and diabetes status.Immune profiling of serum samples from a large pancreatitis cohort led to identifying distinct immune markers that could serve as potential biomarkers to differentiate the varying pancreatitis disease states. In addition, the finding of IL-17 signaling in CP could provide insight into the immune mechanisms underlying disease progression.

  View details for DOI 10.1053/j.gastro.2023.03.236

  View details for PubMedID 37061168

• Passive monitoring by smart toilets for precision health. Science translational medicine Ge, T. J., Rahimzadeh, V. N., Mintz, K., Park, W. G., Martinez-Martin, N., Liao, J. C., Park, S. M. 2023; 15 (681): eabk3489

  Abstract

  Smart toilets are a key tool for enabling precision health monitoring in the home, but such passive monitoring has ethical considerations.

  View details for DOI 10.1126/scitranslmed.abk3489

  View details for PubMedID 36724240

• ACG Clinical Guideline: Diagnosis and Management of Gastrointestinal Subepithelial Lesions. The American journal of gastroenterology Jacobson, B. C., Bhatt, A., Greer, K. B., Lee, L. S., Park, W. G., Sauer, B. G., Shami, V. M. 2023; 118 (1): 46-58

  Abstract

  Subepithelial lesions (SEL) of the GI tract represent a mix of benign and potentially malignant entities including tumors, cysts, or extraluminal structures causing extrinsic compression of the gastrointestinal wall. SEL can occur anywhere along the GI tract and are frequently incidental findings encountered during endoscopy or cross-sectional imaging. This clinical guideline of the American College of Gastroenterology was developed using the Grading of Recommendations Assessment, Development, and Evaluation process and is intended to suggest preferable approaches to a typical patient with a SEL based on the currently available published literature. Among the recommendations, we suggest endoscopic ultrasound (EUS) with tissue acquisition to improve diagnostic accuracy in the identification of solid nonlipomatous SEL and EUS fine-needle biopsy alone or EUS fine-needle aspiration with rapid on-site evaluation sampling of solid SEL. There is insufficient evidence to recommend surveillance vs resection of gastric gastrointestinal stromal tumors (GIST) <2 cm in size. Owing to their malignant potential, we suggest resection of gastric GIST >2 cm and all nongastric GIST. When exercising clinical judgment, particularly when statements are conditional suggestions and/or treatments pose significant risks, health-care providers should incorporate this guideline with patient-specific preferences, medical comorbidities, and overall health status to arrive at a patient-centered approach.

  View details for DOI 10.14309/ajg.0000000000002100

  View details for PubMedID 36602835

• Characterizing gastrointestinal dysfunction after pancreatic resection: a single-center retrospective study. BMC gastroenterology Bromley-Dulfano, R., August, A. T., Li, A. Y., Park, W., Visser, B. 2022; 22 (1): 488

  Abstract

  BACKGROUND: There are many well-described potential gastrointestinal (GI) side effects of pancreatic resection that can cause patients to suffer from chronic malabsorption, diarrhea, and persistent nausea. These GI symptoms can affect postoperative recovery, initiation of adjuvant therapy, and overall quality of life (QOL). The purpose of this study is to quantify the incidence of post-procedural complications and identify patients at higher risk for experiencing GI dysfunction after pancreatectomy.METHODS: A retrospective review of patients who underwent pancreatic resection at a single institution between January 2014 and December 2019 was performed. Demographics, operative factors, and postoperative gastrointestinal symptomatology and treatments were obtained by chart review. Significance tests were performed to compare GI dysfunction between patient subgroups.RESULTS: A total of 545 patients underwent pancreatic resection; within the cohort 451 patients (83%) underwent a pancreaticoduodenectomy (PD) and the most common indication was pancreatic adenocarcinoma. Two-thirds of patients (67%) reported gastrointestinal symptoms persisting beyond hospitalization. Only 105 patients (20%) were referred to gastroenterology for evaluation with 30 patients (5.5%) receiving a formal diagnosis. Patients who underwent PD were more likely to report GI symptoms and patients who identified as Caucasian were more likely to be referred to gastroenterology for evaluation.CONCLUSIONS: Gastrointestinal dysfunction after pancreatic resection occurs frequently yet only a small percentage of patients are referred for formal testing and diagnosis. There also appears to be a racial difference in referral patterns. Patients would benefit if earlier attention was dedicated to the diagnosis and corresponding treatment for postoperative digestive health disorders to optimize treatment planning and QOL.

  View details for DOI 10.1186/s12876-022-02565-7

  View details for PubMedID 36435757

• A reduced pancreatic polypeptide response is associated with new onset pancreatogenic diabetes versus type 2 diabetes. The Journal of clinical endocrinology and metabolism Hart, P. A., Kudva, Y. C., Yadav, D., Andersen, D. K., Li, Y., Toledo, F. G., Wang, F., Bellin, M. D., Bradley, D., Brand, R. E., Cusi, K., Fisher, W., Mather, K., Park, W. G., Saeed, Z., Considine, R. V., Graham, S. C., Rinaudo, J. A., Serrano, J., Goodarzi, M. O. 2022

