Browsing by Author "Pandol, Stephen J."

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    Association of Chronic Pancreatitis Pain Features With Physical, Mental, and Social Health
    (Elsevier, 2023) Yadav, Dhiraj; Askew, Robert L.; Palermo, Tonya; Li, Liang; Andersen, Dana K.; Chen, Minxing; Fisher, William E.; Fogel, Evan L.; Forsmark, Christopher E.; Hart, Phil A.; Othman, Mohamed O.; Pandol, Stephen J.; Park, Walter G.; Topazian, Mark D.; Van Den Eeden, Stephen K.; Swaroop Vege, Santhi; Yang, Yunlong; Serrano, Jose; Conwell, Darwin L.; Consortium for the Study of Chronic Pancreatitis; Diabetes, and Pancreatic Cancer (CPDPC); Medicine, School of Medicine
    Background and aims: Pain is a cardinal symptom of chronic pancreatitis (CP). Using Patient-Reported Outcomes Measurement Information System (PROMIS) measures, we characterized physical and mental health and symptom profiles of a well-defined cohort of individuals with CP and compared them with control subjects. 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. Methods: We analyzed baseline data in 488 CP patients and 254 control subjects enrolled in PROCEED (Prospective Evaluation of Chronic Pancreatitis for Epidemiologic and Translational Studies), 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 7 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. Results: 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 had a higher prevalence of clinically significant depression, anxiety, sleep disturbance, and physical disability (odds ratios, 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 (odds ratios, 2.80-5.38). Conclusions: 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.
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    Association of Serum Endocannabinoid Levels with Pancreatitis and Pancreatitis-Related Pain
    (Mary Ann Liebert, 2025) Goodman, Marc T.; Lombardi, Christina; Torrens, Alexa; Bresee, Catherine; Saloman, Jami L.; Li, Liang; Yang, Yunlong; Fisher, William E.; Fogel, Evan L.; Forsmark, Christopher E.; Conwell, Darwin L.; Hart, Phil A.; Park, Walter G.; Topazian, Mark; Vege, Santhi S.; Van Den Eeden, Stephen K.; Bellin, Melena D.; Andersen, Dana K.; Serrano, Jose; Yadav, Dhiraj; Pandol, Stephen J.; Piomelli, Daniele; Consortium for the Study of Chronic Pancreatitis, Diabetes, and Pancreatic Cancer (CPDPC); Medicine, School of Medicine
    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.
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    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
    (Wolters Kluwer, 2023) Saloman, Jami L.; Conwell, Darwin L.; Fogel, Evan; Vege, Santhi Swaroop; Li, Liang; Li, Shuang; Andersen, Dana K.; Fisher, William E.; Forsmark, Christopher E.; Hart, Phil A.; Pandol, Stephen J.; Park, Walter G.; Evans Phillips, Anna; Topazian, Mark; Van Den Eeden, Stephen K.; Serrano, Jose; Yadav, Dhiraj; Consortium for the Study of Chronic Pancreatitis, Diabetes and Pancreatic Cancer; Medicine, School of Medicine
    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.
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    Circulating immune signatures across clinical stages of chronic pancreatitis: a pilot study
    (Wolters Kluwer, 2024) Hagn-Meincke, Rasmus; Hart, Phil A.; Andersen, Dana K.; Vege, Santhi S.; Fogel, Evan L.; Serrano, Jose; Bellin, Melena D.; Topazian, Mark D.; Conwell, Darwin L.; Li, Liang; Van Den Eeden, Stephen K.; Drewes, Asbjørn M.; Pandol, Stephen J.; Forsmark, Chris E.; Fisher, William E.; Yadav, Dhiraj; Olesen, Søren S.; Park, Walter G.; Consortium for the Study of Chronic Pancreatitis, Diabetes, and Pancreatic Cancer (CPDPC); Medicine, School of Medicine
    Objective: This pilot study seeks to identify serum immune signatures across clinical stages of patients with chronic pancreatitis (CP). Methods: 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. Results: 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. Conclusion: 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.
