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Wu H, Liao B, Ji T, Huang J, Ma K, Luo Y. Diagnostic value of CRP for predicting the severity of acute pancreatitis: a systematic review and meta-analysis. Biomarkers 2024; 29:494-503. [PMID: 39417604 DOI: 10.1080/1354750x.2024.2415463] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/06/2024] [Accepted: 10/04/2024] [Indexed: 10/19/2024]
Abstract
BACKGROUND C-reactive protein (CRP) is a pentameric protein commonly used as a biomarker of inflammation or stress response which can be obtained during routine blood tests. Therefore, we conducted a systematic review and meta-analysis to explore its ability to predict the severity of acute pancreatitis (AP). This meta-analysis was registered in the PROSPERO system (registration number: CRD42022353769). METHODS 41 studies with 6156 cases of acute pancreatitis, retrieved from PubMed, Cochrane Library, Springer, and Embase databases, were incorporated. We calculated the pooled estimates for predicting the severity of acute pancreatitis based on CRP levels. We also calculated the combined negative likelihood ratio (NLR), combined positive likelihood ratio (PLR) and combined diagnostic odds ratio (DOR) using a bivariate mixed model. Sensitivity analysis was used to examine the robustness of the results. Factors associated with heterogeneity were identified by meta-regression analysis. A summary operating characteristic (SROC) curve was generated to assess the diagnostic value of CRP in predicting severe acute pancreatitis. Fagan's test was used to calculate likelihood ratios and post-test probabilities, and publication bias was gauged by asymmetry tests. RESULTS SROC analysis yielded an AUC of 0.85 (95%CI: 0.81-0.88) with a sensitivity of 0.76 (95%CI: 0.69-0.83) and specificity of 0.79 (95%CI: 0.74-0.83). The combined NLR, PLR and DOR were 0.30 (0.23-0.40), 3.66 (2.94-4.55) and 12.19 (8.05-18.44) respectively. Sensitivity analysis demonstrated the stability of our results after omitting any study. Finally, meta-regression analysis indicated that the description of the reference test, prospective design, blinding method and spectrum of the disease could account for heterogeneity in this meta-analysis. CONCLUSION CRP has significant value as a biomarker for assessing AP severity. Besides, other parameters such as patient history, physical signs, and imaging should be considered to determine disease severity.
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Affiliation(s)
- Hongsheng Wu
- Hepatobiliary Pancreatic Surgery Department, Huadu District People's Hospital of Guangzhou, Guangzhou, China
| | - Biling Liao
- Hepatobiliary Pancreatic Surgery Department, Huadu District People's Hospital of Guangzhou, Guangzhou, China
| | - Tengfei Ji
- Hepatobiliary Pancreatic Surgery Department, Huadu District People's Hospital of Guangzhou, Guangzhou, China
| | - Jianbin Huang
- Hepatobiliary Pancreatic Surgery Department, Huadu District People's Hospital of Guangzhou, Guangzhou, China
| | - Keqiang Ma
- Hepatobiliary Pancreatic Surgery Department, Huadu District People's Hospital of Guangzhou, Guangzhou, China
| | - Yumei Luo
- Hepatobiliary Pancreatic Surgery Department, Huadu District People's Hospital of Guangzhou, Guangzhou, China
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Lee SH, Choe JW, Cheon YK, Choi M, Jung MK, Jang DK, Jo JH, Lee JM, Kim EJ, Han SY, Choi YH, Seo HI, Lee DH, Lee HS. Revised Clinical Practice Guidelines of the Korean Pancreatobiliary Association for Acute Pancreatitis. Gut Liver 2023; 17:34-48. [PMID: 35975642 PMCID: PMC9840919 DOI: 10.5009/gnl220108] [Citation(s) in RCA: 9] [Impact Index Per Article: 4.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/17/2022] [Revised: 04/27/2022] [Accepted: 04/29/2022] [Indexed: 02/01/2023] Open
Abstract
Acute pancreatitis can range from a mild, self-limiting disease requiring no more than supportive care, to severe disease with life-threatening complications. With the goal of providing a recommendation framework for clinicians to manage acute pancreatitis, and to contribute to improvements in national health care, the Korean Pancreatobiliary Association (KPBA) established the Korean guidelines for acute pancreatitis management in 2013. However, many challenging issues exist which often lead to differences in clinical practices. In addition, with newly obtained evidence regarding acute pancreatitis, there have been great changes in recent knowledge and information regarding this disorder. Therefore, the KPBA committee underwent an extensive revision of the guidelines. The revised guidelines were developed using the Delphi method, and the main topics of the guidelines include the following: diagnosis, severity assessment, initial treatment, nutritional support, convalescent treatment, and the treatment of local complications and necrotizing pancreatitis. Specific recommendations are presented, along with the evidence levels and recommendation grades.