  Abstract

  PURPOSE: Pancreatogenic diabetes refers to diabetes mellitus (DM) that develops in the setting of a disease of the exocrine pancreas, including pancreatic ductal adenocarcinoma (PDAC) and chronic pancreatitis (CP). We sought to evaluate whether a blunted nutrient response of pancreatic polypeptide (PP) can differentiate these DM subtypes from type 2 DM (T2DM).METHODS: Subjects with new onset DM (<3 years duration) in the setting of PDAC (PDAC-DM, n=28), CP (CP-DM, n=38), or T2DM (n=99) completed a standardized mixed meal tolerance test (MMTT), then serum PP concentrations were subsequently measured at a central laboratory. Two-way comparisons of PP concentrations between groups were performed using Wilcoxon rank-sum test and analysis of covariance (ANCOVA) while adjusting for age, sex, and BMI.RESULTS: The fasting PP concentration was lower in both PDAC-DM and CP-DM groups than the T2DM group (p=0.03 and <0.01, respectively). The fold change in PP at 15 minutes following meal stimulation was significantly lower in the PDAC-DM (median 1.869) and CP-DM (1.813) groups compared to T2DM (3.283, p<0.01 for both comparisons). The area under the curve (AUC) of PP concentration was significantly lower in both PDAC-DM and CP-DM groups than T2DM regardless of the interval used for calculation, and remained significant after adjustments.CONCLUSIONS: Fasting PP concentrations and the response to meal stimulation are reduced in new onset DM associated with PDAC or CP compared to T2DM. These findings support further investigations into the use of PP concentrations to characterize pancreatogenic DM, and to understand the pathophysiological role in exocrine pancreatic diseases. (NCT03460769).

  View details for DOI 10.1210/clinem/dgac670

  View details for PubMedID 36404274

• Development of a Clinical Prediction Model for Diabetes in Chronic Pancreatitis: The PREDICT3c Study. Diabetes care Jeon, C., Hart, P. A., Li, L., Yang, Y., Chang, E., Bellin, M. D., Fisher, W. E., Fogel, E. L., Forsmark, C. E., Park, W. G., Van Den Eeden, S. K., Vege, S. S., Serrano, J., Whitcomb, D. C., Andersen, D. K., Conwell, D. L., Yadav, D., Goodarzi, M. O. 2022

  Abstract

  OBJECTIVE: Diabetes that arises from chronic pancreatitis (CP) is associated with increased morbidity and mortality. Methods to predict which patients with CP are at greatest risk for diabetes are urgently needed. We aimed to examine independent risk factors for diabetes in a large cohort of patients with CP.RESEARCH DESIGN AND METHODS: This cross-sectional study comprised 645 individuals with CP enrolled in the PROCEED study, of whom 276 had diabetes. We conducted univariable and multivariable regression analyses of potential risk factors for diabetes. Model performance was assessed by area under the receiver operating characteristic curve (AUROC) analysis, and accuracy was evaluated by cross validation. Exploratory analyses were stratified according to the timing of development of diabetes relative to the diagnosis of pancreatitis.RESULTS: Independent correlates of diabetes in CP included risk factors for type 2 diabetes (older age, overweight/obese status, male sex, non-White race, tobacco use) as well as pancreatic disease-related factors (history of acute pancreatitis complications, nonalcoholic etiology of CP, exocrine pancreatic dysfunction, pancreatic calcification, pancreatic atrophy) (AUROC 0.745). Type 2 diabetes risk factors were predominant for diabetes occurring before pancreatitis, and pancreatic disease-related factors were predominant for diabetes occurring after pancreatitis.CONCLUSIONS: Multiple factors are associated with diabetes in CP, including canonical risk factors for type 2 diabetes and features associated with pancreatitis severity. This study lays the groundwork for the future development of models integrating clinical and nonclinical data to identify patients with CP at risk for diabetes and identifies modifiable risk factors (obesity, smoking) on which to focus for diabetes prevention.

  View details for DOI 10.2337/dc22-1414

  View details for PubMedID 36382801

• Accurate Identification of Mucinous Pancreatic Cystic Lesions Using Small-Volume Analytes. The Journal of surgical research Caiazza, F., Conroy, P. C., Ivry, S. L., York, T., Lin, J., Hernandez, S., Hoffmann, T. J., Francis, S. S., Park, W. G., Yip-Schneider, M. T., Schmidt, C. M., Brand, R., Craik, C. S., Kirkwood, K. 2022

  Abstract

  INTRODUCTION: The accurate identification of mucinous pancreatic cystic lesions (PCLs) is paramount for cancer risk stratification. Cyst fluid carcinoembryonic antigen (CEA), the only routinely used test, requires high volumes and has low sensitivity. We aimed to compare the performance of two investigational small-volume biomarkers, glucose and the protease gastricsin, to CEA for PCL classification.METHODS: We obtained cyst fluid samples from 81 patients with pathologically confirmed PCLs from four institutions between 2003 and 2016. Gastricsin activity was measured using an internally quenched fluorescent substrate. Glucose levels were measured with a standard glucometer. CEA levels were obtained from the medical record. Models using Classification and Regression Trees were created to predict mucinous status. Model performance was evaluated using nested cross-validation.RESULTS: Gastricsin activity, CEA, and glucose levels from patients with mucinous (n=50) and nonmucinous (n=31) PCLs were analyzed. Area under the curve (AUC) was similar for individual classifiers (gastricsin volume normalized [GVN] 0.88; gastricsin protein concentration normalized [GPN] 0.95; glucose 0.83; CEA 0.84). The combination of two classifiers did not significantly improve AUC, with CEA+GVN (0.88) performing similarly to CEA+GPN (0.95), GVN+glucose (0.87), GPN+glucose (0.95), and CEA+glucose (0.84). The three-analyte combination performed similarly to single and dual classifiers (GPN+glucose+CEA AUC 0.95; GVN+glucose+CEA AUC 0.87). After multiple comparison corrections, there were no significant differences between the individual, dual, and triple classifiers.CONCLUSIONS: Gastricsin and glucose performed similarly to CEA and required <5% of the volume required for CEA; these classifiers may be useful in patients with limited cyst fluid. Future multicenter prospective studies are needed to validate and compare these novel small-volume biomarkers.