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    Clinical Trials in Pancreatitis: Opportunities and Challenges in the Design and Conduct of Patient-Focused Clinical Trials in Recurrent Acute and Chronic Pancreatitis: Summary of a National Institute of Diabetes and Digestive and Kidney Diseases Workshop
    (Wolters Kluwer, 2022) Hart, Phil A.; Andersen, Dana K.; Lyons, Erica; Cote, Gregory A.; Cruz-Monserrate, Zobeida; Dworkin, Robert H.; Elmunzer, B. Joseph; Fogel, Evan L.; Forsmark, Christopher E.; Gilron, Ian; Golden, Megan; Gozu, Aysegul; McNair, Lindsay; Pandol, Stephen J.; Perito, Emily R.; Evans Phillips, Anna; Rabbitts, Jennifer A.; Whitcomb, David C.; Windsor, John A.; Yadav, Dhiraj; Palermo, Tonya M.; Medicine, School of Medicine
    Recurrent acute pancreatitis and chronic pancreatitis represent high morbidity diseases, which are frequently associated with chronic abdominal pain, pancreatic insufficiencies, and reduced quality of life. Currently, there are no therapies to reverse or delay disease progression, and clinical trials are needed to investigate potential interventions that would address this important gap. This conference report provides details regarding information shared during a National Institute of Diabetes and Digestive and Kidney Diseases-sponsored workshop on Clinical Trials in Pancreatitis that sought to clearly delineate the current gaps and opportunities related to the design and conduct of patient-focused trials in recurrent acute pancreatitis and chronic pancreatitis. Key stakeholders including representatives from patient advocacy organizations, physician investigators (including clinical trialists), the US Food and Drug Administration, and the National Institutes of Health convened to discuss challenges and opportunities with particular emphasis on lessons learned from trials in participants with other painful conditions, as well as the value of incorporating the patient perspective throughout all stages of trials.
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    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
    (Wolters Kluwer, 2022) Tirkes, Temel; Chinchilli, Vernon M.; Bagci, Ulas; Parker, Jason G.; Zhao, Xuandong; Dasyam, Anil K.; Feranec, Nicholas; Grajo, Joseph R.; Shah, Zarine K.; Poullos, Peter D.; Spilseth, Benjamin; Zaheer, Atif; Xie, Karen L.; Wachsman, Ashley M.; Campbell-Thompson, Martha; Conwell, Darwin L.; Fogel, Evan L.; Forsmark, Christopher E.; Hart, Phil A.; Pandol, Stephen J.; Park, Walter G.; Pratley, Richard E.; Yazici, Cemal; Laughlin, Maren R.; Andersen, Dana K.; Serrano, Jose; Bellin, Melena D.; Yadav, Dhiraj; Type 1 Diabetes in Acute Pancreatitis Consortium (T1DAPC); Radiology and Imaging Sciences, School of Medicine
    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) following acute pancreatitis (AP). A subset of participants in the DREAM study will enroll and undergo serial MRI examinations using a specific research protocol. We aim to differentiate at-risk individuals from those who remain euglycemic by identifying parenchymal features following 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 computerized tomography and MRI scans with DM development.
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    Diabetes Mellitus and Obesity as Risk Factors for Pancreatic Cancer
    (Elsevier, 2018-04) Eibl, Guido; Cruz-Monserrate, Zobeida; Korc, Murray; Petrov, Maxim S.; Goodarzi, Mark O.; Fisher, William E.; Habtezion, Aida; Lugea, Aurelia; Pandol, Stephen J.; Hart, Phil A.; Andersen, Dana K.; Medicine, School of Medicine
    Pancreatic ductal adenocarcinoma (PDAC) is among the deadliest types of cancer. The worldwide estimates of its incidence and mortality in the general population are eight cases per 100,000 person-years and seven deaths per 100,000 person-years, and they are significantly higher in the United States than in the rest of the world. The incidence of this disease in the United States is more than 50,000 new cases in 2017. Indeed, total deaths due to PDAC are projected to increase dramatically to become the second leading cause of cancer-related deaths before 2030. Considering the failure to date to efficiently treat existing PDAC, increased effort should be undertaken to prevent this disease. A better understanding of the risk factors leading to PDAC development is of utmost importance to identify and formulate preventive strategies. Large epidemiologic and cohort studies have identified risk factors for the development of PDAC, including obesity and type 2 diabetes mellitus. This review highlights the current knowledge of obesity and type 2 diabetes as risk factors for PDAC development and progression, their interplay and underlying mechanisms, and the relation to diet. Research gaps and opportunities to address this deadly disease are also outlined.
