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Kawka M, Lucas A, Riad AM, Hawkins D, de Madaria E, West H, Jakaityte I, Lee MJ, Kouli O, Ruanne R, Gujjuri RR, Brown S, Cambridge WA, Pandanaboyana S, Kamarajah SK, McLean KA. Quality of life instruments in acute and chronic pancreatitis: a consensus-based standards for the selection of health measurement instruments (COSMIN) approach. HPB (Oxford) 2024; 26:859-872. [PMID: 38735815 DOI: 10.1016/j.hpb.2024.04.004] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/22/2023] [Revised: 04/07/2024] [Accepted: 04/18/2024] [Indexed: 05/14/2024]
Abstract
BACKGROUND Pancreatitis is a common surgical emergency, associated with pain and poor quality of life for patients. However, assessment of patient-reported outcome measures in these patients is unclear. This study aimed to identify and evaluate the methodological quality of the health-related quality of life instruments used for patients with acute or chronic pancreatitis. METHODS Prospective studies that evaluated health-related quality of life in acute or chronic pancreatitis were identified from systematic review of MEDLINE, EMBASE, and Web of Science until 28th June 2023 (PROSPERO: CRD42021274743). Instrument characteristics were extracted, and methodological quality assessed using COSMIN (COnsensus-based Standards for the selection of health status Measurement Instruments) guidelines and GRADE approach. Narrative synthesis was conducted, with recommendations for use based on COSMIN criteria, evaluated according to World Health Organisation (WHO) quality of life domains. RESULTS From 3850 records screened, 41 quality of life instruments were identified across 138 studies included. The majority (69.8%, n = 26) were designed to assess general health-related quality of life, whereas the remainder were abdominal-specific (n = 5) or pancreas-specific (n = 10). Only ten instruments (24.3%) demonstrated sufficient content validity, incorporating items in ≥5 WHO quality of life domains. However, only nine instruments (21.9%) incorporated public and patient involvement. Only the Gastrointestinal Quality of Life Index and PAN-PROMISE met the criteria to be recommended for use based on COSMIN methodological assessment. CONCLUSION There is significant heterogeneity in instruments used to assess quality of life after pancreatitis, with almost all instruments considered insufficient. Robust, validated, and relevant instruments are needed to better understand and determine appropriate interventions to improve quality of life for these patients.
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Manrai M, Singh AK, Birda CL, Shah J, Dutta A, Bhadada SK, Kochhar R. Diabetes mellitus as a consequence of acute severe pancreatitis: Unraveling the mystery. World J Diabetes 2023; 14:1212-1225. [PMID: 37664472 PMCID: PMC10473947 DOI: 10.4239/wjd.v14.i8.1212] [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: 03/28/2023] [Revised: 05/19/2023] [Accepted: 07/06/2023] [Indexed: 08/11/2023] Open
Abstract
The occurrence of diabetes mellitus (DM) in pancreatitis is being increasingly recognized lately. Diabetes can develop not only with chronic pancreatitis but even after the first episode of acute pancreatitis (AP). The incidence of diabetes after AP varies from 18% to 23% in 3 years and reaches up to 40% over 5 years. The exact pathogenesis of diabetes after AP is poorly understood and various mechanisms proposed include loss of islet cell mass, AP-induced autoimmunity, and alterations in the insulin incretin axis. Risk factors associated with increased risk of diabetes includes male sex, recurrent attacks of pancreatitis, presence of pancreatic exocrine insufficiency and level of pancreatitic necrosis. Diagnosis of post-pancreatitis DM (PPDM) is often excluded. Treatment includes a trial of oral antidiabetic drugs in mild diabetes. Often, insulin is required in uncontrolled diabetes. Given the lack of awareness of this metabolic disorder after AP, this review will evaluate current information on epidemiology, risk factors, diagnosis and management of PPDM and identify the knowledge gaps.
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Affiliation(s)
- Manish Manrai
- Department of Internal Medicine, Armed Forces Medical College, Pune 411040, Maharashtra, India
| | - Anupam K Singh
- Department of Gastroenterology, Postgraduate Institute of Medical Education and Research, Chandigarh 160012, India
| | - Chhagan Lal Birda
- Department of Gastroenterology, All India Institutes of Medical Sciences, Jodhpur 342001, India
| | - Jimil Shah
- Department of Gastroenterology, Postgraduate Institute of Medical Education and Research, Chandigarh 160012, India
| | - Aditya Dutta
- Department of Endocrinology, Max Hospital, New Delhi 110017, India
| | - Sanjay Kumar Bhadada
- Department of Endocrinology, Postgraduate Institute of Medical Education and Research, Chandigarh 160012, India
| | - Rakesh Kochhar
- Department of Gastroenterology, Postgraduate Institute of Medical Education and Research, Chandigarh 160012, India
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3
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Giorga A, Hughes M, Parker S, Smith A, Young A. Quality of life after severe acute pancreatitis: systematic review. BJS Open 2023; 7:zrad067. [PMID: 37619216 PMCID: PMC10449419 DOI: 10.1093/bjsopen/zrad067] [Citation(s) in RCA: 2] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/12/2022] [Revised: 04/13/2023] [Accepted: 05/14/2023] [Indexed: 08/26/2023] Open
Abstract
BACKGROUND Severe acute pancreatitis, the most severe form of acute pancreatitis, can alter pancreatic morphology, physiology, and function resulting in long-term morbidity, even after a single episode. This review assesses long-term outcomes and quality of life of severe acute pancreatitis. METHODS A comprehensive literature review was conducted across MEDLINE, Embase, Scopus, and PubMed electronic databases on 18 January 2021 and updated on 26 April 2022 to ensure no new literature had been omitted. All studies were prospective or retrospective, included adult patients (>18 years) presenting with acute pancreatitis for whom data on long-term outcomes specifically after severe acute pancreatitis were reported. Quantitative and qualitative data extraction and synthesis were carried out and no meta-analysis was performed. Outcome measures included aetiology and mortality of severe acute pancreatitis, length of stay, endocrine and exocrine pancreatic insufficiency, chronic symptoms, and quality of life compared with healthy controls as assessed by validated questionnaires. RESULTS Fourteen retrospective cohort studies were included, for a total of 779 patients, using quality of life questionnaires. The most common aetiology of severe acute pancreatitis was biliary (36 per cent) followed by alcoholic (29 per cent). Mortality rate ranged from 5 to 35 per cent and length of stay ranged from 2 to 367 days. Quality of life was somewhat lower in patients with exocrine insufficiency, but unaffected by endocrine insufficiency or chronic symptoms. Quality of life was more likely to be reduced in the first 4 years but normalize thereafter and was more likely to be negatively affected where alcohol was the aetiology. In four studies, the relationship between disease severity and lower quality of life was investigated, and a significant correlation was found. CONCLUSION The review shows how a single episode of severe acute pancreatitis can have a variable effect on long-term quality of life, which is different to previous studies showing a strong reduction in quality of life. This could indicate that in current times treatment modalities are more effective.
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Affiliation(s)
- Andrea Giorga
- Department of Pancreatic Surgery, St James's University Hospital, Leeds Teaching Hospitals Trust, Leeds, UK
| | - Michael Hughes
- Department of Pancreatic Surgery, St James's University Hospital, Leeds Teaching Hospitals Trust, Leeds, UK
| | - Simon Parker
- Organisational Behaviour and Human Resource Management, Nottingham University Business School, UK
| | - Andrew Smith
- Department of Pancreatic Surgery, St James's University Hospital, Leeds Teaching Hospitals Trust, Leeds, UK
| | - Alistair Young
- Department of Pancreatic Surgery, St James's University Hospital, Leeds Teaching Hospitals Trust, Leeds, UK
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4
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Jamal S, Khan MZ, Kichloo A, Edigin E, Bailey B, Aljadah M, Hussaian I, Rahman AU, Ahmad M, Kanjwal K. The Effect of Atrial Fibrillation on Inpatient Outcomes of Patients with Acute Pancreatitis: A Two-year National Inpatient Sample Database Study. J Innov Card Rhythm Manag 2021; 11:4338-4344. [PMID: 33408954 PMCID: PMC7769503 DOI: 10.19102/icrm.2020.111205] [Citation(s) in RCA: 6] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/26/2020] [Accepted: 08/20/2020] [Indexed: 12/12/2022] Open
Abstract
Limited published data exist regarding the association of atrial fibrillation (AF) and acute pancreatitis. To test our hypothesis that AF increases mortality and clinical outcomes in patients with acute pancreatitis, we conducted a cross-sectional data review of the National Inpatient Sample (NIS) database. The NIS database was reviewed for the collection of data on patient hospitalizations in 2016 and 2017. Patients diagnosed with acute pancreatitis with and without concomitant AF were included in the analysis. The International Classification of Diseases, 10th revision coding system was used for the variables of interest. The Stata software program (StataCorp LLC, College Station, TX, USA) was used to perform statistical analyses. The chi-squared test or analysis of variance was used to identify differences in demographic characteristics between the groups. The study population included two groups of patients: those with acute pancreatitis only (n = 542,440) and those with both acute pancreatitis and AF (n = 32,790). The group with acute pancreatitis and AF had a two- to threefold higher rate of mortality [adjusted odds ratio (OR): 2.59; 95% confidence interval (CI): 2.04-3.28] and increased length of stay (adjusted OR: 1.28; 95% CI: 1.08-1.48). Also, significantly higher odds of sepsis (adjusted OR: 2.49; 95% CI: 2.06-3.01), congestive heart failure (adjusted OR: 3.16; 95% CI: 2.87-3.49), acute coronary syndrome (adjusted OR: 1.61; 95% CI: 1.17-2.21), stroke (adjusted OR: 3.94; 95% CI: 1.42-10.93), and acute kidney injury (adjusted OR: 1.42; 95% CI: 1.30-1.55) were observed in patients with acute pancreatitis and AF relative to in patients with acute pancreatitis only. Our results suggest AF increases mortality in patients with acute pancreatitis and that patients with acute pancreatitis and AF are at greater risk of worse clinical outcomes.
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Affiliation(s)
- Shakeel Jamal
- Department of Internal Medicine, St. Mary's of Michigan, Saginaw, MI, USA.,Central Michigan University College of Medicine, Saginaw, MI, USA
| | - Muhammad Zatmar Khan
- Department of Internal Medicine, St. Mary's of Michigan, Saginaw, MI, USA.,Central Michigan University College of Medicine, Saginaw, MI, USA
| | - Asim Kichloo
- Department of Internal Medicine, St. Mary's of Michigan, Saginaw, MI, USA.,Central Michigan University College of Medicine, Saginaw, MI, USA
| | | | - Beth Bailey
- Central Michigan University College of Medicine, Saginaw, MI, USA
| | - Michael Aljadah
- Medical College of Wisconsin Affiliated Hospitals, Milwaukee, WI, USA
| | - Ishtiaq Hussaian
- Department of Gastroenterology, Cleveland Clinic Florida, Weston, FL, USA
| | - Asad Ur Rahman
- Department of Gastroenterology, Cleveland Clinic Florida, Weston, FL, USA
| | - Muhammad Ahmad
- Central Michigan University College of Medicine, Saginaw, MI, USA
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Richardson A, Park WG. Acute pancreatitis and diabetes mellitus: a review. Korean J Intern Med 2021; 36:15-24. [PMID: 33147904 PMCID: PMC7820652 DOI: 10.3904/kjim.2020.505] [Citation(s) in RCA: 6] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/14/2020] [Accepted: 11/02/2020] [Indexed: 02/08/2023] Open
Abstract
Diabetes following acute pancreatitis (AP) is becoming increasingly recognized. It is unclear what subtype of diabetes mellitus (DM) occurs; however, type 3c diabetes mellitus (T3cDM) is gaining increasing recognition. T3cDM has differing pathophysiology than other subtypes of DM and therefore differing disease course and treatment. Current studies have examined the incidence and prevalence of DM following AP, and meta-analyses have shown around 15% develop DM at 1 year with an increasing proportion developing DM at 5 years. It has been observed that some patients have transient hyperglycemia following AP episode with a subset developing persistent impaired glucose metabolism; however, the exact timeline is not well defined. The data on risk factors for developing DM after AP is limited and mixed; however, it is likely that severity of AP may impact the propensity to develop DM. Screening guidelines have not been established following AP; however, screening 1-year post-event will likely capture a sizable proportion of newly developed DM. The endocrine and exocrine pancreas are closely linked, and studies have found significant overlap in dysfunction of both after AP. Finally, there are some data to suggest that diabetes predisposes patients to structural changes in the pancreas and increased risk of developing AP.
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Affiliation(s)
- Allyson Richardson
- Department of Internal Medicine, Stanford University Medical Center, Stanford, CA,
USA
| | - Walter G. Park
- Department of Gastroenterology and Hepatology, Stanford University Medical Center, Stanford, CA,
USA
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6
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Sherif AE, McFadyen R, Boyd J, Ventre C, Glenwright M, Walker K, Zheng X, White A, McFadyen L, Connon E, Damaskos D, Steven M, Wackett A, Thomson E, Cameron DC, MacLeod J, Baxter S, Semple S, Morris D, Clark-Stewart S, Graham C, Mole DJ. Study protocol for resolution of organ injury in acute pancreatitis (RESORP): an observational prospective cohort study. BMJ Open 2020; 10:e040200. [PMID: 33293311 PMCID: PMC7722833 DOI: 10.1136/bmjopen-2020-040200] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/08/2020] [Revised: 08/05/2020] [Accepted: 09/07/2020] [Indexed: 11/04/2022] Open
Abstract
INTRODUCTION Survivors of acute pancreatitis (AP) have shorter overall survival and increased incidence of new-onset cardiovascular, respiratory, liver and renal disease, diabetes mellitus and cancer compared with the general population, but the mechanisms that explain this are yet to be elucidated. Our aim is to characterise the precise nature and extent of organ dysfunction following an episode of AP. METHODS AND ANALYSIS This is an observational prospective cohort study in a single centre comprising a University hospital with an acute and emergency receiving unit and clinical research facility. Participants will be adult patient admitted with AP. Participants will undergo assessment at recruitment, 3 months and 3 years. At each time point, multiple biochemical and/or physiological assessments to measure cardiovascular, respiratory, liver, renal and cognitive function, diabetes mellitus and quality of life. Recruitment was from 30 November 2017 to 31 May 2020; last follow-up measurements is due on 31 May 2023. The primary outcome measure is the incidence of new-onset type 3c diabetes mellitus during follow-up. Secondary outcome measures include: quality of life analyses (SF-36, Gastrointestinal Quality of Life Index); montreal cognitive assessment; organ system physiological performance; multiomics predictors of AP severity, detection of premature cellular senescence. In a nested cohort within the main cohort, individuals may also consent to multiparameter MRI scan, echocardiography, pulmonary function testing, cardiopulmonary exercise testing and pulse-wave analysis. ETHICS AND DISSEMINATION This study has received the following approvals: UK IRAS Number 178615; South-east Scotland Research Ethics Committee number 16/SS/0065. Results will be made available to AP survivors, caregivers, funders and other researchers. Publications will be open-access. TRIAL REGISTRATION NUMBERS ClinicalTrials.gov Registry (NCT03342716) and ISRCTN50581876; Pre-results.