  View details for DOI 10.1016/j.jss.2022.08.014

  View details for PubMedID 36369049

• Prospective, Multi-Institutional, Real-Time Next-Generation Sequencing of Pancreatic Cyst Fluid Reveals Diverse Genomic Alterations that Improve the Clinical Management of Pancreatic Cysts. Gastroenterology Paniccia, A., Polanco, P. M., Boone, B. A., Wald, A. I., McGrath, K., Brand, R. E., Khalid, A., Kubiliun, N., O'Broin-Lennon, A. M., Park, W. G., Klapman, J., Tharian, B., Inamdar, S., Fasanella, K., Nasr, J., Chennat, J., Das, R., DeWitt, J., Easler, J. J., Bick, B., Singh, H., Fairley, K. J., Sarkaria, S., Sawas, T., Skef, W., Slivka, A., Tavakkoli, A., Thakkar, S., Kim, V., Vanderveldt, H. D., Richardson, A., Wallace, M. B., Brahmbhatt, B., Engels, M., Gabbert, C., Dugum, M., El-Dika, S., Bhat, Y., Ramrakhiani, S., Bakis, G., Rolshud, D., Millspaugh, G., Tielleman, T., Schmidt, C., Mansour, J., Marsh, W., Ongchin, M., Centeno, B., Monaco, S. E., Ohori, N. P., Lajara, S., Thompson, E. D., Hruban, R. H., Bell, P. D., Smith, K., Permuth, J. B., Vandenbussche, C., Ernst, W., Grupillo, M., Kaya, C., Hogg, M., He, J., Wolfgang, C. L., Lee, K. K., Zeh, H., Zureikat, A., Nikiforova, M. N., Singhi, A. D. 2022

  Abstract

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

  View details for DOI 10.1053/j.gastro.2022.09.028

  View details for PubMedID 36209796

• Development of a Clinical Screening Tool for Exocrine Pancreatic Insufficiency in Patients With Chronic Pancreatitis Othman, M., Kort, J., Yu, J., Singh, V., Forsmark, C., Lara, L., Park, W., Zhang, Z., Yadav, D. LIPPINCOTT WILLIAMS & WILKINS. 2022: S9

  View details for Web of Science ID 000897916000010

• Quantitative MRI of chronic pancreatitis: results from a multi-institutional prospective study, magnetic resonance imaging as a non-invasive method for assessment of pancreatic fibrosis (MINIMAP). Abdominal radiology (New York) Tirkes, T., Yadav, D., Conwell, D. L., Territo, P. R., Zhao, X., Persohn, S. A., Dasyam, A. K., Shah, Z. K., Venkatesh, S. K., Takahashi, N., Wachsman, A., Li, L., Li, Y., Pandol, S. J., Park, W. G., Vege, S. S., Hart, P. A., Topazian, M., Andersen, D. K., Fogel, E. L., Consortium for the Study of Chronic Pancreatitis, D. 2022

  Abstract

  PURPOSE: To determine if quantitative MRI techniques can be helpful to evaluate chronic pancreatitis (CP) in a setting of multi-institutional study.METHODS: This study included a subgroup of participants (n=101) enrolled in the Prospective Evaluation of Chronic Pancreatitis for Epidemiologic and Translational Studies (PROCEED) study (NCT03099850) from February 2019 to May 2021. MRI was performed on 1.5T using Siemens and GE scanners at seven clinical centers across the USA. Quantitative MRI parameters of the pancreas included T1 relaxation time, extracellular volume (ECV) fraction, apparent diffusion coefficient (ADC), and fat signal fraction. We report the diagnostic performance and mean values within the control (n=50) and CP (n=51) groups. The T1, ECV and fat signal fraction were combined to generate the quantitative MRI score (Q-MRI).RESULTS: There was significantly higher T1 relaxation time; mean 669ms (±171) vs. 593ms (±82) (p=0.006), ECV fraction; 40.2% (±14.7) vs. 30.3% (±11.9) (p<0.001), and pancreatic fat signal fraction; 12.2% (±5.5) vs. 8.2% (±4.4) (p<0.001) in the CP group compared to controls. The ADC was similar between groups (p=0.45). The AUCs for the T1, ECV, and pancreatic fat signal fraction were 0.62, 0.72, and 0.73, respectively. The composite Q-MRI score improved the diagnostic performance (cross-validated AUC: 0.76).CONCLUSION: Quantitative MR parameters evaluating the pancreatic parenchyma (T1, ECV fraction, and fat signal fraction) are helpful in the diagnosis of CP. A Q-MRI score that combines these three MR parameters improves diagnostic performance. Further studies are warranted with larger study populations including patients with acute and recurrent acute pancreatitis and longitudinal follow-ups.

