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Chhoda A, McHenry N, Liyen Cartelle A, Bocchino R, Kahan T, Shah I, Zuberi SA, Anderson K, Freedman SD, Sheth SG. Impact of Ethno-racial Factors on Clinical Outcomes and Health Care Utilization in Chronic Pancreatitis. J Racial Ethn Health Disparities 2025; 12:1877-1886. [PMID: 38702491 DOI: 10.1007/s40615-024-02017-w] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/23/2023] [Revised: 04/17/2024] [Accepted: 04/28/2024] [Indexed: 05/06/2024]
Abstract
BACKGROUND Healthcare disparities adversely affect clinical outcomes in racial and ethnic minorities. Chronic pancreatitis (CP) is a complex disorder, and pressures for time and cost-containment may amplify the disparity for minorities in this condition. This study aimed to assess ethno-racial differences in the clinical outcomes of CP patients cared for at our institution. METHODS This is a study of CP patients with available ethno-racial information followed at our pancreas center. We reviewed their demographics, comorbidities, clinical outcomes, and resource utilization: pain, frequent flares (≥ 2/year), local complications, psychosocial variables, exocrine, and endocrine insufficiency, imaging, endoscopic procedures, and surgeries. The outcomes underwent logistic regression to ascertain association(s) with covariates and were expressed as odds ratio (95% confidence intervals). RESULTS Of the 445 CP patients, there were 23 Hispanics, 330 Non-Hispanic Whites, 47 Non-Hispanic Blacks, 16 Asian Americans, and 29 patients from Other/mixed races. Over a median follow-up of 7 years, no significant differences in the pain profile (p = 0.36), neuromodulator use (p = 0.94), and opioid use for intermittent (p = 0.34) and daily pain (p = 0.80) were observed. Frequent flares were associated with Hispanic ethnicity [2.98(1.20-7.36); p = 0.02], despite adjustment for smoking [2.21(1.11-4.41); p = 0.02)] and alcohol [1.88(1.06-3.35); p = 0.03]. Local complications (pseudocysts, mesenteric thrombosis, and biliary obstruction), exocrine and endocrine dysfunction, and healthcare resource utilization (cross-sectional imaging, endoscopic procedures, celiac blocks, or surgeries) were comparable across all ethno-racial groups. CONCLUSIONS Although no significant differences in clinical outcomes, and health resource utilization were noted across ethno-racial groups, Hispanic ethnicity had significant association with CP flares. This study calls for further investigation of an understudied minority population with CP.
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Affiliation(s)
- Ankit Chhoda
- Division of Gastroenterology, Beth Israel Deaconess Medical Center, Harvard Medical School, 330 Brookline Ave, Rabb 423, Boston, MA, 02215, USA
| | - Nicole McHenry
- Division of Gastroenterology, Beth Israel Deaconess Medical Center, Harvard Medical School, 330 Brookline Ave, Rabb 423, Boston, MA, 02215, USA
| | - Anabel Liyen Cartelle
- Division of Gastroenterology, Beth Israel Deaconess Medical Center, Harvard Medical School, 330 Brookline Ave, Rabb 423, Boston, MA, 02215, USA
| | - Rachel Bocchino
- Division of Gastroenterology, Beth Israel Deaconess Medical Center, Harvard Medical School, 330 Brookline Ave, Rabb 423, Boston, MA, 02215, USA
| | - Tamara Kahan
- Division of Gastroenterology, Beth Israel Deaconess Medical Center, Harvard Medical School, 330 Brookline Ave, Rabb 423, Boston, MA, 02215, USA
| | - Ishani Shah
- Division of Gastroenterology, University of Utah Hospital, Salt Lake City, USA
| | - Shaharyar A Zuberi
- Division of Gastroenterology, Beth Israel Deaconess Medical Center, Harvard Medical School, 330 Brookline Ave, Rabb 423, Boston, MA, 02215, USA
| | - Kelsey Anderson
- Division of Gastroenterology, Beth Israel Deaconess Medical Center, Harvard Medical School, 330 Brookline Ave, Rabb 423, Boston, MA, 02215, USA
| | - Steven D Freedman
- Division of Gastroenterology, Beth Israel Deaconess Medical Center, Harvard Medical School, 330 Brookline Ave, Rabb 423, Boston, MA, 02215, USA
| | - Sunil G Sheth
- Division of Gastroenterology, Beth Israel Deaconess Medical Center, Harvard Medical School, 330 Brookline Ave, Rabb 423, Boston, MA, 02215, USA.
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Kahan TF, Noriega M, Liyen-Cartelle A, Bocchino R, Anderson K, Zuberi SA, Shah I, Olivares M, Kelly J, Freedman SD, Rabinowitz L, Chhoda A, Sheth SG. Investigation of Geospatial Disparities in Chronic Pancreatitis Outcomes. Pancreas 2025; 54:e407-e413. [PMID: 39626183 DOI: 10.1097/mpa.0000000000002449] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/25/2024] [Accepted: 11/19/2024] [Indexed: 01/11/2025]
Abstract
OBJECTIVES Chronic pancreatitis (CP) is a fibro-inflammatory disorder characterized by abdominal pain and pancreatic insufficiency resulting in significant morbidity. This study evaluates the impact of geospatial parameters assessed using the Social Vulnerability Index (SVI) on CP outcomes. MATERIALS AND METHODS We retrospectively analyzed CP patients with available addresses followed at our pancreas center. We reviewed demographics, number of CP flares, local complications, healthcare-resource utilization, and outpatient opioid prescriptions. Regression analysis was performed to assess the association between outcomes and SVI (divided into 4 quartiles [I-IV; IV being most vulnerable]). RESULTS Among 324 CP patients followed over 8 years, we noted trends of higher dependence on governmental insurance or no insurance among patients in higher SVI quartiles (III/IV vs I/II) but no differences in demographics, comorbidities, or etiology of CP. Among patients in higher SVI quartiles, we noted significantly higher frequency of hospitalizations for CP flares and reduced opioid use. Rates of exocrine and endocrine pancreatic dysfunction and healthcare-resource utilization were similar across SVI quartiles. CONCLUSIONS Residence in the most vulnerable neighborhoods may be associated with reduced opioid use and more frequent CP flares, suggesting possible inadequate pain control in these patients. These findings should guide prospective investigation of the impact of geospatial social determinants of health in CP.
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Affiliation(s)
- Tamara F Kahan
- Department of Medicine, Beth Israel Deaconess Medical Center, Boston, MA
| | - Marco Noriega
- Division of Gastroenterology, Department of Medicine, Beth Israel Deaconess Medical Center, Boston, MA
| | | | - Rachel Bocchino
- Division of Gastroenterology, Department of Medicine, Beth Israel Deaconess Medical Center, Boston, MA
| | - Kelsey Anderson
- Department of Medicine, Beth Israel Deaconess Medical Center, Boston, MA
| | - Shaharyar A Zuberi
- Department of Medicine, Beth Israel Deaconess Medical Center, Boston, MA
| | - Ishani Shah
- University of Utah Hospital, University of Utah, Salt Lake City, UT
| | - Miriam Olivares
- Yale New-Haven Hospital, Yale New-Haven Health System, New Haven, CT
| | - Jill Kelly
- Yale New-Haven Hospital, Yale New-Haven Health System, New Haven, CT
| | - Steven D Freedman
- Division of Gastroenterology, Department of Medicine, Beth Israel Deaconess Medical Center, Boston, MA
| | - Loren Rabinowitz
- Division of Gastroenterology, Department of Medicine, Beth Israel Deaconess Medical Center, Boston, MA
| | - Ankit Chhoda
- Division of Gastroenterology, Department of Medicine, Beth Israel Deaconess Medical Center, Boston, MA
| | - Sunil G Sheth
- Division of Gastroenterology, Department of Medicine, Beth Israel Deaconess Medical Center, Boston, MA
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Grewal US, Chandar AK. Underuse of Pancreatic Enzyme Replacement Therapy Among Patients With Gastroenteropancreatic Neuroendocrine Neoplasms and Exocrine Pancreatic Insufficiency. Pancreas 2025; 54:e387-e388. [PMID: 40094514 DOI: 10.1097/mpa.0000000000002477] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/09/2024] [Accepted: 01/13/2025] [Indexed: 03/19/2025]
Affiliation(s)
- Udhayvir S Grewal
- Division of Hematology, Oncology, and Blood and Marrow Transplantation, University of Iowa Hospitals and Clinics
- Neuroendocrine Tumor Program, Holden Comprehensive Cancer Center, Iowa City, IA
| | - Apoorva K Chandar
- Division of Gastroenterology and Hepatology, University Hospitals Cleveland Medical Center, Cleveland, OH
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Choate R, Conwell DL, Hill RL, Adams AS, Yadav D, Yazici C. Health Inequities in Pancreatic Disorders in the Black/African American Community. J Racial Ethn Health Disparities 2025:10.1007/s40615-025-02402-z. [PMID: 40140238 DOI: 10.1007/s40615-025-02402-z] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/06/2024] [Revised: 03/12/2025] [Accepted: 03/14/2025] [Indexed: 03/28/2025]
Abstract
Pancreatic diseases, such as acute pancreatitis (AP), chronic pancreatitis (CP), and pancreatic ductal adenocarcinoma (PDAC), disproportionately affect Black/African American (AA) communities in the United States, leading to high incidence, prevalence, and mortality rates. This paper outlines disparities in pancreatic diseases among AAs and explores contributing factors beyond individual biology and behavior, emphasizing the role of social determinants of health (SDoH), including poor access to healthcare, lack of inclusion in research studies, and other crucial systemic and structural factors in historically marginalized AA communities. This review identifies barriers to pancreatic disease research in AAs and advocates for addressing healthcare disparities through community engagement, healthcare workforce diversity, partnerships with minority-serving healthcare facilities, and community-led initiatives targeting lifestyle modification. In conclusion, reducing pancreatic disease disparities in AA communities requires acknowledging systemic influences, engaging frontline communities, implementing innovative healthcare delivery models, addressing modifiable risk factors and structural inequities, and promoting inclusivity in research and healthcare.
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Affiliation(s)
- Radmila Choate
- Department of Epidemiology and Environmental Health, College of Public Health, University of Kentucky, 111 Washington Ave, Suite 215, Lexington, KY, 40536, USA.
| | - Darwin L Conwell
- Department of Internal Medicine, College of Medicine, University of Kentucky, Lexington, KY, USA
| | - Rachel L Hill
- Division of Biomedical Informatics, College of Medicine, University of Kentucky, Lexington, KY, USA
| | - Alyce Sophia Adams
- Department of Health Policy and Department of Epidemiology and Population Health, School of Medicine, Stanford University, Stanford, CA, USA
| | - Dhiraj Yadav
- Division of Gastroenterology & Hepatology, Medical Center, University of Pittsburgh, Pittsburgh, PA, USA
| | - Cemal Yazici
- Department of Medicine, Division of Gastroenterology and Hepatology, University of Illinois Chicago, Chicago, IL, USA
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Kim YE, Yu MH, Nam CM, Kang ES. Effects of Pancreatitis and Type 2 Diabetes Mellitus on the Development of Pancreatic Cancer: A Nationwide Nested Case-Control Study. Diabetes Metab J 2025; 49:252-263. [PMID: 40073907 PMCID: PMC11960203 DOI: 10.4093/dmj.2024.0277] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/30/2024] [Accepted: 10/23/2024] [Indexed: 03/14/2025] Open
Abstract
BACKGRUOUND Despite diabetes mellitus (DM) and pancreatitis being known risk factors for pancreatic cancer, patients with these conditions are not included in pancreatic cancer screening due to the low incidence of pancreatic cancer in these populations. This study aimed to determine the high-risk subgroup of patients with diabetes and pancreatitis that would benefit from pancreatic cancer screening. METHODS A nested case-control study was conducted using data from the National Health Information Database of the Korean National Health Insurance Service. Patients were categorized into the following groups: type 2 diabetes mellitus only (T2DM-only), pancreatitis-only (PAN-only), T2DM followed by pancreatitis (T2DM-PAN), post-pancreatitis diabetes mellitus (PPDM), and no diabetes and no pancreatitis (NDNP). Conditional logistic regression was used to determine significant associations of each group with pancreatic cancer development risk. RESULTS The risk of pancreatic cancer was significantly higher in the T2DM-PAN (adjusted odds ratio [AOR], 4.96; 95% confidence interval [CI], 4.48 to 5.49) and PPDM (AOR, 4.71; 95% CI, 4.12 to 5.37) groups than in the NDNP group. Compared to patients in the NDNP group, those with PPDM using insulin had a 17-fold increased risk (AOR, 16.72; 95% CI, 9.50 to 29.43), and individuals with PPDM who had diabetes for less than 3 years had a more than 8-fold increased risk of pancreatic cancer (AOR, 8.83; 95% CI, 5.99 to 13.01). CONCLUSION In patients with post-pancreatitis diabetes, insulin use or shorter duration of diabetes was associated with a higher risk of pancreatic cancer, suggesting that patients in these subgroups may require close monitoring for pancreatic cancer development.
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Affiliation(s)
- Young-eun Kim
- Division of Endocrinology and Metabolism, Department of Internal Medicine, Yonsei University College of Medicine, Seoul, Korea
| | - Min Heui Yu
- SENTINEL Team, Division of Endocrinology, Department of Internal Medicine, Yonsei University College of Medicine, Seoul, Korea
| | - Chung Mo Nam
- Department of Preventive Medicine, Yonsei University College of Medicine, Seoul, Korea
- Institute of Health Services Research, Yonsei University College of Medicine, Seoul, Korea
| | - Eun Seok Kang
- Division of Endocrinology and Metabolism, Department of Internal Medicine, Yonsei University College of Medicine, Seoul, Korea
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Dunbar EK, Greer PJ, Saloman JL, Albers KM, Yadav D, Whitcomb DC. Genetics of constant and severe pain in the NAPS2 cohort of recurrent acute and chronic pancreatitis patients. THE JOURNAL OF PAIN 2025; 27:104754. [PMID: 39674387 DOI: 10.1016/j.jpain.2024.104754] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Subscribe] [Scholar Register] [Received: 06/04/2024] [Revised: 10/08/2024] [Accepted: 12/03/2024] [Indexed: 12/16/2024]
Abstract
Recurrent acute and chronic pancreatitis (RAP, CP) are complex, progressive inflammatory diseases with variable pain experiences impacting patient function and quality of life. The genetic variants and pain pathways in patients contributing to most severe pain experiences are unknown. We used previously genotyped individuals with RAP/CP from the North American Pancreatitis Study II (NAPS2) of European Ancestry for nested genome-wide associated study (GWAS) for pain-severity, chronicity, or both. Lead variants from GWAS were determined using FUMA. Loci with p<1e-5 were identified for post-hoc candidate identification. Transcriptome-wide association studies (TWAS) identified loci in cis and trans to the lead variants. Serum from phenotyped individuals with CP from the PROspective Evaluation of Chronic Pancreatitis for EpidEmiologic and Translational StuDies (PROCEED) was assessed for BDNF levels using Meso Scale Discovery Immunoassay. We identified four pain systems defined by candidate genes: 1) Pancreas-associated injury/stress mitigation genes include: REG gene cluster, CTRC, NEURL3 and HSF22. 2) Neural development and axon guidance tracing genes include: SNPO, RGMA, MAML1 and DOK6 (part of the RET complex). 3) Genes linked to psychiatric stress disorders include TMEM65, RBFOX1, and ZNF385D. 4) Genes in the dorsal horn pain-modulating BDNF/neuropathic pathway included SYNPR, NTF3 and RBFOX1. In an independent cohort BDNF was significantly elevated in patients with constant-severe pain. Extension and expansion of this exploratory study may identify pathway- and mechanism-dependent targets for individualized pain treatments in CP patients. PERSPECTIVE: Pain is the most distressing and debilitating feature of chronic pancreatitis. Yet many patients with chronic pancreatitis have little or no pain. The North American Pancreatitis Study II (NAPS2) includes over 1250 pancreatitis patients of all progressive stages with all clinical and phenotypic characteristics carefully recorded. Pain did not correlate well with disease stage, inflammation, fibrosis or other features. Here we spit the patients into groups with the most severe pain and/or chronic pain syndromes and compared them genetically with patients reporting mild or minimal pain. Although some genetic variants associated with pain were expressed in cells (1) of the pancreas, most genetic variants were linked to genes expressed in the nervous system cells associated with (2) neural development and axon guidance (as needed for the descending inhibition pathway), (3) psychiatric stress disorders, and (4) cells regulating sensory nerves associated with BDNF and neuropathic pain. Similar and overlapping genetic variants in systems 2 -4 are also seen in pain syndromes form other organs. The implications for treating pancreatic pain are great in that we can no longer focus on just the pancreas. Furthermore, new treatments designed for pain disorders in other tissues may be effective in some patient with pain syndromes from the pancreas. Further research is needed to replicate and extend these observations so that new, genetics-guided rational treatments can be developed and delivered.
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Affiliation(s)
- Ellyn K Dunbar
- Department of Medicine, University of Pittsburgh, Pittsburgh, PA, USA; Department of Human Genetics, Graduate School of Public Health, University of Pittsburgh, Pittsburgh, PA, USA
| | - Phil J Greer
- Department of Medicine, University of Pittsburgh, Pittsburgh, PA, USA
| | - Jami L Saloman
- Department of Medicine, University of Pittsburgh, Pittsburgh, PA, USA; Department of Neurobiology, Pittsburgh Center for Pain Research, University of Pittsburgh, Pittsburgh, PA, USA; Pittsburgh Center for Pain Research, University of Pittsburgh, Pittsburgh, PA, USA
| | - Kathryn M Albers
- Department of Medicine, University of Pittsburgh, Pittsburgh, PA, USA; Department of Neurobiology, Pittsburgh Center for Pain Research, University of Pittsburgh, Pittsburgh, PA, USA; Pittsburgh Center for Pain Research, University of Pittsburgh, Pittsburgh, PA, USA
| | - Dhiraj Yadav
- Department of Medicine, University of Pittsburgh, Pittsburgh, PA, USA
| | - David C Whitcomb
- Department of Medicine, University of Pittsburgh, Pittsburgh, PA, USA; Department of Human Genetics, Graduate School of Public Health, University of Pittsburgh, Pittsburgh, PA, USA; Department of Neurobiology, Pittsburgh Center for Pain Research, University of Pittsburgh, Pittsburgh, PA, USA; Department of Cell Biology & Molecular Physiology, University of Pittsburgh, Pittsburgh, PA, USA.