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Affiliation(s)
- Ahmed E Sherif
- Clinical Surgery, University of Edinburgh, Edinburgh, UK
| | - Rory McFadyen
- Clinical Surgery, University of Edinburgh, Edinburgh, UK
| | - Julia Boyd
- Edinburgh Clinical Trials Unit, University of Edinburgh, Edinburgh, UK
| | - Chiara Ventre
- Clinical Surgery, University of Edinburgh, Edinburgh, UK
| | | | - Kim Walker
- Clinical Research Facility, NHS Lothian, Edinburgh, UK
| | - Xiaozhong Zheng
- Centre for Inflammation Research, University of Edinburgh, Edinburgh, UK
| | - Audrey White
- Clinical Research Facility, NHS Lothian, Edinburgh, UK
| | | | - Emma Connon
- Clinical Research Facility, NHS Lothian, Edinburgh, UK
| | | | - Michelle Steven
- Edinburgh Clinical Trials Unit, University of Edinburgh, Edinburgh, UK
| | - Anthony Wackett
- Edinburgh Clinical Trials Unit, University of Edinburgh, Edinburgh, UK
| | - Euan Thomson
- Anaesthesia and Critical Care, NHS Lothian, Edinburgh, UK
| | | | - Jill MacLeod
- Respiratory Physiology, NHS Lothian, Edinburgh, UK
| | - Shaun Baxter
- Respiratory Physiology, NHS Lothian, Edinburgh, UK
| | - Scott Semple
- Centre for Cardiovascular Science, University of Edinburgh, Edinburgh, UK
| | - David Morris
- Centre for Inflammation Research, University of Edinburgh, Edinburgh, UK
| | | | - Catriona Graham
- Epidemiology and Statistics Core, Edinburgh Clinical Research Facility, University of Edinburgh, Edinburgh, UK
| | - Damian J Mole
- Clinical Surgery, University of Edinburgh, Edinburgh, UK
- Centre for Inflammation Research, University of Edinburgh, Edinburgh, UK
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7
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Tu J, Zhang J, Yang Y, Xu Q, Ke L, Tong Z, Li W, Li J. Comparison of pancreatic function and quality of life between patients with infected pancreatitis necrosis undergoing open necrosectomy and minimally invasive drainage: A long-term study. Exp Ther Med 2020; 20:75. [PMID: 32968432 PMCID: PMC7500036 DOI: 10.3892/etm.2020.9203] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/02/2019] [Accepted: 03/10/2020] [Indexed: 12/11/2022] Open
Abstract
The present study aimed to determine whether a difference in pancreatic function and quality of life (QoL) is present between patients with infected pancreatitis necrosis (IPN) undergoing open necrosectomy (ON) and minimally invasive drainage (MID). The medical records of patients with IPN discharged from Jinling Hospital were retrospectively analyzed. Pancreatic function and QoL were compared between patients treated with ON and MID. Pancreatic endocrine and exocrine function were assessed using the oral glucose tolerance test and fecal elastase-1 (FE-1) test, respectively. The standard Short Form 36 health questionnaire was used to evaluate the QoL of patients. The analysis included 101 patients who underwent either ON (n=40, 39.6%) or MID (n=61, 60.4%). There were no significant differences in exocrine and endocrine pancreatic function between the two groups evaluated based on FE-1, fasting blood glucose, glycated hemoglobin and 2-h plasma glucose (P<0.05). The scores of the QoL questionnaire were significantly higher in patients treated with MID than in patients treated with ON, including the scores of general health perception (19.39±3.07 vs. 17.37±3.63, P=0.003), vitality (18.93±2.88 vs. 17.57±3.47, P=0.035), social role functioning (8.85±1.43 vs. 8.15±1.98, P=0.042), emotional role functioning (5.33±1.07 vs. 4.82±1.25, P=0.034), mental health (24.21±3.31 vs. 22.57±3.91, P=0.026) and the total QoL score (125.12±13.16 vs. 116.50±16.94, P=0.005). In conclusion, although the initial health of the patient may have influenced the treatment provided, patients with IPN who received MID achieved a better post-treatment QoL than those treated with ON. No significant differences between the two groups were observed regarding the endocrine and exocrine functions of the pancreas.
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Affiliation(s)
- Jianfeng Tu
- Research Institute of General Surgery, Jinling Hospital, Medical School of Nanjing University, Nanjing, Jiangsu 210002, P.R. China.,Department of Emergency Medicine, Zhejiang Provincial People's Hospital, People's Hospital of Hangzhou Medical College, Hangzhou, Zhejiang 310014, P.R. China.,Institute of Innovation and Entrepreneurship, Hangzhou Medical College, Hangzhou, Zhejiang 310053, P.R. China.,Department of General Surgery, Akesu First People's Hospital, Akesu, Xinjiang 843000, P.R. China
| | - Jingzhu Zhang
- Research Institute of General Surgery, Jinling Hospital, Medical School of Nanjing University, Nanjing, Jiangsu 210002, P.R. China
| | - Yue Yang
- Institute of Innovation and Entrepreneurship, Hangzhou Medical College, Hangzhou, Zhejiang 310053, P.R. China
| | - Qiuran Xu
- Department of Emergency Medicine, Zhejiang Provincial People's Hospital, People's Hospital of Hangzhou Medical College, Hangzhou, Zhejiang 310014, P.R. China
| | - Lu Ke
- Research Institute of General Surgery, Jinling Hospital, Medical School of Nanjing University, Nanjing, Jiangsu 210002, P.R. China
| | - Zhihui Tong
- Research Institute of General Surgery, Jinling Hospital, Medical School of Nanjing University, Nanjing, Jiangsu 210002, P.R. China
| | - Weiqin Li
- Research Institute of General Surgery, Jinling Hospital, Medical School of Nanjing University, Nanjing, Jiangsu 210002, P.R. China
| | - Jieshou Li
- Research Institute of General Surgery, Jinling Hospital, Medical School of Nanjing University, Nanjing, Jiangsu 210002, P.R. China
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8
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Duggan SN, O'Connor DB, Antanaitis A, Campion JR, Lawal O, Ahmed M, Tisdall AR, Sherlock M, Boran G, le Roux C, Gibney J, Conlon KC. Metabolic dysfunction and diabetes mellitus during long-term follow-up of severe acute pancreatitis: A case-matched study. Pancreatology 2020; 20:813-821. [PMID: 32522508 DOI: 10.1016/j.pan.2020.03.016] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/30/2020] [Revised: 03/07/2020] [Accepted: 03/27/2020] [Indexed: 12/11/2022]
Abstract
BACKGROUND/OBJECTIVES Endocrine insufficiency following severe acute pancreatitis (SAP) leads to diabetes of the exocrine pancreas, (type 3c diabetes mellitus), however it is not known how this metabolic phenotype differs from that of type 2 diabetes, or how the two subtypes can be differentiated. We sought to determine the prevalence of diabetes following SAP, and to analyse the behaviour of glucose and pancreatic hormones across a 2-h oral glucose tolerance test (OGTT). METHODS Twenty-six patients following SAP (mean (range) duration of first SAP episode to study time of 119.3 (14.8-208.9) months) along with 26 matched controls underwent an OGTT with measurement of glucose, insulin, c-peptide, glucagon and pancreatic polypeptide (PP) at fasting/15/90/120min. Beta-cell area was estimated using the 15min c-peptide/glucose ratio, and insulin resistance (IR) using homeostasis model assessment (HOMA) and oral glucose insulin sensitivity (OGIS) models. RESULTS The prevalence of diabetes/prediabetes was 54% following SAP (38.5% newly-diagnosed compared to 19.2% newly-diagnosed controls). Estimated beta-cell area and IR did not differ between groups. AUC c-peptide was lower in SAP versus controls. AUC insulin and AUC c-peptide were lower in SAP patients with diabetes versus controls with diabetes; between-group differences were observed at the 90 and 120 min time-points only. Half of new diabetes cases in SAP patients were only identified at the 120min timepoint. CONCLUSIONS Diabetes and pre-diabetes occur frequently following SAP and are difficult to distinguish from type 2 diabetes in controls but are characterised by reduced insulin and c-peptide at later stages of an OGTT. Consistent with this observation, most new post SAP diabetes cases were diagnosed by 2-h glucose levels only.
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Affiliation(s)
- Sinead N Duggan
- Department of Surgery, Trinity College Dublin, The University of Dublin, Trinity Centre for Health Sciences, Tallaght University Hospital, Dublin 24, Ireland.
| | - Donal B O'Connor
- Department of Surgery, Trinity College Dublin, The University of Dublin, Trinity Centre for Health Sciences, Tallaght University Hospital, Dublin 24, Ireland
| | - Andrius Antanaitis
- Diabetes Complications Research Centre, Conway Institute, University College Dublin, Dublin 4, Ireland
| | - John R Campion
- Department of Gastroenterology, Tallaght University Hospital, Dublin 24, Ireland
| | - Oladapo Lawal
- Department of Surgery, Trinity College Dublin, The University of Dublin, Trinity Centre for Health Sciences, Tallaght University Hospital, Dublin 24, Ireland
| | - Mohamed Ahmed
- Department of Endocrinology, Tallaght University Hospital, Dublin 24, Ireland
| | - Ana Rakovac Tisdall
- Department of Clinical Chemistry, Tallaght University Hospital, Dublin 24, Ireland
| | - Mark Sherlock
- Department of Endocrinology, Tallaght University Hospital, Dublin 24, Ireland; Department of Endocrinology, Beaumont Hospital and Royal College of Surgeons, Ireland
| | - Gerard Boran
- Department of Clinical Chemistry, Tallaght University Hospital, Dublin 24, Ireland
| | - Carel le Roux
- Diabetes Complications Research Centre, Conway Institute, University College Dublin, Dublin 4, Ireland
| | - James Gibney
- Department of Endocrinology, Tallaght University Hospital, Dublin 24, Ireland
| | - Kevin C Conlon
- Department of Surgery, Trinity College Dublin, The University of Dublin, Trinity Centre for Health Sciences, Tallaght University Hospital, Dublin 24, Ireland
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9
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Prior history of acute pancreatitis predicts poor survival in patients with resectable pancreatic ductal adenocarcinoma. Pancreatology 2020; 20:716-721. [PMID: 32249060 DOI: 10.1016/j.pan.2020.02.016] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/05/2019] [Revised: 02/06/2020] [Accepted: 02/23/2020] [Indexed: 12/11/2022]
Abstract
BACKGROUND/OBJECTIVES Mounting evidence has suggested that acute pancreatitis (AP) is a risk factor for pancreatic ductal adenocarcinoma (PDAC), but its role in survival in PDAC patients was rarely investigated. The objective was to investigate the association of a history of AP with survival among PDAC patients who underwent surgical resection. METHODS A retrospective cohort study comprising 632 patients who were diagnosed with resectable PDAC was conducted. Survival was evaluated by history of AP prior to a diagnosis of PDAC using Kaplan-Meier methods and log-rank tests. Multivariate analyses for mortality were estimated using the Cox proportional hazards model. Propensity score matching methods were used to balance the difference of clinical characteristics between patients with and without AP history. RESULTS The log-rank tests showed that patients with a history of AP had a worse overall survival than those without a history of AP (p = 0.006). The multivariable-adjusted hazard ratio (HR) for mortality comparing participants with AP to those without AP was 1.808 (95% CI: 1.241-2.632, p = 0.002). Patients with a recent history of AP (<2 years), rather than patients with a remote history of AP (≥2 years), were found to have significantly worse survival (p = 0.014) than those without a history of AP. After adjusted for PSM, history of AP remained an independent survival predictor of PDAC following surgical resection. CONCLUSIONS Our findings indicate that a history of AP, especially a recent history of AP, is associated with poor survival among patients with resectable pancreatic ductal adenocarcinoma.
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10
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Bendor CD, Bardugo A, Zucker I, Cukierman-Yaffe T, Lutski M, Derazne E, Shohat T, Mosenzon O, Tzur D, Sapir A, Pinhas-Hamiel O, Kibbey RG, Raz I, Afek A, Gerstein HC, Tirosh A, Twig G. Childhood Pancreatitis and Risk for Incident Diabetes in Adulthood. Diabetes Care 2020; 43:145-151. [PMID: 31694859 PMCID: PMC7011197 DOI: 10.2337/dc19-1562] [Citation(s) in RCA: 22] [Impact Index Per Article: 4.4] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/03/2019] [Accepted: 10/14/2019] [Indexed: 02/05/2023]
Abstract
OBJECTIVE The relationship between acute pancreatitis and incident diabetes is unclear. We assessed whether a resolved single event of acute pancreatitis in childhood was associated with incident diabetes in adulthood. RESEARCH DESIGN AND METHODS A nationwide, population-based study of 1,802,110 Israeli adolescents (mean age 17.4 years [range 16-20]) who were examined before compulsory military service between 1979 and 2008 and whose data were linked to the Israeli National Diabetes Registry (INDR). Resolved pancreatitis was defined as a history of a single event of acute pancreatitis with normal pancreatic function at enrollment. Logistic regression analysis was applied. RESULTS Incident diabetes developed in 4.6% of subjects with resolved pancreatitis (13 of 281; none of these cases were identified as type 1 diabetes) and 2.5% among the unexposed group (44,463 of 1,801,716). Resolved acute pancreatitis was associated with incident diabetes with an odds ratio (OR) of 2.23 (95% CI 1.25-3.98) with adjustment for age, sex, and birth year. Findings persisted after further adjustments for baseline BMI and sociodemographic confounders (OR 2.10 [95% CI 1.15-3.84]). Childhood pancreatitis was associated with a diagnosis of diabetes at a younger age, with 92% of diabetes case subjects diagnosed before 40 years of age compared with 47% in the unexposed group (P = 0.002). The association accentuated when the study sample was limited to individuals of unimpaired health or normal BMI at baseline. CONCLUSIONS A history of acute pancreatitis in childhood with normal pancreatic function in late adolescence is a risk factor for incident type 2 diabetes, especially at young adulthood.