  View details for DOI 10.1007/s00261-022-03654-7

  View details for PubMedID 36038644

• T1 signal intensity ratio of the pancreas as an imaging biomarker for the staging of chronic pancreatitis. Abdominal radiology (New York) Tirkes, T., Dasyam, A. K., Shah, Z. K., Fogel, E. L., Vege, S. S., Li, L., Li, S., Chang, S. T., Farinas, C. A., Grajo, J. R., Mawad, K., Takahashi, N., Venkatesh, S. K., Wachsman, A., Fisher, W. E., Forsmark, C. E., Hart, P. A., Pandol, S. J., Park, W. G., Van Den Eeden, S. K., Yang, Y., Topazian, M., Andersen, D. K., Serrano, J., Conwell, D. L., Yadav, D., Consortium for the Study of Chronic Pancreatitis, D. 2022

  Abstract

  PURPOSE: Our purpose was to validate the T1 SIR (T1 score) as an imaging biomarker for the staging of CP in a large, multi-institutional, prospective study.METHODS: The prospective study population included 820 participants enrolled in the PROCEED study from nine clinical centers between June 2017 and December 2021. A radiologist at each institution used a standardized method to measure the T1 signal intensity of the pancreas and the reference organs (spleen, paraspinal muscle, liver), which was used to derive respective T1 scores. Participants were stratified according to the seven mechanistic stages of chronic pancreatitis (MSCP 0-6) based on their clinical history, MRCP, and CT findings.RESULTS: The mean pancreas-to-spleen T1 score was 1.30 in participants with chronic abdominal pain, 1.22 in those with acute or recurrent acute pancreatitis, and 1.03 in definite CP. After adjusting for covariates, we observed a linear, progressive decline in the pancreas-to-spleen T1 score with increasing MSCP from 0 to 6. The mean pancreas-to-spleen T1 scores were 1.34 (MSCP 0), 1.27 (MSCP 1), 1.21 (MSCP 2), 1.16 (MSCP 3), 1.18 (MSCP 4), 1.12 (MSCP 5), and 1.05 (MSCP 6) (p<0.0001). The pancreas-to-liver and pancreas-to-muscle T1 scores showed less linear trends and wider confidence intervals.CONCLUSION: The T1 score calculated by SIR of the pancreas-to-spleen shows a negative linear correlation with the progression of chronic pancreatitis. It holds promise as a practical imaging biomarker in evaluating disease severity in clinical research and practice.

  View details for DOI 10.1007/s00261-022-03611-4

  View details for PubMedID 35857066

• Management of Incidentally Detected Gallbladder Polyps: Society of Radiologists in Ultrasound Consensus Conference Recommendations. Radiology Kamaya, A., Fung, C., Szpakowski, J., Fetzer, D. T., Walsh, A. J., Alimi, Y., Bingham, D. B., Corwin, M. T., Dahiya, N., Gabriel, H., Park, W. G., Porembka, M. R., Rodgers, S. K., Tublin, M. E., Yuan, X., Zhang, Y., Middleton, W. D. 2022: 213079

  Abstract

  Gallbladder polyps (also known as polypoid lesions of the gallbladder) are a common incidental finding. The vast majority of gallbladder polyps smaller than 10 mm are not true neoplastic polyps but are benign cholesterol polyps with no inherent risk of malignancy. In addition, recent studies have shown that the overall risk of gallbladder cancer is not increased in patients with small gallbladder polyps, calling into question the rationale for frequent and prolonged follow-up of these common lesions. In 2021, a Society of Radiologists in Ultrasound, or SRU, consensus conference was convened to provide recommendations for the management of incidentally detected gallbladder polyps at US. See also the editorial by Sidhu and Rafailidis in this issue.

  View details for DOI 10.1148/radiol.213079

  View details for PubMedID 35787200

• Design and Rationale for the Use of Magnetic Resonance Imaging Biomarkers to Predict Diabetes After Acute Pancreatitis in the Diabetes RElated to Acute Pancreatitis and Its Mechanisms Study: From the Type 1 Diabetes in Acute Pancreatitis Consortium. Pancreas Tirkes, T., Chinchilli, V. M., Bagci, U., Parker, J. G., Zhao, X., Dasyam, A. K., Feranec, N., Grajo, J. R., Shah, Z. K., Poullos, P. D., Spilseth, B., Zaheer, A., Xie, K. L., Wachsman, A. M., Campbell-Thompson, M., Conwell, D. L., Fogel, E. L., Forsmark, C. E., Hart, P. A., Pandol, S. J., Park, W. G., Pratley, R. E., Yazici, C., Laughlin, M. R., Andersen, D. K., Serrano, J., Bellin, M. D., Yadav, D., Type 1 Diabetes in Acute Pancreatitis Consortium (T1DAPC) 2022; 51 (6): 586-592

  Abstract

  ABSTRACT: This core component of the Diabetes RElated to Acute pancreatitis and its Mechanisms (DREAM) study will examine the hypothesis that advanced magnetic resonance imaging (MRI) techniques can reflect underlying pathophysiologic changes and provide imaging biomarkers that predict diabetes mellitus (DM) after acute pancreatitis (AP). A subset of participants in the DREAM study will enroll and undergo serial MRI examinations using a specific research protocol. The aim of the study is to differentiate at-risk individuals from those who remain euglycemic by identifying parenchymal features after AP. Performing longitudinal MRI will enable us to observe and understand the natural history of post-AP DM. We will compare MRI parameters obtained by interrogating tissue properties in euglycemic, prediabetic, and incident diabetes subjects and correlate them with metabolic, genetic, and immunological phenotypes. Differentiating imaging parameters will be combined to develop a quantitative composite risk score. This composite risk score will potentially have the ability to monitor the risk of DM in clinical practice or trials. We will use artificial intelligence, specifically deep learning, algorithms to optimize the predictive ability of MRI. In addition to the research MRI, the DREAM study will also correlate clinical computed tomography and MRI scans with DM development.