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Park SK, Conwell DL, Hart PA, Li S, Stello K, Fogel EL, Fisher WE, Forsmark CE, Pandol SJ, Park WG, Topazian M, Serrano J, Vege SS, Van Den Eeden SK, Li L, Yadav D, Saloman JL. Evaluation of Chronic Pancreatitis Prognosis Score in an American Cohort. Clin Transl Gastroenterol 2024; 15:e00758. [PMID: 39137098 PMCID: PMC11596705 DOI: 10.14309/ctg.0000000000000758] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/03/2024] [Accepted: 07/31/2024] [Indexed: 08/15/2024] Open
Abstract
INTRODUCTION 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. METHODS The Chronic Pancreatitis, Diabetes, and Pancreatic Cancer consortium provided data and serum from subjects with chronic pancreatitis (N = 279). COPPS was calculated with baseline data and stratified by severity (low, moderate, and high). Primary endpoints included number and duration of hospitalizations during 12-month follow-up. RESULTS 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 hospitalizations. 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. DISCUSSION 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 PROspective Evaluation of Chronic Pancreatitis for EpidEmiologic and Translational StuDies 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.
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Affiliation(s)
- Soo Kyung Park
- Department of Biostatistics, MD Anderson Cancer Center, Houston, Texas, USA
| | - Darwin L. Conwell
- Department of Internal Medicine, University of Kentucky College of Medicine, Lexington, Kentucky, USA
| | - Phil A. Hart
- Division of Gastroenterology, Hepatology and Nutrition, The Ohio State University Wexner Medical Center, Columbus, Ohio, USA
| | - Shuang Li
- Department of Biostatistics, MD Anderson Cancer Center, Houston, Texas, USA
| | - Kimberly Stello
- Division of Gastroenterology, Hepatology and Nutrition, Department of Medicine, University of Pittsburgh, Pittsburgh, Pennsylvania, USA
| | - Evan L. Fogel
- Digestive and Liver Disorders, Department of Medicine, Indiana University, Indianapolis, Indiana, USA
| | - William E. Fisher
- Department of Surgery, Baylor College of Medicine, Houston, Texas, USA
| | - Christopher E. Forsmark
- Division of Gastroenterology, Hepatology and Nutrition, University of Florida, Gainesville, Florida, USA
| | - Stephen J. Pandol
- Division of Digestive and Livers Diseases, Cedars-Sinai Medical Center, Los Angeles, California, USA
| | - Walter G. Park
- Division of Gastroenterology and Hepatology, Department of Medicine, Stanford University, Stanford, California, USA
| | - Mark Topazian
- Division of Gastroenterology and Hepatology, Mayo Clinic, Rochester, Minnesota, USA
| | - Jose Serrano
- Division of Digestive Diseases and Nutrition, NIDDK, NIH, Bethesda, Maryland, USA
| | - Santhi Swaroop Vege
- Division of Gastroenterology and Hepatology, Mayo Clinic, Rochester, Minnesota, USA
| | | | - Liang Li
- Department of Biostatistics, MD Anderson Cancer Center, Houston, Texas, USA
| | - Dhiraj Yadav
- Division of Gastroenterology, Hepatology and Nutrition, Department of Medicine, University of Pittsburgh, Pittsburgh, Pennsylvania, USA
| | - Jami L. Saloman
- Division of Gastroenterology, Hepatology and Nutrition, Department of Medicine, University of Pittsburgh, Pittsburgh, Pennsylvania, USA
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Choate R, Bradley D, Conwell D, Yazici C. Healthcare disparities in pancreatitis: knowledge gaps and next steps. Curr Opin Gastroenterol 2024; 40:422-430. [PMID: 38967932 DOI: 10.1097/mog.0000000000001058] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 07/06/2024]
Abstract
PURPOSE OF REVIEW This review examines current research on healthcare disparities in pancreatitis, identifies knowledge gaps, and proposes strategies to develop targeted multilevel interventions to address inequities in pancreatitis care. RECENT FINDINGS Current literature has identified patient, disease, and healthcare-level factors contributing to disparities in risk factors and health outcomes of pancreatitis. Moreover, social structures, economic systems, social vulnerability, and policy significantly influence the pancreatitis care continuum. SUMMARY Understanding the root causes of health inequities is critical to developing effective approaches for the prevention, early detection, and management of pancreatitis.
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Affiliation(s)
- Radmila Choate
- University of Kentucky College of Public Health, Lexington, Kentucky
| | | | - Darwin Conwell
- University of Kentucky College of Medicine, Lexington, Kentucky
| | - Cemal Yazici
- University of Illinois Chicago, Chicago, Illinois, USA
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Sarraf P, Agrawal R, Alrashdan H, Agarwal M, Boulay B, Mutlu ER, Tussing-Humphreys L, Conwell D, Kim S, Layden BT, Yazici C. Racial and Ethnic Minorities With Acute Pancreatitis Live in Neighborhoods With Higher Social Vulnerability Scores. Pancreas 2024; 53:e317-e322. [PMID: 38416846 PMCID: PMC10959690 DOI: 10.1097/mpa.0000000000002308] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 03/01/2024]
Abstract
OBJECTIVES The primary objective was to determine differences in Social Vulnerability Index (SVI) scores among minorities (African-Americans and Hispanics) with acute pancreatitis (AP) compared with non-Hispanic whites (NHWs) with AP. The secondary objectives were to determine differences in diet, sulfidogenic bacteria gene copy numbers (gcn) and hydrogen sulfide (H2S) levels between the 2 groups. MATERIALS AND METHODS Patients with AP were enrolled during hospitalization (n = 54). Patient residential addresses were geocoded, and the Centers for Disease Control and Prevention's SVI scores were appended. Dietary intake and serum H2S levels were determined. Microbial DNAs were isolated from stool, and gcn of sulfidogenic bacteria were determined. RESULTS Minorities had higher SVI scores compared with NHWs ( P = 0.006). They also had lower consumption of beneficial nutrients such as omega-3 fatty acids [stearidonic ( P = 0.019), and eicosapentaenoic acid ( P = 0.042)], vitamin D ( P = 0.025), and protein from seafood ( P = 0.031). Lastly, minorities had higher pan-dissimilatory sulfite reductase A ( pan-dsrA ) gcn ( P = 0.033) but no significant differences in H2S levels ( P = 0.226). CONCLUSION Minorities with AP have higher SVI compared with NHWs with AP. Higher SVI scores, lower consumption of beneficial nutrients, and increased gcn of pan-dsrA in minorities with AP suggest that neighborhood vulnerability could be contributing to AP inequities.
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Affiliation(s)
- Paya Sarraf
- Division of Internal Medicine, University of Illinois Chicago, Chicago, Illinois
| | - Rohit Agrawal
- Division of Gastroenterology and Hepatology, Department of Medicine, University of Illinois Chicago, Chicago, Illinois
| | - Haya Alrashdan
- Division of Gastroenterology and Hepatology, Department of Medicine, University of Illinois Chicago, Chicago, Illinois
| | - Mitali Agarwal
- Department of Digestive Health, Orlando Regional Medical Center, Orlando, FL
| | - Brian Boulay
- Division of Gastroenterology and Hepatology, Department of Medicine, University of Illinois Chicago, Chicago, Illinois
| | - Ece R. Mutlu
- Division of Gastroenterology and Hepatology, Department of Medicine, University of Illinois Chicago, Chicago, Illinois
| | | | - Darwin Conwell
- Division of Gastroenterology, Department of Medicine, University of Kentucky, Lexington, Kentucky
| | - Sage Kim
- Department of Health Policy and Administration, University of Illinois Chicago School of Public Health, Chicago, Illinois
| | - Brian T. Layden
- Division of Endocrinology, Diabetes, and Metabolism, Department of Medicine, University of Illinois Chicago, Chicago, Illinois
- Jesse Brown VA Medical Center, Chicago, IL, USA
| | - Cemal Yazici
- Division of Gastroenterology and Hepatology, Department of Medicine, University of Illinois Chicago, Chicago, Illinois
- Jesse Brown VA Medical Center, Chicago, IL, USA
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10
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Niu C, Zhang J, Zhu K, Liu H, Okolo PI. The hidden dangers of chronic pancreatitis in pregnancy: Evidence from a large-scale population study. Dig Liver Dis 2023; 55:1712-1718. [PMID: 37474413 DOI: 10.1016/j.dld.2023.07.001] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/18/2023] [Revised: 06/14/2023] [Accepted: 07/03/2023] [Indexed: 07/22/2023]
Abstract
BACKGROUND Chronic pancreatitis is a debilitating condition that can affect women of childbearing age, and its impact on maternal and perinatal outcomes is poorly understood. AIMS Our findings aim to help healthcare providers counsel pregnant women with chronic pancreatitis and make informed clinical decisions. METHODS In this study, hospital discharge records from the National Inpatient Sample database between 2009 and 2019 were retrospectively analyzed to investigate maternal primary outcomes and primary perinatal outcomes. RESULTS The study findings suggest an association between chronic pancreatitis and elevated rates of gestational diabetes (AOR 1.63, 95% CI 1.19-2.23) and gestational hypertensive complications(AOR 2.48, 95% CI 1.87-3.29). Pregnancies among women with chronic pancreatitis showed an increased likelihood of preterm labor (AOR 3.10, 95% CI 2.40-4.00) and small for gestational age (AOR 2.40, 95% CI 1.35-3.08). Furthermore, it appears that patients with alcohol-induced chronic pancreatitis present a considerably higher risk of fetal death (OR 17.15, 95% CI 2.29-128.26). The study also revealed that those chronic pancreatitis patients with a history of chronic renal failure could be more prone to developing gestational hypertensive complications (OR 20.09, 95%CI 2.07-194.93). Moreover, associations were observed between chronic pancreatitis pregnancies and lengthier hospital stays as well as elevated hospital costs. CONCLUSIONS Our research has uncovered a heightened risk of complications associated with chronic pancreatitis for mothers and fetuses. The implications of our findings are critical for healthcare professionals, particularly those involved in preconception counseling.
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Affiliation(s)
- Chengu Niu
- Internal Medicine Residency Program, Rochester General Hospital, 1425 Portland Avenue, Rochester, NY 14621, USA.
| | - Jing Zhang
- Harbin Medical University, Harbin 150081, China
| | - Kaiwen Zhu
- Internal Medicine Residency Program, Rochester General Hospital, 1425 Portland Avenue, Rochester, NY 14621, USA
| | - Hongli Liu
- Internal Medicine Residency Program, Rochester General Hospital, 1425 Portland Avenue, Rochester, NY 14621, USA
| | - Patrick I Okolo
- Division of Gastroenterology, Rochester General Hospital, Rochester, NY 14621, USA
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11
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de Rijk FEM, van Veldhuisen CL, Kempeneers MA, Issa Y, Boermeester MA, Besselink MG, Kelder JC, van Santvoort HC, de Jonge PJF, Verdonk RC, Bruno MJ. Quality of Life in Patients With Definite Chronic Pancreatitis: A Nationwide Longitudinal Cohort Study. Am J Gastroenterol 2023; 118:1428-1438. [PMID: 36996496 DOI: 10.14309/ajg.0000000000002266] [Citation(s) in RCA: 11] [Impact Index Per Article: 5.5] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/18/2022] [Accepted: 03/17/2023] [Indexed: 04/01/2023]
Abstract
INTRODUCTION Chronic pancreatitis (CP) has a negative impact on quality of life (QoL). Because CP is a chronic condition, multiple assessments of QoL are required to obtain a thorough understanding of its impact on patients. Such studies are currently lacking. This study aims to gain insight into the course and predictors of QoL in patients with CP using prospective longitudinal data from a large cohort of patients. METHODS Post hoc analysis of consecutive patients with definite CP registered in a prospective database between 2011 and 2019 in the Netherlands. Patient and disease characteristics, nutritional status, pain severity, medication usage, pancreatic function, and pancreatic interventions were assessed from medical records and through standard follow-up questionnaires. The physical and mental component summary scales of the Short-Form 36 were used to assess physical and mental QoL at baseline and during follow-up. The course of both physical and mental QoL and their associated factors were longitudinally assessed by using generalized linear mixed models. RESULTS Overall, 1,165 patients with definite CP were included for this analysis. During 10-year follow-up, generalized linear mixed model analyses revealed improvements in both physical (41.6-45.2, P < 0.001) and mental (45.9-46.6, P = 0.047) QoL. Younger age, current alcohol consumption, employment, no need for dietetic consultation, no steatorrhea, lower Izbicki pain score, and pain coping mechanism were positively associated with physical QoL ( P < 0.05). For mental QoL, a positive correlation was found between employment, nonalcoholic CP, no need for dietetic consultation, no steatorrhea, lower Izbicki pain score, pain coping mechanism, and surgical treatment. No association was observed between disease duration and longitudinal QoL per patient. DISCUSSION This nationwide study provides insight into the dynamics of physical and mental QoL in patients with CP over time. Important and potentially influenceable factors to improve QoL are nutritional status, exocrine pancreatic function, employment status, and patients' coping strategy.
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Affiliation(s)
- Florence E M de Rijk
- Department of Gastroenterology and Hepatology, Erasmus University Medical Center, Rotterdam, the Netherlands
- Department of Research and Development, St. Antonius Hospital, Nieuwegein, the Netherlands
| | - Charlotte L van Veldhuisen
- Department of Research and Development, St. Antonius Hospital, Nieuwegein, the Netherlands
- Amsterdam UMC, location University of Amsterdam, Department of Surgery, Amsterdam, the Netherlands
- Amsterdam Gastroenterology Endocrinology Metabolism, Amsterdam, the Netherlands
| | - Marinus A Kempeneers
- Amsterdam UMC, location University of Amsterdam, Department of Surgery, Amsterdam, the Netherlands
- Amsterdam Gastroenterology Endocrinology Metabolism, Amsterdam, the Netherlands
| | - Yama Issa
- Amsterdam UMC, location University of Amsterdam, Department of Surgery, Amsterdam, the Netherlands
- Amsterdam Gastroenterology Endocrinology Metabolism, Amsterdam, the Netherlands
| | - Marja A Boermeester
- Amsterdam UMC, location University of Amsterdam, Department of Surgery, Amsterdam, the Netherlands
- Amsterdam Gastroenterology Endocrinology Metabolism, Amsterdam, the Netherlands
| | - Marc G Besselink
- Amsterdam UMC, location University of Amsterdam, Department of Surgery, Amsterdam, the Netherlands
- Amsterdam Gastroenterology Endocrinology Metabolism, Amsterdam, the Netherlands
| | - Johannes C Kelder
- Department of statistics, St. Antonius Hospital, Nieuwegein, the Netherlands
| | - Hjalmar C van Santvoort
- Department of Surgery, St. Antonius Hospital, Nieuwegein, the Netherlands
- Department of Surgery, University Medical Center Utrecht, Utrecht, the Netherlands
| | - Pieter Jan F de Jonge
- Department of Gastroenterology and Hepatology, Erasmus University Medical Center, Rotterdam, the Netherlands
| | - Robert C Verdonk
- Department of Gastroenterology and Hepatology, St. Antonius Hospital, Nieuwegein, the Netherlands
| | - Marco J Bruno
- Department of Gastroenterology and Hepatology, Erasmus University Medical Center, Rotterdam, the Netherlands
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12
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Lu M, Sun Y, Feldman R, Saul M, Althouse A, Arteel G, Yadav D. Coexistent alcohol-related cirrhosis and chronic pancreatitis have a comparable phenotype to either disease alone: A comparative retrospective analysis. World J Hepatol 2023; 15:431-440. [PMID: 37034239 PMCID: PMC10075006 DOI: 10.4254/wjh.v15.i3.431] [Citation(s) in RCA: 2] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/07/2022] [Revised: 02/03/2023] [Accepted: 03/09/2023] [Indexed: 04/11/2023] Open
Abstract
BACKGROUND Alcohol use disorder is a prevalent disease in the United States. It is a well-demonstrated cause of recurrent and long-standing liver and pancreatic injury which can lead to alcohol-related liver cirrhosis (ALC) and chronic pancreatitis (ACP). ALC and ACP are associated with significant healthcare utilization, cost burden, and mortality. The prevalence of coexistent disease (CD) ranges widely in the literature and the intersection between ALC and ACP is inconsistently characterized. As such, the clinical profile of coexistent ALC and ACP remains poorly understood. We hypothesized that patients with CD have a worse phenotype when compared to single organ disease.
AIM To compare the clinical profile and outcomes of patients with CD from those with ALC or ACP Only.
METHODS In this retrospective comparative analysis, we reviewed international classification of disease 9/10 codes and electronic health records of adult patients with verified ALC Only (n = 135), ACP Only (n = 87), and CD (n = 133) who received care at UPMC Presbyterian-Shadyside Hospital. ALC was defined by histology, imaging or clinical evidence of cirrhosis or hepatic decompensation. ACP was defined by imaging findings of pancreatic calcifications, moderate-severe pancreatic duct dilatation, irregularity or atrophy. We compared demographics, pertinent clinical variables, healthcare utilization, and mortality for patients with CD with those who had single organ disease.
RESULTS Compared to CD or ACP Only, patients with ALC Only were more likely to be older, Caucasian, have higher body mass index, and Hepatitis B or C infection. CD patients (vs ALC Only) were less likely to have imaging evidence of cirrhosis and portal hypertension despite possessing similar MELD-Na and Child C scores at the most recent contact. CD patients (vs ACP Only) were less likely to have acute or recurrent acute pancreatitis, diabetes mellitus, insulin use, oral pancreatic enzyme therapy, and need for endoscopic therapy or pancreatic surgery. The number of hospitalizations in patients with CD were similar to ACP Only but significantly higher than ALC Only. The overall mortality in patients with CD was similar to ALC Only but trended to be higher than ACP Only (P = 0.10).
CONCLUSION CD does not have a worse phenotype compared with single organ disease. The dominant phenotype in CD is similar to ALC Only which should be the focus in longitudinal follow-up.