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Affiliation(s)
- Cole D Bendor
- Department of Military Medicine, Hebrew University, Jerusalem, Israel.,Israel Defense Forces Medical Corps, Ramat Gan, Israel
| | - Aya Bardugo
- Department of Military Medicine, Hebrew University, Jerusalem, Israel.,Israel Defense Forces Medical Corps, Ramat Gan, Israel
| | - Inbar Zucker
- Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel.,Ministry of Health, Israel Center for Disease Control, Ramat Gan, Israel
| | - Tali Cukierman-Yaffe
- Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel.,Institute of Endocrinology, Chaim Sheba Medical Center at Tel Hashomer, Ramat Gan, Israel
| | - Miri Lutski
- Ministry of Health, Israel Center for Disease Control, Ramat Gan, Israel
| | - Estela Derazne
- Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel
| | - Tammy Shohat
- Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel.,Ministry of Health, Israel Center for Disease Control, Ramat Gan, Israel
| | - Ofri Mosenzon
- The Diabetes Unit, Division of Internal Medicine, Hadassah Hebrew University Hospital, Jerusalem, Israel
| | - Dorit Tzur
- Department of Military Medicine, Hebrew University, Jerusalem, Israel.,Israel Defense Forces Medical Corps, Ramat Gan, Israel
| | - Ari Sapir
- Department of Military Medicine, Hebrew University, Jerusalem, Israel.,Israel Defense Forces Medical Corps, Ramat Gan, Israel
| | - Orit Pinhas-Hamiel
- Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel.,Pediatric Endocrine and Diabetes Unit, Edmond and Lily Safra Children's Hospital, Chaim Sheba Medical Center at Tel Hashomer, Ramat Gan, Israel
| | - Richard G Kibbey
- Department of Internal Medicine, Yale University School of Medicine, New Haven, CT.,Department of Cellular and Molecular Physiology, Yale University School of Medicine, New Haven, CT
| | - Itamar Raz
- The Diabetes Unit, Division of Internal Medicine, Hadassah Hebrew University Hospital, Jerusalem, Israel
| | - Arnon Afek
- Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel.,Central Management, Chaim Sheba Medical Center at Tel Hashomer, Ramat Gan, Israel
| | | | - Amir Tirosh
- Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel.,Institute of Endocrinology, Chaim Sheba Medical Center at Tel Hashomer, Ramat Gan, Israel
| | - Gilad Twig
- Department of Military Medicine, Hebrew University, Jerusalem, Israel .,Israel Defense Forces Medical Corps, Ramat Gan, Israel.,Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel.,Institute of Endocrinology, Chaim Sheba Medical Center at Tel Hashomer, Ramat Gan, Israel
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11
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Zhi M, Zhu X, Lugea A, Waldron RT, Pandol SJ, Li L. Incidence of New Onset Diabetes Mellitus Secondary to Acute Pancreatitis: A Systematic Review and Meta-Analysis. Front Physiol 2019; 10:637. [PMID: 31231233 PMCID: PMC6558372 DOI: 10.3389/fphys.2019.00637] [Citation(s) in RCA: 73] [Impact Index Per Article: 12.2] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/14/2019] [Accepted: 05/06/2019] [Indexed: 12/14/2022] Open
Abstract
Background and Aims: Patients who have an episode of acute pancreatitis (AP) frequently develop diabetes mellitus (DM) over time. The reported incidence of DM after AP varies depending on the severity, etiology and the extent of pancreatic necrosis during AP. We performed a systematic review to determine the incidence of new-onset DM after AP episode (s), and compared the rate of DM in AP patients based upon different disease characteristics. Methods: A total of 31 relevant studies with 13894 subjects were collected from Medline, Embase, and Web of Science. Stata 15 software was used for data analyses in the meta-analysis. Results: The random-effects pooled incidence was 23.0% for DM (95% CI 16.0-31.0%) and 15.0% (95% CI 9.0-23.0%) for DM treated with insulin. We noted substantial heterogeneity in incidence estimates for DM and DM treated with insulin (I 2 = 95.61 and 71.78%; both p < 0·001). The DM incidence was higher in the populations that had a severe AP (SAP) episode than in those with mild acute pancreatitis (MAP) (39 vs. 14%). Patients that displayed pancreatic necrosis during the AP attack(s) had a higher frequency of DM than those without necrosis (37 vs. 11%). In addition, the pooled incidence of DM was higher after alcoholic compared to biliary AP (28 vs. 12%). The incidence of insulin use after SAP and alcoholic AP was 21 and 18%, respectively, with very low heterogeneities. According to duration of follow-up, the pooled rate of DM and insulin use within 5 years after AP was 20 and 14%, while the rate associated with follow-up duration of more than 5 years was elevated to 37 and 25%, respectively. On meta-regression, year of publication, male proportion, age at DM test, and duration of follow-up were neither positively nor negatively associated with the incidence of DM and DM treated with insulin in patients who had a prior AP attack. Conclusion: Patients with AP developed DM after discharge from hospital with a frequency of about 23%. SAP, alcoholic AP and acute necrotizing pancreatitis (ANP) were associated with increased incidence of DM. Assessments of severity, etiology, and pancreatic necrosis are critical for predicting DM development after AP.
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Affiliation(s)
- Mengmeng Zhi
- Department of Endocrinology, Affiliated ZhongDa Hospital, School of Medicine, Southeast University, Nanjing, China
| | - Xiangyun Zhu
- Department of Endocrinology, Affiliated ZhongDa Hospital, School of Medicine, Southeast University, Nanjing, China
| | - Aurelia Lugea
- Division of Gastroenterology, Department of Medicine, Cedars-Sinai Medical Center, Los Angeles, CA, United States
| | - Richard T. Waldron
- Division of Gastroenterology, Department of Medicine, Cedars-Sinai Medical Center, Los Angeles, CA, United States
| | - Stephen J. Pandol
- Division of Gastroenterology, Department of Medicine, Cedars-Sinai Medical Center, Los Angeles, CA, United States
| | - Ling Li
- Department of Endocrinology, Affiliated ZhongDa Hospital, School of Medicine, Southeast University, Nanjing, China
- Institute of Pancreas, Southeast University, Nanjing, China
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12
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Patients' Perceptions of Experiences of Recovering From Acute Pancreatitis: An Interview Study. Gastroenterol Nurs 2019; 42:233-241. [PMID: 31145247 DOI: 10.1097/sga.0000000000000375] [Citation(s) in RCA: 6] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/18/2022] Open
Abstract
The incidence of registered admissions in inpatient care with a diagnosis of acute pancreatitis was 58 per 100,000 capita in Sweden during the year 2013. Although acute pancreatitis is a well-explored area, there is a demand for research from the patients' perceptions. The aim of this study was to describe patients' perceptions of recovering from acute pancreatitis. Data collection for this phenomenographical study included 16 individual semistructured interviews. Analysis was done according to the 7 steps suggested by . Recovery after acute pancreatitis was perceived within 5 categories; a time of physical suffering, an emotional journey, challenges to the usual life and its good qualities, barriers and need for social support, and healthcare as an important factor. Physical and emotional symptoms influence recovery after acute pancreatitis by challenging the good things and things that are taken for granted in everyday life. Promoting factors toward good recovery was a proper support from the social network as well as healthcare providers.
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13
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Long-term Outcome and Causes of Death for Working-age Patients Hospitalized Due to Acute Pancreatitis With a Median Follow-up of 10 Years. Ann Surg 2019; 269:932-936. [DOI: 10.1097/sla.0000000000002612] [Citation(s) in RCA: 15] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/14/2022]
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14
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Long D, Wang Y, Wang H, Wu X, Yu L. Correlation of Serum and Ascitic Fluid Soluble Form Urokinase Plasminogen Activator Receptor Levels With Patient Complications, Disease Severity, Inflammatory Markers, and Prognosis in Patients With Severe Acute Pancreatitis. Pancreas 2019; 48:335-342. [PMID: 30768571 PMCID: PMC6426350 DOI: 10.1097/mpa.0000000000001247] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/18/2018] [Accepted: 10/17/2018] [Indexed: 12/25/2022]
Abstract
Supplemental digital content is available in the text. Objectives The aim of the study was to investigate the correlation of serum and ascitic fluid soluble form urokinase plasminogen activator receptor (suPAR) levels with patients' complications, disease severity, inflammatory markers, and prognosis in patients with severe acute pancreatitis (SAP). Methods Fifty patients with SAP, 47 patients with mild acute pancreatitis, and 50 healthy controls were enrolled. Serum samples were obtained from all participants after enrollment; meanwhile, ascitic fluid samples were collected from 20 patients with SAP who developed ascites. Serum and ascitic fluid suPAR levels were determined by enzyme-linked immunosorbent assay. Results Serum suPAR level was greatly elevated in patients with SAP than patients with mild acute pancreatitis and healthy controls. Receiver operating characteristic curve showed that serum suPAR presented with good value in predicting risk of pancreatic necrosis, pancreatic infection, and multiple organ dysfunction syndrome, whereas serum suPAR did not predict mortality. Serum suPAR level was also positively correlated with Acute Physiology and Chronic Health Evaluation II score, Balthazar index, and Sequential Organ Failure Assessment score. As to ascitic fluid suPAR, it was positively correlated with serum suPAR level, Acute Physiology and Chronic Health Evaluation II score, Sequential Organ Failure Assessment score, risk of pancreatic infection, and multiple organ dysfunction syndrome. Conclusions Serum and ascetic fluid suPAR levels could be served as markers for disease severity and risk of severe complications in patients with SAP.
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Affiliation(s)
- Ding Long
- From the Intensive Care Unit, The Central Hospital of Wuhan, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China
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15
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Ma JH, Yuan YJ, Lin SH, Pan JY. Nomogram for predicting diabetes mellitus after the first attack of acute pancreatitis. Eur J Gastroenterol Hepatol 2019; 31:323-328. [PMID: 30433890 PMCID: PMC6380448 DOI: 10.1097/meg.0000000000001307] [Citation(s) in RCA: 10] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/30/2018] [Accepted: 10/18/2018] [Indexed: 12/18/2022]
Abstract
BACKGROUND Diabetes mellitus can occur after acute pancreatitis (AP), but there are currently no tools for evaluating the risk of developing diabetes after an attack of AP. The aim of the study was to develop a nomogram for prediction of new-onset diabetes mellitus after the first attack of AP. PATIENTS AND METHODS We enrolled 616 patients with first-attack AP. We collected and statistically analyzed demographic data (age, BMI, and duration of hospitalization) and laboratory data (glucose, low-density lipoprotein cholesterol, triglyceride, and cholesterol). RESULTS Univariate analysis suggested duration of hospitalization (P=0.0003), BMI (P=0.0059), cholesterol (P=0.0005), triglyceride (P=0.0005), hemoglobin (P=0.0229), and glucose (P<0.001) at admission were significantly associated with newly developed diabetes after the first-attack AP. Multivariate analysis showed that age [odds ratio (OR)=1.01; 95% confidence interval (CI): 1.00-1.03; P=0.045], BMI (OR=1.06; 95% CI: 1.01-1.12; P=0.018), glucose (OR=1.07; 95% CI: 1.02-1.12; P=0.008), triglyceride (OR=1.03; 95% CI: 1.00-1.06; P=0.035), and low-density lipoprotein-cholesterol (OR=1.18; 95% CI: 1.00-1.38; P=0.044) at admission were important predictors. CONCLUSION The nomogram is a potentially clinically useful tool for predicting new-onset diabetes, which is currently clinically unprecedented. This finding is not confined to the patients with severe AP but is also for patients who have recovered from mild AP. The nomogram must to be validated externally.
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Affiliation(s)
- Ji-Hong Ma
- Intensive Care Unit, the First Affiliated Hospital of Wenzhou Medical University
- Department of Medicine, the Xi’an Jiaotong University, Xi’an, Shanxi, China
| | - You-Jun Yuan
- Department of Emergency, Wenzhou Central Hospital, Wenzhou
| | - Su-Han Lin
- Department of Emergency, Wenzhou Central Hospital, Wenzhou
| | - Jing-Ye Pan
- Intensive Care Unit, the First Affiliated Hospital of Wenzhou Medical University
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16
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Huang W, de la Iglesia-García D, Baston-Rey I, Calviño-Suarez C, Lariño-Noia J, Iglesias-Garcia J, Shi N, Zhang X, Cai W, Deng L, Moore D, Singh VK, Xia Q, Windsor JA, Domínguez-Muñoz JE, Sutton R. Exocrine Pancreatic Insufficiency Following Acute Pancreatitis: Systematic Review and Meta-Analysis. Dig Dis Sci 2019; 64:1985-2005. [PMID: 31161524 PMCID: PMC6584228 DOI: 10.1007/s10620-019-05568-9] [Citation(s) in RCA: 64] [Impact Index Per Article: 10.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/23/2018] [Accepted: 02/26/2019] [Indexed: 02/07/2023]
Abstract
BACKGROUND/OBJECTIVES The epidemiology of exocrine pancreatic insufficiency (EPI) after acute pancreatitis (AP) is uncertain. We sought to determine the prevalence, progression, etiology and pancreatic enzyme replacement therapy (PERT) requirements for EPI during follow-up of AP by systematic review and meta-analysis. METHODS Scopus, Medline and Embase were searched for prospective observational studies or randomized clinical trials (RCTs) of PERT reporting EPI during the first admission (between the start of oral refeeding and before discharge) or follow-up (≥ 1 month of discharge) for AP in adults. EPI was diagnosed by direct and/or indirect laboratory exocrine pancreatic function tests. RESULTS Quantitative data were analyzed from 370 patients studied during admission (10 studies) and 1795 patients during follow-up (39 studies). The pooled prevalence of EPI during admission was 62% (95% confidence interval: 39-82%), decreasing significantly during follow-up to 35% (27-43%; risk difference: - 0.34, - 0.53 to - 0.14). There was a two-fold increase in the prevalence of EPI with severe compared with mild AP, and it was higher in patients with pancreatic necrosis and those with an alcohol etiology. The prevalence decreased during recovery, but persisted in a third of patients. There was no statistically significant difference between EPI and new-onset pre-diabetes/diabetes (risk difference: 0.8, 0.7-1.1, P = 0.33) in studies reporting both. Sensitivity analysis showed fecal elastase-1 assay detected significantly fewer patients with EPI than other tests. CONCLUSIONS The prevalence of EPI during admission and follow-up is substantial in patients with a first attack of AP. Unanswered questions remain about the way this is managed, and further RCTs are indicated.