  View details for DOI 10.1097/MPA.0000000000002080

  View details for PubMedID 36206463

• Standard Operating Procedures for Biospecimen Collection, Processing, and Storage: From the Type 1 Diabetes in Acute Pancreatitis Consortium. Pancreas Wasserfall, C., Dyer, A., Speake, C., Andersen, D. K., Baab, K. T., Bellin, M. D., Broach, J. R., Campbell-Thompson, M., Chinchilli, V. M., Lee, P. J., Park, W. G., Pratley, R. E., Saloman, J. L., Sims, E. K., Tang, G., Yadav, D., Yazici, C., Conwell, D. L., Type 1 Diabetes in Acute Pancreatitis Consortium (T1DAPC) 2022; 51 (6): 593-597

  Abstract

  ABSTRACT: Differences in methods for biospecimen collection, processing, and storage can yield considerable variability and error. Therefore, best practices for standard operating procedures are critical for successful discovery, development, and validation of disease biomarkers. Here, we describe standard operating procedures developed for biospecimen collection during the DREAM (Diabetes RElated to Acute pancreatitis and its Mechanisms) Study within the Type 1 Diabetes in Acute Pancreatitis Consortium. Notably, these protocols were developed using an integrative process based on prior consortium experience and with input from working groups with expertise in immunology, pancreatitis, and diabetes. Publication and adoption consistent biospecimen protocols will inform future studies and allow for better comparisons across different metabolic research efforts.

  View details for DOI 10.1097/MPA.0000000000002077

  View details for PubMedID 36206464

• Rationale and Design for the Diabetes RElated to Acute Pancreatitis and Its Mechanisms Study: A Prospective Cohort Study From the Type 1 Diabetes in Acute Pancreatitis Consortium. Pancreas Hart, P. A., Papachristou, G. I., Park, W. G., Dyer, A., Chinchilli, V. M., Afghani, E., Akshintala, V. S., Andersen, D. K., Buxbaum, J. L., Conwell, D. L., Dungan, K. M., Easler, J. J., Fogel, E. L., Greenbaum, C. J., Kalyani, R. R., Korc, M., Kozarek, R., Laughlin, M. R., Lee, P. J., Maranki, J. L., Pandol, S. J., Phillips, A. E., Serrano, J., Singh, V. K., Speake, C., Tirkes, T., Toledo, F. G., Trikudanathan, G., Vege, S. S., Wang, M., Yazici, C., Zaheer, A., Forsmark, C. E., Bellin, M. D., Yadav, D., Type 1 Diabetes in Acute Pancreatitis Consortium (T1DAPC) 2022; 51 (6): 568-574

  Abstract

  ABSTRACT: Acute pancreatitis (AP) is a disease characterized by an acute inflammatory phase followed by a convalescent phase. Diabetes mellitus (DM) was historically felt to be a transient phenomenon related to acute inflammation; however, it is increasingly recognized as an important late and chronic complication. There are several challenges that have prevented precisely determining the incidence rate of DM after AP and understanding the underlying mechanisms. The DREAM (Diabetes RElated to Acute Pancreatitis and its Mechanisms) Study is a prospective cohort study designed to address these and other knowledge gaps to provide the evidence needed to screen for, prevent, and treat DM after AP. In the following article, we summarize literature regarding the epidemiology of DM after AP and provide the rationale and an overview of the DREAM study.

  View details for DOI 10.1097/MPA.0000000000002079

  View details for PubMedID 36206460

• Characterizing mechanism-based pain phenotypes in patients with chronic pancreatitis: a cross-sectional analysis of the PROspective Evaluation of Chronic Pancreatitis for EpidEmiologic and Translational StuDies. Pain Saloman, J. L., Conwell, D. L., Fogel, E., Vege, S. S., Li, L., Li, S., Andersen, D. K., Fisher, W. E., Forsmark, C. E., Hart, P. A., Pandol, S. J., Park, W. G., Phillips, A. E., Topazian, M., Van Den Eeden, S. K., Serrano, J., Yadav, D., Consortium for the Study of Chronic Pancreatitis, D. a. 2022