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Affiliation(s)
- Michael Lu
- Department of Medicine, University of Pittsburgh Medical Center, Pittsburgh, PA 15213, United States
| | - Yujie Sun
- Department of Medicine, University of Pittsburgh Medical Center, Pittsburgh, PA 15213, United States
| | - Robert Feldman
- Department of Medicine, Center for Research on Health Care Data, Pittsburgh, PA 15213, United States
| | - Melissa Saul
- Department of Medicine, University of Pittsburgh Medical Center, Pittsburgh, PA 15213, United States
| | - Andrew Althouse
- Department of Medicine, Center for Research on Health Care Data, Pittsburgh, PA 15213, United States
| | - Gavin Arteel
- Division of Gastroenterology, Hepatology, and Nutrition, University of Pittsburgh Medical Center, Pittsburgh, PA 15213, United States
| | - Dhiraj Yadav
- Department of Medicine, Division of Gastroenterology, Hepatology and Nutrition, University of Pittsburgh Medical Center, Pittsburgh, PA 15213, United States
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13
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Yadav D, Whitcomb DC, Tang G, Slivka A, Bellin M. Autoimmunity May Explain Diabetes in a Subset of Patients With Recurrent Acute and Chronic Pancreatitis: A Pilot Study. Clin Gastroenterol Hepatol 2023; 21:226-228.e1. [PMID: 34793964 DOI: 10.1016/j.cgh.2021.11.011] [Citation(s) in RCA: 6] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/03/2021] [Accepted: 11/10/2021] [Indexed: 02/07/2023]
Abstract
Pancreatogenic diabetes mellitus, also termed type 3c diabetes (T3cD), or glucose intolerance develops in 25%-75% of adults with chronic pancreatitis (CP). The primary pathophysiologic defect in T3cD is insulin deficiency, thought to result largely from "bystander" injury to the islets from fibrotic changes in the exocrine pancreas and cytokine-induced beta cell dysfunction from intrapancreatic inflammation.1.
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Affiliation(s)
- Dhiraj Yadav
- Division of Gastroenterology, Hepatology and Nutrition, Department of Medicine, University of Pittsburgh Medical Center, Pittsburgh, Pennsylvania.
| | - David C Whitcomb
- Division of Gastroenterology, Hepatology and Nutrition, Department of Medicine, Department of Cell Biology & Physiology, Department of Human Genetics, University of Pittsburgh Medical Center, Pittsburgh, Pennsylvania
| | - Gong Tang
- Department of Biostatistics, Graduate School of Public Health, University of Pittsburgh, Pittsburgh, Pennsylvania
| | - Adam Slivka
- Division of Gastroenterology, Hepatology and Nutrition, Department of Medicine, University of Pittsburgh Medical Center, Pittsburgh, Pennsylvania
| | - Melena Bellin
- Division of Endocrinology and Metabolism, Department of Pediatrics, University of Minnesota Medical Center, Minneapolis, Minnesota
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McGrew SJ, Raines AM, Walker RL, Leonard SJ, Vujanovic AA. Posttraumatic Stress, Alcohol Use, and Alcohol Use Motives among Non-Hispanic Black/African American College Students: The Role of Emotion Regulation. J Dual Diagn 2023; 19:3-15. [PMID: 36583682 PMCID: PMC10337772 DOI: 10.1080/15504263.2022.2160037] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/31/2022]
Abstract
OBJECTIVE The associations between posttraumatic stress disorder (PTSD) symptom severity, alcohol use, and alcohol use motives are well-established. Emotion regulation difficulties have been implicated in the association between PTSD symptoms and alcohol use. A dearth of empirical work, however, has examined these associations among Black/African American college students, a population with high prevalence of exposure to potentially traumatic events, PTSD symptomatology, and alcohol-related consequences. METHODS This study examined PTSD symptoms, emotion regulation difficulties, and alcohol use severity and motives among a sample of Black/African American trauma-exposed college students (N = 282; 77.4% identified as female; M age = 22.36, SD = 4.71). RESULTS PTSD symptom severity was related to alcohol use and coping and conformity motives for alcohol use through heightened emotion regulation difficulties. Findings were significant above and beyond the effects of trauma load (i.e., number of potentially traumatic event types experienced). CONCLUSIONS This study extends past work to an understudied population and contributes to groundwork for culturally informed interventions.
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Affiliation(s)
| | - Amanda M. Raines
- Southeast Louisiana Veterans Healthcare System and Louisiana State University School of Medicine
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15
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Palmer B, Petrik M. Psychological Evaluation and Management of Chronic Pancreatitis. Gastroenterol Clin North Am 2022; 51:799-813. [PMID: 36375997 DOI: 10.1016/j.gtc.2022.07.006] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/04/2022]
Abstract
Chronic pancreatitis is a chronic digestive disorder that greatly diminishes the quality of life and is associated with significant psychological distress. A best practice recommendation in treating chronic pancreatitis is offering care in a multidisciplinary model that includes access to a behavioral health provider among other medical professionals. Behavioral interventions for patients with chronic pancreatitis have promise to improve the management of pain, comorbid psychiatric symptoms, and quality of life. If surgical interventions such as a total pancreatectomy islet autotransplant are considered, evaluating and mitigating psychosocial risk factors may aid the selection of appropriate candidates.
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Affiliation(s)
- Brooke Palmer
- Department of Medicine, Division of General Internal Medicine, University of Minnesota Medical School, MMC 741, 420 Delaware Street Southeast, Minneapolis, MN 55455, USA
| | - Megan Petrik
- Department of Medicine, Division of General Internal Medicine, University of Minnesota Medical School, MMC 741, 420 Delaware Street Southeast, Minneapolis, MN 55455, USA.
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16
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Singh VK, Whitcomb DC, Banks PA, AlKaade S, Anderson MA, Amann ST, Brand RE, Conwell DL, Cote GA, Gardner TB, Gelrud A, Guda N, Forsmark CE, Lewis M, Sherman S, Muniraj T, Romagnuolo J, Tan X, Tang G, Sandhu BS, Slivka A, Wilcox CM, Yadav D. Acute pancreatitis precedes chronic pancreatitis in the majority of patients: Results from the NAPS2 consortium. Pancreatology 2022; 22:1091-1098. [PMID: 36404201 PMCID: PMC10122210 DOI: 10.1016/j.pan.2022.10.004] [Citation(s) in RCA: 9] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/12/2022] [Revised: 09/19/2022] [Accepted: 10/22/2022] [Indexed: 11/05/2022]
Abstract
INTRODUCTION The mechanistic definition of chronic pancreatitis (CP) identifies acute pancreatitis (AP) as a precursor stage. We hypothesized that clinical AP frequently precedes the diagnosis of CP and is associated with patient- and disease-related factors. We describe the prevalence, temporal relationship and associations of AP in a well-defined North American cohort. METHODS We evaluated data from 883 patients with CP prospectively enrolled in the North American Pancreatitis Studies across 27 US centers between 2000 and 2014. We determined how often patients had one or more episodes of AP and its occurrence in relationship to the diagnosis of CP. We used multivariable logistic regression to determine associations for prior AP. RESULTS There were 624/883 (70.7%) patients with prior AP, among whom 161 (25.8%) had AP within 2 years, 115 (18.4%) within 3-5 years, and 348 (55.8%) >5 years prior to CP diagnosis. Among 504 AP patients with available information, 436 (86.5%) had >1 episode. On multivariable analyses, factors associated with increased odds of having prior AP were a younger age at CP diagnosis, white race, abdominal pain, pseudocyst(s) and pancreatic duct dilatation/stricture, while factors associated with a lower odds of having prior AP were exocrine insufficiency and pancreatic atrophy. When compared with patients with 1 episode, those with >1 AP episode were diagnosed with CP an average of 5 years earlier. CONCLUSIONS Nearly three-quarters of patients were diagnosed with AP prior to CP diagnosis. Identifying which AP patients are at-risk for future progression to CP may provide opportunities for primary and secondary prevention.
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Affiliation(s)
- Vikesh K Singh
- Pancreatitis Center, Division of Gastroenterology, Johns Hopkins Medical Institutions, Baltimore, MD, USA.
| | - David C Whitcomb
- Division of Gastroenterology, Hepatology & Nutrition, University of Pittsburgh Medical Center, Pittsburgh, PA, USA
| | - Peter A Banks
- Division of Gastroenterology, Brigham & Women's Hospital, Boston, MA, USA
| | | | | | | | - Randall E Brand
- Division of Gastroenterology, Hepatology & Nutrition, University of Pittsburgh Medical Center, Pittsburgh, PA, USA
| | - Darwin L Conwell
- Department of Internal Medicine, University of Kentucky College of Medicine, Lexington, KY, USA
| | - Gregory A Cote
- Division of Gastroenterology, Oregon Health Science University, Portland, OR, USA
| | - Timothy B Gardner
- Division of Gastroenterology & Hepatology, Dartmouth-Hitchcock Medical Center, Hanover, NH, USA
| | | | - Nalini Guda
- Aurora St. Luke's Medical Center, Milwaukee, WI, USA
| | - Christopher E Forsmark
- Division of Gastroenterology, Hepatology & Nutrition, University of Florida, Gainesville, FL, USA
| | - Michele Lewis
- Division of Gastroenterology & Hepatology, Mayo Clinic, Jacksonville, FL, USA
| | - Stuart Sherman
- Division of Gastroenterology & Hepatology, Indiana University, Indianapolis, IN, USA
| | | | - Joseph Romagnuolo
- Palmetto Health, Columbia Gastroenterology Associates, Columbia, SC, USA
| | - Xiaoqing Tan
- Department of Biostatistics, University of Pittsburgh, Pittsburgh, PA, USA
| | - Gong Tang
- Department of Biostatistics, University of Pittsburgh, Pittsburgh, PA, USA
| | | | - Adam Slivka
- Division of Gastroenterology, Hepatology & Nutrition, University of Pittsburgh Medical Center, Pittsburgh, PA, USA
| | - C Mel Wilcox
- Division of Gastroenterology & Hepatology, University of Alabama, Birmingham, AL, USA
| | - Dhiraj Yadav
- Division of Gastroenterology, Hepatology & Nutrition, University of Pittsburgh Medical Center, Pittsburgh, PA, USA
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17
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Lew D, Kamal F, Phan K, Randhawa K, Cornwell S, Bangolo AI, Weissman S, Pandol SJ. Epidemiologic risk factors for patients admitted with chronic pancreatitis and pancreatic ductal adenocarcinoma in the United States. World J Clin Oncol 2022. [DOI: https://doi.org/10.5306/wjco.v13.i11.907] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/03/2022] Open
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18
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Lew D, Kamal F, Phan K, Randhawa K, Cornwell S, Bangolo AI, Weissman S, Pandol SJ. Epidemiologic risk factors for patients admitted with chronic pancreatitis and pancreatic ductal adenocarcinoma in the United States. World J Clin Oncol 2022; 13:907-917. [PMID: 36483975 PMCID: PMC9724185 DOI: 10.5306/wjco.v13.i11.907] [Citation(s) in RCA: 6] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/28/2022] [Revised: 09/08/2022] [Accepted: 11/07/2022] [Indexed: 11/21/2022] Open
Abstract
BACKGROUND Epidemiological studies of chronic pancreatitis (CP) and its association with pancreatic ductal adenocarcinoma (PDAC) are limited. Understanding demographic and ethno-racial factors may help identify patients at the highest risk for CP and PDAC.
AIM To evaluate the ethno-racial risk factors for CP and its association with PDAC. The secondary aim was to evaluate hospitalization outcomes in patients admitted with CP and PDAC.
METHODS This retrospective cohort study used the 2016 and 2017 National Inpatient Sample databases. Patients included in the study had ICD-10 codes for CP and PDAC. The ethnic, socioeconomic, and racial backgrounds of patients with CP and PDAC were analyzed.
RESULTS Hospital admissions for CP was 29 per 100000, and 2890 (0.78%) had PDAC. Blacks [adjusted odds ratio (aOR) 1.13], men (aOR 1.35), age 40 to 59 (aOR 2.60), and being overweight (aOR 1.34) were significantly associated with CP (all with P < 0.01). In patients with CP, Whites (aOR 1.23), higher income, older age (aOR 1.05), and being overweight (aOR 2.40) were all significantly associated with PDAC (all with P < 0.01). Men (aOR 1.81) and Asians (aOR 15.19) had significantly increased mortality (P < 0.05). Hispanics had significantly increased hospital length of stay (aOR 5.24) (P < 0.05).
CONCLUSION Based on this large, nationwide analysis, black men between 40-59 years old and overweight are at significantly increased risk for admission with CP. White men older than 40 years old and overweight with higher income were found to have significant associations with CP and PDAC. This discrepancy may reflect underlying differences in healthcare access and utilization among different socioeconomic and ethno-racial groups.
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Affiliation(s)
- Daniel Lew
- Department of Gastroenterology, Cedars-Sinai Medical Center, Los Angeles, CA 90048, United States
| | - Fatima Kamal
- Department of Internal Medicine, Hackensack Meridian Health/Palisades Medical Center, North Bergen, NJ 07047, United States
| | - Khiem Phan
- Department of Internal Medicine, Hackensack Meridian Health/Palisades Medical Center, North Bergen, NJ 07047, United States
| | - Karamvir Randhawa
- Department of Internal Medicine, Hackensack Meridian Health/Palisades Medical Center, North Bergen, NJ 07047, United States
| | - Sam Cornwell
- Department of Internal Medicine, Hackensack Meridian Health/Palisades Medical Center, North Bergen, NJ 07047, United States
| | - Ayrton I Bangolo
- Department of Internal Medicine, Hackensack Meridian Health/Palisades Medical Center, North Bergen, NJ 07047, United States
| | - Simcha Weissman
- Department of Internal Medicine, Hackensack Meridian Health/Palisades Medical Center, North Bergen, NJ 07047, United States
| | - Stephen J Pandol
- Department of Gastroenterology, Cedars-Sinai Medical Center, Los Angeles, CA 90048, United States
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Uc A, Cress GA, Wang F, Abu-El-Haija M, Ellery KM, Fishman DS, Gariepy CE, Gonska T, Lin TK, Liu QY, Mehta M, Maqbool A, McFerron BA, Morinville VD, Ooi CY, Perito ER, Schwarzenberg SJ, Sellers ZM, Serrano J, Shah U, Troendle DM, Wilschanski M, Zheng Y, Yuan Y, Lowe ME, Consortium for the Study of Chronic Pancreatitis, Diabetes and Pancreatic Cancer. Analysis of INSPPIRE-2 Cohort: Risk Factors and Disease Burden in Children With Acute Recurrent or Chronic Pancreatitis. J Pediatr Gastroenterol Nutr 2022; 75:643-649. [PMID: 35976273 PMCID: PMC9617760 DOI: 10.1097/mpg.0000000000003590] [Citation(s) in RCA: 11] [Impact Index Per Article: 3.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/04/2023]
Abstract
OBJECTIVES The objective of this study is to investigate risk factors and disease burden in pediatric acute recurrent pancreatitis (ARP) and chronic pancreatitis (CP). METHODS Data were obtained from INternational Study group of Pediatric Pancreatitis: In search for a cuRE-2 (INSPPIRE-2), the largest multi-center prospective cohort study in pediatric patients with ARP or CP. RESULTS Of 689 children, 365 had ARP (53%), 324 had CP (47%). CP was more commonly associated with female sex, younger age at first acute pancreatitis (AP) attack, Asian race, family history of CP, lower BMI%, genetic and obstructive factors, PRSS1 mutations and pancreas divisum. CFTR mutations, toxic-metabolic factors, medication use, hypertriglyceridemia, Crohn disease were more common in children with ARP. Constant or frequent abdominal pain, emergency room (ER) visits, hospitalizations, medical, endoscopic or surgical therapies were significantly more common in CP, episodic pain in ARP. A total of 33.1% of children with CP had exocrine pancreatic insufficiency (EPI), 8.7% had diabetes mellitus. Compared to boys, girls were more likely to report pain impacting socialization and school, medical therapies, cholecystectomy, but no increased opioid use. There was no difference in race, ethnicity, age at first AP episode, age at CP diagnosis, duration of disease, risk factors, prevalence of EPI or diabetes between boys and girls. Multivariate analysis revealed that family history of CP, constant pain, obstructive risk factors were predictors of CP. CONCLUSIONS Children with family history of CP, constant pain, or obstructive risk factors should raise suspicion for CP.
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Affiliation(s)
- Aliye Uc
- University of Iowa, Stead Family Children’s Hospital, Iowa City, IA
| | | | - Fuchenchu Wang
- The University of Texas, MD Anderson Cancer Center, Houston, TX
| | - Maisam Abu-El-Haija
- Cincinnati Children’s Hospital Medical Center, College of Medicine, University of Cincinnati, Cincinnati, OH
| | | | - Douglas S. Fishman
- Division of Pediatric Gastroenterology, Hepatology and Nutrition, Baylor College of Medicine and Texas Children’s Hospital, Houston, TX
| | | | | | - Tom K. Lin
- Cincinnati Children’s Hospital Medical Center, College of Medicine, University of Cincinnati, Cincinnati, OH
| | - Quin Y. Liu
- Cedars-Sinai Medical Center, Los Angeles, CA
| | - Megha Mehta
- University of Texas Southwestern Medical School, Dallas, TX
| | - Asim Maqbool
- Children’s Hospital of Philadelphia, Philadelphia, PA
| | - Brian A. McFerron
- Riley Hospital for Children, Indiana University School of Medicine, Indianapolis, IN
| | | | - Chee Y. Ooi
- School of Women’s and Children’s Health, Faculty of Medicine, University of New South Wales and Sydney Children’s Hospital Randwick Sydney, Sydney, Australia
| | | | | | | | - Jose Serrano
- Division of Digestive Diseases and Nutrition, National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK), Bethesda, MD
| | - Uzma Shah
- Massachusetts General Hospital for Children, Harvard Medical School, Boston, MA
| | | | | | - Yuhua Zheng
- Children’s Hospital Los Angeles, Los Angeles, CA
| | - Ying Yuan
- The University of Texas, MD Anderson Cancer Center, Houston, TX
| | - Mark E. Lowe
- Washington University School of Medicine, St. Louis, MO
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20
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Racial/Ethnic Disparities in the Management of Pediatric Acute Pancreatitis Across Children's Hospitals. J Pediatr Gastroenterol Nutr 2022; 75:650-655. [PMID: 36305883 DOI: 10.1097/mpg.0000000000003597] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/10/2022]
Abstract
OBJECTIVES Racial or ethnic disparities in health care delivery and resource utilization have been reported in a variety of pediatric diseases. In acute pancreatitis (AP), there is an association between Black race and increased inpatient mortality. Data on the association of race and ethnicity and resource use for managing pediatric AP are lacking. The aim of this study is to investigate this potential association in pediatric AP. METHODS Retrospective study of children 0-18 years diagnosed with AP in the Pediatric Health Information System (PHIS) database from 2012 to 2018. Descriptive statistics were used to summarize cohort characteristics. Race/ethnicity classifications included non-Hispanic Black (NHB), non-Hispanic White (NHW, used as reference), Hispanic, and "Other." Associations between patient characteristics and race/ethnicity were determined using χ2 tests. Generalized linear mixed regression model was used to determine the association of race/ethnicity with odds of resource utilization, costs, and length of hospital stay after adjusting for covariates with a random intercept for site. RESULTS Five thousand nine hundred sixty-three patients from 50 hospitals were included. Adjusted analysis showed that NHB children hospitalized with AP were at lower odds of receiving opioids in the first 24 hours [adjusted odds ratio (aOR) = 0.82, 95% confidence interval (CI) = 0.70-0.98] and receiving intravenous fluids during the hospitalization (aOR = 0.64, 95% CI = 0.43-0.96) when compared with NHW children. Additionally, NHB and Hispanic children had a prolonged adjusted mean length of hospital stay and higher hospital costs when compared with NHW children. Although there was no significant association between race/ethnicity and diagnosis of pancreatic necrosis or sepsis, Hispanic and "Other" children were at higher odds of receiving antibiotics during hospitalization for AP (aOR = 1.33, 95% CI = 1.13-1.57 and aOR = 1.37, 95% CI = 1.09-1.73, respectively) than NHW children. CONCLUSIONS Disparities exist in utilization of health care interventions for pediatric AP patients by race/ethnicity. Future studies should investigate why these disparities exist and if these disparities affect outcomes.