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Affiliation(s)
- Sang Hyub Lee
- Department of Internal Medicine and Liver Research Institute, Seoul National University Hospital, Seoul National University College of Medicine, Seoul, Korea
| | - Jung Wan Choe
- Department of Internal Medicine, Korea University Ansan Hospital, Korea University College of Medicine, Ansan, Korea
| | - Young Koog Cheon
- Department of Internal Medicine, Konkuk University Medical Center, Konkuk University School of Medicine, Seoul, Korea
| | - Miyoung Choi
- Division of Health Technology Assessment Research, National Evidence-based Healthcare Collaborating Agency, Seoul, Korea
| | - Min Kyu Jung
- Department of Internal Medicine, School of Medicine, Kyungpook National University, Daegu, Korea
| | - Dong Kee Jang
- Department of Internal Medicine, Seoul Metropolitan Government Seoul National University Boramae Medical Center, Seoul National University College of Medicine, Seoul, Korea
| | - Jung Hyun Jo
- Department of Internal Medicine, Yonsei University College of Medicine, Seoul, Korea
| | - Jae Min Lee
- Department of Internal Medicine, Gyeongsang National University Changwon Hospital, Gyeongsang National University College of Medicine, Changwon, Korea
| | - Eui Joo Kim
- Department of Internal Medicine, Gil Medical Center, Gachon University College of Medicine, Incheon, Korea
| | - Sung Yong Han
- Department of Internal Medicine, Biomedical Research Institute, Pusan National University Hospital, Pusan National University School of Medicine, Busan, Korea
| | - Young Hoon Choi
- Department of Internal Medicine, Seoul St. Mary’s Hospital, College of Medicine, The Catholic University of Korea, Seoul, Korea
| | - Hyung-Il Seo
- Department of Surgery, Biomedical Research Institute, Pusan National University Hospital, Pusan National University School of Medicine, Busan, Korea
| | - Dong Ho Lee
- Department of Radiology, Seoul National University Hospital, Seoul National University College of Medicine, Seoul, Korea
| | - Hong Sik Lee
- Department of Internal Medicine, Korea University Anam Hospital, Korea University College of Medicine, Seoul, Korea,Corresponding AuthorHong Sik Lee, ORCIDhttps://orcid.org/0000-0001-9726-5416, E-mail
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Li J, Chen Z, Li L, Lai T, Peng H, Gui L, He W. Interleukin-6 is better than C-reactive protein for the prediction of infected pancreatic necrosis and mortality in patients with acute pancreatitis. Front Cell Infect Microbiol 2022; 12:933221. [PMID: 36467730 PMCID: PMC9716459 DOI: 10.3389/fcimb.2022.933221] [Citation(s) in RCA: 20] [Impact Index Per Article: 6.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/30/2022] [Accepted: 09/12/2022] [Indexed: 09/16/2023] Open
Abstract
INTRODUCTION This study aimed to identify whether interleukin-6 (IL-6) is better than C-reactive protein (CRP) for the prediction of severe acute pancreatitis (SAP), infected pancreatic necrosis (IPN), and mortality. METHODS Sixty-seven patients with acute pancreatitis (AP) who were hospitalized within 48 h of onset and received serum CRP and IL-6 tests from September 2018 to September 2019 were included. Spearman's correlation was performed to assess their associations with severity. The areas under the curve (AUCs) for the prediction of SAP, organ failure, pancreatic necrosis, IPN, and mortality were estimated using receiver operating characteristic curves. RESULT Serum CRP and IL-6 levels were significantly positively correlated with the severity of AP (p < 0.05). The AUC for the prediction of SAP based on the CRP level was 0.78 (95% CI, 0.66-0.89) and that based on the IL-6 level was 0.69 (95% CI, 0.56-0.82). For the prediction of organ failure and pancreatic necrosis, CRP was more accurate than IL-6 (AUC 0.80 vs. 0.72 and 0.75 vs. 0.68, respectively). However, CRP was less accurate than IL-6 for predicting mortality and IPN (AUC 0.70 vs. 0.75 and 0.65 vs. 0.81, respectively). Systemic inflammatory response syndrome plus CRP was more accurate than systemic inflammatory response syndrome plus IL-6 (AUC 0.79 vs. 0.72) for the prediction of SAP. CONCLUSIONS IL-6 was more accurate than CRP for predicting mortality and IPN in patients with AP.