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Affiliation(s)
- Wei Huang
- 0000 0004 1770 1022grid.412901.fDepartment of Integrated Traditional Chinese and Western Medicine, Sichuan Provincial Pancreatitis Center and West China-Liverpool Biomedical Research Center, West China Hospital, Sichuan University, Chengdu, China
| | - Daniel de la Iglesia-García
- 0000 0000 8816 6945grid.411048.8Department of Gastroenterology and Hepatology, Health Research Institute of Santiago (IDIS), University Hospital of Santiago de Compostela, Santiago de Compostela, Spain
| | - Iria Baston-Rey
- 0000 0000 8816 6945grid.411048.8Department of Gastroenterology and Hepatology, Health Research Institute of Santiago (IDIS), University Hospital of Santiago de Compostela, Santiago de Compostela, Spain
| | - Cristina Calviño-Suarez
- 0000 0000 8816 6945grid.411048.8Department of Gastroenterology and Hepatology, Health Research Institute of Santiago (IDIS), University Hospital of Santiago de Compostela, Santiago de Compostela, Spain
| | - Jose Lariño-Noia
- 0000 0000 8816 6945grid.411048.8Department of Gastroenterology and Hepatology, Health Research Institute of Santiago (IDIS), University Hospital of Santiago de Compostela, Santiago de Compostela, Spain
| | - Julio Iglesias-Garcia
- 0000 0000 8816 6945grid.411048.8Department of Gastroenterology and Hepatology, Health Research Institute of Santiago (IDIS), University Hospital of Santiago de Compostela, Santiago de Compostela, Spain
| | - Na Shi
- 0000 0004 1770 1022grid.412901.fDepartment of Integrated Traditional Chinese and Western Medicine, Sichuan Provincial Pancreatitis Center and West China-Liverpool Biomedical Research Center, West China Hospital, Sichuan University, Chengdu, China
| | - Xiaoying Zhang
- 0000 0004 1770 1022grid.412901.fDepartment of Integrated Traditional Chinese and Western Medicine, Sichuan Provincial Pancreatitis Center and West China-Liverpool Biomedical Research Center, West China Hospital, Sichuan University, Chengdu, China ,0000 0004 1936 8470grid.10025.36Liverpool Pancreatitis Research Group, Royal Liverpool University Hospital, Institute of Translational Medicine, University of Liverpool, Liverpool, UK
| | - Wenhao Cai
- 0000 0004 1770 1022grid.412901.fDepartment of Integrated Traditional Chinese and Western Medicine, Sichuan Provincial Pancreatitis Center and West China-Liverpool Biomedical Research Center, West China Hospital, Sichuan University, Chengdu, China
| | - Lihui Deng
- 0000 0004 1770 1022grid.412901.fDepartment of Integrated Traditional Chinese and Western Medicine, Sichuan Provincial Pancreatitis Center and West China-Liverpool Biomedical Research Center, West China Hospital, Sichuan University, Chengdu, China
| | - Danielle Moore
- 0000 0004 1936 8470grid.10025.36Liverpool Pancreatitis Research Group, Royal Liverpool University Hospital, Institute of Translational Medicine, University of Liverpool, Liverpool, UK
| | - Vikesh K. Singh
- 0000 0001 2171 9311grid.21107.35Pancreatitis Center, Division of Gastroenterology, Johns Hopkins Medical Institutions, Baltimore, USA
| | - Qing Xia
- 0000 0004 1770 1022grid.412901.fDepartment of Integrated Traditional Chinese and Western Medicine, Sichuan Provincial Pancreatitis Center and West China-Liverpool Biomedical Research Center, West China Hospital, Sichuan University, Chengdu, China
| | - John A. Windsor
- 0000 0004 0372 3343grid.9654.eSurgical and Translational Research Center, Faculty of Medical and Health Sciences, University of Auckland, Auckland, New Zealand
| | - J. Enrique Domínguez-Muñoz
- 0000 0000 8816 6945grid.411048.8Department of Gastroenterology and Hepatology, Health Research Institute of Santiago (IDIS), University Hospital of Santiago de Compostela, Santiago de Compostela, Spain
| | - Robert Sutton
- 0000 0004 1936 8470grid.10025.36Liverpool Pancreatitis Research Group, Royal Liverpool University Hospital, Institute of Translational Medicine, University of Liverpool, Liverpool, UK
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17
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Ventre C, Nowell S, Graham C, Kidd D, Skouras C, Mole DJ. Survival and new-onset morbidity after critical care admission for acute pancreatitis in Scotland: a national electronic healthcare record linkage cohort study. BMJ Open 2018; 8:e023853. [PMID: 30552270 PMCID: PMC6303604 DOI: 10.1136/bmjopen-2018-023853] [Citation(s) in RCA: 8] [Impact Index Per Article: 1.1] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/26/2018] [Revised: 11/05/2018] [Accepted: 11/07/2018] [Indexed: 01/25/2023] Open
Abstract
INTRODUCTION Severe acute pancreatitis (AP) requiring critical care admission (ccAP) impacts negatively on long-term survival. OBJECTIVE To document organ-specific new morbidity and identify risk factors associated with premature mortality after an episode of ccAP. DESIGN Cohort study. SETTING Electronic healthcare registries in Scotland. PARTICIPANTS The ccAP cohort included 1471 patients admitted to critical care with AP between 1 January 2008 and 31 December 2010 followed up until 31 December 2014. The population cohort included 3450 individuals from the general population of Scotland frequency-matched for age, sex and social deprivation. METHODS Record linkage of routinely collected electronic health data with population matching. PRIMARY AND SECONDARY OUTCOME MEASURES Patient demographics, comorbidity (Charlson Comorbidity Index), acute physiology, organ support and other critical care data were linked to records of mortality (death certificate data) and new-onset morbidity. Kaplan-Meier and Cox regression analyses were used to identify risk factors associated with mortality. RESULTS 310 patients with AP died during the index admission. Outcomes were not ascertained for five patients, and the deprivation quintile was not known for six patients. 340 of 1150 patients in the resulting postdischarge ccAP cohort died during the follow-up period. Greater comorbidity measured by the Charlson score, prior to ccAP, negatively influenced survival in the hospital and after discharge. The odds of developing new-onset diabetes mellitus after ccAP compared with the general population were 10.70 (95% CI 5.74 to 19.94). A new diagnosis of myocardial infarction, stroke, heart failure, liver disease, peptic ulcer, renal failure, cancer, peripheral vascular disease and lung disease was more frequent in the ccAP cohort than in the general population. CONCLUSIONS The persistent deleterious impact of severe AP on long-term outcome and survival is multifactorial in origin, influenced by pre-existing patient characteristics and acute episode features. Further mechanistic and epidemiological investigation is warranted.
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Affiliation(s)
- Chiara Ventre
- Surgery, School of Medicine, University of Edinburgh, Edinburgh, UK
| | - Sian Nowell
- Electronic Data Research and Innovation Service (eDRIS), NHS National Services Scotland, Edinburgh, UK
| | - Catriona Graham
- Edinburgh Clinical Trials Unit, University of Edinburgh, Edinburgh, UK
| | - Doug Kidd
- Electronic Data Research and Innovation Service (eDRIS), NHS National Services Scotland, Edinburgh, UK
| | - Christos Skouras
- Surgery, School of Medicine, University of Edinburgh, Edinburgh, UK
| | - Damian J Mole
- Surgery, School of Medicine, University of Edinburgh, Edinburgh, UK
- MRC Centre for Inflammation Research, University of Edinburgh, Edinburgh, UK
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18
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Umapathy C, Raina A, Saligram S, Tang G, Papachristou GI, Rabinovitz M, Chennat J, Zeh H, Zureikat AH, Hogg ME, Lee KK, Saul MI, Whitcomb DC, Slivka A, Yadav D. Natural History After Acute Necrotizing Pancreatitis: a Large US Tertiary Care Experience. J Gastrointest Surg 2016; 20:1844-1853. [PMID: 27619808 DOI: 10.1007/s11605-016-3264-2] [Citation(s) in RCA: 39] [Impact Index Per Article: 4.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/16/2016] [Accepted: 08/24/2016] [Indexed: 02/06/2023]
Abstract
BACKGROUND Most studies of acute necrotizing pancreatitis (ANP) focus on short-term outcomes. We evaluated long-term survival and outcomes following ANP. METHODS Patients treated for ANP at the University of Pittsburgh Medical Center from 2001 to 2008 were studied. Data on presentation and course during initial hospitalization and follow-up (median 34 months) was extracted. RESULTS Mean age of patients (n = 167) was 53 ± 16 years; 70 % were male, 94 % white, 71 % transfers, 52 % biliary etiology, and 78 % had first-attack of acute pancreatitis. Majority had severe disease with high Acute Physiology and Chronic Health Evaluation II (APACHE-II) score (median 11), length of stay (median 26 days), intensive care unit (ICU) admission (87 %), presence of systemic inflammatory response syndrome (SIRS) (90 %), persistent organ failure (60 %), and infected necrosis (50 %). Intervention was needed in 74 %. Eighteen (10.8 %) patients died during index hospitalization, 9 (5.4 %) during the first year, and 13 (7.8 %) after 1 year. Median survival was significantly shorter when compared with age- and sex-matched US general population (9.1 vs. 26.1 years, p < 0.001). Increasing age (HR 1.05), persistent organ failure (HR 4.5), and >50 % necrosis (HR 3.8) were independent predictors of death at 1 year. In eligible patients, new-onset diabetes, oral pancreatic enzyme replacement therapy, and disability were noted in 45, 25, and 53 %, respectively. CONCLUSION ANP significantly impacts long-term survival. A high proportion of patients develop functional derangement and disability following ANP.
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Affiliation(s)
| | - Amit Raina
- Division of Gastroenterology, Hepatology, and Nutrition, East Carolina University, Greenville, NC, USA
| | - Shreyas Saligram
- Division of Gastroenterology, Hepatology, and Motility, University of Kansas Medical Center, Kansas City, KS, USA
| | - Gong Tang
- Department of Biostatistics, University of Pittsburgh, Pittsburgh, PA, USA
| | - Georgios I Papachristou
- Division of Gastroenterology, Hepatology, and Nutrition, University of Pittsburgh School of Medicine, 200 Lothrop Street, M-2, C-Wing, Pittsburgh, PA, 15213, USA
| | - Mordechai Rabinovitz
- Division of Gastroenterology, Hepatology, and Nutrition, University of Pittsburgh School of Medicine, 200 Lothrop Street, M-2, C-Wing, Pittsburgh, PA, 15213, USA
| | - Jennifer Chennat
- Division of Gastroenterology, Hepatology, and Nutrition, University of Pittsburgh School of Medicine, 200 Lothrop Street, M-2, C-Wing, Pittsburgh, PA, 15213, USA
| | - Herbert Zeh
- Division of Surgical Oncology, University of Pittsburgh, Pittsburgh, PA, USA
| | - Amer H Zureikat
- Division of Surgical Oncology, University of Pittsburgh, Pittsburgh, PA, USA
| | - Melissa E Hogg
- Division of Surgical Oncology, University of Pittsburgh, Pittsburgh, PA, USA
| | - Kenneth K Lee
- Division of Surgical Oncology, University of Pittsburgh, Pittsburgh, PA, USA
| | - Melissa I Saul
- Department of Biomedical Informatics, University of Pittsburgh, Pittsburgh, PA, USA
| | - David C Whitcomb
- Division of Gastroenterology, Hepatology, and Nutrition, University of Pittsburgh School of Medicine, 200 Lothrop Street, M-2, C-Wing, Pittsburgh, PA, 15213, USA
| | - Adam Slivka
- Division of Gastroenterology, Hepatology, and Nutrition, University of Pittsburgh School of Medicine, 200 Lothrop Street, M-2, C-Wing, Pittsburgh, PA, 15213, USA
| | - Dhiraj Yadav
- Division of Gastroenterology, Hepatology, and Nutrition, University of Pittsburgh School of Medicine, 200 Lothrop Street, M-2, C-Wing, Pittsburgh, PA, 15213, USA.
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19
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Wetterholm E, Linders J, Merza M, Regner S, Thorlacius H. Platelet-derived CXCL4 regulates neutrophil infiltration and tissue damage in severe acute pancreatitis. Transl Res 2016; 176:105-18. [PMID: 27183218 DOI: 10.1016/j.trsl.2016.04.006] [Citation(s) in RCA: 26] [Impact Index Per Article: 2.9] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/29/2015] [Revised: 04/13/2016] [Accepted: 04/14/2016] [Indexed: 12/22/2022]
Abstract
Platelets are known to play an important role in acute pancreatitis (AP) via promotion of neutrophil accumulation, although mechanisms behind platelet-dependent accumulation of neutrophils in the pancreas remain elusive. Platelets contain a wide spectrum of different pro-inflammatory compounds, such as chemokines. CXCL4 (platelet factor 4) is one of the most abundant chemokine in platelets, and we hypothesized that CXCL4 might be involved in platelet-dependent accumulation of neutrophils in the inflamed pancreas. The aim of this study was to examine the role of CXCL4 in severe AP. Pancreatitis was provoked by infusion of taurocholate into the pancreatic duct or by intraperitoneal administration of L-arginine in C57BL/6 mice. Animals were treated with an antibody against platelets or CXCL4 before induction of pancreatitis. Plasma and lung levels of CXCL2, CXCL4, and interleukin (IL)-6 were determined by use of enzyme-linked immunosorbent assay. Flow cytometry was used to examine surface expression of macrophage-1 (Mac-1) on neutrophils. Plasma was obtained from healthy individuals (controls) and patients with AP. Challenge with taurocholate increased plasma levels of CXCL4, and depletion of platelets markedly reduced plasma levels of CXCL4 indicating that circulating levels of CXCL4 are mainly derived from platelets in AP. Inhibition of CXCL4 reduced taurocholate-induced neutrophil recruitment, IL-6 secretion, edema formation, amylase release, and tissue damage in the pancreas. However, immunoneutralization of CXCL4 had no effect on CXCL2-evoked neutrophil expression of Mac-1 or chemotaxis in vitro, suggesting an indirect effect of CXCL4 on neutrophil recruitment in AP. Targeting CXCL4 significantly attenuated plasma and lung levels of CXCL2, which is a potent neutrophil chemoattractant, and inhibition of the CXCL2 receptor attenuated neutrophil infiltration and tissue damage in the inflamed pancreas. A significant role of CXCL4 was confirmed in an alternate model of AP induced by L-arginine challenge. Moreover, patients with AP had significantly increased plasma levels of CXCL4 compared with healthy controls. These findings' results suggest that platelet-derived CXCL4 is a potent stimulator of neutrophil accumulation in AP and that this is mediated via generation of CXCL2 in the inflamed pancreas. We conclude that CXCL4 plays an important role in pancreatic inflammation and that targeting CXCL4 might be a useful way to ameliorate tissue damage in AP.