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The Pancreas and Known Factors of Acute Pancreatitis. J Clin Med 2022; 11:jcm11195565. [PMID: 36233433 PMCID: PMC9571992 DOI: 10.3390/jcm11195565] [Citation(s) in RCA: 20] [Impact Index Per Article: 6.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/08/2022] [Revised: 08/11/2022] [Accepted: 08/30/2022] [Indexed: 11/16/2022] Open
Abstract
Pancreatitis is regarded by clinicians as one of the most complicated and clinically challenging of all disorders affecting the abdomen. It is classified on the basis of clinical, morphological, and histological criteria. Causes of acute pancreatitis can easily be identified in 75–85% of patients. The main causes of acute, recurrent acute, and chronic pancreatitis are gallstone migration and alcohol abuse. Other causes are uncommon, controversial, or unexplained. For instance, cofactors of all forms of pancreatitis are pancreas divisum and hypertriglyceridemia. Another factor that should be considered is a complication of endoscopic retrograde cholangiopancreatography: post-endoscopic retrograde cholangiopancreatography acute pancreatitis. The aim of this study is to present the known risk factors for acute pancreatitis, beginning with an account of the morphology, physiology, and development of the pancreas.
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Hart PA, Yadav D, Li L, Appana S, Fisher W, Fogel E, Forsmark CE, Park WG, Pandol S, Topazian MD, Van Den Eden SK, Vege SS, Bradley D, Serrano J, Conwell DL. High Prevalence of Osteopathy in Chronic Pancreatitis: A Cross-sectional Analysis From the PROCEED Study. Clin Gastroenterol Hepatol 2022; 20:2005-2013. [PMID: 34571258 PMCID: PMC8942866 DOI: 10.1016/j.cgh.2021.09.026] [Citation(s) in RCA: 13] [Impact Index Per Article: 4.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/03/2021] [Revised: 09/17/2021] [Accepted: 09/18/2021] [Indexed: 02/07/2023]
Abstract
BACKGROUND & AIMS 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. METHODS 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. RESULTS 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 = .02) and spontaneous fractures (3.9% vs 0; P = .04). On multivariate analysis, older age (odds ratio [OR], 1.29 per 5 years; 95% confidence interval [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 body mass index 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 other patient and disease-related features of CP. CONCLUSION In the largest study of patients with CP 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.
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Affiliation(s)
- Phil A Hart
- Division of Gastroenterology, Hepatology, and Nutrition, The Ohio State University Wexner Medical Center, Columbus, Ohio
| | - Dhiraj Yadav
- Division of Gastroenterology, Hepatology, and Nutrition, University of Pittsburgh Medical Center, Pittsburgh, Pennsylvania
| | - Liang Li
- Department of Biostatistics, MD Anderson Cancer Center, Houston, Texas
| | - Savi Appana
- Department of Biostatistics, MD Anderson Cancer Center, Houston, Texas
| | - William Fisher
- Department of Surgery, Baylor College of Medicine, Houston, Texas
| | - Evan Fogel
- Division of Gastroenterology and Hepatology, Indiana University, Indianapolis, Indiana
| | - Chris E Forsmark
- Division of Gastroenterology, University of Florida, Gainesville, Florida
| | - Walter G Park
- Division of Gastroenterology & Hepatology, Stanford University, Stanford, California
| | - Stephen Pandol
- Division of Gastroenterology and Hepatology, Cedars-Sinai Medical Center, Los Angeles, California
| | - Mark D Topazian
- Division of Gastroenterology and Hepatology, Mayo Clinic, Rochester, Minnesota
| | | | - Santhi Swaroop Vege
- Division of Gastroenterology and Hepatology, Mayo Clinic, Rochester, Minnesota
| | - David Bradley
- Division of Endocrinology, Diabetes, and Metabolism, The Ohio State University Wexner Medical Center, Columbus, Ohio
| | - Jose Serrano
- Division of Digestive Diseases and Nutrition, National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, Bethesda, Maryland
| | - Darwin L Conwell
- Division of Gastroenterology, Hepatology, and Nutrition, The Ohio State University Wexner Medical Center, Columbus, Ohio.
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23
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Choi J, Oh TG, Jung HW, Park KY, Shin H, Jo T, Kang DS, Chanda D, Hong S, Kim J, Hwang H, Ji M, Jung M, Shoji T, Matsushima A, Kim P, Mun JY, Paik MJ, Cho SJ, Lee IK, Whitcomb DC, Greer P, Blobner B, Goodarzi MO, Pandol SJ, Rotter JI, Fan W, Bapat SP, Zheng Y, Liddle C, Yu RT, Atkins AR, Downes M, Yoshihara E, Evans RM, Suh JM. Estrogen-Related Receptor γ Maintains Pancreatic Acinar Cell Function and Identity by Regulating Cellular Metabolism. Gastroenterology 2022; 163:239-256. [PMID: 35461826 PMCID: PMC9233018 DOI: 10.1053/j.gastro.2022.04.013] [Citation(s) in RCA: 16] [Impact Index Per Article: 5.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/02/2021] [Revised: 02/22/2022] [Accepted: 04/03/2022] [Indexed: 12/02/2022]
Abstract
BACKGROUND & AIMS Mitochondrial dysfunction disrupts the synthesis and secretion of digestive enzymes in pancreatic acinar cells and plays a primary role in the etiology of exocrine pancreas disorders. However, the transcriptional mechanisms that regulate mitochondrial function to support acinar cell physiology are poorly understood. Here, we aim to elucidate the function of estrogen-related receptor γ (ERRγ) in pancreatic acinar cell mitochondrial homeostasis and energy production. METHODS Two models of ERRγ inhibition, GSK5182-treated wild-type mice and ERRγ conditional knock-out (cKO) mice, were established to investigate ERRγ function in the exocrine pancreas. To identify the functional role of ERRγ in pancreatic acinar cells, we performed histologic and transcriptome analysis with the pancreas isolated from ERRγ cKO mice. To determine the relevance of these findings for human disease, we analyzed transcriptome data from multiple independent human cohorts and conducted genetic association studies for ESRRG variants in 2 distinct human pancreatitis cohorts. RESULTS Blocking ERRγ function in mice by genetic deletion or inverse agonist treatment results in striking pancreatitis-like phenotypes accompanied by inflammation, fibrosis, and cell death. Mechanistically, loss of ERRγ in primary acini abrogates messenger RNA expression and protein levels of mitochondrial oxidative phosphorylation complex genes, resulting in defective acinar cell energetics. Mitochondrial dysfunction due to ERRγ deletion further triggers autophagy dysfunction, endoplasmic reticulum stress, and production of reactive oxygen species, ultimately leading to cell death. Interestingly, ERRγ-deficient acinar cells that escape cell death acquire ductal cell characteristics, indicating a role for ERRγ in acinar-to-ductal metaplasia. Consistent with our findings in ERRγ cKO mice, ERRγ expression was significantly reduced in patients with chronic pancreatitis compared with normal subjects. Furthermore, candidate locus region genetic association studies revealed multiple single nucleotide variants for ERRγ that are associated with chronic pancreatitis. CONCLUSIONS Collectively, our findings highlight an essential role for ERRγ in maintaining the transcriptional program that supports acinar cell mitochondrial function and organellar homeostasis and provide a novel molecular link between ERRγ and exocrine pancreas disorders.
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Affiliation(s)
- Jinhyuk Choi
- Graduate School of Medical Science and Engineering, Korea Advanced Institute of Science and Technology, Daejeon, Republic of Korea
| | - Tae Gyu Oh
- Gene Expression Laboratory, Salk Institute for Biological Studies, La Jolla, California
| | - Hee-Won Jung
- Graduate School of Medical Science and Engineering, Korea Advanced Institute of Science and Technology, Daejeon, Republic of Korea
| | - Kun-Young Park
- Graduate School of Medical Science and Engineering, Korea Advanced Institute of Science and Technology, Daejeon, Republic of Korea
| | - Hyemi Shin
- Graduate School of Medical Science and Engineering, Korea Advanced Institute of Science and Technology, Daejeon, Republic of Korea
| | - Taehee Jo
- Graduate School of Medical Science and Engineering, Korea Advanced Institute of Science and Technology, Daejeon, Republic of Korea
| | - Du-Seock Kang
- Graduate School of Medical Science and Engineering, Korea Advanced Institute of Science and Technology, Daejeon, Republic of Korea
| | - Dipanjan Chanda
- Leading-Edge Research Center for Drug Discovery and Development for Diabetes and Metabolic Disease, Kyungpook National University Hospital, Daegu, Republic of Korea; Bio-Medical Research Institute, Kyungpook National University Hospital, Daegu, Republic of Korea
| | - Sujung Hong
- Graduate School of Medical Science and Engineering, Korea Advanced Institute of Science and Technology, Daejeon, Republic of Korea
| | - Jina Kim
- New Drug Development Center, Daegu-Gyeongbuk Medical Innovation Foundation, Daegu, Republic of Korea
| | - Hayoung Hwang
- New Drug Development Center, Daegu-Gyeongbuk Medical Innovation Foundation, Daegu, Republic of Korea
| | - Moongi Ji
- College of Pharmacy, Sunchon National University, Suncheon, Republic of Korea
| | - Minkyo Jung
- Neural Circuit Research Group, Korea Brain Research Institute, Daegu, Republic of Korea
| | - Takashi Shoji
- Department of Medicine, Kyoto University, Kyoto, Japan
| | - Ayami Matsushima
- Laboratory of Structure-Function Biochemistry, Department of Chemistry, Faculty of Science, Kyushu University, Fukuoka, Japan
| | - Pilhan Kim
- Graduate School of Medical Science and Engineering, Korea Advanced Institute of Science and Technology, Daejeon, Republic of Korea
| | - Ji Young Mun
- Neural Circuit Research Group, Korea Brain Research Institute, Daegu, Republic of Korea
| | - Man-Jeong Paik
- College of Pharmacy, Sunchon National University, Suncheon, Republic of Korea
| | - Sung Jin Cho
- New Drug Development Center, Daegu-Gyeongbuk Medical Innovation Foundation, Daegu, Republic of Korea
| | - In-Kyu Lee
- Leading-Edge Research Center for Drug Discovery and Development for Diabetes and Metabolic Disease, Kyungpook National University Hospital, Daegu, Republic of Korea; Bio-Medical Research Institute, Kyungpook National University Hospital, Daegu, Republic of Korea; Research Institute of Aging and Metabolism, Kyungpook National University, Daegu, Republic of Korea; Department of Internal Medicine, Kyungpook National University Hospital, School of Medicine, Kyungpook National University, Daegu, Republic of Korea
| | - David C Whitcomb
- Ariel Precision Medicine, Pittsburgh, Pennsylvania; Department of Medicine, University of Pittsburgh, Pittsburgh, Pennsylvania; Department of Cell Biology and Molecular Physiology and the Department of Human Genetics, University of Pittsburgh, Pittsburgh, Pennsylvania
| | - Phil Greer
- Ariel Precision Medicine, Pittsburgh, Pennsylvania; Department of Medicine, University of Pittsburgh, Pittsburgh, Pennsylvania
| | - Brandon Blobner
- Department of Medicine, University of Pittsburgh, Pittsburgh, Pennsylvania
| | - Mark O Goodarzi
- Division of Endocrinology, Diabetes and Metabolism, Department of Medicine, Cedars-Sinai Medical Center, Los Angeles, California
| | - Stephen J Pandol
- Cedars-Sinai Cancer, Cedars-Sinai Medical Center, Los Angeles, California; Karsh Division of Gastroenterology and Hepatology, Cedars-Sinai Medical Center, Los Angeles, California
| | - Jerome I Rotter
- The Institute for Translational Genomics and Population Sciences, Department of Pediatrics, The Lundquist Institute for Biomedical Innovation at Harbor-UCLA Medical Center, Torrance, California; Departments of Pediatrics and Human Genetics, David Geffen School of Medicine at University of California-Los Angeles, Los Angeles, California
| | - Weiwei Fan
- Gene Expression Laboratory, Salk Institute for Biological Studies, La Jolla, California
| | - Sagar P Bapat
- Gene Expression Laboratory, Salk Institute for Biological Studies, La Jolla, California; Department of Laboratory Medicine, University of California-San Francisco, San Francisco, California; Diabetes Center, University of California-San Francisco, San Francisco, California; Nomis Laboratories for Immunobiology and Microbial Pathogenesis, Salk Institute for Biological Studies, La Jolla, California
| | - Ye Zheng
- Nomis Laboratories for Immunobiology and Microbial Pathogenesis, Salk Institute for Biological Studies, La Jolla, California
| | - Chris Liddle
- Storr Liver Centre, Westmead Institute for Medical Research and Sydney School of Medicine, University of Sydney, Westmead, New South Wales, Australia
| | - Ruth T Yu
- Gene Expression Laboratory, Salk Institute for Biological Studies, La Jolla, California
| | - Annette R Atkins
- Gene Expression Laboratory, Salk Institute for Biological Studies, La Jolla, California
| | - Michael Downes
- Gene Expression Laboratory, Salk Institute for Biological Studies, La Jolla, California
| | - Eiji Yoshihara
- Gene Expression Laboratory, Salk Institute for Biological Studies, La Jolla, California; The Lundquist Institute for Biomedical Innovation at Harbor-UCLA Medical Center, Torrance, California; David Geffen School of Medicine at University of California-Los Angeles, Los Angeles, California.
| | - Ronald M Evans
- Gene Expression Laboratory, Salk Institute for Biological Studies, La Jolla, California.
| | - Jae Myoung Suh
- Graduate School of Medical Science and Engineering, Korea Advanced Institute of Science and Technology, Daejeon, Republic of Korea.
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24
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Arteel GE, Singhvi A, Feldman R, Althouse AD, Bataller R, Saul M, Yadav D. Coexistent Alcohol-Related Liver Disease and Alcohol-Related Pancreatitis: Analysis of a Large Health Care System Cohort. Dig Dis Sci 2022; 67:2543-2551. [PMID: 33961195 PMCID: PMC9366918 DOI: 10.1007/s10620-021-07010-5] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/24/2021] [Accepted: 04/14/2021] [Indexed: 12/09/2022]
Abstract
INTRODUCTION Although coexistence of alcohol-related liver disease (ALD) and pancreatitis (ALP) is seen in clinical practice, a clear understanding of the overlap between these diseases is lacking. Moreover, the relative risks for certain population groups have not been studied. We determined the prevalence and coexistence of ALD and ALP in patients with an alcohol use disorder using retrospective analysis of a large patient cohort from Western Pennsylvania. We specifically emphasized the analysis of underrepresented populations, including women and blacks. METHODS We identified all unique patients who received care in UPMC health system during 2006-2017 with at least one International Classification of Diseases versions 9 and/or 10 codes for alcohol misuse, ALD and pancreatitis. We noted their sex, race and age of first diagnosis and duration of contact. RESULTS Among 89,774 patients that fit our criteria, the prevalence of ALD, ALP and coexistent ALD and ALP in patients with alcohol misuse was 11.7%, 7.4% and 2.5%, respectively. Prevalence of ALP in ALD was 16.4%, and ALD in ALP was 33.1%. Prevalence of ALP in ALD was slightly more prevalent in women (18.6% vs. 15.6%, p < 0.001). Prevalence of ALP in ALD was 2-4 folds greater in blacks than other races. DISCUSSION A sizeable fraction of patients with ALD or ALP has coexistent disease. This is the first study to identify that blacks are at a higher risk for ALP in the presence of ALD. Future studies should define the clinical impact of coexistent disease on clinical presentation and short- and long-term outcomes.
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Affiliation(s)
- Gavin E Arteel
- Division of Gastroenterology, Hepatology and Nutrition, Department of Medicine, University of Pittsburgh, Pittsburgh, PA, USA
| | - Ajay Singhvi
- Division of Gastroenterology, Hepatology and Nutrition, Department of Medicine, University of Pittsburgh, Pittsburgh, PA, USA
| | - Robert Feldman
- Division of General Internal Medicine, Department of Medicine, University of Pittsburgh, Pittsburgh, PA, USA
| | - Andrew D Althouse
- Division of General Internal Medicine, Department of Medicine, University of Pittsburgh, Pittsburgh, PA, USA
| | - Ramon Bataller
- Division of Gastroenterology, Hepatology and Nutrition, Department of Medicine, University of Pittsburgh, Pittsburgh, PA, USA
| | - Melissa Saul
- Department of Medicine, University of Pittsburgh, Pittsburgh, PA, USA
| | - Dhiraj Yadav
- Division of Gastroenterology, Hepatology and Nutrition, Department of Medicine, University of Pittsburgh, Pittsburgh, PA, USA.
- University of Pittsburgh Medical Center, 200 Lothrop St, M2, C-Wing, Pittsburgh, PA, 15213, USA.
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25
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Schlosser T, Fischer D, Büttner S, Blank V, Hoffmeister A. Cystic fibrosis transmembrane conductance regulator function in patients with chronic pancreatitis. Medicine (Baltimore) 2022; 101:e28904. [PMID: 35212296 PMCID: PMC8878632 DOI: 10.1097/md.0000000000028904] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/11/2021] [Accepted: 02/02/2022] [Indexed: 11/26/2022] Open
Abstract
BACKGROUND Pathogenesis of chronic pancreatitis (CP) is still not entirely understood with many patients probably having more than 1 underlying etiology. Besides toxic-metabolic factors, genetics contribute to disease development. Mutations in cystic fibrosis transmembrane conductance regulator (CFTR) are shown to increase risk for CP. Activity of CFTR can easily be accessed in vivo by measurement of nasal potential difference (PD). METHODS We compared in this monocentric study 17 CP patients from the outpatient unit of our university hospital with 30 healthy controls regarding nasal PDs by using a superfusion protocol. Additionally, demographic and lifestyle data of all persons were recorded. RESULTS Seventeen patients (12% female, median age 48 years) with CP and 30 healthy volunteers (47% female, 25 years) were included in the study. Patients with CP had a significant higher proportion of CFTR dysfunction (P = .04). Furthermore, demographics differed between the 2 groups with CP patients being older (P < .001). There were differences in daily alcohol consumption (P = .001) and smoking habits (smokers vs nonsmokers: P = .01, pack years: P = .002). CONCLUSIONS PD measurement is an easily accessible way to show CFTR dysfunction as an etiological factor of CP. Cigarette smoking might impair CFTR function and therefore be 1 preventable cause of CP evolution.