  Abstract

  ABSTRACT: Pain is common in chronic pancreatitis (CP) and profoundly reduces quality of life (QoL). Multiple underlying mechanisms contribute to a heterogenous pain experience and reduce efficacy of pain management. This study was designed to characterize the distribution of mechanism-based pain phenotypes in painful CP. The data analyzed were collected as part of the PROspective Evaluation of Chronic Pancreatitis for EpidEmiologic and Translational StuDies, an NCI/NIDDK-funded longitudinal study of the natural history of CP. The PROspective Evaluation of Chronic pancreatitis for EpidEmiologic and translational stuDies includes patient-reported outcome (PRO) measures of pain, medication use, global health, and QoL. Of subjects (N = 681) with CP, 80% experienced abdominal pain within the year before enrollment. Subjects who experienced pain in the week before enrollment (N = 391) completed PROMIS Neuropathic and Nociceptive Pain Quality instruments which were then used to classify them by pain type: 40% had nociceptive, 5% had neuropathic-like, and 32% had both types of pain. The prevalence of having both types of pain was higher among women and subjects with diabetes mellitus, whereas nociceptive-only pain was more prevalent among men and those with pancreatic duct stricture. Other factors, including pain medication use and healthcare utilization, did not differ between groups based on pain type. Subjects in the Both group had significantly worse health and QoL scores relative to those with nociceptive-only pain, suggesting that using psychosocial pain surveys may be useful for understanding pain subtypes in patients with CP. Additional research is needed to identify biochemical and biophysical signatures that may associate with and predict responses to mechanism-specific interventions.

  View details for DOI 10.1097/j.pain.0000000000002710

  View details for PubMedID 36149018

• ASSOCIATION OF CHRONIC PANCREATITIS PAIN FEATURES WITH PHYSICAL, MENTAL AND SOCIAL HEALTH Yadav, D., Askew, R. L., Palermo, T. M., Li, L., Andersen, D. K., Chen, M., Fisher, W. E., Fogel, E. L., Forsmark, C., Hart, P. A., Othman, M. O., Pandol, S. J., Park, W. G., Topazian, M., Van Den Eeden, S. K., Vege, S., Yang, Y., Serrano, J., Conwell, D. L. W B SAUNDERS CO-ELSEVIER INC. 2022: S195

  Abstract

  Pain is a cardinal symptom of chronic pancreatitis (CP). Using PROMIS measures, we characterized physical and mental health and symptom profiles of a well-defined cohort of individuals with CP and compared them to controls. Among patients with CP, we also examined associations between pain (intensity, temporal nature) and PROMIS symptom profiles and the prevalence of clinically significant psychological comorbidities.We analyzed baseline data in 488 CP patients and 254 controls enrolled in PROCEED, an ongoing longitudinal cohort study. Participants completed the PROMIS-Global Health, which captures global physical and mental health, and the PROMIS-29 profile which captures seven symptom domains. Self-reported pain was categorized by severity (none, mild-moderate, severe) and temporal nature (none, intermittent, constant). Demographic and clinical data were obtained from the PROCEED database.Pain was significantly associated with impairments in physical and mental health. Compared with participants with no pain, CP participants with severe pain (but not mild-moderate pain) had more decrements in each PROMIS domain in multivariable models (effect sizes: 2.54-7.03), and higher prevalence of clinically significant depression, anxiety, sleep disturbance and physical disability (odds ratios, ORs: 2.11-4.74). Similar results were noted for constant pain (but not intermittent pain) for PROMIS domains (effect sizes: 4.08-10.37), and clinically significant depression, anxiety, sleep disturbance and physical disability (ORs: 2.80-5.38).Severe and constant pain are major drivers for poor psychological and physical health in CP. Systematic evaluation and management of psychiatric comorbidities and sleep disturbance should be incorporated into routine management of patients with CP.gov number-NCT03099850.

  View details for Web of Science ID 000826446200467

  View details for PubMedID 36191836

• Pilot-phase PET/CT study targeting integrin alphavbeta6 in pancreatic cancer patients using the cystine-knot peptide-based 18F-FP-R01-MG-F2. European journal of nuclear medicine and molecular imaging Nakamoto, R., Ferri, V., Duan, H., Hatami, N., Goel, M., Rosenberg, J., Kimura, R., Wardak, M., Haywood, T., Kellow, R., Shen, B., Park, W., Iagaru, A., Gambhir, S. S. 2021

  Abstract

  PURPOSE: A novel cystine-knot peptide-based PET radiopharmaceutical, 18F-FP-R01-MG-F2 (knottin), was developed to selectively bind to human integrin alphavbeta6 which is overexpressed in pancreatic cancer. The purpose of this study is to evaluate the safety, biodistribution, dosimetry, and lesion uptake of 18F-FP-R01-MG-F2 in patients with pancreatic cancer.METHODS: Fifteen patients (6 men, 9 women) with histologically confirmed pancreatic cancer were prospectively enrolled and underwent knottin PET/CT between March 2017 and February 2021 (ClinicalTrials.gov Identifier NCT02683824). Vital signs and laboratory results were collected before and after the imaging scans. Maximum standardized uptake values (SUVmax) and mean SUV (SUVmean) were measured in 24 normal tissues and pancreatic cancer lesions for each patient. From the biodistribution data, the organ doses and whole-body effective dose were calculated using OLINDA/EXM software.RESULTS: There were no significant changes in vital signs or laboratory values that qualified as adverse events or serious adverse events. At 1h post-injection, areas of high 18F-FP-R01-MG-F2 uptake included the pituitary gland, stomach, duodenum, kidneys, and bladder (average SUVmean: 9.7-14.5). Intermediate uptake was found in the normal pancreas (average SUVmean: 4.5). Mild uptake was found in the lungs and liver (average SUVmean<1.0). The effective dose was calculated to be 2.538*10-2mSv/MBq. Knottin PET/CT detected all known pancreatic tumors in the 15 patients, although it did not detect small peri-pancreatic lymph nodes of less than 1cm in short diameter in two of three patients who had lymph node metastases at surgery. Knottin PET/CT detected distant metastases in the lungs (n=5), liver (n=4), and peritoneum (n=2), confirmed by biopsy and/or contrast-enhanced CT.CONCLUSION: 18F-FP-R01-MG-F2 is a safe PET radiopharmaceutical with an effective dose comparable to other diagnostic agents. Evaluation of the primary pancreatic cancer and distant metastases with 18F-FP-R01-MG-F2 PET is feasible, but larger studies are required to define the role of this approach.TRIAL REGISTRATION: NCT02683824.