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Affiliation(s)
| | | | | | | | | | | | - Wenhua He
- Pancreatic Disease Centre, Department of Gastroenterology, The First Affiliated Hospital of Nanchang University, Nanchang, China
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CTRP3 ameliorates cerulein-induced severe acute pancreatitis in mice via SIRT1/NF-κB/p53 axis. Biosci Rep 2021; 40:222486. [PMID: 32219332 PMCID: PMC7560515 DOI: 10.1042/bsr20200092] [Citation(s) in RCA: 13] [Impact Index Per Article: 3.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/12/2020] [Revised: 03/22/2020] [Accepted: 03/26/2020] [Indexed: 12/14/2022] Open
Abstract
Severe acute pancreatitis (SAP) is a common and life-threatening clinical acute abdominal disease. C1q/tumor necrosis factor-related protein 3 (CTRP3), a novel paralog of adiponectin, has been identified as a crucial regulator in multiple types of inflammatory disorders. However, the biological role of CTRP3 in SAP remains poorly understood. The present study aimed to characterize the role of CTRP3 in SAP and illuminate the potential mechanisms involved. In the current study, SAP mouse models were induced by seven hourly intraperitoneal injection of cerulein (50 μg/kg) and an immediate intraperitoneal injection of lipopolysaccharide (10 mg/kg) after the last cerulein administration. Histological examination and serological analysis demonstrated that SAP mouse models were successfully established. Herein, we found that CTRP3 expression was significantly decreased in the pancreatic tissues of SAP mice compared with normal control mice. Furthermore, we explored the effects of CTRP3 rescue in SAP mice and discovered that CTRP3 overexpression attenuated pathological lesions, inhibited inflammatory mediator release and repressed acinar cell apoptosis. Notably, mechanistic studies revealed that CTRP3 overexpression suppressed NF-κB p65 phosphorylation and p53 acetylation to alleviate cerulein-induced SAP in mouse models through activation of silent information regulator 1 (SIRT1), a nicotinamide adenine dinucleotide-dependent protein deacetylase. Collectively, our data indicate that CTRP3 may exert its protective effects in SAP mice via regulation of SIRT1-mediated NF-κB and p53 signaling pathways, implying a promising therapeutic strategy against SAP.
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Kuzi S, Mazaki-Tovi M, Suchodolski JS, Rimer D, Lidbury JA, Steiner JM, Buono A, Nivy R, Segev G, Aroch I. Protease inhibitors, inflammatory markers, and their association with outcome in dogs with naturally occurring acute pancreatitis. J Vet Intern Med 2020; 34:1801-1812. [PMID: 32893923 PMCID: PMC7517856 DOI: 10.1111/jvim.15895] [Citation(s) in RCA: 16] [Impact Index Per Article: 3.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/06/2020] [Revised: 08/15/2020] [Accepted: 08/19/2020] [Indexed: 12/13/2022] Open
Abstract
Background Acute pancreatitis (AP) presumably is associated with pancreatic protease activation, protease inhibitor (PI) depletion, and inflammatory mediator secretion. Objectives Examine PIs and inflammatory mediator concentrations in dogs with AP and their association with death. Animals Thirty‐one dogs diagnosed with AP based on clinical signs, ultrasonographic findings, and increased canine pancreatic lipase immunoreactivity (cPLI) and 51 healthy control dogs. Methods Antithrombin and α2‐antiplasmin activity (ATA and α2AP, respectively) and concentrations of α1‐proteinase inhibitor (α1PI), α2‐macroglobulin (α2MG), C‐reactive protein (CRP), interleukins (ILs)‐2,6,8 and tumor necrosis factor‐α (TNF‐α) were prospectively measured. Severity of AP was assessed by clinical severity scoring systems. Results Mortality rate was 19%. Antithrombin activity was lower (P = .004) and maximal CRP, IL‐6, and TNF‐α concentrations higher (P < .04) in the AP group compared to the controls, whereas IL‐2, IL‐8, α1PI, and α2AP concentrations did not differ between groups. Serum α2MG concentration was not reliably detected. Serum cPLI, CRP, and IL‐6 concentrations were significantly and positively correlated. The ATA was lower (P = .04), and canine acute pancreatitis severity (CAPS) scores higher (P = .009) in nonsurvivors compared to survivors. Higher CAPS scores were associated (P < .05) with decreased ATA and increased cPLI, CRP, and IL‐6 concentrations. Conclusions and Clinical Importance Systemic inflammation in dogs with AP is manifested by increased inflammatory mediator concentrations, correlating with cPLI and CRP concentrations. Hypoantithrombinemia is associated with death. Serum concentrations of α2AP and α1PI are less useful prognostic markers. The CAPS score is a useful prognostic marker in dogs with AP.