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Affiliation(s)
- Tobias Schlosser
- Division of Gastroenterology, Department of Medicine II, Leipzig University Medical Center, Leipzig, Germany
| | - Daniel Fischer
- Division of Gastroenterology, Department of Medicine II, Leipzig University Medical Center, Leipzig, Germany
- Outpatient Psychiatry and Psychotherapy, Leipzig, Germany
| | - Sandra Büttner
- Division of Gastroenterology, Department of Medicine II, Leipzig University Medical Center, Leipzig, Germany
| | - Valentin Blank
- Division of Gastroenterology, Department of Medicine II, Leipzig University Medical Center, Leipzig, Germany
| | - Albrecht Hoffmeister
- Division of Gastroenterology, Department of Medicine II, Leipzig University Medical Center, Leipzig, Germany
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26
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Li H, Wen W, Luo J. Targeting Endoplasmic Reticulum Stress as an Effective Treatment for Alcoholic Pancreatitis. Biomedicines 2022; 10:biomedicines10010108. [PMID: 35052788 PMCID: PMC8773075 DOI: 10.3390/biomedicines10010108] [Citation(s) in RCA: 9] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/19/2021] [Revised: 12/28/2021] [Accepted: 12/30/2021] [Indexed: 02/04/2023] Open
Abstract
Pancreatitis and alcoholic pancreatitis are serious health concerns with an urgent need for effective treatment strategies. Alcohol is a known etiological factor for pancreatitis, including acute pancreatitis (AP) and chronic pancreatitis (CP). Excessive alcohol consumption induces many pathological stress responses; of particular note is endoplasmic reticulum (ER) stress and adaptive unfolded protein response (UPR). ER stress results from the accumulation of unfolded/misfolded protein in the ER and is implicated in the pathogenesis of alcoholic pancreatitis. Here, we summarize the possible mechanisms by which ER stress contributes to alcoholic pancreatitis. We also discuss potential approaches targeting ER stress and UPR in developing novel therapeutic strategies for the disease.
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Affiliation(s)
- Hui Li
- Department of Pathology, Carver College of Medicine, University of Iowa, Iowa City, IA 52242, USA; (H.L.); (W.W.)
| | - Wen Wen
- Department of Pathology, Carver College of Medicine, University of Iowa, Iowa City, IA 52242, USA; (H.L.); (W.W.)
| | - Jia Luo
- Department of Pathology, Carver College of Medicine, University of Iowa, Iowa City, IA 52242, USA; (H.L.); (W.W.)
- Iowa City VA Health Care System, Iowa City, IA 52246, USA
- Correspondence: ; Tel.: +1-319-335-2256
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27
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Petrik ML, Freeman ML, Trikudanathan G. Multidisciplinary Care for Adults With Chronic Pancreatitis: Incorporating Psychological Therapies to Optimize Outcomes. Pancreas 2022; 51:4-12. [PMID: 35195589 DOI: 10.1097/mpa.0000000000001953] [Citation(s) in RCA: 7] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/10/2022]
Abstract
ABSTRACT Chronic pancreatitis (CP) is associated with a high disease burden, extensive negative impact on quality of life, increased rates of depression and anxiety, and significant health care utilization and expenditures. Pain is a hallmark feature of CP, present in up to 90% of patients with this condition, and can lead to high rates of disability, hospitalization, and opioid medication use. Current perspectives on the management of CP have evolved to advocate a multidisciplinary approach which offers new pathways for helping patients manage symptoms. Psychologists play an important role in a multidisciplinary team effort by applying scientifically based psychological principles and techniques to improve pain and adaptation to chronic illness. This review will detail the fundamentals of delivering psychological interventions for adults with CP managed in an outpatient setting. Recommendations for integrating psychological care in multidisciplinary management of CP will be offered. Future directions for psychological care in CP multidisciplinary teams are also discussed.
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Affiliation(s)
- Megan L Petrik
- From the Division of General Internal Medicine, Department of Medicine
| | - Martin L Freeman
- Division of Gastroenterology, Hepatology, and Nutrition, Department of Medicine, University of Minnesota Medical School, Minneapolis, MN
| | - Guru Trikudanathan
- Division of Gastroenterology, Hepatology, and Nutrition, Department of Medicine, University of Minnesota Medical School, Minneapolis, MN
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28
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Whitcomb DC. Central role of the sentinel acute pancreatitis event (SAPE) model in understanding recurrent acute pancreatitis (RAP): Implications for precision medicine. Front Pediatr 2022; 10:941852. [PMID: 36046477 PMCID: PMC9421067 DOI: 10.3389/fped.2022.941852] [Citation(s) in RCA: 10] [Impact Index Per Article: 3.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/11/2022] [Accepted: 07/21/2022] [Indexed: 11/13/2022] Open
Abstract
Traditional approaches to understanding the origins of chronic pancreatitis (CP) and find treatments led to abysmal failure. Thus, no drugs now exists to meet this need. Outdated concepts of the etiopathogenesis of CP have been replaced with new insights and disease models that provide the framework for early detection of the pathogenic pancreatitis process. Application of these principals require a new paradigm in disease definition and management, i.e. personalized / precision medicine. The key is acute pancreatitis (AP) starting with the first (sentinel) acute pancreatitis (AP) event (SAPE). This event sensitizes the pancreas to recurrent acute pancreatitis (RAP) as ongoing stressors drive various inflammatory responses to cause CP. The problem is the complex etiologies of AP and the additional genetic and environmental factors that promote progression to RAP and CP. This paper provides a background on the key conceptual changes that facilitate new approaches and the rationale for using mechanism-specific therapies to prevent RAP and CP.
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Affiliation(s)
- David C Whitcomb
- Cell Biology and Molecular Physiology, and Human Genetics, Division of Gastroenterology, Hepatology and Nutrition (Chief 1999-2016), University of Pittsburgh and UPMC, Pittsburgh, PA, United States.,Ariel Precision Medicine, Pittsburgh, PA, United States
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29
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Study of Association of Genetic Risk Loci for Anxiety and PTSD With Pain in Pancreatitis Needs More Discussion. Am J Gastroenterol 2022; 117:193. [PMID: 34613938 DOI: 10.14309/ajg.0000000000001522] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/11/2022]
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30
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Saloman JL, Tang G, Stello KM, Hall KE, Wang X, AlKaade S, Banks PA, Brand RE, Conwell DL, Coté GA, Forsmark CE, Gardner TB, Gelrud A, Lewis MD, Sherman S, Slivka A, Whitcomb DC, Yadav D. Serum biomarkers for chronic pancreatitis pain patterns. Pancreatology 2021; 21:1411-1418. [PMID: 34602367 PMCID: PMC8629935 DOI: 10.1016/j.pan.2021.09.016] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/08/2021] [Revised: 09/15/2021] [Accepted: 09/25/2021] [Indexed: 12/11/2022]
Abstract
OBJECTIVES Chronic pancreatitis (CP) is associated with debilitating refractory pain. Distinct subtypes of CP pain have been previously characterized based on severity (none, mild-moderate, severe) and temporal (none, intermittent, constant) nature of pain, but no mechanism-based tools are available to guide pain management. This exploratory study was designed to determine if potential pain biomarkers could be detected in patient serum and whether they associate with specific pain patterns. METHODS Cytokines, chemokines, and peptides associated with nociception and pain were measured in legacy serum samples from CP patients (N = 99) enrolled in the North American Pancreatitis Studies. The unsupervised hierarchical cluster analysis was applied to cluster CP patients based on their biomarker profile. Classification and regression tree was used to assess whether these biomarkers can predict pain outcomes. RESULTS The hierarchical cluster analysis revealed a subset of patients with predominantly constant, mild-moderate pain exhibited elevated interleukin-1β (IL-1β), interleukin-6 (IL-6), interleukin-2 (IL-2), tumor necrosis factor alpha (TNFα), and monocyte chemoattractant protein-1 (MCP1) whereas patients with higher interleukin-4 (IL-4), interleukin-8 (IL-8) and calcitonin gene related peptide (CGRP) were more likely to have severe pain. Interestingly, analyses of each individual biomarker revealed that patients with constant pain had reduced circulating TNFα and fractalkine. Patients with severe pain exhibited a significant reduction in TNFα as well as trends towards lower levels of IL-6 and substance P. DISCUSSION The observations from this study indicate that unique pain experiences within the chronic pancreatitis population can be associated with distinct biochemical signatures. These data indicate that further hypothesis-driven analyses combining biochemical measurements and detailed pain phenotyping could be used to develop precision approaches for pain management in patients with chronic pancreatitis.
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Affiliation(s)
- Jami L. Saloman
- Department of Medicine, Division of Gastroenterology, Hepatology and Nutrition, School of Medicine, University of Pittsburgh, PA, USA,Pittsburgh Center for Pain Research, School of Medicine, University of Pittsburgh, PA, USA,Department of Neurobiology, School of Medicine, University of Pittsburgh, PA, USA
| | - Gong Tang
- Department of Biostatistics, Graduate School of Public Health, University of Pittsburgh, Pittsburgh, PA, USA
| | - Kimberly M. Stello
- Department of Medicine, Division of Gastroenterology, Hepatology and Nutrition, School of Medicine, University of Pittsburgh, PA, USA
| | - Kristen E. Hall
- Department of Medicine, Division of Gastroenterology, Hepatology and Nutrition, School of Medicine, University of Pittsburgh, PA, USA
| | - Xianling Wang
- Department of Biostatistics, Graduate School of Public Health, University of Pittsburgh, Pittsburgh, PA, USA
| | | | | | - Randall E. Brand
- Department of Medicine, Division of Gastroenterology, Hepatology and Nutrition, School of Medicine, University of Pittsburgh, PA, USA
| | - Darwin L. Conwell
- The Ohio State University Wexner Medical Center, Columbus, Ohio, USA
| | - Gregory A. Coté
- Medical University of South Carolina, Charleston, South Carolina, USA
| | - Christopher E. Forsmark
- Division of Gastroenterology, Hepatology, and Nutrition, University of Florida, Gainesville, FL, USA
| | - Timothy B. Gardner
- Section of Gastroenterology and Hepatology, Geisel School of Medicine at Dartmouth, Lebanon, NH, USA
| | - Andres Gelrud
- Department of Internal Medicine, Miami Cancer Institute, Gastro Health, Miami, FL, USA
| | - Michele D. Lewis
- Department of Medicine, Division of Gastroenterology and Hepatology, Mayo Clinic, Jacksonville, FL, USA
| | - Stuart Sherman
- Indiana University School of Medicine, Indianapolis, IN, USA
| | - Adam Slivka
- Department of Medicine, Division of Gastroenterology, Hepatology and Nutrition, School of Medicine, University of Pittsburgh, PA, USA
| | - David C. Whitcomb
- Department of Medicine, Division of Gastroenterology, Hepatology and Nutrition, School of Medicine, University of Pittsburgh, PA, USA,Pittsburgh Center for Pain Research, School of Medicine, University of Pittsburgh, PA, USA,Departments of Cell Biology & Physiology, and Human Genetics, University of Pittsburgh, PA, USA
| | - Dhiraj Yadav
- Department of Medicine, Division of Gastroenterology, Hepatology and Nutrition, School of Medicine, University of Pittsburgh, PA, USA
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31
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Assessment of pain associated with chronic pancreatitis: An international consensus guideline. Pancreatology 2021; 21:1256-1284. [PMID: 34391675 DOI: 10.1016/j.pan.2021.07.004] [Citation(s) in RCA: 24] [Impact Index Per Article: 6.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/13/2021] [Revised: 07/16/2021] [Accepted: 07/16/2021] [Indexed: 12/11/2022]
Abstract
Pain is the most common symptom in chronic pancreatitis (CP) with a major impact on quality of life. Few validated questionnaires to assess pain in CP exist, and the lack of consensus negatively impacts clinical management, research and meta-analysis. This guideline aims to review generic pain questionnaires for their usability in CP, to outline how pain assessment can be modified by confounding factors and pain types, to assess the value of additional measures such as quality of life, mental health and quantitative sensory testing, and finally to review pain assessment questionnaires used specifically in CP. A systematic review was done to answer 27 questions that followed the PICO (Population; Intervention; Comparator; Outcome) template. Quality of evidence of the statements was judged by Grades of Recommendation, Assessment, Development and Evaluation (GRADE) criteria. The manuscript was sent for review to 36 experts from various disciplines and continents in a multi-stage Delphi process, and finally reviewed by patient representatives. Main findings were that generic pain instruments are valid in most settings, but aspects of pain are specific for CP (including in children), and instruments have to account for the wide phenotypic variability and development of sensitization of the central nervous system. Side effects to treatment and placebo effects shall also be considered. Some multidimensional questionnaires are validated for CP and are recommended together with assessment of quality of life and psychiatric co-morbidities. This guideline will result in more homogeneous and comprehensive pain assessment to potentially improve management of painful CP.
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Dunbar EK, Greer PJ, Amann ST, Alkaade S, Banks P, Brand R, Conwell DL, Forsmark CE, Gardner TB, Guda NM, Lewis MD, Machicado JD, Muniraj T, Papachristou GI, Romagnuolo J, Sandhu BS, Sherman S, Slivka A, Wilcox CM, Yadav D, Whitcomb DC. Pain Experience in Pancreatitis: Strong Association of Genetic Risk Loci for Anxiety and PTSD in Patients With Severe, Constant, and Constant-Severe Pain. Am J Gastroenterol 2021; 116:2128-2136. [PMID: 34236339 PMCID: PMC8531869 DOI: 10.14309/ajg.0000000000001366] [Citation(s) in RCA: 10] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/11/2021] [Accepted: 06/01/2021] [Indexed: 12/11/2022]
Abstract
INTRODUCTION Recurrent acute pancreatitis (RAP) and chronic pancreatitis (CP) are progressive inflammatory syndromes with variable features. Pain is the primary feature that contributes to low physical and mental quality of life with a third of patients reporting severe pain. Pain experience is worsened by depression. Here, we tested the hypothesis that genetic risk of the psychiatric conditions of anxiety and post-traumatic stress disorder (PTSD) is associated with pain in CP and RAP + CP subjects. METHODS The study cohort included phenotyped and genotyped RAP and CP patients from the North American Pancreatitis Study II of European Ancestry. Candidate genetic association studies were based on the absence of pain vs pain that is constant, constant-severe, or severe. Twenty-eight candidate genetic loci for anxiety and PTSD risk were identified in the literature and were the focus of this study. RESULTS We identified 24 significant pain-associated single nucleotide polymorphisms within 13 loci across the 3 pain patterns in CP and RAP + CP (P < 0.002). Thirteen anxiety or PTSD genes were within these pain loci indicating nonrandom associations (P < 4.885 × 10-23). CTNND2 was associated with all pain categories and all pancreatitis etiologies. Implicated systems include neuronal signaling (HTR2A, DRD3, NPY, and BDNF), hypothalamic-pituitary-adrenal axis (NR3C1 and FKBP5), and cell-cell interaction (CTNND2 and THBS2). DISCUSSION A component of constant and severe pain in patients with RAP and CP is associated with genetic predisposition to anxiety and PTSD. Identification of patients at risk eligible for trials of targeted treatment as a component of a multidisciplinary pain management strategy should be formally evaluated.