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Affiliation(s)
- Erik Wetterholm
- Department of Clinical Sciences, Malmö, Section for Surgery, Lund University, Malmö, Sweden
| | - Johan Linders
- Department of Clinical Sciences, Malmö, Section for Surgery, Lund University, Malmö, Sweden
| | - Mohammed Merza
- Department of Clinical Sciences, Malmö, Section for Surgery, Lund University, Malmö, Sweden
| | - Sara Regner
- Department of Clinical Sciences, Malmö, Section for Surgery, Lund University, Malmö, Sweden
| | - Henrik Thorlacius
- Department of Clinical Sciences, Malmö, Section for Surgery, Lund University, Malmö, Sweden.
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20
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Pendharkar SA, Asrani VM, Xiao AY, Yoon HD, Murphy R, Windsor JA, Petrov MS. Relationship between pancreatic hormones and glucose metabolism: A cross-sectional study in patients after acute pancreatitis. Am J Physiol Gastrointest Liver Physiol 2016; 311:G50-8. [PMID: 27173509 DOI: 10.1152/ajpgi.00074.2016] [Citation(s) in RCA: 56] [Impact Index Per Article: 6.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/17/2016] [Accepted: 05/04/2016] [Indexed: 01/31/2023]
Abstract
Abnormal glucose metabolism is present in almost 40% of patients after acute pancreatitis, but its pathophysiology has been poorly investigated. Pancreatic hormone derangements have been sparingly studied to date, and their relationship with abnormal glucose metabolism is largely unknown. The aim was to investigate the associations between pancreatic hormones and glucose metabolism after acute pancreatitis, including the effect of potential confounders. This was a cross-sectional study of 83 adult patients after acute pancreatitis. Fasting venous blood was collected from all patients and used for analysis of insulin, glucagon, pancreatic polypeptide, amylin, somatostatin, C-peptide, glucose, and hemoglobin A1c. Statistical analyses were conducted using the modified Poisson regression, multivariable linear regression, and Spearman's correlation. Age, sex, body mass index, recurrence of acute pancreatitis, duration from first attack, severity, and etiology were adjusted for. Increased insulin was significantly associated with abnormal glucose metabolism after acute pancreatitis, in both unadjusted (P = 0.038) and adjusted (P = 0.001) analyses. Patients with abnormal glucose metabolism also had significantly decreased pancreatic polypeptide (P = 0.001) and increased amylin (P = 0.047) in adjusted analyses. Somatostatin, C-peptide, and glucagon were not changed significantly in both unadjusted and adjusted analyses. Increased insulin resistance and reduced insulin clearance may be important components of hyperinsulinemic compensation in patients after acute pancreatitis. Increased amylin and reduced pancreatic polypeptide fasting levels characterize impaired glucose homeostasis. Clinical studies investigating islet-cell hormonal responses to mixed-nutrient meal testing and euglycemic-hyperinsulinemic clamps are now warranted for further insights into the role of pancreatic hormones in glucose metabolism derangements secondary to pancreatic diseases.
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Affiliation(s)
| | - Varsha M Asrani
- Department of Surgery, University of Auckland, Auckland, New Zealand
| | - Amy Y Xiao
- Department of Surgery, University of Auckland, Auckland, New Zealand
| | - Harry D Yoon
- Department of Surgery, University of Auckland, Auckland, New Zealand
| | - Rinki Murphy
- Department of Medicine, University of Auckland, Auckland, New Zealand
| | - John A Windsor
- Department of Surgery, University of Auckland, Auckland, New Zealand
| | - Maxim S Petrov
- Department of Surgery, University of Auckland, Auckland, New Zealand;
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Abstract
This article reviews advances in the management of acute pancreatitis. Medical treatment has been primarily supportive for this diagnosis, and despite extensive research efforts, there are no pharmacologic therapies that improve prognosis. The current mainstay of management, notwithstanding the ongoing debate regarding the volume, fluid type, and rate of administration, is aggressive intravenous fluid resuscitation. Although antibiotics were used consistently for prophylaxis in severe acute pancreatitis to prevent infection, they are no longer used unless infection is documented. Enteral nutrition, especially in patients with severe acute pancreatitis, is considered a cornerstone in management of this disease.
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Affiliation(s)
| | - Timothy B Gardner
- Geisel School of Medicine at Dartmouth, Hanover, NH, USA; Section of Gastroenterology and Hepatology, Dartmouth Hitchcock Medical Center, One Medical Center Drive, Lebanon, NH 03756, USA.
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Abstract
This article will review the recent advances in managing acute pancreatitis. Supportive care has long been the standard of treatment for this disease despite extensive, but ultimately unsuccessful, efforts to develop disease-specific pharmacologic therapies. The primary interventions center on aggressive fluid resuscitation, initiation of early enteral nutrition, targeted antibiotic therapy, and the management of complications. In this article, we will detail treatment of acute pancreatitis with a focus on intravenous fluid resuscitation, enteral feeding, and the current evidence behind the use of antibiotics and other pharmacologic therapies.
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Affiliation(s)
- Nigeen Janisch
- Department of Gastroenterology and Hepatology, Dartmouth-Hitchcock Medical Center, Lebanon, NH, USA
| | - Timothy Gardner
- Department of Gastroenterology and Hepatology, Dartmouth-Hitchcock Medical Center, Lebanon, NH, USA
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Tsai MS, Lin CL, Hsu YC, Lee HM, Kao CH. Long-term risk of pancreatitis and diabetes after cholecystectomy in patients with cholelithiasis but no pancreatitis history: a 13-year follow-up study. Eur J Intern Med 2015; 26:540-4. [PMID: 26143191 DOI: 10.1016/j.ejim.2015.06.013] [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: 05/21/2015] [Revised: 06/21/2015] [Accepted: 06/22/2015] [Indexed: 11/27/2022]
Abstract
BACKGROUND & AIM Patients with biliary pancreatitis are suggested to undergo cholecystectomy to prevent the recurrence of pancreatitis. However, it remains controversial whether cholecystectomy is associated with reduced risks of pancreatitis and diabetes in patients with cholelithiasis and no history of pancreatitis. METHODS From Taiwan's National Health Insurance Research Database, we identified the following cohorts and analyzed the long-term risks of pancreatitis and diabetes in each cohort: 1) cholecystectomy cohort: cholelithiasis patients who had no history of pancreatitis and diabetes and underwent cholecystectomy; and 2) comparison cohort: cholelithiasis patients who had no history of pancreatitis and diabetes and did not undergo cholecystectomy. RESULTS The cholecystectomy group and the comparison group had similar distributions of age, sex, and comorbidities, except for hyperlipidemia. The proportion of patients in the cholecystectomy group who underwent endoscopic cholangiographic procedures was higher than that in the comparison group. Cholecystectomy was associated with a reduced risk of pancreatitis (adjusted hazard ratio [HR], 0.49; 95% confidence interval [CI], 0.36-0.68). Age-specific analyses showed that pancreatitis risk was decreased in patients younger than 50 and older than 65years. Both men and women exhibited reduced risks of pancreatitis after cholecystectomy. However, cholecystectomy was not associated with changes in the risk for diabetes. CONCLUSION Cholecystectomy for cholelithiasis is associated with a reduced risk of pancreatitis, but not of diabetes, in patients without previous history of pancreatitis and diabetes.
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Affiliation(s)
- Ming-Shian Tsai
- Department of General Surgery, E-Da Hospital and I-Shou University, Kaohsiung, Taiwan
| | - Cheng-Li Lin
- Management Office for Health Data, China Medical University Hospital, Taichung, Taiwan; College of Medicine, China Medical University, Taichung, Taiwan
| | - Yao-Chun Hsu
- Department of Gastroenterology, E-Da Hospital and I-Shou University, Kaohsiung, Taiwan
| | - Hui-Ming Lee
- Department of General Surgery, E-Da Hospital and I-Shou University, Kaohsiung, Taiwan
| | - Chia-Hung Kao
- Graduate Institute of Clinical Medical Science, College of Medicine, China Medical University, Taichung, Taiwan; School of Medicine, College of Medicine, China Medical University, Taichung, Taiwan; Department of Nuclear Medicine and PET Center, China Medical University Hospital, Taichung, Taiwan.
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Vujasinovic M, Makuc J, Tepes B, Marolt A, Kikec Z, Robac N. Impact of a clinical pathway on treatment outcome in patients with acute pancreatitis. World J Gastroenterol 2015; 21:9150-9155. [PMID: 26290642 PMCID: PMC4533047 DOI: 10.3748/wjg.v21.i30.9150] [Citation(s) in RCA: 10] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/18/2015] [Revised: 04/23/2015] [Accepted: 06/16/2015] [Indexed: 02/07/2023] Open
Abstract
AIM: To determine the impact of a clinical pathway (CP) on acute pancreatitis (AP) treatment outcome.
METHODS: A retrospective analysis of medical records was performed. We compared the results of AP treatment outcome over two time periods in our centre, before (2006-2007) and after (2010-2012) the implementation of a CP. The CP comprised the following indicators of quality: performance of all laboratory tests on admission (including lipids and carbohydrate deficient transferrin), determination of AP aetiology, abdomen ultrasound (US) within the first 24 h after admission, contrast-enhanced computed tomography of the abdomen in all cases of suspected pancreatic necrosis, appropriately selected and sufficiently used antibiotic therapy (if necessary), pain control, adequate hydration, control of haemodynamic parameters and transfer to the Intensive Care Unit (ICU) (if necessary), endoscopic retrograde cholangiopancreatography (ERCP) in biliary AP, surgical treatment (if necessary), and advice on outpatient follow-up after discharge. A comparison of the length of stay with that in other Slovenian hospitals was also performed.
RESULTS: There were 139 patients treated in the three-year period after the introduction of a CP, of which 81 (58.3%) were male and 58 (41.7%) female. The patients’ mean age was 59.6 ± 17.3 years. The most common aetiologies were alcoholism and gallstones (38.8% each), followed by unexplained (11.5%), drug-induced, hypertriglyceridemia, post ERCP (2.9% each) and tumours (2.2%). Antibiotic therapy was prescribed in 72 (51.8%) patients. Abdominal US was performed in all patients within the first 24 h after admission. Thirty-two (23.0%) patients were treated in the ICU. Four patients died (2.9%). In comparison to 2006-2007, we found an increased number of alcoholic and biliary AP and an associated decrease in the number of unexplained aetiology cases. The use of antibiotics also significantly decreased after the implementation of a CP (from 70.3% to 51.8%; P = 0.003). There was no statistically significant difference in mortality (1.8% vs 2.9%). The length of stay was significantly shorter when compared to the Slovenian average (P = 0.018).
CONCLUSION: The introduction of a CP has improved the treatment of patients with AP, as assessed by all of the observed parameters.
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Landahl P, Ansari D, Andersson R. Severe Acute Pancreatitis: Gut Barrier Failure, Systemic Inflammatory Response, Acute Lung Injury, and the Role of the Mesenteric Lymph. Surg Infect (Larchmt) 2015; 16:651-6. [PMID: 26237406 DOI: 10.1089/sur.2015.034] [Citation(s) in RCA: 44] [Impact Index Per Article: 4.4] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/18/2022] Open
Abstract
BACKGROUND Severe acute pancreatitis (AP) often leads to distant organ dysfunction with a high morbidity and mortality rate. The most common and earliest organ to fail is the lungs, but the exact pathophysiological mechanisms underlying the disease are still unclear. No successful targeted therapy exists, and treatment is limited to organ supportive care. It is believed that the gut is involved in the development of distant organ failure, as severe AP is associated with changes in the microcirculation, gut permeability/motility, bacterial translocation, and activation of the gut-associated lymphoid tissue (GALT). Experimental evidence implicates the mesenteric lymph as a primary route for these toxic factors to gain access to the systemic circulation. This literature overview was made to survey these mechanisms and the potential of surgical interventions on the thoracic duct as a means of therapy. METHODS Review of the pertinent English-language literature. RESULTS In experimental studies, interruption of mesenteric lymphatic flow has preventive qualities for acute lung injury (ALI) in the setting of critical illness with various etiologies. Experimentally, diversion of mesenteric lymph is able to prevent ALI if done before its development, whereas a later intervention partially reduces the lung damage. Few studies have investigated surgical approaches to the thoracic duct in human beings under these circumstances, and the ones that have been performed are of low quality and have conflicting results. It seems likely that the intervention would need to be performed prior to the development of ALI to obtain maximum benefits, which complicates its application clinically, because prediction of ALI cannot today be done with high precision. CONCLUSION Studies are ongoing to identify the factors carried in mesenteric lymph that may cause end-organ failure (e.g., ALI) and, once recognized, might allow the development of novel targeted agents that would modify the disease course.
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Affiliation(s)
- Per Landahl
- Department of Surgery, Clinical Sciences Lund, Lund University, Skåne University Hospital , Lund, Sweden
| | - Daniel Ansari
- Department of Surgery, Clinical Sciences Lund, Lund University, Skåne University Hospital , Lund, Sweden
| | - Roland Andersson
- Department of Surgery, Clinical Sciences Lund, Lund University, Skåne University Hospital , Lund, Sweden
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Vujasinovic M, Tepes B, Makuc J, Rudolf S, Zaletel J, Vidmar T, Seruga M, Birsa B. Pancreatic exocrine insufficiency, diabetes mellitus and serum nutritional markers after acute pancreatitis. World J Gastroenterol 2014; 20:18432-18438. [PMID: 25561813 PMCID: PMC4277983 DOI: 10.3748/wjg.v20.i48.18432] [Citation(s) in RCA: 34] [Impact Index Per Article: 3.1] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/25/2014] [Revised: 06/22/2014] [Accepted: 08/28/2014] [Indexed: 02/07/2023] Open
Abstract
AIM: To investigate impairment and clinical significance of exocrine and endocrine pancreatic function in patients after acute pancreatitis (AP).