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Affiliation(s)
- Sharon Kuzi
- Department of Small Animal Internal Medicine, The Hebrew University Veterinary Teaching Hospital and Koret School of Veterinary Medicine, Hebrew University of Jerusalem, Rehovot, Israel
| | - Michal Mazaki-Tovi
- Department of Small Animal Internal Medicine, The Hebrew University Veterinary Teaching Hospital and Koret School of Veterinary Medicine, Hebrew University of Jerusalem, Rehovot, Israel
| | - Jan S Suchodolski
- Gastrointestinal Laboratory, Texas A&M University, College Station, Texas, USA
| | - Dar Rimer
- Department of Small Animal Internal Medicine, The Hebrew University Veterinary Teaching Hospital and Koret School of Veterinary Medicine, Hebrew University of Jerusalem, Rehovot, Israel
| | - Jonathan A Lidbury
- Gastrointestinal Laboratory, Texas A&M University, College Station, Texas, USA
| | - Joerg M Steiner
- Gastrointestinal Laboratory, Texas A&M University, College Station, Texas, USA
| | - Agostino Buono
- Gastrointestinal Laboratory, Texas A&M University, College Station, Texas, USA
| | - Ran Nivy
- Department of Small Animal Internal Medicine, The Hebrew University Veterinary Teaching Hospital and Koret School of Veterinary Medicine, Hebrew University of Jerusalem, Rehovot, Israel
| | - Gilad Segev
- Department of Small Animal Internal Medicine, The Hebrew University Veterinary Teaching Hospital and Koret School of Veterinary Medicine, Hebrew University of Jerusalem, Rehovot, Israel
| | - Itamar Aroch
- Department of Small Animal Internal Medicine, The Hebrew University Veterinary Teaching Hospital and Koret School of Veterinary Medicine, Hebrew University of Jerusalem, Rehovot, Israel
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Karim T, Jain A, Kumar V, Kumar RB, Kumar L, Patel M. Clinical and Severity Profile of Acute Pancreatitis in a Hospital for Low Socioeconomic Strata. Indian J Endocrinol Metab 2020; 24:416-421. [PMID: 33489847 PMCID: PMC7810056 DOI: 10.4103/ijem.ijem_447_20] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/14/2020] [Accepted: 07/15/2020] [Indexed: 11/04/2022] Open
Abstract
INTRODUCTION There is an upsurge in the incidence of acute pancreatitis over the last few decades; although the case fatality rate has remained unchanged. This may either be due to increased incidence of gallstone disease or improvement in diagnostic modalities. It is a potentially life threatening disease with varying severity of presentation. METHODS This observational analytical study was conducted in the Department of General Surgery in our hospital for a period of one year. All patients of acute pancreatitis were included in the study as per inclusion & exclusion criteria. OBSERVATIONS AND RESULTS Total 62 Patients were included in the study. Gall stones disease is the most common cause of acute pancreatitis. The mean age of the patients in the study was 39 years. 28 females and 34 male patients were present. 22 patients of the patients had severe disease as per Atlanta classification. Four out of these 22 severe pancreatitis patients expired. All patients in the severe pancreatitis group had mild to life threatening complications and pleural effusion was the most common followed by necrosis. There was notable difference in terms of hospital stay between mild group and severe group of AP. CONCLUSION The clinician should be aware that acute pancreatitis can occur in any age group and gender due to different etiology. The severity of AP does not depend on etiology, age or gender and it is associated with significant morbidity and mortality. SAP can be diagnosed on clinicoradiological basis and appropriate management can be done in those patients.