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Affiliation(s)
- Ellyn K Dunbar
- Department of Medicine, University of Pittsburgh, Pittsburgh, Pennsylvania, USA
- Department of Human Genetics, Graduate School of Public Health, University of Pittsburgh, Pittsburgh, Pennsylvania, USA
| | - Phil J Greer
- Department of Medicine, University of Pittsburgh, Pittsburgh, Pennsylvania, USA
- Current Address: Ariel Precision Medicine, Pittsburgh, Pennsylvania, USA
| | | | - Samer Alkaade
- Department of Medicine, St. Louis University, St. Louis, Missouri, USA
- Current affiliation: Mercy Clinic Gastroenterology St. Louis, Missouri, USA
| | - Peter Banks
- Department of Medicine, Harvard University, Brigham and Woman's Hospital, Boston, Massachusetts, USA
| | - Randall Brand
- Department of Medicine, University of Pittsburgh, Pittsburgh, Pennsylvania, USA
| | - Darwin L Conwell
- Department of Medicine, Harvard University, Brigham and Woman's Hospital, Boston, Massachusetts, USA
- Current address: Department of Internal Medicine, Division of Gastroenterology, Hepatology, and Nutrition, The Ohio State University Wexner Medical Center, Columbus, Ohio, USA
| | - Christopher E Forsmark
- Department of Medicine, University of Florida College of Medicine, Gainesville, Florida, USA
| | - Timothy B Gardner
- Section of Gastroenterology and Hepatology, Dartmouth-Hitchcock Medical Center, Lebanon, New Hampshire, USA
| | - Nalini M Guda
- Aurora St. Luke's Medical Center, GI Associates, Milwaukee, Wisconsin, USA
- Department of Medicine, School of Medicine and Public Health, University of Wisconsin, Madison, Wisconsin, USA
| | - Michele D Lewis
- Department of Medicine, Division of Gastroenterology and Hepatology, Mayo Clinic, Jacksonville, Florida, USA
| | - Jorge D Machicado
- Department of Medicine, University of Pittsburgh, Pittsburgh, Pennsylvania, USA
- Current address: Division of Gastroenterology and Hepatology, Mayo Clinic Health System, Eau Claire, Wisconsin, USA
| | - Thiruvengadam Muniraj
- Department of Medicine, University of Pittsburgh, Pittsburgh, Pennsylvania, USA
- Current address: Department of Medicine, Yale University, New Haven, Connecticut, USA
| | - Georgios I Papachristou
- Department of Medicine, University of Pittsburgh, Pittsburgh, Pennsylvania, USA
- Current address: Department of Internal Medicine, Division of Gastroenterology, Hepatology, and Nutrition, The Ohio State University Wexner Medical Center, Columbus, Ohio, USA
| | - Joseph Romagnuolo
- Department of Medicine, Medical University of South Carolina, Charleston, South Carolina, USA
- Current address: Ralph H. Johnson VAMC, Charleston, South Carolina, USA
| | - Bimaljit S Sandhu
- Department of Medicine, Medical College of Virginia, Richmond, Virginia, USA
- Current address: St. Mary's Hospital, Richmond, Virginia, USA
| | - Stuart Sherman
- Department of Medicine, Indiana University, Indianapolis, Indiana, USA
| | - Adam Slivka
- Department of Medicine, University of Pittsburgh, Pittsburgh, Pennsylvania, USA
| | - C Mel Wilcox
- Department of Medicine, University of Alabama at Birmingham, Birmingham, Alabama, USA
| | - Dhiraj Yadav
- Department of Medicine, University of Pittsburgh, Pittsburgh, Pennsylvania, USA
| | - David C Whitcomb
- Department of Medicine, University of Pittsburgh, Pittsburgh, Pennsylvania, USA
- Department of Human Genetics, Graduate School of Public Health, University of Pittsburgh, Pittsburgh, Pennsylvania, USA
- Department of Cell Biology & Molecular Physiology, and Center for Pain Research, University of Pittsburgh, Pittsburgh, Pennsylvania, USA
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Jeon CY, Feldman R, Althouse A, AlKaade S, Brand RE, Guda N, Sandhu BS, Singh VK, Wilcox CM, Slivka A, Gelrud A, Whitcomb DC, Yadav D. Lifetime smoking history and cohort-based smoking prevalence in chronic pancreatitis. Pancreatology 2021; 21:S1424-3903(21)00473-7. [PMID: 34116939 PMCID: PMC8628024 DOI: 10.1016/j.pan.2021.05.302] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/14/2021] [Revised: 05/21/2021] [Accepted: 05/22/2021] [Indexed: 12/11/2022]
Abstract
BACKGROUND/OBJECTIVE Smoking prevalence in patients with chronic pancreatitis [CP] is high. We aimed to understand lifetime history of smoking and cohort trends in CP patients to inform effective strategies for smoking cessation. METHOD Data on 317 CP patients from the North American Pancreatitis Study 2 [NAPS2] Continuation and Validation Study and the NAPS2 Ancillary Study were analyzed. Smoking history was assessed for each phase of life from the onset of smoking to study enrollment. Data on second-hand smoke and drinking history were also collected. We compared demographic factors, drinking history, pain level and pancreas morphology by smoking status at age 25 (non-smoking, <1 pack per day [PPD], ≥1 PPD). We compared smoking prevalence by birth cohorts: 1930-1949, 1950-1969, 1970-1989. RESULT Fifty-one percent of CP patients reported smoking at the time of enrollment. Those who smoked ≥1 PPD at age 25 smoked a cumulative total of 30.3 pack-years of cigarettes over a lifetime. Smoking at age 25 was associated with greater lifetime drinking and greater exposure to second-hand smoke at home and at workplace. Pancreatic atrophy and pseudocysts were more common among smokers. Pancreatic pain was more severe among smokers, and 12-13% of smokers reported smoking to alleviate pain. Male CP patients born in 1950-1969 reported the highest peak prevalence of smoking, and female CP patients born in 1970-1989 reported highest peak prevalence of smoking. CONCLUSION CP patients exhibit intense and sustained smoking behavior once established in the 20s. Regardless, cohort analyses demonstrate that the behaviors could potentially be altered by policy changes.
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Affiliation(s)
- Christie Y Jeon
- Cedars Sinai Cancer, Cedars-Sinai Medical Center, Los Angeles, CA, USA; Department of Epidemiology, UCLA Fielding School of Public Health, Los Angeles, CA, USA.
| | - Robert Feldman
- Center for Research on Healthcare Data Center, University of Pittsburgh, Pittsburgh, PA, USA
| | - Andrew Althouse
- Center for Research on Healthcare Data Center, University of Pittsburgh, Pittsburgh, PA, USA
| | | | - Randall E Brand
- Division of Gastroenterology, Hepatology and Nutrition, University of Pittsburgh School of Medicine, Pittsburgh, PA, USA
| | - Nalini Guda
- Aurora St. Luke's Medical Center, Milwaukee, WI, USA
| | | | - Vikesh K Singh
- Pancreatitis Center, Division of Gastroenterology, Johns Hopkins Medical Institutions, Baltimore, MD, USA
| | - C Mel Wilcox
- Division of Gastroenterology and Hepatology, University of Alabama Birmingham, AL, USA
| | - Adam Slivka
- Division of Gastroenterology, Hepatology and Nutrition, University of Pittsburgh School of Medicine, Pittsburgh, PA, USA
| | | | - David C Whitcomb
- Division of Gastroenterology, Hepatology and Nutrition, University of Pittsburgh School of Medicine, Pittsburgh, PA, USA
| | - Dhiraj Yadav
- Division of Gastroenterology, Hepatology and Nutrition, University of Pittsburgh School of Medicine, Pittsburgh, PA, USA
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Vipperla K, Kanakis A, Slivka A, Althouse AD, Brand RE, Phillips AE, Chennat J, Papachristou GI, Lee KK, Zureikat AH, Whitcomb DC, Yadav D. Natural course of pain in chronic pancreatitis is independent of disease duration. Pancreatology 2021; 21:649-657. [PMID: 33674197 DOI: 10.1016/j.pan.2021.01.020] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/06/2020] [Revised: 01/23/2021] [Accepted: 01/25/2021] [Indexed: 02/07/2023]
Abstract
OBJECTIVES Pain burn-out during the course of chronic pancreatitis (CP), proposed in the 1980s, remains controversial, and has clinical implications. We aimed to describe the natural course of pain in a well-characterized cohort. METHODS We constructed the clinical course of 279 C P patients enrolled from 2000 to 2014 in the North American Pancreatitis Studies from UPMC by retrospectively reviewing their medical records (median observation period, 12.4 years). We assessed abdominal pain at different time points, characterized pain pattern (Type A [short-lived pain episodes] or B [persistent pain and/or clusters of recurrent severe pain]) and recorded information on relevant covariates. RESULTS Pain at any time, at the end of follow-up, Type A pain pattern or B pain pattern was reported by 89.6%, 46.6%, 34% and 66% patients, respectively. In multivariable analyses, disease duration (time from first diagnosis of pancreatitis to end of observation) did not associate with pain - at last clinical contact (OR, 1.0, 95% CI 0.96-1.03), at NAPS2 enrollment (OR 1.02, 95% CI 0.96-1.07) or Type B pain pattern (OR 1.01, 95% CI 0.97-1.04). Patients needing endoscopic or surgical therapy (97.8 vs. 75.2%, p < 0.001) and those with alcohol etiology (94.7 vs. 84.9%, p = 0.007) had a higher prevalence of pain. In multivariable analyses, invasive therapy associated with Type B pain and pain at last clinical contact. CONCLUSIONS Only a subset of CP patients achieve durable pain relief. There is urgent need to develop new strategies to evaluate and manage pain, and to identify predictors of response to pain therapies for CP.
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Affiliation(s)
- Kishore Vipperla
- Division of Gastroenterology, Hepatology and Nutrition, University of Pittsburgh Medical Center, Pittsburgh, PA, USA
| | - Allison Kanakis
- Division of General Medicine, Department of Medicine, University of Pittsburgh Medical Center, Pittsburgh, PA, USA
| | - Adam Slivka
- Division of Gastroenterology, Hepatology and Nutrition, University of Pittsburgh Medical Center, Pittsburgh, PA, USA
| | - Andrew D Althouse
- Center for Research on Health Care Data Center, Department of Medicine, University of Pittsburgh, PA, USA
| | - Randall E Brand
- Division of Gastroenterology, Hepatology and Nutrition, University of Pittsburgh Medical Center, Pittsburgh, PA, USA
| | - Anna E Phillips
- Division of Gastroenterology, Hepatology and Nutrition, University of Pittsburgh Medical Center, Pittsburgh, PA, USA
| | - Jennifer Chennat
- Division of Gastroenterology, Hepatology and Nutrition, University of Pittsburgh Medical Center, Pittsburgh, PA, USA
| | - Georgios I Papachristou
- Division of Gastroenterology, Hepatology and Nutrition, Ohio State University Wexner Medical Center, Columbus, OH, USA
| | - Kenneth K Lee
- Division of Surgical Oncology, University of Pittsburgh Medical Center, Pittsburgh, PA, USA
| | - Amer H Zureikat
- Division of Surgical Oncology, University of Pittsburgh Medical Center, Pittsburgh, PA, USA
| | - David C Whitcomb
- Division of Gastroenterology, Hepatology and Nutrition, University of Pittsburgh Medical Center, Pittsburgh, PA, USA
| | - Dhiraj Yadav
- Division of Gastroenterology, Hepatology and Nutrition, University of Pittsburgh Medical Center, Pittsburgh, PA, USA.
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Lewis MD, Talluri J, Wilcox CM, Abberbock JN, Tang G, Conwell DL, Banks PA, Cote GA, Sherman S, Alkaade S, Gardner TB, Anderson MA, Sandhu BS, Muniraj T, Forsmark CE, Guda N, Gelrud A, Romagnuolo J, Brand R, LaRusch J, Amann ST, Slivka A, Whitcomb DC, Yadav D. Differences in Age at Onset of Symptoms, and Effects of Genetic Variants, in Patients With Early vs Late-Onset Idiopathic Chronic Pancreatitis in a North American Cohort. Clin Gastroenterol Hepatol 2021; 19:349-357. [PMID: 32240833 PMCID: PMC7529676 DOI: 10.1016/j.cgh.2020.03.047] [Citation(s) in RCA: 8] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/10/2020] [Revised: 03/13/2020] [Accepted: 03/22/2020] [Indexed: 02/07/2023]
Abstract
BACKGROUND & AIMS Idiopathic chronic pancreatitis (ICP) is the second most common subtype of CP. In 1994, researchers reported the bimodal age at onset of ICP symptoms: early onset ICP (EO-ICP; median age, 19.2 y) and late-onset ICP (LO-ICP; median age, 56.2 y). Ages of onset and clinical features of ICP differed from those of alcohol-related CP (ACP). However, variants in PRSS1 had not yet been associated with ICP. We reexamined ages of onset of ICP in a large, North American cohort of patients, and investigated the effects of genetic factors and alcohol use in patients with EO-ICP, LO-ICP, and ACP. METHODS We performed a cross-sectional analysis of patients with CP of European ancestry enrolled in the North American Pancreatitis Study 2, a prospective study of 1195 patients with CP from 26 centers in the United States from August 2000 through December 2014. We compared age at onset of symptoms for 130 patients with CP who were lifetime abstainers from alcohol (61 patients with early onset and 69 patients with late onset), 308 light to moderate alcohol drinkers with CP, and 225 patients with ACP and heavy to very heavy alcohol use. DNA from available patients was analyzed for variants associated with CP in SPINK1, CFTR, and CTRC. The Kruskal-Wallis test was used to compare continuous variables across groups and based on genetic variants. RESULTS Median ages at onset of symptoms were 20 years for patients with EO-ICP and no alcohol use, 58 years for patients with LO-ICP and no alcohol use, 47 years for light to moderate alcohol drinkers with CP, and 44 years for patients with ACP. A higher proportion of patients with EO-ICP had constant pain (65%) than patients with LO-ICP (31%) (P = .04). A higher proportion of patients with ACP had pseudocysts (43%) than patients with EO-ICP (11%) (P = .001). A higher proportion of patients with EO-ICP had pathogenic variants in SPINK1, CFTR, or CTRC (49%) than patients with LO-ICP (23%), light to moderate alcohol drinking with CP (26%), or ACP (23%) (P = .001). Among patients with variants in SPINK1, those with EO-ICP had onset of symptoms at a median age of 12 years, and light to moderate alcohol drinkers with CP had an age at onset of 24 years. Among patients with variants in CFTR, light to moderate alcohol drinkers had an age at onset of symptoms of 41 years, but this variant did not affect age at onset of EO-ICP or ACP. CONCLUSIONS We confirmed previously reported ages at onset of symptoms for EO-ICP and LO-ICP in a North American cohort. We found differences in clinical features among patients with EO-ICP, LO-ICP, and ACP. Almost half of patients with EO-ICP have genetic variants associated with CP, compared with approximately one quarter of patients with LO-CP or ACP. Genetic variants affect ages at onset of symptoms in some groups.
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Affiliation(s)
- Michele D Lewis
- Division of Gastroenterology and Hepatology, Mayo Clinic, Jacksonville, Florida.
| | - Jyothsna Talluri
- Department of Medicine, University of Pittsburgh, Pittsburgh, Pennsylvania
| | - C Mel Wilcox
- Division of Gastroenterology, University of Alabama at Birmingham, Birmingham, Alabama
| | - Judah N Abberbock
- Division of Biostatistics, University of Pittsburgh, Pittsburgh, Pennsylvania
| | - Gong Tang
- Division of Biostatistics, University of Pittsburgh, Pittsburgh, Pennsylvania
| | - Darwin L Conwell
- Division of Gastroenterology, Brigham and Women's Hospital, Boston, Massachusetts
| | - Peter A Banks
- Division of Gastroenterology, Brigham and Women's Hospital, Boston, Massachusetts
| | - Gregory A Cote
- Division of Gastroenterology, Indiana University School of Medicine, Indianapolis, Indiana
| | - Stuart Sherman
- Division of Gastroenterology, Indiana University School of Medicine, Indianapolis, Indiana
| | - Samer Alkaade
- Division of Gastroenterology, Saint Louis University School of Medicine, St. Louis, Missouri
| | - Timothy B Gardner
- Division of Gastroenterology, Dartmouth-Hitchcock Medical Center, Lebanon, New Hampshire
| | - Michelle A Anderson
- Division of Gastroenterology, University of Michigan School of Medicine, Ann Arbor, Michigan
| | - Bimaljit S Sandhu
- Division of Gastroenterology, Virginia Commonwealth University School of Medicine, Richmond, Virginia
| | | | - Chris E Forsmark
- Division of Gastroenterology, University of Florida College of Medicine, Gainesville, Florida
| | | | - Andres Gelrud
- Division of Gastroenterology, University of Chicago School of Medicine, Chicago, Illinois
| | - Joseph Romagnuolo
- Division of Gastroenterology, Medical University of South Carolina, Charleston, South Carolina
| | - Randall Brand
- Division of Gastroenterology, University of Pittsburgh, Pittsburgh, Pennsylvania
| | - Jessica LaRusch
- Division of Gastroenterology, University of Pittsburgh, Pittsburgh, Pennsylvania
| | | | - Adam Slivka
- Division of Gastroenterology, University of Pittsburgh, Pittsburgh, Pennsylvania
| | - David C Whitcomb
- Division of Gastroenterology, University of Pittsburgh, Pittsburgh, Pennsylvania
| | - Dhiraj Yadav
- Division of Gastroenterology, University of Pittsburgh, Pittsburgh, Pennsylvania
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Messallam AA, Body CB, Berger S, Sakaria SS, Chawla S. Impact of early aggressive fluid resuscitation in acute pancreatitis. Pancreatology 2021; 21:69-73. [PMID: 33257225 DOI: 10.1016/j.pan.2020.11.006] [Citation(s) in RCA: 9] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/21/2020] [Revised: 08/30/2020] [Accepted: 11/19/2020] [Indexed: 12/11/2022]
Abstract
BACKGROUND/OBJECTIVES Acute pancreatitis management guidelines recommend early aggressive hydration to improve clinical outcomes. We aim to evaluate the influence of early fluid therapy (total intravenous fluids in the first 24 h [IVF/24hrs]) on clinical outcomes in patients with acute pancreatitis. METHODS This was a retrospective chart review of all patients admitted for acute pancreatitis between July 2011 to December 2015. IVF/24hrs was categorized into 3 groups according to tertiles. Logistic regression was performed to evaluate predictors of persistent organ failure and in-hospital mortality. RESULTS A total of 310 patients were included: Conservative (IVF/24hrs < 2.8L, n = 102), Moderate (IVF/24hrs 2.8-4.475L, n = 105) and Aggressive (IVF/24hrs ≥ 4.475, n = 103). Most patients (80.6%) were African Americans, 91.3% had mild acute pancreatitis (BISAP score ≤ 2). The Aggressive IVF group had higher incidence of persistent organ failure (16.5% vs 4.9% and 7.6%, p = 0.013), and longer length of hospital stay (9.2 ± 10.7 vs 6.5 ± 7.3 and 6.8 ± 5.7 days, P = 0.032). However, IVF/24hr did not correlate with length of hospital stay (PCC 0.08, p = 0.174). On multivariate analysis, only organ failure at admission was an independent predictor of persistent organ failure (OR 16.1, p < 0.001). Persistent organ failure and local complications were found to be the only independent predictors in-hospital mortality (OR 27.6, p < 0.001 and OR 16.95, p = 0.001 respectively). There was no difference in clinical outcomes in African Americans compared to other races. CONCLUSIONS More aggressive early IVF therapy in a predominantly mild acute pancreatitis cohort, was not associated with improvement in persistent organ failure, length of hospital stay, or in-hospital mortality.
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Affiliation(s)
- Ahmed A Messallam
- Division of Digestive Diseases, Emory University School of Medicine, Atlanta, GA, USA
| | - Cameron B Body
- Division of Digestive Diseases, Emory University School of Medicine, Atlanta, GA, USA
| | - Stephen Berger
- Division of Digestive Diseases, Emory University School of Medicine, Atlanta, GA, USA
| | - Sonali S Sakaria
- Division of Digestive Diseases, Emory University School of Medicine, Atlanta, GA, USA
| | - Saurabh Chawla
- Division of Digestive Diseases, Emory University School of Medicine, Atlanta, GA, USA.
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Marfil-Garza BA, Kim R, Shapiro AMJ, Kin T. Frequency of Obliteration of the Dorsal and Ventral Ducts of the Pancreas in Islet Transplantation. Dig Dis Sci 2021; 66:218-223. [PMID: 32086688 DOI: 10.1007/s10620-020-06145-1] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/10/2019] [Accepted: 02/11/2020] [Indexed: 02/07/2023]
Abstract
BACKGROUND Islet isolation is an essential process in every human islet transplantation protocol. Intraductal enzyme delivery followed by adequate distention of the pancreas is the most critical step in islet isolation. Anomalies of the pancreatic duct system can significantly affect this process. Thus, identification and characterization of ductal patency is of paramount importance to achieve optimal islet isolation. AIMS To investigate the frequency of duct obliteration in the human pancreas and explore donor/patient characteristics associated with specific ductal variations. METHODS We examined ductal patency of pancreata allocated for islet allotransplantation (n = 597) and autotransplantation (n = 21) after removal of the duodenum during islet isolation procedure. Donor/patient factors were reviewed from the batch files. RESULTS Among 559 deceased donor pancreata without pancreas divisum (n = 38, 6.4%), both ducts were patent in 50.1%, only ventral duct was patent in 46.7%, and only dorsal duct was patent in 3.2%. Donor age was not associated with the frequency of obliterated dorsal duct. Black race tended to have the higher frequency of patent dorsal duct. As expected, pancreas divisum was more frequent in chronic pancreatitis cases (n = 6, 28.6%). Within 7 cases of chronic pancreatitis with unknown etiology, we encountered one case of ventral duct obliteration. CONCLUSIONS The minor duodenal papilla and aging do not likely play an important role in the occurrence of dorsal duct obliteration. Although frequency of obliterated ventral duct was low in our population, physicians, including gastroenterologists and endoscopists, as well as islet transplantation researchers should be aware of this possibility.