METHODS: Patients with AP were invited to participate in the study. Severity of AP was determined by the Atlanta classification and definitions revised in 2012. Pancreatic exocrine insufficiency (PEI) was diagnosed by the concentration of fecal elastase-1. An additional work-up, including laboratory testing of serum nutritional markers for determination of malnutrition, was offered to all patients with low levels of fecal elastase-1 FE. Hemoglobin A1c or oral glucose tolerance tests were also performed in patients without prior diabetes mellitus, and type 3c diabetes mellitus (T3cDM) was diagnosed according to American Diabetes Association criteria.
RESULTS: One hundred patients were included in the study: 75% (75/100) of patients had one attack of AP and 25% (25/100) had two or more attacks. The most common etiology was alcohol. Mild, moderately severe and severe AP were present in 67, 15 and 18% of patients, respectively. The mean time from attack of AP to inclusion in the study was 2.7 years. PEI was diagnosed in 21% (21/100) of patients and T3cDM in 14% (14/100) of patients. In all patients with PEI, at least one serologic nutritional marker was below the lower limit of normal. T3cDM was more frequently present in patients with severe AP (P = 0.031), but was also present in some patients with mild and moderately severe AP. PEI was present in all degrees of severity of AP. There were no statistically significantly differences according to gender, etiology and number of AP attacks.
CONCLUSION: As exocrine and endocrine pancreatic insufficiency can develop after AP, routine follow-up of patients is necessary, for which serum nutritional panel measurements can be useful.
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Vipperla K, Papachristou GI, Easler J, Muddana V, Slivka A, Whitcomb DC, Yadav D. Risk of and factors associated with readmission after a sentinel attack of acute pancreatitis. Clin Gastroenterol Hepatol 2014; 12:1911-9. [PMID: 24815327 DOI: 10.1016/j.cgh.2014.04.035] [Citation(s) in RCA: 60] [Impact Index Per Article: 5.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/09/2014] [Revised: 04/27/2014] [Accepted: 04/29/2014] [Indexed: 02/07/2023]
Abstract
BACKGROUND & AIMS Few data are available on how many patients are readmitted to the hospital after attacks of acute pancreatitis. We aimed to determine the risk and factors that determine early (within 30 days) and late (after 30 days) readmission of patients with acute pancreatitis. METHODS In a retrospective study, we collected and analyzed data on 127 surviving patients (median age, 53 y; 52% male; 83% white) hospitalized at the University of Pittsburgh Medical Center for a sentinel attack of acute pancreatitis, enrolled in the Severe Acute Pancreatitis Study from June 2003 through April 2010, and who had follow-up data. Information was collected on demographics, clinical profile, risk score at discharge (based on a recently developed scoring system), and details of readmissions during the follow-up period (median, 36 mo). RESULTS Of the 127 patients, 52% were transfers from another care center and 32% required admission to the intensive care unit. Etiologies for pancreatitis were biliary (47%), idiopathic (13%), alcohol associated (12%), and others (28%). Pancreatic necrosis (28%), persistent organ failure (27%), and peripancreatic fluid collections (19%) were common. The median length of stay was 9 days. A total of 108 readmissions occurred for 43 patients (34%). Early readmissions (n = 21) occurred more frequently for patients with smoldering (ongoing) symptoms or local complications than for those without. Late readmissions (n = 22) occurred more frequently for patients with recurrent pancreatitis than for those without. Male sex, alcohol-associated disease, and severe disease increased the risks of readmission and recurrence. The risk for readmission was lower among nontransferred patients (23%) and patients without necrosis or organ failure (16%). Risk for readmission increased with the number of points on the weighted scoring system. CONCLUSIONS Approximately one-third of patients hospitalized for acute pancreatitis are readmitted, usually as a result of smoldering symptoms, local complications, or recurrent attacks. Studies are needed to determine whether individualized discharge planning, with consideration of the etiology of acute pancreatitis, can reduce the risk for readmission.
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Affiliation(s)
- Kishore Vipperla
- Division of Gastroenterology and Hepatology, University of Pittsburgh Medical Center, Pittsburgh, Pennsylvania
| | - Georgios I Papachristou
- Division of Gastroenterology and Hepatology, University of Pittsburgh Medical Center, Pittsburgh, Pennsylvania
| | - Jeffrey Easler
- Division of Gastroenterology and Hepatology, University of Pittsburgh Medical Center, Pittsburgh, Pennsylvania
| | - Venkata Muddana
- Division of Gastroenterology and Hepatology, University of Pittsburgh Medical Center, Pittsburgh, Pennsylvania
| | - Adam Slivka
- Division of Gastroenterology and Hepatology, University of Pittsburgh Medical Center, Pittsburgh, Pennsylvania
| | - David C Whitcomb
- Division of Gastroenterology and Hepatology, University of Pittsburgh Medical Center, Pittsburgh, Pennsylvania
| | - Dhiraj Yadav
- Division of Gastroenterology and Hepatology, University of Pittsburgh Medical Center, Pittsburgh, Pennsylvania.
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Vallance AE, Wilson CH, Charnley RM. Minimal access drainage procedures for patients with necrotising pancreatitis. Cochrane Database Syst Rev 2014. [DOI: 10.1002/14651858.cd011081] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/21/2022]
Affiliation(s)
- Abigail E Vallance
- The Freeman Hospital; Hepato-Pancreato-Biliary Surgical Unit; Freeman Road High Heaton Newcastle-upon-Tyne UK NE7 7DN
| | - Colin H Wilson
- The Freeman Hospital; Institute of Transplantation; Freeman Road High Heaton Newcastle upon Tyne Tyne and Wear UK NE7 7DN
| | - Richard M Charnley
- The Freeman Hospital; Hepato-Pancreato-Biliary Surgical Unit; Freeman Road High Heaton Newcastle-upon-Tyne UK NE7 7DN
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Abstract
OBJECTIVE This study aimed to evaluate the burden and pattern of pancreatitis-related readmissions after index hospitalization for acute pancreatitis (AP). METHODS We identified all unique white or black Allegheny County residents with first hospital admission for AP from 1996 to 2005 using the Pennsylvania Health Care Cost Containment Council data set. The final study population consisted of patients (n = 6010) who survived index admission and had follow-up data on readmissions. The etiology was determined using associated diagnosis codes. We analyzed pancreatitis-related readmissions until the third quarter of 2007 (median follow-up time, 39 months). RESULTS The absolute risk and total burden of readmissions were 21.9% and 2947 for primary AP, respectively, 5.8% and 812 for primary chronic pancreatitis (CP), respectively, and 32.3% and 6612 for any pancreatitis diagnosis, respectively. Patients with alcohol etiology (etiology on index admission in 20.3%; responsible for 41.6%-50.4% readmissions) and subsequent diagnosis of CP (any CP diagnosis, 12.8%; responsible for 73% readmissions) accounted for a disproportionately higher fraction of readmissions. Readmission risk decreased with increasing age. A small fraction of patients accounted for most readmissions. CONCLUSIONS Readmission after AP is influenced by demographics, etiology, and subsequent CP diagnosis. Future studies should focus on understanding the factors driving readmissions in high-risk individuals to develop strategies for reducing pancreatitis-related readmissions and health care costs.
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Das SLM, Singh PP, Phillips ARJ, Murphy R, Windsor JA, Petrov MS. Newly diagnosed diabetes mellitus after acute pancreatitis: a systematic review and meta-analysis. Gut 2014; 63:818-31. [PMID: 23929695 DOI: 10.1136/gutjnl-2013-305062] [Citation(s) in RCA: 264] [Impact Index Per Article: 24.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/12/2022]
Abstract
BACKGROUND Diabetes mellitus (DM) is common in the general population and it poses a heavy burden to society in the form of long-term disability, healthcare use and costs. The pancreas is a key player in glucose homeostasis, but the occurrence of newly diagnosed DM after acute pancreatitis (AP), the most frequent disease of the pancreas, has never been assessed systematically. The aim of this study was to conduct a systematic literature review to determine the prevalence and time course of DM and related conditions after the first attack of AP as well as the impact of covariates. METHODS Relevant literature cited in three electronic databases (Scopus, EMBASE and MEDLINE) was reviewed independently by two authors. The main outcome measures studied were newly diagnosed prediabetes, DM, or DM treated with insulin. Pooled prevalence and 95% CIs were calculated for all outcomes. RESULTS A total of 24 prospective clinical studies, involving 1102 patients with first episode of AP, met all the eligibility criteria. Prediabetes and/or DM was observed in 37% (95% CI 30% to 45%) individuals after AP. The pooled prevalence of prediabetes, DM and treatment with insulin after AP was 16% (95% CI 9% to 24%), 23% (95% CI 16% to 31%), and 15% (95% CI 9% to 21%), respectively. Newly diagnosed DM developed in 15% of individuals within 12 months after first episode of AP and the risk increased significantly at 5 years (relative risk 2.7 (95% CI 1.9 to 3.8)). A similar trend was observed with regard to treatment with insulin. The severity of AP, its aetiology, individuals' age and gender had minimal effect on the studied outcomes. CONCLUSIONS Patients with AP often develop prediabetes and/or DM after discharge from hospital, and have a greater than twofold increased risk of DM over 5 years. Further studies are warranted to determine the optimal strategy for its detection and whether the risk of developing DM after AP can be reduced.
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Affiliation(s)
- Stephanie L M Das
- Department of Surgery, The University of Auckland, , Auckland, New Zealand
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Lappalainen-Lehto R, Koistinen N, Aalto M, Huhtala H, Sand J, Nordback I, Seppä K. Goal-related outcome after acute alcohol-pancreatitis -- a two-year follow-up study. Addict Behav 2013; 38:2805-9. [PMID: 24018221 DOI: 10.1016/j.addbeh.2013.07.008] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/30/2013] [Revised: 06/12/2013] [Accepted: 07/15/2013] [Indexed: 12/14/2022]
Abstract
The aim of this study was to find out if an acute pancreatitis leads the patients to reduce their alcohol consumption and if there are factors predicting the outcome. We also observed which factors affected the choice of patient's personal drinking goal, e.g., abstinence or moderate drinking, how this goal changed during the follow-up and how the goal affected the change in drinking habits. In 2001-2005, 120 patients treated in Tampere University Hospital for their first alcohol-related acute pancreatitis were interviewed before discharge from the hospital and at the two-year follow-up. All patients had at least one intervention session for their alcohol use. Of the patients 87 (72.5%) completed the study. The alcohol consumption level and its changes, personal drinking goal of the patients, the factors affecting the choice and the changes of the goal were observed. Most (96.4%) of the patients were willing to reduce their drinking. At follow-up, 34 (40.5%) patients succeeded in reducing their alcohol consumption under the pre-set moderate drinking level. The only factor predicting alcohol use was the number of hospitalization days due to the acute alcohol-related pancreatitis (p=0.015). Those who chose abstinence seemed to succeed more often in stopping drinking or reducing their drinking below risk levels as compared to those with moderation goal (47.9% vs. 28.6%, p=0.075). The only abstinence-goal predicting factor was the concern of the relatives, friends or doctors (p=0.001). All 6 patients who needed intensive care chose abstinence-goal. During the follow-up period the goal changed. At baseline, the majority chose abstinence but two years after pancreatitis, the majority was striving for moderate drinking. A serious illness seems to be a good opportunity to change and to motivate patients. Even if abstinence is recommended to patients with alcohol-related pancreatitis, communication of individual goals is important in the motivation process of the patients.
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Garip G, Sarandöl E, Kaya E. Effects of disease severity and necrosis on pancreatic dysfunction after acute pancreatitis. World J Gastroenterol 2013; 19:8065-8070. [PMID: 24307801 PMCID: PMC3848155 DOI: 10.3748/wjg.v19.i44.8065] [Citation(s) in RCA: 40] [Impact Index Per Article: 3.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/28/2013] [Revised: 07/03/2013] [Accepted: 09/17/2013] [Indexed: 02/06/2023] Open
Abstract
AIM: To evaluate the effects of disease severity and necrosis on organ dysfunctions in acute pancreatitis (AP).
METHODS: One hundred and nine patients treated as AP between March 2003 and September 2007 with at least 6 mo follow-up were included. Patients were classified according to severity of the disease, necrosis ratio and localization. Subjective clinical evaluation and fecal pancreatic elastase-I (FPE-I) were used for exocrine dysfunction evaluation, and oral glucose tolerance test was completed for endocrine dysfunction. The correlation of disease severity, necrosis ratio and localization with exocrine and endocrine dysfunction were investigated.
RESULTS: There were 58 male and 51 female patients, and mean age was 56.5 ± 15.7. Of the patients, 35.8% had severe AP (SAP) and 27.5% had pancreatic necrosis. Exocrine dysfunction was identified in 13.7% of the patients [17.9% were in SAP, 11.4% were in mild AP (MAP)] and 34.7% of all of the patients had endocrine dysfunction (56.4% in SAP and 23.2% in MAP). In patients with SAP and necrotizing AP (NAP), FPE-Ilevels were lower than the others (P < 0.05 and 0.001 respectively) and in patients having pancreatic head necrosis or near total necrosis, FPE-1 levels were lower than 200 μg/g stool. Forty percent of the patients who had undergone necrosectomy developed exocrine dysfunction. Endocrine dysfunction was more significant in patients with SAP and NAP (P < 0.001). All of the patients in the necrosectomy group had endocrine dysfunction.
CONCLUSION: Patients with SAP, NAP, pancreatic head necrosis and necrosectomy should be followed for pancreatic functions.
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Sayilir A, Beyazit Y, Yesil Y, Albayrak M, Ekiz F, Celik T, Suvak B, Torun S, Ibiş M. Plasma thrombin-activatable fibrinolysis inhibitor as an indicator of inflammation and disease severity in acute pancreatitis. Clin Res Hepatol Gastroenterol 2012; 36:498-504. [PMID: 22230218 DOI: 10.1016/j.clinre.2011.12.006] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/10/2011] [Revised: 11/28/2011] [Accepted: 12/05/2011] [Indexed: 02/04/2023]
Abstract
AIM In addition to suppressing fibrinolysis, thrombin activatable fibrinolysis inhibitor (TAFI) was suggested to be involved in inflammation. To date, no study has been published that reports the role of TAFI in acute pancreatitis (AP). Therefore, the objective of the present study was to investigate the role of plasma TAFI as an indicator of inflammation in AP, and its association with disease severity. METHODS Plasma TAFI antigen levels quantitatively determined by using ELISA kits in 21 AP patients at onset and remission and 17 healthy controls. Associations of TAFI with inflammatory markers to determine AP and disease severity were assessed. To predict the severity of AP, modified Glasgow prognostic score (mGPS) and computerized tomography severity index (CTSI) were used for each subject. RESULTS Plasma TAFI levels was higher in AP patients at onset of the disease compared with healthy controls. The disease severity according to mGPS was significantly correlated with TAFI levels. Overall, accuracy of TAFI in determining AP was 83.3% with a sensitivity, specificity, NPV and PPV of 80.9%, 85.7%, 81.8%, and 85% respectively (AUC: 0.915). CONCLUSIONS The present study for the first time demonstrated that TAFI is elevated in AP. The appraisal of TAFI levels in patients with AP in conjunction with other markers of inflammation may provide additional information in estimating AP severity.