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    Diagnosis of chronic pancreatitis using semi-quantitative MRI features of the pancreatic parenchyma: results from the multi-institutional MINIMAP study Temel Tirkes1,18, Dhiraj Yadav2
    (Springer, 2023) Tirkes, Temel; Yadav, Dhiraj; Conwell, Darwin L.; Territo, Paul R.; Zhao, Xuandong; Persohn, Scott A.; Dasyam, Anil K.; Shah, Zarine K.; Venkatesh, Sudhakar K.; Takahashi, Naoki; Wachsman, Ashley; Li, Liang; Li, Yan; Pandol, Stephen J.; Park, Walter G.; Swaroop Vege, Santhi; Hart, Phil A.; Topazian, Mark; Andersen, Dana K.; Fogel, Evan L.; Consortium for the Study of Chronic Pancreatitis, Diabetes, Pancreatic Cancer (CPDPC); Radiology and Imaging Sciences, School of Medicine
    Purpose: To determine the diagnostic performance of parenchymal MRI features differentiating CP from controls. Methods: 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). Results: 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. Conclusion: 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.
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    Distinct serum immune profiles define the spectrum of acute and chronic pancreatitis from the multi-center PROCEED study
    (AGA, 2023-07) Lee, Bomi; Jones, Elaina K.; Manohar, Murli; Li, Liang; Yadav, Dhiraj; Conwell, Darwin L.; Hart, Phil A.; Vege, Santhi Swaroop; Fogel, Evan L.; Serrano, Jose; Anderson, Dana; Bellin, Melena D.; Topazian, Mark D.; Van Den Eeden, Stephen K.; Pandol, Stephen J.; Forsmark, Chris E.; Fisher, William E.; Park, Walter G.; Husain, Sohail Z.; Habtezion, Aida; Medicine, School of Medicine
    Background & Aims Pancreatitis is a disease continuum, starting with acute pancreatitis (AP) and progressing in some cases 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 examined whether patient serum immune profiling could identify noninvasive biomarkers and provide mechanistic insight into the disease continuum of pancreatitis. Methods Using Olink immunoassay, we assessed the protein levels of 92 immune markers in serum samples from participants enrolled in the Prospective Evaluation of Chronic Pancreatitis for Epidemiologic and Translational Studies (PROCEED) study of the Chronic Pancreatitis, Diabetes, and Pancreatic Cancer (CPDPC) consortium. Samples (N = 231) were obtained from individuals without pancreatic disease (n = 56) and from those with chronic abdominal pain (CAP) (n = 24), AP (n = 38), RAP (n = 56), and CP (n = 57). Results A total of 33 immune markers differentiated the combined pancreatitis groups from controls. Immune markers related to interleukin (IL) 17 signaling distinguished CP from AP and RAP. Similarly, the serum level of IL17A and C-C motif chemokine ligand 20 differentiated CP from CAP, suggesting the involvement of T helper 17 cells in CP pathogenesis. The receiver operator characteristic curve with 2 immune markers (IL17A and sulfotransferase 1A1) could differentiate CP from CAP (optimistic area under the curve = 0.78). The 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. Conclusions 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 IL17 signaling in CP could provide insight into the immune mechanisms underlying disease progression.
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    Editorial: Innovations in Imaging for Early Diagnosis and Monitoring for Patients With Gastrointestinal Cancer
    (Frontiers Media, 2022-05-27) Pandol, Stephen J.; Tirkes, Temel; Li, Debiao; Radiology and Imaging Sciences, School of Medicine