  View details for DOI 10.1007/s00259-021-05595-7

  View details for PubMedID 34729628

• Novel circulating and tissue monocytes as well as macrophages in pancreatitis and recovery. Gastroenterology Manohar, M., Jones, E. K., Rubin, S. J., Subrahmanyam, P. B., Swaminathan, G., Mikhail, D., Bai, L., Singh, G., Wei, Y., Sharma, V., Siebert, J. C., Maecker, H. T., Husain, S. Z., Park, W. G., Pandol, S. J., Habtezion, A. 2021

  Abstract

  BACKGROUND AND AIMS: Acute pancreatitis (AP) is an inflammatory disease with mild to severe course that is associated with local and systemic complications and significant mortality. Uncovering inflammatory pathways that lead to progression and recovery will inform ways to monitor and/or develop effective therapies.METHODS: We performed single-cell mass cytometry (CyTOF) analysis to identify pancreatic and systemic inflammatory signals during mild (referred as AP), severe AP (SAP) and recovery using two independent experimental models and blood from AP and recurrent AP (RAP) patients. Flowcytometric validation of monocytes subsets identified by CyTOF analysis was performed independently.RESULTS: Ly6C+ inflammatory monocytes were most altered cells in the pancreas during experimental AP, recovery, and SAP. Deep profiling uncovered heterogeneity among pancreatic and blood monocytes and identified seven novel subsets during AP and recovery, and six monocyte subsets during SAP. Notably, a dynamic shift in pancreatic CD206+ macrophage population was observed during AP and recovery. Deeper profiling of the CD206+ macrophage identified seven novel subsets during AP, recovery and SAP. DE analysis of these novel monocyte and CD206+ macrophage subsets revealed significantly altered surface (CD44, CD54, CD115, CD140a, CD196, PDPN) and functional markers (IFN-gamma, IL-4, IL-22, LAP-TGF-beta, TNF-alpha, T-bet, RoRgammat) that were associated with recovery and SAP. Moreover, a targeted functional analysis further revealed distinct expression of pro- and anti-inflammatory cytokines by pancreatic CD206+ macrophage subsets as the disease either progressed or resolved. Similarly, we identified heterogeneity among circulating classical inflammatory monocytes (CD14+CD16-) and novel subsets in patients with AP and RAP.CONCLUSION: We identified several novel monocyte/macrophage subsets with unique phenotype and functional characteristics that are associated with AP, recovery, and SAP. Our findings highlight differential innate immune responses during AP progression and recovery that can be leveraged for future disease monitoring and targeting.

  View details for DOI 10.1053/j.gastro.2021.08.033

  View details for PubMedID 34450180

• Novel Circulating and Tissue Monocytes As Well As Macrophages in Pancreatitis and Recovery Manohar, M., Jones, E. K., Rubin, S. S., Subrahmanyam, P. B., Mikhail, D., Bai, L., Singh, G., Wei, Y., Sharma, V., Swaminathan, G., Siebert, J. C., Maecker, H. T., Park, W., Pandol, S. J., Husain, S., Habtezion, A. LIPPINCOTT WILLIAMS & WILKINS. 2021: 1079-1080

  View details for Web of Science ID 000706786400172

• Pilot Comparison of F-18-FP-R01-MG-F2 and F-18-FDG PET in Patients with Pancreatic Cancer Nakamoto, R., Duan, H., Ferri, V., Hatami, N., Goel, M., Kimura, R., Wardak, M., Haywood, T., Shen, B., Park, W., Iagaru, A. SOC NUCLEAR MEDICINE INC. 2021

  View details for Web of Science ID 000713713600182

• Biodistribution and Safety of F-18-FP-R(0)1-MG-F2 Knottin PET Tracer in Patients with Pancreatic Cancer Nakamoto, R., Duan, H., Ferri, V., Hatami, N., Goel, M., Kimura, R., Wardak, M., Haywood, T., Shen, B., Park, W., Iagaru, A. SOC NUCLEAR MEDICINE INC. 2021

  View details for Web of Science ID 000713713600186

• Development of a Cost Measure for Screening/Surveillance Colonoscopy for the Merit-Based Incentive Payment System. Gastroenterology Park, W. G., Sandhu, A., MaCurdy, T., collaborators of the Clinical Subcommittee for Screening/Surveillance Colonoscopy, U. A., Choradia, N., Schmitt, C., Koscheski, C., Lam, J., Bounds, S., Do, R., Feinberg, L., Vail, D., Nagavarapu, S., Bhattacharya, J. 2021