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Affiliation(s)
- Braulio A Marfil-Garza
- Clinical Islet Transplant Program, University of Alberta, 210 College Plaza 8215-112 St, Edmonton, AB, T6G2C8, Canada
| | - Ryekjang Kim
- Department of Pharmacology, University of Alberta, Edmonton, AB, Canada
| | - A M James Shapiro
- Clinical Islet Transplant Program, University of Alberta, 210 College Plaza 8215-112 St, Edmonton, AB, T6G2C8, Canada
| | - Tatsuya Kin
- Clinical Islet Transplant Program, University of Alberta, 210 College Plaza 8215-112 St, Edmonton, AB, T6G2C8, Canada.
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Psychiatric Comorbidity in Patients With Chronic Pancreatitis Associates With Pain and Reduced Quality of Life. Am J Gastroenterol 2020; 115:2077-2085. [PMID: 32740078 DOI: 10.14309/ajg.0000000000000782] [Citation(s) in RCA: 42] [Impact Index Per Article: 8.4] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/11/2022]
Abstract
INTRODUCTION Abdominal pain, frequent in patients with chronic pancreatitis (CP), has a negative impact on quality of life (QOL). Psychiatric comorbidities including anxiety and depression are associated with pain, but their prevalence and effects on QOL in CP have not been quantified. We studied the prevalence of anxiety and depression in patients with CP and their associated patient and disease characteristics and impact on QOL. METHODS This was a cross-sectional, multicenter prospective study. Patients were screened with the Hospital Anxiety and Depression Scale questionnaire. A Hospital Anxiety and Depression Scale score >7 on the respective anxiety or depression subscales indicated the presence of anxiety or depression and was used as a surrogate for the diagnosis of psychiatric comorbidities. Patient demographics, disease characteristics, QOL (EORTC-QLQ-C30), and pain symptoms (Brief Pain Inventory Short Form) were compared between patients with and without psychiatric comorbidities. RESULTS One hundred seventy-one patients with CP (mean age 53.8 ± 13.7 years, 60% men) were included. Anxiety and depression were present in 80 (46.8%) and 66 (38.6%) patients, with overlap in 50 (29%). Patients with anxiety or depression reported higher pain prevalence, pain severity, and pain interference scores (all P < 0.001). Psychiatric comorbidities also associated with reduced global health scores and functional subscales (all P < 0.001) and higher symptom burden (P ≤ 0.03). An independent association was noted between global health status and depression (P < 0.001). DISCUSSION Psychiatric comorbidities are prevalent in patients with CP and associated with pain and QOL. Where the effect of anxiety on QOL may be mediated via pain, depression is independently related to QOL. These findings warrant consideration in the management of patients with CP.
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Sugumar K, Deshpande A. Outcomes of pain management in chronic pancreatitis: experience from a tertiary care hospital in India. Turk J Surg 2020; 36:359-367. [PMID: 33778395 PMCID: PMC7963307 DOI: 10.47717/turkjsurg.2020.4924] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/30/2020] [Accepted: 10/03/2020] [Indexed: 11/23/2022]
Abstract
OBJECTIVES Chronic pancreatitis (CP) is a progressive inflammatory disorder that leads to irreversible destruction of exocrine and endocrine parenchyma. Little is known about outcomes of CP in the Indian subcontinent. We aim to study the treatment outcomes of CP in terms of pain severity in a tertiary hospital in India. MATERIAL AND METHODS This is a prospective cohort study of 75 patients diagnosed with CP. Data regarding patient demographics, symptoms, and imaging findings were recorded. Pain severity was recorded objectively by the visual analogue scale (VAS). Cambridge score was calculated, and patients were classified into mild, moderate and severe categories. Patients were treated appropriately, and pain scores were monitored at 3 months and 6 months after initial visit. RESULTS Alcohol was the most common etiology (54%) followed by idiopathic/unknown causes (34%). Cambridge score or morphology on imaging did not affect pain severity (p>0.05). History of smoking and larger duct diameter decreased the effectiveness of treatment in reducing pain while higher post prandial sugar levels increased effectiveness (p<0.05). Pain relief did not differ between the treatment groups including analgesics, endoscopic or surgery (p>0.05). CONCLUSION CP presents earlier in the Indian population and represents a unique population with a greater proportion of idiopathic cases than western countries. Rather than pancreatic morphology or Cambridge score alone, a combination of morphology, pain severity and functional status can be utilized for formulating an individualized treatment plan. Present treatment strategies prove effective in treatment of CP.
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Affiliation(s)
- Kavin Sugumar
- Seth GS and King Edward Memorial Hospital, Clinic of Surgery, Mumbai, India
| | - Aparna Deshpande
- Seth GS and King Edward Memorial Hospital, Clinic of Surgery, Mumbai, India
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Jeon CY, Feldman R, Pendergast FJ, AlKaade S, Brand RE, Guda N, Sandhu BS, Singh VK, Wilcox CM, Slivka A, Whitcomb DC, Yadav D. Divergent trends in lifetime drinking and smoking between Black and White Americans diagnosed with chronic pancreatitis. Pancreatology 2020; 20:1667-1672. [PMID: 33132046 PMCID: PMC7737506 DOI: 10.1016/j.pan.2020.10.031] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/15/2020] [Revised: 09/08/2020] [Accepted: 10/08/2020] [Indexed: 12/11/2022]
Abstract
BACKGROUND/OBJECTIVES Black Americans are at increased risk of chronic pancreatitis (CP) compared to their White counterparts. We aimed to describe the race-specific smoking history and lifetime drinking in patients diagnosed with CP. METHODS We analyzed data on 334 Black and White CP participants of the North American Pancreatitis Study 2 Continuation and Validation Study and Ancillary Study. Lifetime drinking history and lifetime smoking history were collected through in-person interviews. Intensity, frequency, duration and current status of drinking and smoking were compared between Black and White CP participants, stratified by physician-defined alcohol etiology. In addition, drinking levels at each successive decades in life (20s, 30s, 40s) were compared by race and graphically portrayed as heat diagrams. RESULTS Among patients with alcoholic CP, current smoking levels were not different by race (67-70%), but a smaller proportion of Black patients reported having smoked 1 or more packs per day in the past (32%) as compared to White patients (58%, p < 0.0001). Black patients were more likely to report current consumption of alcohol (31%), as opposed to White patients (17%, p = 0.016). Black patients also reported more intense drinking at age 35 and 45 years as compared to White patients, while age at CP onset were similar between the two groups. CONCLUSION We found more intense drinking but less intense smoking history in Black CP patients as compared to White CP patients. Effective alcohol abstinence and smoking cessation program with sustained impact are needed in CP patients.
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Affiliation(s)
- Christie Y Jeon
- Cedars Sinai Cancer, Cedars-Sinai Medical Center, Los Angeles, CA, USA; Department of Epidemiology, UCLA Fielding School of Public Health, Los Angeles, CA, USA.
| | - Robert Feldman
- Center for Research on Healthcare Data Center, University of Pittsburgh, Pittsburgh, PA, USA
| | | | | | - Randall E Brand
- Division of Gastroenterology, Hepatology and Nutrition, University of Pittsburgh School of Medicine, Pittsburgh, PA, USA
| | - Nalini Guda
- Aurora St. Luke's Medical Center, Milwaukee, WI, USA
| | | | - Vikesh K Singh
- Pancreatitis Center, Division of Gastroenterology, Johns Hopkins Medical Institutions, Baltimore, MD, USA
| | - C Mel Wilcox
- Division of Gastroenterology and Hepatology, University of Alabama Birmingham, AL, USA
| | - Adam Slivka
- Division of Gastroenterology, Hepatology and Nutrition, University of Pittsburgh School of Medicine, Pittsburgh, PA, USA
| | - David C Whitcomb
- Division of Gastroenterology, Hepatology and Nutrition, University of Pittsburgh School of Medicine, Pittsburgh, PA, USA
| | - Dhiraj Yadav
- Division of Gastroenterology, Hepatology and Nutrition, University of Pittsburgh School of Medicine, Pittsburgh, PA, USA
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Dunbar E, Greer PJ, Melhem N, Alkaade S, Amann ST, Brand R, Coté GA, Forsmark CE, Gardner TB, Gelrud A, Guda NM, LaRusch J, Lewis MD, Machicado JD, Muniraj T, Papachristou GI, Romagnuolo J, Sandhu BS, Sherman S, Wilcox CM, Singh VK, Yadav D, Whitcomb DC. Constant-severe pain in chronic pancreatitis is associated with genetic loci for major depression in the NAPS2 cohort. J Gastroenterol 2020; 55:1000-1009. [PMID: 32681239 PMCID: PMC9124361 DOI: 10.1007/s00535-020-01703-w] [Citation(s) in RCA: 26] [Impact Index Per Article: 5.2] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/07/2020] [Accepted: 06/17/2020] [Indexed: 02/07/2023]
Abstract
BACKGROUND Pain is the most debilitating symptom of recurrent acute pancreatitis (RAP) and chronic pancreatitis (CP) and often requires chronic opioids or total pancreatectomy with islet autotransplantation to manage. Pain is a complex experience that can be exacerbated by depression and vice versa. Our aim was to test the hypothesis that depression-associated genes are associated with a constant-severe pain experience in RAP/CP patients. STUDY A retrospective study was done using North American Pancreatitis Study II (NAPS2) genotyped RAP and CP patients with completed case report forms (n = 1,357). Subjects were divided based on pattern of pain and pain severity as constant-severe pain (n = 787) versus not constant-severe pain (n = 570) to conduct a nested genome-wide association study. The association between reported antidepressant medication use and depression gene loci was tested. RESULTS Constant-severe pain was reported in 58% (n = 787) of pancreatitis patients. No differences in sex or alcohol consumption were found based on pain severity. Antidepressant use was reported in 28% (n = 223), and they had lower SF-12 mental quality of life (MCS, p < 2.2 × 10- 16). Fifteen loci associated with constant-severe pain (p < 0.00001) were found to be in or near depression-associated genes including ROBO2, CTNND2, SGCZ, CNTN5 and BAIAP2. Three of these genes respond to antidepressant use (SGCZ, ROBO2, and CTNND2). CONCLUSION Depression is a major co-factor in the pain experience. This genetic predisposition to depression may have utility in counseling patients and in instituting early antidepressant therapy for pain management of pancreatitis patients. Prospective randomized trials are warranted. CLINICAL TRIALS REGISTRATION Clinicaltriasl.gov.# NCT01545167.
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Affiliation(s)
- Ellyn Dunbar
- Department of Medicine, University of Pittsburgh, Room 401.4, 3708 Fifth Ave, Pittsburgh, PA, 15213, USA
- Department of Human Genetics, Graduate School of Public Health, University of Pittsburgh, Pittsburgh, PA, USA
| | - Phil J Greer
- Department of Medicine, University of Pittsburgh, Room 401.4, 3708 Fifth Ave, Pittsburgh, PA, 15213, USA
| | - Nadine Melhem
- Department of Psychiatry, University of Pittsburgh, Pittsburgh, PA, USA
| | - Samer Alkaade
- Department of Medicine, St. Louis University, St. Louis, MO, USA
- Mercy Clinic Gastroenterology, St. Louis, MO, USA
| | | | - Randall Brand
- Department of Medicine, University of Pittsburgh, Room 401.4, 3708 Fifth Ave, Pittsburgh, PA, 15213, USA
| | - Gregory A Coté
- Indiana University School of Medicine, Indianapolis, IN, USA
- Department of Medicine, Medical University of South Carolina, Charleston, SC, USA
| | | | - Timothy B Gardner
- Section of Gastroenterology and Hepatology, Dartmouth-Hitchcock Medical Center, Lebanon, NH, USA
| | - Andres Gelrud
- Department of Medicine, University of Pittsburgh, Room 401.4, 3708 Fifth Ave, Pittsburgh, PA, 15213, USA
- Department of Medicine, University of Cincinnati, Cincinnati, OH, USA
- GastroHealth, Miami, FL, USA
| | | | - Jessica LaRusch
- Department of Medicine, University of Pittsburgh, Room 401.4, 3708 Fifth Ave, Pittsburgh, PA, 15213, USA
- Ariel Precision Medicine, Pittsburgh, PA, USA
| | - Michele D Lewis
- Department of Medicine, Division of Gastroenterology and Hepatology, Mayo Clinic, Jacksonville, FL, USA
| | - Jorge D Machicado
- Department of Medicine, University of Pittsburgh, Room 401.4, 3708 Fifth Ave, Pittsburgh, PA, 15213, USA
- Division of Gastroenterology and Hepatology, Mayo Clinic Health System, Eau Claire, WI, USA
| | - Thiruvengadam Muniraj
- Department of Medicine, University of Pittsburgh, Room 401.4, 3708 Fifth Ave, Pittsburgh, PA, 15213, USA
- Department of Medicine, Yale University Medical Center, New Haven, CT, USA
| | - Georgios I Papachristou
- Department of Medicine, University of Pittsburgh, Room 401.4, 3708 Fifth Ave, Pittsburgh, PA, 15213, USA
- Department of Medicine, The Ohio State University, Columbus, OH, USA
| | - Joseph Romagnuolo
- Department of Medicine, Medical University of South Carolina, Charleston, SC, USA
- Ralph H. Johnson VAMC, Charleston, SC, USA
| | - Bimaljit S Sandhu
- Department of Medicine, Medical College of Virginia, Richmond, VA, USA
- St Mary's Hospital, Richmond, VA, USA
| | - Stuart Sherman
- Indiana University School of Medicine, Indianapolis, IN, USA
| | - Charles M Wilcox
- Department of Medicine, University of Alabama At Birmingham, Birmingham, AL, USA
| | - Vikesh K Singh
- Department of Medicine, Johns Hopkins Medical Institutions, Baltimore, MD, USA
| | - Dhiraj Yadav
- Department of Medicine, University of Pittsburgh, Room 401.4, 3708 Fifth Ave, Pittsburgh, PA, 15213, USA
| | - David C Whitcomb
- Department of Medicine, University of Pittsburgh, Room 401.4, 3708 Fifth Ave, Pittsburgh, PA, 15213, USA.
- Department of Human Genetics, Graduate School of Public Health, University of Pittsburgh, Pittsburgh, PA, USA.
- Department of Cell Biology and Molecular Physiology, University of Pittsburgh, Pittsburgh, PA, USA.
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Zhan W, Akshintala V, Greer PJ, Greer JB, Alkaade S, Anderson MA, Muniraj T, Papachristou GI, Sandhu BS, Slivka A, Wilcox CM, Bellin MD, Singh VK, Yadav D, Brand RE, Whitcomb DC. Low serum trypsinogen levels in chronic pancreatitis: Correlation with parenchymal loss, exocrine pancreatic insufficiency, and diabetes but not CT-based cambridge severity scores for fibrosis. Pancreatology 2020; 20:1368-1378. [PMID: 32967795 DOI: 10.1016/j.pan.2020.08.025] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.4] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/29/2020] [Revised: 08/26/2020] [Accepted: 08/30/2020] [Indexed: 12/11/2022]
Abstract
BACKGROUND Chronic pancreatitis (CP) is a complex inflammatory disorder of the pancreas affecting acinar cells, duct cells, islet cells and inflammatory cells including fibrosis-producing stellate cells. Serum trypsinogen is a biomarkers of acinar cell function. AIM To define the degree of correlation between low trypsinogen levels as a marker of acinar cell function and variable features of CP. METHODS Serum samples from previously ascertained and well phenotyped case and control subjects from the North American Pancreatitis Study II (NAPS2) were used to measure serum trypsinogen levels in a commercial laboratory. Control samples were used to define normal ranges and compared with levels in CP patients with defined features. RESULTS A final cohort of 279 CP patients and 262 controls from the NAPS2 studies were evaluated. In controls trypsinogen had a mean of 34.96 ng/ml and SD = 11.99. Cut-off values for low trypsinogen ranged from <20 to 10 ng/ml and very low trypsinogen at <10 ng/ml. Compared to controls, CP was associated with very low trypsinogen levels (p < 0.0001). Within CP, very low trypsinogen levels correlated with parenchymal loss (pancreatic surgery [p < 0.05]; atrophy with calcifications, [p < 0.001]), EPI (p < 0.01, trend p < 0.001) and diabetes (trend p < 0.01) but not CT-based criteria for fibrosis (pancreatic duct dilation, irregularity, strictures). CONCLUSIONS Very low serum trypsinogen levels correlate with measures of acinar cell loss including surgical resection, atrophic-calcific CP, diabetes and functional symptoms EPI but not duct morphology criteria. Serum trypsinogen levels correlate with decreased acinar cell function and therefore have biomarker utility clinical management.
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Affiliation(s)
- Wei Zhan
- Department of Medicine, University of Pittsburgh, Pittsburgh, PA, USA
| | - Venkata Akshintala
- Department of Medicine, Johns Hopkins Medical Institutions, Baltimore, MD, USA
| | - Phil J Greer
- Department of Medicine, University of Pittsburgh, Pittsburgh, PA, USA
| | - Julia B Greer
- Department of Medicine, University of Pittsburgh, Pittsburgh, PA, USA
| | - Samer Alkaade
- Department of Medicine, Saint Louis University, St. Louis, MO, USA
| | | | | | | | - Bimaljit S Sandhu
- Department of Medicine, Virginia Commonwealth University, Richmond, VA, USA
| | - Adam Slivka
- Department of Medicine, University of Pittsburgh, Pittsburgh, PA, USA
| | - C Mel Wilcox
- Department of Medicine, University of Alabama Birmingham, Birmingham, AL, USA
| | - Melena D Bellin
- Department of Pediatrics, University of Minnesota Medical Center and Masonic Children's Hospital, Minneapolis, MN, USA
| | - Vikesh K Singh
- Department of Medicine, Johns Hopkins Medical Institutions, Baltimore, MD, USA
| | - Dhiraj Yadav
- Department of Medicine, University of Pittsburgh, Pittsburgh, PA, USA
| | - Randall E Brand
- Department of Medicine, University of Pittsburgh, Pittsburgh, PA, USA
| | - David C Whitcomb
- Department of Medicine, University of Pittsburgh, Pittsburgh, PA, USA; Department of Cell Biology and Molecular Physiology, University of Pittsburgh, Pittsburgh, PA, USA; Department of Human Genetics, Graduate School of Public Health, University of Pittsburgh, Pittsburgh, PA, USA.