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Affiliation(s)
- Abdurrahim Sayilir
- Department of Gastroenterology, Turkiye Yuksek İhtisas Teaching and Research Hospital, Kızılay Sk. No: 2, 06100, Sıhhiye Ankara, Turkey.
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Ke L, Ni HB, Tong ZH, Li WQ, Li N, Li JS. D-dimer as a marker of severity in patients with severe acute pancreatitis. JOURNAL OF HEPATO-BILIARY-PANCREATIC SCIENCES 2012; 19:259-65. [PMID: 21667053 DOI: 10.1007/s00534-011-0414-5] [Citation(s) in RCA: 35] [Impact Index Per Article: 2.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 01/21/2023]
Abstract
BACKGROUND/PURPOSE Coagulative disorder is known to occur in the early phase of severe acute pancreatitis (SAP) and D: -dimer is a commonly used clinical parameter of hemostasis. The aim of this study was to assess the value of the plasma D: -dimer level as a marker of severity in the first 3 days after admission in patients with SAP. METHODS From January 2009 to February 2011, 45 patients admitted for SAP were included in this observational study. The D: -dimer level was measured on a daily basis during days 1-3 after admission and the acute physiology and chronic health evaluation (APACHE) II score, sequential organ failure assessment (SOFA) score, and other clinical parameters were recorded at the same time. The maximum and the mean D: -dimer values were used for analysis and compared with other prognostic factors of SAP. RESULTS Both the maximum and mean levels of D: -dimer were significantly different between patients with and without clinical variables such as multiple-organ dysfunction syndrome (MODS), need for surgical intervention, and the presence of pancreatic infection. The D: -dimer level also showed great precision for the prediction of MODS and secondary infection. Additionally, the D: -dimer level correlated well with two usual markers of SAP severity-the APACHE II score and the C-reactive protein level. CONCLUSION D: -dimer measurement is a useful, easy, and inexpensive early prognostic marker of the evolution and complications of SAP.
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Affiliation(s)
- Lu Ke
- Department of General Surgery, Jinling Hospital, Nanjing University School of Medicine, Nanjing 210002, China
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Abdulla A, Awla D, Hartman H, Weiber H, Jeppsson B, Regnér S, Thorlacius H. Platelets regulate P-selectin expression and leukocyte rolling in inflamed venules of the pancreas. Eur J Pharmacol 2012; 682:153-60. [DOI: 10.1016/j.ejphar.2012.02.014] [Citation(s) in RCA: 16] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/10/2011] [Revised: 01/31/2012] [Accepted: 02/09/2012] [Indexed: 12/12/2022]
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Liu Z, Shen Y, Cui N, Yang J. Clinical observation of immunity for severe acute pancreatitis. Inflammation 2012; 34:426-31. [PMID: 20842417 DOI: 10.1007/s10753-010-9249-5] [Citation(s) in RCA: 10] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/21/2022]
Abstract
The aim of our study was to observe the dynamic changes of immunity for patients with severe acute pancreatitis (SAP) and intervention by traditional Chinese medicine. Twenty-three patients who met the inclusion criteria were randomized to combined treatment of traditional Chinese medicine and Western medicine (TCM) or conventional western medicine treatment (WM) groups. The clinical data for all patients were collected. Peripheral venous blood samples were obtained from patients on days 1, 7, 14, and 28 after admission. Biochemical data including the percentage of CD4+/CD8+/natural killer (NK) cells/B lymphocytes/HLA-DR and CD4+/CD8+ ratio in serum were determined by flow cytometer. Patients' characteristics and immunity at admission were similar between the two groups. The secondary infection was different. The levels of T-lymphocyte subsets in the TCM group were quite different from the WM group, with much more the percentage of CD4+ and the CD4+/CD8+ ratio on days 7, 14, and 28 and much less the percentage of CD8+ on days 4 and 28. On days 14 and 28, the levels of NK cells and B lymphocytes were significantly higher in the TCM group compared with the controls. Compared with the TCM group, the levels of HLA-DR were significantly decreased in the WM group on days 7, 14, and 28. The immune dysregulation exists in the development and progression of SAP. The combined treatment of traditional Chinese medicine and western medicine can upregulate the patient's immune and maintain the immune balance.
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Affiliation(s)
- ZhiMin Liu
- Nankai Hospital, Nankai Clinical School, Tianjin Medical University, Tianjin, 300010, People's Republic of China
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The complex exocrine-endocrine relationship and secondary diabetes in exocrine pancreatic disorders. J Clin Gastroenterol 2011; 45:850-61. [PMID: 21897283 DOI: 10.1097/mcg.0b013e31822a2ae5] [Citation(s) in RCA: 25] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/11/2022]
Abstract
The pancreas is a dual organ with exocrine and endocrine functions. The interrelationship of the endocrine-exocrine parts of the pancreas is a complex one, but recent clinical and experimental studies have expanded our knowledge. Many disorders primarily of the exocrine pancreas, often solely in the clinical realm of gastroenterologists are associated with diabetes mellitus (DM). Although, the DM becoming disorders are often grouped with type 2 diabetes, the pathogenesis, clinical manifestations and management differ. We review here data on the association of exocrine-endocrine pancreas, the many hormones of the pancreas and their possible effects on the exocrine functions followed by data on the epidemiology, pathogenesis, and management of DM in chronic pancreatitis, cystic fibrosis, pancreatic cancer, and clinical states after pancreatic surgery.
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Abstract
OBJECTIVE This study aimed to investigate the impairment of pancreatic endocrine function and the associated risk factors after acute pancreatitis (AP). METHODS Fifty-nine patients were subjected to tests of pancreatic function after an attack of pancreatitis. The mean time after the event was 3.5 years. Pancreatic endocrine function was evaluated by fasting blood glucose (FBG), glycosylated hemoglobin, fasting blood insulin, and C-peptide. Homeostasis model assessment was used to evaluate insulin resistance and islet β-cell function. Pancreatic exocrine function was evaluated by fecal elastase 1. Factors that could influence endocrine function were also investigated. RESULTS Nineteen patients (32%) were found to have elevated FBG, whereas 5 (8%) had abnormal glycosylated hemoglobin levels. The levels of FBG, fasting blood insulin, and C-peptide were higher in patients than in controls (P < 0.01). The islet β-cell function of patients was lower than that of controls (P < 0.01), whereas insulin resistance index was higher among patients (P < 0.01). Obesity, hyperlipidemia, and diabetes-related symptoms were found to be associated with endocrine insufficiency. Pancreatic exocrine functional impairment was found at the same time. CONCLUSIONS Endocrine functional impairment with insulin resistance was found in patients after AP. Obesity, hyperlipidemia, and diabetes-related symptoms increased the likelihood of developing functional impairment after AP.
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Oskarsson V, Mehrabi M, Orsini N, Hammarqvist F, Segersvärd R, Andrén-Sandberg A, Sadr Azodi O. Validation of the harmless acute pancreatitis score in predicting nonsevere course of acute pancreatitis. Pancreatology 2011; 11:464-8. [PMID: 21968430 DOI: 10.1159/000331502] [Citation(s) in RCA: 29] [Impact Index Per Article: 2.1] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/26/2011] [Accepted: 08/04/2011] [Indexed: 12/11/2022]
Abstract
BACKGROUND The Harmless Acute Pancreatitis Score (HAPS) is a scoring algorithm to identify patients with nonsevere acute pancreatitis. The aim of this study was to evaluate the reproducibility of HAPS outside its original study setting. METHOD Baseline information of all hospitalized patients with acute pancreatitis at Karolinska University Hospital, Stockholm, Sweden, between 2004 and 2009 was collected. The parameters constituting HAPS were signs of peritonitis, hematocrit and serum creatinine levels. Since hematocrit was not available in all patients, complete sample analysis was performed by replacing hematocrit with hemoglobin (strongly correlated with hematocrit; r = 0.86). RESULTS In total, 531 patients with a first-time or a recurrent attack of acute pancreatitis were included. Among 353 patients with complete information on parameters constituting HAPS, 79 patients were predicted to have a nonsevere course, of whom 1 patient developed severe acute pancreatitis. The specificity of HAPS in predicting a nonsevere course of acute pancreatitis was 96.3% (95% CI: 81.0-99.9) with a corresponding positive predictive value of 98.7% (95% CI: 93.1-100). Complete sample analysis replacing hematocrit with hemoglobin level predicted a nonsevere course in 182 patients, of whom 2 patients had severe acute pancreatitis (94.3% specificity and 98.9% positive predictive value). CONCLUSION HAPS is a highly specific scoring algorithm that predicts a nonsevere course of acute pancreatitis. Therefore, HAPS might be an additional tool in the clinical assessment of acute pancreatitis where early screening is important to treat the patients at an optimal level of care.
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Affiliation(s)
- V Oskarsson
- Department of Gastrointestinal Surgery, Karolinska University Hospital, Stockholm, Sweden.
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Abdulla A, Awla D, Thorlacius H, Regnér S. Role of neutrophils in the activation of trypsinogen in severe acute pancreatitis. J Leukoc Biol 2011; 90:975-82. [PMID: 21810937 DOI: 10.1189/jlb.0411195] [Citation(s) in RCA: 73] [Impact Index Per Article: 5.2] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/13/2022] Open
Abstract
The relationship between inflammation and proteolytic activation in pancreatitis is an unresolved issue in pancreatology. The purpose of this study was to define the influence of neutrophils on trypsinogen activation in severe AP. Pancreatitis was induced by infusion of taurocholate into the pancreatic duct in C57BL/6 mice. For neutrophil depletion, an anti-Gr-1 antibody was administered before pancreatitis induction. Administration of the anti-Gr-1 antibody reduced circulating neutrophils by 97%. Pancreatic TAP and serum amylase levels increased 2 h and 24 h after induction of pancreatitis. Neutrophil depletion reduced pancreatic TAP and serum amylase levels at 24 h but not at 2 h after pancreatitis induction. Pancreatic MPO and infiltration of neutrophils, as well as MIP-2 levels, were increased 24 h after taurocholate infusion. Two hours after taurocholate administration, no significant pancreatic infiltration of neutrophils was observed. Injection of the anti-Gr-1 antibody abolished MPO activity, neutrophil accumulation, and MIP-2 levels, as well as acinar cell necrosis, hemorrhage, and edema in the pancreas at 24 h. Moreover, taurocholate-provoked tissue damage and MPO activity in the lung were normalized by neutrophil depletion. Intravital fluorescence microscopy revealed a 97% reduction of leukocytes in the pancreatic microcirculation after administration of the anti-Gr-1 antibody. Our data demonstrate that initial trypsinogen activation is independent of neutrophils, whereas later activation is dependent on neutrophils in the pancreas. Neutrophils are critical in mediating pancreatic and lung tissue damage in severe AP.
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Affiliation(s)
- Aree Abdulla
- Department of Surgery, Clinical Sciences, Lund University, Malmö, Sweden
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Nøjgaard C, Matzen P, Bendtsen F, Andersen JR, Christensen E, Becker U. Factors associated with long-term mortality in acute pancreatitis. Scand J Gastroenterol 2011; 46:495-502. [PMID: 21091094 DOI: 10.3109/00365521.2010.537686] [Citation(s) in RCA: 14] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/04/2023]
Abstract
BACKGROUND AND AIMS Knowledge of the long-term prognosis of acute pancreatitis (AP) is limited. The aims were to investigate: (1) prognostic factors associated with long-term mortality in patients with AP; (2) whether or not the level of serum (S-)amylase at admission had an impact on the prognosis; (3) causes of death in these patients. METHODS During 1977-1982, patients who were admitted to the five main hospitals in Copenhagen with a diagnosis of AP or chronic pancreatitis (CP) were included in a prospective cohort, the Copenhagen Pancreatitis Study (CPS); in 2008, they were followed up by linkage to the Danish Registries. The analyzed subcohort consisted of 352 patients with probable AP (n = 54) or definite AP (n = 298). RESULTS Multivariate Cox regression analysis showed that significant factors associated with mortality were age, alcohol, and diabetes, whereas female gender, co-living and employment were associated with better survival. The S-amylase level had no impact on mortality. The most frequent causes of death were cardiovascular diseases, digestive diseases, and malignancies. CONCLUSIONS Age, alcohol and diabetes had a significant impact on survival whereas the S-amylase level did not.
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Affiliation(s)
- Camilla Nøjgaard
- Department of Gastroenterology, Hvidovre Hospital, Copenhagen, Denmark.
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Abdulla A, Awla D, Jeppsson B, Regnér S, Thorlacius H. CD40L is not involved in acute experimental pancreatitis. Eur J Pharmacol 2011; 659:85-8. [PMID: 21419763 DOI: 10.1016/j.ejphar.2011.03.008] [Citation(s) in RCA: 6] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/24/2010] [Revised: 01/17/2011] [Accepted: 03/08/2011] [Indexed: 01/02/2023]
Abstract
Recent data suggest that platelets not only control thrombosis and hemostasis but may also regulate inflammatory processes such as acute pancreatitis. However, the specific role of platelet-derived mediators in the pathophysiology of acute pancreatitis is not known. Herein, we examined the role of CD40 ligand (CD40L, CD154) in different models of acute pancreatitis. Acute pancreatitis was induced by repetitive caerulein administration (50μg/kg, i.p.) or infusion of sodium taurocholate (5%-10μl) into the pancreatic duct in wild-type C57BL/6 and CD40L-deficient mice. Neutrophil infiltration, myeloperoxidase (MPO), macrophage inflammatory protein-2 (MIP-2) levels, acinar cell necrosis, edema and hemorrhage in the pancreas as well as serum amylase activity and lung levels of MPO were quantified 24h after induction of acute pancreatitis. Caerulein and taurocholate challenge caused a clear-cut pancreatic damage characterized by increased acinar cell necrosis, neutrophil infiltration, focal hemorrhage, edema formation as well as increased levels of serum amylase and MIP-2 in the pancreas and lung MPO and histological damage. Notably, CD40L gene-deficient animals exhibited a similar phenotype as wild-type mice after challenge with caerulein and taurocholate. Similarly, administration of an antibody directed against CD40L had no effect against acute pancreatitis. Our data suggest that CD40L does not play a functional role in experimental acute pancreatitis. Thus, other candidates than CD40L needs to be explored in order to identify platelet-derived mediators in the pathophysiology of acute pancreatitis.