  View details for DOI 10.1053/j.gastro.2021.03.040

  View details for PubMedID 33798526

• 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. n., Banerjee, S. n. 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

• High Prevalence of Osteopathy in Chronic Pancreatitis: A Cross-sectional Analysis from the PROCEED Study. Clinical gastroenterology and hepatology : the official clinical practice journal of the American Gastroenterological Association Hart, P. A., Yadav, D., Li, L., Appana, S., Fisher, W., Fogel, E., Forsmark, C. E., Park, W. G., Pandol, S., Topazian, M. D., Van Den Eden, S. K., Vege, S. S., Bradley, D., Serrano, J., Conwell, D. L. 2021

  Abstract

  Chronic pancreatitis (CP) is associated with osteopathy (osteoporosis or osteopenia). However, existing literature is mostly limited to retrospective or administrative studies that have not clearly defined the prevalence and risk factors. Our aim was to identify patient- and disease-related associations with osteopathy in a prospective cohort study of CP.We studied 282 subjects with definitive CP enrolled in the PROCEED study who had a baseline dual-energy X-ray absorptiometry (DXA) scan. Osteopenia and osteoporosis were defined using the lowest T-scores. Clinical data were collected using standardized case report forms. Comparisons were performed with a multivariate logistic regression model with forward selection to identify risk factors for osteopathy.The majority of subjects had osteopathy on DXA scan (56.0%; 17.0% osteoporosis; 39.0% osteopenia). Subjects with osteopathy had a higher prevalence of traumatic (40.0% vs. 26.4%, p=0.02) and spontaneous fractures (3.9% vs. 0, p=0.04). On multivariate analysis, older age (OR 1.29 per 5 years, 95% CI 1.15-1.45), female sex (OR 3.08, 95% CI 1.75-5.43), white race (OR 2.68, 95% CI 1.20-6.01), and underweight BMI category (OR 7.40, 95% CI 1.56-34.99) were associated with higher probability of osteopathy. There were no significant associations between osteopathy and patient and disease-related features of CP.In the largest study of CP patients who underwent DXA screening, the majority had osteopathy. There are overlapping risk factors with osteopathy in the general population, but the high prevalence in men and younger women supports the need for future investigations into the mechanisms of bone loss in CP. ClinicalTrials.gov number, NCT03099850.

  View details for DOI 10.1016/j.cgh.2021.09.026

  View details for PubMedID 34571258

• 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

• 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

• Novel rigidizing overtube for colonoscope stabilization and loop prevention (with video). Gastrointestinal endoscopy Wei, M. T., Hwang, J. H., Watson, R. R., Park, W. n., Friedland, S. n. 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

• Prevalence, risk factors and clinical outcomes of COVID-19 in patients with a history of pancreatitis in Northern California. Gut Gubatan, J. n., Levitte, S. n., Patel, A. n., Balabanis, T. n., Sharma, A. n., Jones, E. n., Lee, B. n., Manohar, M. n., Swaminathan, G. n., Park, W. n., Habtezion, A. n. 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

• 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

• 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

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

• 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

• 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. 2018; 47 (10): 1244-1248

  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 DOI 10.1097/MPA.0000000000001169

  View details for PubMedID 30325864

  View details for PubMedCentralID PMC6432934

• 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. 2018; 47 (10): 1229-1238

  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 DOI 10.1097/MPA.0000000000001170

  View details for PubMedID 30325862

• 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 < .0001). With a threshold of ≤ 50 mg/dL, cyst fluid glucose was 92% sensitive, 87% specific, and 90% accurate in diagnosing mucinous pancreatic cysts. In comparison, cyst fluid carcinoembryonic antigen with a threshold of >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

• 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): 1489-1491

  View details for DOI 10.1016/j.cgh.2017.07.018

  View details for PubMedID 28923572

• 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 μL 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 μL 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/μL. 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

• 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. n., Brugge, W. R., Canto, M. I., Chang, K. J., Chari, S. T., DeWitt, J. n., Hwang, J. H., Khashab, M. A., Kim, K. n., Levy, M. J., McGrath, K. n., Park, W. G., Singhi, A. n., Stevens, T. n., Thompson, C. C., Topazian, M. D., Wallace, M. B., Wani, S. n., Waxman, I. n., Yadav, D. n., 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

• 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. n., Goenka, M. K., Ferreira, M. n., Gutierrez, S. C., Singh, V. K., Kamal, A. n., Gonzalez-Gonzalez, J. A., Pelaez-Luna, M. n., Gulla, A. n., Zarnescu, N. O., Triantafyllou, K. n., Barbu, S. T., Easler, J. n., Ocampo, C. n., Capurso, G. n., Archibugi, L. n., Cote, G. A., Lambiase, L. n., Kochhar, R. n., Chua, T. n., Tiwari, S. C., Nawaz, H. n., Park, W. G., de-Madaria, E. n., Lee, P. J., Wu, B. U., Greer, P. J., Dugum, M. n., Koutroumpakis, E. n., Akshintala, V. n., Gougol, A. n. 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

• 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 μL 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/μL. 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 α1 chain, but not α2 smooth muscle actin or transforming growth factor-β. 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

• 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

• 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

• 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 DOI 10.1097/MOG.0000000000000293

  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

• 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

• 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

• 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

• 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

• 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