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Abstract
The Toxic-metabolic, Idiopathic, Genetic, Autoimmune, Recurrent and severe acute pancreatitis and Obstructive (TIGAR-O) Pancreatitis Risk/Etiology Checklist (TIGAR-O_V1) is a broad classification system that lists the major risk factors and etiologies of recurrent acute pancreatitis, chronic pancreatitis, and overlapping pancreatic disorders with or without genetic, immunologic, metabolic, nutritional, neurologic, metaplastic, or other features. New discoveries and progressive concepts since the 2001 TIGAR-O list relevant to understanding and managing complex pancreatic disorders require an update to TIGAR-O_V2 with both a short (S) and long (L) form. The revised system is designed as a hierarchical checklist for health care workers to quickly document and track specific factors that, alone or in combinations, may contribute to progressive pancreatic disease in individual patients or groups of patients and to assist in treatment selection. The rationale and key clinical considerations are summarized for each updated classification item. Familiarity with the structured format speeds up the completion process and supports thoroughness and consideration of complex or alternative diagnoses during evaluation and serves as a framework for communication. The structured approach also facilitates the new health information technologies that required high-quality data for accurate precision medicine. A use primer accompanies the TIGAR-O_V2 checklist with rationale and comments for health care workers and industries caring for patients with pancreatic diseases.
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Singhvi A, Abromitis R, Althouse AD, Bataller R, Arteel GE, Yadav D. Coexistence of alcohol-related pancreatitis and alcohol-related liver disease: A systematic review and meta-analysis. Pancreatology 2020; 20:1069-1077. [PMID: 32800649 PMCID: PMC7970449 DOI: 10.1016/j.pan.2020.07.412] [Citation(s) in RCA: 6] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/16/2020] [Revised: 07/02/2020] [Accepted: 07/28/2020] [Indexed: 12/11/2022]
Abstract
BACKGROUND Available estimates of coexistent alcohol-related pancreatitis (ALP) and alcohol-related liver disease (ALD) vary widely, and factors that determine coexistent disease are largely unknown. We performed a systematic review of published literature with the primary aim to generate robust estimates for coexistent alcohol-related chronic pancreatitis (ACP) and alcohol-related cirrhosis (ALC). METHODS We searched PubMed, EMBASE, and Web of Science databases from inception until February 2018. Studies included were those in English-language, sample size ≥25 and allowed calculation of the coexistent disease. Pooled estimates were calculated using a random-effects model approach. RESULTS Twenty-nine (including 5 autopsy studies) of 2000 eligible studies met inclusion criteria. Only 6.9% included patients were female. Fifteen studies enabled calculation of ACP in ALC, and 11 for ALC in ACP. Pooled prevalence of ACP in ALC was 16.2% (95% CI 10.4-24.5) overall, and 15.5% (95% CI 8.0-27.7) when data were limited to clinical studies. Corresponding prevalence for ALC in ACP was 21.5% (95% CI 12.0-35.6) and 16.9% (95% CI 11.5-24.3), respectively. There was significant heterogeneity among studies (I2 - 65-92%). Pooled prevalence for ALP in ALD or ALD in ALP in clinical studies were 15.2% and 39%, respectively. None of the studies reported outcomes in patients with coexistent disease. CONCLUSION A sizeable fraction of patients with ACP or ALC have coexistent disease. Future studies should define the prevalence of coexistent disease in women and minority populations, and the consequences of coexistent disease on clinical presentation and short- and long-term outcomes.
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Affiliation(s)
- Ajay Singhvi
- Division of Gastroenterology, Hepatology & Nutrition, University of Pittsburgh Medical Center, Pittsburgh, PA, United States
| | - Rebecca Abromitis
- Health Sciences Library System, University of Pittsburgh, Pittsburgh, PA, United States
| | - Andrew D Althouse
- Division of General Internal Medicine, University of Pittsburgh Medical Center, Pittsburgh, PA, United States
| | - Ramon Bataller
- Division of Gastroenterology, Hepatology & Nutrition, University of Pittsburgh Medical Center, Pittsburgh, PA, United States
| | - Gavin E Arteel
- Division of Gastroenterology, Hepatology & Nutrition, University of Pittsburgh Medical Center, Pittsburgh, PA, United States
| | - Dhiraj Yadav
- Division of Gastroenterology, Hepatology & Nutrition, University of Pittsburgh Medical Center, Pittsburgh, PA, United States.
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45
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Bone health assessment in clinical practice is infrequenty performed in patients with chronic pancreatitis. Pancreatology 2020; 20:1109-1114. [PMID: 32826169 PMCID: PMC9148534 DOI: 10.1016/j.pan.2020.07.396] [Citation(s) in RCA: 8] [Impact Index Per Article: 1.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/24/2020] [Revised: 06/22/2020] [Accepted: 07/21/2020] [Indexed: 02/07/2023]
Abstract
BACKGROUND Chronic pancreatitis (CP) patients have a high prevalence of osteoporotic fractures. In addition to prevalence of osteoporotic fractures, we evaluated how often bone health is assessed by dual-energy x-ray absorptiometry (DXA) in clinical practice, and the performance of Fracture Risk Assessment Tool (FRAX®) in predicting fracture risk in CP patients. METHODS Medical records of CP patients age ≥40 years prospectively enrolled in the North American Pancreatitis Study 2 (NAPS2) from the University of Pittsburgh Medical Center from 2000 to 2014 were retrospectively reviewed to gather additional relevant data before, at, and after enrollment until December 2016. We determined if patients underwent DXA, compared their observed prevalence of fractures with published data from two large US studies based on administrative data, and their predicted fracture risk with US population based on FRAX®. RESULTS Only 21% (49/239) patients were evaluated by DXA during their care. The observed cumulative prevalence of fragility fractures in NAPS2 CP patients (9.2%, 95% confidence interval 5.9-13.6) was significantly greater than in controls (1.46% and 2.16%, p ≤ 0.001 for each comparison) and CP patients (4.66%, and 5.13%, p < 0.005 for each comparison) in the two US administrative data studies. The FRAX® 10-year probability of major osteoporotic fracture of ≥20% (5.1% vs. 8.3%, p > 0.05) and for hip fracture of ≥3% (19.6% vs. 18.9%, p > 0.05) in NAPS2 CP patients did not differ from the US population. CONCLUSIONS Despite their high risk of fragility fractures, bone health is infrequently assessed in CP patients. FRAX® may not adequately predict fracture risk in CP patients.
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46
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Role of the Immune System and the Circadian Rhythm in the Pathogenesis of Chronic Pancreatitis: Establishing a Personalized Signature for Improving the Effect of Immunotherapies for Chronic Pancreatitis. Pancreas 2020; 49:1024-1032. [PMID: 32833942 DOI: 10.1097/mpa.0000000000001626] [Citation(s) in RCA: 25] [Impact Index Per Article: 5.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/12/2022]
Abstract
Pancreatitis, in both acute and chronic forms, poses a major therapeutic challenge and is associated with great morbidity and several complications. The nature of pancreatic injury in chronic pancreatitis (CP) and the wide range of causative processes that lead to CP have made effective therapy a true unmet need. Multiple physiological, genetic, environmental, and behavioral factors contribute to the development of CP. As a result, several fields of research are aimed at identifying and addressing the factors that contribute to pancreatic injury. In this article, we review the current understanding of the pathogenesis and natural history of CP. We focus on the autonomous nervous system, immune system, and role of a chronobiological therapeutic approach to alleviate symptoms and prevent or reverse pancreatic injury associated with CP. We aim to demonstrate that individualizing chronopharmacological treatments for CP is a promising direction for future treatment using immune, nervous, and circadian systems.
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Valente R, Waldthaler A, Scandavini CM, Vujasinovic M, Del Chiaro M, Arnelo U, Löhr JM. Conservative Treatment of Chronic Pancreatitis: A Practical Approach. Scand J Surg 2020; 109:59-68. [PMID: 32192418 DOI: 10.1177/1457496920905559] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/18/2022]
Abstract
BACKGROUND Chronic pancreatitis is a long-standing, inflammatory condition of the pancreas that leads to the progressive damage and loss of function of pancreatic parenchyma and to the development of possible locoregional and systemic medical complications. MATERIALS AND METHODS In this review, we tried to summarize the current evidence on non-surgical treatment trying to suggest a practical approach to the management of chronic pancreatitis. RESULTS Besides the unclear pathophysiological mechanism and a poorly unknown epidemiology, chronic pancreatitis is a complex syndrome that displays different possible challenges for physicians. Despite being traditionally considered as a benign disease, chronic pancreatitis encompasses 10-year mortality rates which are superior to the ones reported for some of the most common cancers. CONCLUSIONS Chronic pancreatitis encompasses the management of multiple and complex medical co-morbidities that needs to be understood and addressed in a multidisciplinary specialist context.
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Affiliation(s)
- R Valente
- Division of Surgery, HPB Disease Unit, Karolinska University Hospital and Karolinska Institutet, Stockholm, Sweden
- CLINTEC, Karolinska Institutet, Stockholm, Sweden
| | - A Waldthaler
- Endoscopy Unit, Karolinska University Hospital, Stockholm, Sweden
| | - C M Scandavini
- Division of Surgery, HPB Disease Unit, Karolinska University Hospital and Karolinska Institutet, Stockholm, Sweden
| | - M Vujasinovic
- CLINTEC, Karolinska Institutet, Stockholm, Sweden
- Endoscopy Unit, Karolinska University Hospital, Stockholm, Sweden
| | - M Del Chiaro
- Division of Surgical Oncology, Department of Surgery, University of Colorado Anschutz Medical Campus, Aurora, CO, USA
| | - U Arnelo
- CLINTEC, Karolinska Institutet, Stockholm, Sweden
| | - J-M Löhr
- Division of Surgery, HPB Disease Unit, Karolinska University Hospital and Karolinska Institutet, Stockholm, Sweden
- CLINTEC, Karolinska Institutet, Stockholm, Sweden
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48
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Olesen SS, Kuhlmann L, Novovic S, Nøjgaard C, Kalaitzakis E, Jensen NM, Engjom T, Dimcevski G, Waage A, Haas SL, Vujasinovic M, Riauka R, Pukitis A, Ozola-Zālīte I, Okhlobystin A, Parhiala M, Laukkarinen J, Drewes AM. Association of multiple patient and disease characteristics with the presence and type of pain in chronic pancreatitis. J Gastroenterol Hepatol 2020; 35:326-333. [PMID: 31314128 DOI: 10.1111/jgh.14783] [Citation(s) in RCA: 9] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/23/2019] [Revised: 06/21/2019] [Accepted: 07/09/2019] [Indexed: 01/27/2023]
Abstract
BACKGROUND AND AIM Pain is the primary symptom of chronic pancreatitis (CP) and associates with a number of patient and disease characteristics. However, the complex interrelations of these parameters are incompletely understood, and pain treatment remains unsatisfactory in a large proportion of patients. The aim of this study is to investigate multiple pain risk factors in a large population of CP patients, with a special emphasis on patients' patterns of smoking and alcohol use. METHODS This was a multicenter, cross-sectional study including 1384 patients with CP. Patient demographics and disease characteristics, as well as current patterns of smoking and alcohol use, were compared for patients with pain (n = 801) versus without pain (n = 583). Multivariate logistic regression models were performed to assess the variables associated with the presence and type of pain (constant vs intermittent pain). RESULTS The mean age of participants was 52.1 ± 14.6 years, and 914 (66%) were men. Active smoking (odds ratio 1.6 [95% confidence interval 1.1-2.2], P = 0.005) and alcohol consumption (odds ratio 1.8 [95% confidence interval 1.1-3.0], P = 0.03) were independently associated with the presence of pain. In addition, patients' age at diagnosis, pancreatic duct pathology, and the presence of pseudocysts, duodenal stenosis, and exocrine pancreatic insufficiency were confirmed as pain risk factors (all P ≤ 0.01). Constant pain, as opposed to intermittent pain, was more frequently reported by smokers (P = 0.03), while alcohol consumption was associated with intermittent pain (P = 0.006). CONCLUSION Multiple patient and disease characteristics, including patterns of smoking and alcohol consumption, associate with the presence and type of pain in patients with CP.
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Affiliation(s)
- Søren S Olesen
- Centre for Pancreatic Diseases, Department of Gastroenterology and Hepatology, Aalborg University Hospital, Aalborg, Denmark
- Clinical Institute, Aalborg University, Aalborg, Denmark
| | - Louise Kuhlmann
- Centre for Pancreatic Diseases, Department of Gastroenterology and Hepatology, Aalborg University Hospital, Aalborg, Denmark
- Clinical Institute, Aalborg University, Aalborg, Denmark
- Department of Internal Medicine, North Denmark Regional Hospital, Hjørring, Denmark
| | - Srdan Novovic
- Department of Gastroenterology, Hvidovre University Hospital, Copenhagen, Denmark
| | - Camilla Nøjgaard
- Department of Gastroenterology, Hvidovre University Hospital, Copenhagen, Denmark
| | - Evangelos Kalaitzakis
- Copenhagen University Hospital/Herlev, University of Copenhagen, Copenhagen, Denmark
| | - Nanna M Jensen
- Abdominalcenter K, Bispebjerg Hospital, Copenhagen, Denmark
| | - Trond Engjom
- Department of Clinical Medicine, University of Bergen, Bergen, Norway
- Department of Medicine, Haukeland University Hospital, Bergen, Norway
| | - Georg Dimcevski
- Department of Clinical Medicine, University of Bergen, Bergen, Norway
| | - Anne Waage
- Department of Surgery, Oslo University Hospital, Oslo, Norway
| | - Stephan L Haas
- Centre for Digestive Diseases, Karolinska University Hospital, Stockholm, Sweden
| | - Miroslav Vujasinovic
- Centre for Digestive Diseases, Karolinska University Hospital, Stockholm, Sweden
| | - Romualdas Riauka
- Department of Surgery, Lithuanian University of Health Sciences, Kaunas, Lithuania
| | - Aldis Pukitis
- Centre of Gastroenterology, Hepatology and Nutrition, Pauls Stradiņš Clinical University Hospital, Riga, Latvia
| | - Imanta Ozola-Zālīte
- Centre of Gastroenterology, Hepatology and Nutrition, Pauls Stradiņš Clinical University Hospital, Riga, Latvia
| | - Alexey Okhlobystin
- Medical Faculty, Sechenov First Moscow State Medical University, Moscow, Russia
| | - Mikael Parhiala
- Department of Gastroenterology and Alimentary Tract Surgery, Tampere University Hospital, Tampere, Finland
- Cancer Center, Faculty of Medicine and Heath Technology, Tampere University, Tampere, Finland
| | - Johanna Laukkarinen
- Department of Gastroenterology and Alimentary Tract Surgery, Tampere University Hospital, Tampere, Finland
- Cancer Center, Faculty of Medicine and Heath Technology, Tampere University, Tampere, Finland
| | - Asbjørn M Drewes
- Centre for Pancreatic Diseases, Department of Gastroenterology and Hepatology, Aalborg University Hospital, Aalborg, Denmark
- Clinical Institute, Aalborg University, Aalborg, Denmark
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Park WG, Li L, Appana S, Wei W, Stello K, Andersen DK, Hughes SJ, Whitcomb DC, Brand RE, Yadav D, Habtezion A. Unique circulating immune signatures for recurrent acute pancreatitis, chronic pancreatitis and pancreatic cancer: A pilot study of these conditions with and without diabetes. Pancreatology 2020; 20:51-59. [PMID: 31791885 PMCID: PMC6983346 DOI: 10.1016/j.pan.2019.11.008] [Citation(s) in RCA: 23] [Impact Index Per Article: 4.6] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/11/2019] [Revised: 11/17/2019] [Accepted: 11/19/2019] [Indexed: 12/11/2022]
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.
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Affiliation(s)
- Walter G Park
- Division of Gastroenterology & Hepatology, Department of Medicine, Stanford University, Stanford, CA, USA.
| | - Liang Li
- Department of Biostatistics, MD Anderson Cancer Center, Houston, TX, USA
| | - Savitri Appana
- Department of Biostatistics, MD Anderson Cancer Center, Houston, TX, USA
| | - Wei Wei
- Taussig Cancer Institute, Cleveland Clinic, Cleveland, OH, USA
| | - Kimberly Stello
- Division of Gastroenterology, Hepatology and Nutrition, Department of Medicine, University of Pittsburgh, Pittsburgh, PA, USA
| | - Dana K Andersen
- Division of Digestive Diseases and Nutrition, National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, Bethesda, MD, USA
| | - Steven J Hughes
- Division of Surgical Oncology, Department of Surgery, University of Florida, Gainesville, FL, USA
| | - David C Whitcomb
- Division of Gastroenterology, Hepatology and Nutrition, Department of Medicine, University of Pittsburgh, Pittsburgh, PA, USA
| | - Randall E Brand
- Division of Gastroenterology, Hepatology and Nutrition, Department of Medicine, University of Pittsburgh, Pittsburgh, PA, USA
| | - Dhiraj Yadav
- Division of Gastroenterology, Hepatology and Nutrition, Department of Medicine, University of Pittsburgh, Pittsburgh, PA, USA
| | - Aida Habtezion
- Division of Gastroenterology & Hepatology, Department of Medicine, Stanford University, Stanford, CA, USA
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Abstract
Chronic pancreatitis is characterized by progressive, irreversible morphologic and functional changes that are most commonly attributed to environmental insults, particularly when there is a genetic or anatomic predisposition. Heavy alcohol use and cigarette smoking are the most common environmental risk factors, but both may be absent. Antecedent episodes of acute pancreatitis occur in about half of patients. Abdominal pain is the most common symptom and requires a tailored approach depending on the anatomic changes in the pancreas. Other clinical manifestations include diabetes mellitus, exocrine pancreatic insufficiency, metabolic bone disease, pancreatic cancer, and anatomic complications. Current disease management is centered on risk factor reduction and screening for and treating disease complications. There are no current therapies to delay or retard disease progression, but there are ongoing efforts to more fully understand the natural history of chronic pancreatitis and underlying mechanisms of disease. These studies are expected to provide insights that will transform our approach to disease management and provide increased hope to patients.
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