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Toouli J, Biankin AV, Oliver MR, Pearce CB, Wilson JS, Wray NH. Management of pancreatic exocrine insufficiency: Australasian Pancreatic Club recommendations. Med J Aust 2010; 193:461-7. [PMID: 20955123 DOI: 10.5694/j.1326-5377.2010.tb04000.x] [Citation(s) in RCA: 70] [Impact Index Per Article: 4.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/06/2010] [Accepted: 06/20/2010] [Indexed: 02/06/2023]
Abstract
Pancreatic exocrine insufficiency (PEI) occurs when the amounts of enzymes secreted into the duodenum in response to a meal are insufficient to maintain normal digestive processes. The main clinical consequence of PEI is fat maldigestion and malabsorption, resulting in steatorrhoea. Pancreatic exocrine function is commonly assessed by conducting a 3-day faecal fat test and by measuring levels of faecal elastase-1 and serum trypsinogen. Pancreatic enzyme replacement therapy is the mainstay of treatment for PEI. In adults, the initial recommended dose of pancreatic enzymes is 25,000 units of lipase per meal, titrating up to a maximum of 80,000 units of lipase per meal. In infants and children, the initial recommended dose of pancreatic enzymes is 500 units of lipase per gram of dietary fat; the maximum daily dose should not exceed 10,000 units of lipase per kilogram of bodyweight. Oral pancreatic enzymes should be taken with meals to ensure adequate mixing with the chyme. Adjunct therapy with acid-suppressing agents may be useful in patients who continue to experience symptoms of PEI despite high-dose enzyme therapy. A dietitian experienced in treating PEI should be involved in patient management. Dietary fat restriction is not recommended for patients with PEI. Patients with PEI should be encouraged to consume small, frequent meals and to abstain from alcohol. Medium-chain triglycerides do not provide any clear nutritional advantage over long-chain triglycerides, but can be trialled in patients who fail to gain or to maintain adequate bodyweight in order to increase energy intake.
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Affiliation(s)
- James Toouli
- Department of Surgery, Flinders Medical Centre, Adelaide, SA, Australia.
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Andersson B, Pendse ML, Andersson R. Pancreatic function, quality of life and costs at long-term follow-up after acute pancreatitis. World J Gastroenterol 2010; 16:4944-51. [PMID: 20954281 PMCID: PMC2957603 DOI: 10.3748/wjg.v16.i39.4944] [Citation(s) in RCA: 42] [Impact Index Per Article: 2.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/06/2023] Open
Abstract
AIM: To evaluate long-term endocrine and exocrine pancreatic function, quality of life and health care costs after mild acute pancreatitis and severe acute pancreatitis (SAP).
METHODS: Patients prospectively included in 2001-2005 were followed-up after 42 (36-53) mo. Pancreatic function was evaluated with laboratory tests, the oral glucose tolerance test (OGTT), fecal elastase-1 and a questionnaire. Short Form (SF)-36, was completed.
RESULTS: Fourteen patients with a history of SAP and 26 with mild acute pancreatitis were included. Plasma glucose after OGTT was higher after SAP (9.2 mmol/L vs 7.0 mmol/L, P = 0.044). Diabetes mellitus or impaired glucose tolerance in fasting plasma glucose and/or 120 min plasma glucose were more common in SAP patients (11/14 vs 11/25, P = 0.037). Sick leave, time until the patients could take up recreational activities and time until they had recovered were all longer after SAP (P < 0.001). No significant differences in SF-36 were seen between the groups, or when comparing with age and gender matched reference groups. Total hospital costs, including primary care, follow-up and treatment of complications, were higher after SAP (median €16 572 vs€5000, P < 0.001).
CONCLUSION: Endocrine pancreatic function was affected, especially after severe disease. SAP requires greater resource use with long recovery, but most patients regained a good quality of life.
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Abdulla A, Awla D, Hartman H, Rahman M, Jeppsson B, Regnér S, Thorlacius H. Role of platelets in experimental acute pancreatitis. Br J Surg 2010; 98:93-103. [PMID: 20882560 DOI: 10.1002/bjs.7271] [Citation(s) in RCA: 27] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 07/22/2010] [Indexed: 01/15/2023]
Abstract
BACKGROUND Platelets not only control thrombosis and haemostasis but may also regulate inflammatory processes. Acute pancreatitis (AP) is characterized by changes in both coagulation and proinflammatory activities. The role of platelets in AP is not yet known. METHODS AP was induced in C57BL/6 mice by repeated caerulein administration (50 µg/kg intraperitoneally). Mice received a platelet-depleting or control antibody before caerulein challenge. Neutrophil infiltration, myeloperoxidase (MPO) and macrophage inflammatory protein (MIP) 2 levels, acinar cell necrosis and haemorrhage in the pancreas, as well as serum amylase activity, were determined 24 h after caerulein injection. In an alternative model of pancreatitis, L-arginine (4 g/kg intraperitoneally) was given twice with an interval of 1 h and tissue samples were taken after 72 h [Correction added after online publication 29 September 2010: in the preceding sentence, 4 mg/kg was corrected to 4 g/kg]. RESULTS Caerulein administration increased acinar cell necrosis, neutrophil infiltration, focal haemorrhage and serum amylase levels. Platelet depletion reduced acinar cell necrosis, haemorrhage and serum amylase levels in AP. Depletion of platelets decreased caerulein-induced MPO levels and neutrophil recruitment in the pancreas. Platelet depletion abolished caerulein-induced MIP-2 generation in the pancreas and circulation. The effects of platelet depletion on necrosis, neutrophils and MPO levels were confirmed in L-arginine-induced pancreatitis. CONCLUSION Platelets play a crucial role in AP by regulating neutrophil infiltration, most likely mediated by MIP-2 production in the pancreas.
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Affiliation(s)
- A Abdulla
- Department of Clinical Sciences, Section for Surgery, Malmö University Hospital, Lund University, S-205 02 Malmö, Sweden
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Uomo G, Gallucci F, Madrid E, Miraglia S, Manes G, Rabitti PG. Pancreatic functional impairment following acute necrotizing pancreatitis: long-term outcome of a non-surgically treated series. Dig Liver Dis 2010; 42:149-52. [PMID: 19836318 DOI: 10.1016/j.dld.2009.08.007] [Citation(s) in RCA: 32] [Impact Index Per Article: 2.1] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/23/2009] [Revised: 07/21/2009] [Accepted: 08/24/2009] [Indexed: 12/11/2022]
Abstract
OBJECTIVES Patients who survive an episode of acute necrotizing pancreatitis may develop endocrine and exocrine pancreatic functional impairment; often these patients have undergone pancreatic surgery during the acute episode. Aim of this study is to report the results of a long-term follow-up of patients recovering from an episode of acute necrotizing pancreatitis which had not been treated surgically during the index hospital admission. DESIGN AND SUBJECTS Sixty-five consecutive patients enrolled between January 1990 and December 1993, prospectively followed through December 2006. RESULTS Median follow-up period was 179.5 months (range 156-203). 40 patients (61.5%) who completed follow-up were analysed. Endocrine function: 2 patients (5%) were diabetic before the pancreatitis episode, and 6 (15.7%) developed overt diabetes; diabetes appeared within the 3rd year after acute pancreatitis in 2 patients, between the 3rd and 4th year in 2 patients, and between the 5th and 6th year in the last 2 patients. Exocrine function: 9 patients (22.5%) showed fecal elastase impairment; in all patients ultrasound was normal and fecal elastase returned above the normal limit during follow-up. CONCLUSIONS After an episode of acute necrotizing pancreatitis treated without surgery, the endocrine and exocrine function is not frequently impaired after long-term follow-up. Reduction in exocrine function is transient and complete recovery is achieved in all patients within a few years.
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Affiliation(s)
- G Uomo
- Internal Medicine Department, Cardarelli Hospital, Via Cardarelli 9, 80131 Naples, Italy.
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Takeyama Y. Long-term prognosis of acute pancreatitis in Japan. Clin Gastroenterol Hepatol 2009; 7:S15-7. [PMID: 19896091 DOI: 10.1016/j.cgh.2009.08.022] [Citation(s) in RCA: 82] [Impact Index Per Article: 5.1] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/20/2009] [Revised: 08/24/2009] [Accepted: 08/24/2009] [Indexed: 02/07/2023]
Abstract
This study was undertaken to evaluate the long-term prognosis of acute pancreatitis (AP) in Japan and to identify factors that predict major complications. In 1987, 2533 patients with moderate or severe acute pancreatitis were registered in a national survey in Japan. Follow-up studies were done in 2000 and in 2004 to evaluate recurrence of acute pancreatitis, transition to chronic pancreatitis, development of diabetes mellitus, and mortality. The relationship between incidence of complications and alcohol consumption during follow-up period was also analyzed. Valid replies were obtained from 714 cases in 2000 and 450 cases in 2004. Recurrence of acute pancreatitis occurred in 145 cases, and the recurrence rate was significantly higher in alcoholic pancreatitis compared with other etiologies. A transition to chronic pancreatitis occurred frequently in alcoholic pancreatitis and inversely correlated with existence of pancreatic necrosis in the initial disease. Complication with diabetes mellitus and the transition to chronic pancreatitis strongly correlated with persistent alcohol intake during follow-up period. During the follow-up period, 199 patients died, and 43 died of malignant disease. Recurrence of acute pancreatitis and a transition to chronic pancreatitis frequently occurred in alcoholic pancreatitis. Transition to chronic pancreatitis was inversely correlated with the existence of pancreatic necrosis at the initial presentation. Mortality as a result of malignant disease was not excessive in the patients with history of acute pancreatitis.
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Affiliation(s)
- Yoshifumi Takeyama
- Department of Surgery, Kinki University School of Medicine, Ohno-higashi, Osaka-sayama, Japan.
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Abstract
BACKGROUND The present study reports functional and morphological changes noted over long-term follow-up in patients with severe acute pancreatitis. METHODS Thirty patients who had completed at least 6 months after recovery were included. Fecal fat, urinary D-xylose, blood sugar, C-peptide, pancreatic changes, and recurrences were studied. RESULTS Etiology was gallstones (12), alcohol (10), both gallstone and alcohol (3), and idiopathic (5). Five patients were managed conservatively while 25 underwent surgery. Mean follow-up was 31.3 months. Exocrine and endocrine insufficiencies were noted in 12 (40%) and were more common in no-necrosis group compared to necrosis group (p = 0.04 and 0.28, respectively) and infected compared to sterile pancreatitis (45% vs. 25%, p = 0.55 and 50% vs. 12%, p = 0.15, respectively). Higher frequency was noted in nonvisualized, partly visualized, and dilated segment of duct. Significant proportion (8/12) had both exocrine and endocrine abnormalities and their incidence decreased as duration of follow-up increased. Urinary D-xylose excretion was abnormal in 16% and noted >1 year postrecovery. Thirty percent required >1 readmission and pain was the commonest cause. CONCLUSIONS Forty percent had functional abnormality; 16% had mucosal absorption abnormality while 30% required >1 readmission. Exocrine and endocrine insufficiencies were more prevalent in first year, and a significant proportion had both. A trend for higher functional insufficiency was observed in infected necrosis, complete or incomplete visualization of main pancreatic duct (MPD), dilated segment of MPD, and pseudocyst.
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Miao B, Cui NQ, Li ZL, Ma T, Zhao G, Wang X. Therapeutic effect of pancreas clearing tablets (Qingyi pian) on severe acute pancreatitis. Shijie Huaren Xiaohua Zazhi 2009; 17:1374-1377. [DOI: 10.11569/wcjd.v17.i13.1374] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/06/2023] Open
Abstract
AIM: To explore the therapeutic effect of pancreatic clearance pills (Qingyi pian) on severe acute pancreatitis.
METHODS: From January 1997 to December 2007, 272 cases of severe acute pancreatitis were randomly divided into traditional Chinese medicine group and control group. Their recurrence and nutritional status were recorded.
RESULTS: The 1-year AP recurrence rate after discharge was 46.3% (126/272). The 1-year AP recurrence rate of the Chinese medicine group was significantly lower than that of the control group (39.9% vs 53.0%, P < 0.05). Nutritional damage score at 6 and 12 mo after discharge was significantly lower in Chinese herb group than in the control group (t = 2.23, 2.77, P < 0.05 or 0.01).
CONCLUSION: Use of pancreatic clearance pills within the first 3 months after discharge reduces long-term AP recurrence rate and improves nutritional status for SAP patients.
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Regnér S, Manjer J, Appelros S, Hjalmarsson C, Sadic J, Borgström A. Protease activation, pancreatic leakage, and inflammation in acute pancreatitis: differences between mild and severe cases and changes over the first three days. Pancreatology 2008; 8:600-7. [PMID: 18849642 DOI: 10.1159/000161011] [Citation(s) in RCA: 30] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/22/2007] [Accepted: 02/21/2008] [Indexed: 12/11/2022]
Abstract
BACKGROUND/AIMS The pathophysiology of acute pancreatitis (AP) may be studied using markers of protease activation (active carboxypeptidase B (aCAP), the activation peptide of carboxypeptidase B (CAPAP)), leakage of pancreatic enzymes (trypsinogen-2, procarboxypeptidase B (proCAP), amylase), and inflammation (monocyte chemoattractant protein-1 (MCP-1), CRP). METHODS This prospective study included 140 cases of AP. Mild (n = 124) and severe (n = 16) cases were compared with respect to serum levels of trypsinogen-2, proCAP, amylase, aCAP, CAPAP (serum/urine), MCP-1 (serum/urine) and CRP on days 1, 2 and 3 from onset of symptoms. All patients with information on all 3 days were included in a time-course analysis (n = 44-55, except amylase: n = 27). RESULTS High levels in severe versus mild cases were seen for trypsinogen-2, CAPAP in serum and urine, and MCP-1 in serum on days 1-3. No differences were seen for proCAP, amylase and aCAP. MCP-1 in urine was significantly elevated on day 1-2, and CRP on day 2-3. CAPAP and MCP-1 levels peaked early and stayed elevated for 48 h in serum. CONCLUSION Protease activation and inflammation are early events in AP, with high levels of these markers within 24 h. Protease activation declines after 48 h, whereas inflammation is present for a longer time.
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Affiliation(s)
- S Regnér
- Department of Surgery, Malmö University Hospital, Lund University, Lund, Sweden.
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