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Affiliation(s)
- Tanweer Karim
- Department of Surgery, ESI PGIMSR, Basaidarapur, New Delhi, India
| | - Atul Jain
- Department of Surgery, ESI PGIMSR, Basaidarapur, New Delhi, India
| | - Vinod Kumar
- Department of Surgery, ESI PGIMSR, Basaidarapur, New Delhi, India
| | - Ram B. Kumar
- Department of Surgery, ESI PGIMSR, Basaidarapur, New Delhi, India
| | - Lalit Kumar
- Department of Surgery, ESI PGIMSR, Basaidarapur, New Delhi, India
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Li Z, Yu X, Werner J, Bazhin AV, D'Haese JG. The role of interleukin-18 in pancreatitis and pancreatic cancer. Cytokine Growth Factor Rev 2019; 50:1-12. [PMID: 31753718 DOI: 10.1016/j.cytogfr.2019.11.001] [Citation(s) in RCA: 40] [Impact Index Per Article: 6.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/02/2019] [Revised: 10/30/2019] [Accepted: 11/04/2019] [Indexed: 02/07/2023]
Abstract
Originally described as an interferon (IFN)-γ-inducing factor, interleukin (IL)-18 has been reported to be involved in Th1 and Th2 immune responses, as well as in activation of NK cells and macrophages. There is convincing evidence that IL-18 plays an important role in various pathologies (i.e. inflammatory diseases, cancer, chronic obstructive pulmonary disease, Crohn's disease and others). Recently, IL-18 has also been shown to execute specific effects in pancreatic diseases, including acute and chronic pancreatitis, as well as pancreatic cancer. The aim of this study was to give a profound review of recent data on the role of IL-18 and its potential as a therapeutic target in pancreatic diseases. The existing data on this topic are in part controversial and will be discussed in detail. Future studies should aim to confirm and clarify the role of IL-18 in pancreatic diseases and unravel their molecular mechanisms.
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Affiliation(s)
- Zhiqiang Li
- Department of General, Visceral, and Transplant Surgery, Ludwig-Maximilians-University Munich, 81377 Munich, Germany; Department of Hepatopancreatobiliary Surgery, The third Xiangya hospital, Central south university, Changsha 410013, Hunan, China
| | - Xiao Yu
- Department of Hepatopancreatobiliary Surgery, The third Xiangya hospital, Central south university, Changsha 410013, Hunan, China
| | - Jens Werner
- Department of General, Visceral, and Transplant Surgery, Ludwig-Maximilians-University Munich, 81377 Munich, Germany; German Cancer Consortium (DKTK), Partner Site Munich, 81377 Munich, Germany
| | - Alexandr V Bazhin
- Department of General, Visceral, and Transplant Surgery, Ludwig-Maximilians-University Munich, 81377 Munich, Germany; German Cancer Consortium (DKTK), Partner Site Munich, 81377 Munich, Germany.
| | - Jan G D'Haese
- Department of General, Visceral, and Transplant Surgery, Ludwig-Maximilians-University Munich, 81377 Munich, Germany
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Nakamura K, Fukatsu K, Sasayama A, Yamaji T. An immune-modulating formula comprising whey peptides and fermented milk improves inflammation-related remote organ injuries in diet-induced acute pancreatitis in mice. BIOSCIENCE OF MICROBIOTA FOOD AND HEALTH 2018; 37:1-8. [PMID: 29387516 PMCID: PMC5787410 DOI: 10.12938/bmfh.17-011] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 05/31/2017] [Accepted: 07/30/2017] [Indexed: 02/06/2023]
Abstract
It has been demonstrated that an immune-modulating enteral formula enriched with whey peptides and fermented milk (IMF) had anti-inflammatory effects in some experimental models when it was administered before the
induction of inflammation. Here, we investigated the anti-inflammatory effects of the IMF administration after the onset of systemic inflammation and investigated whether the IMF could improve the remote organ injuries
in an acute pancreatitis (AP) model. Mice were fasted for 12 hours and then fed a choline-deficient and ethionine-supplemented diet (CDE diet) for 24 hours to induce pancreatitis. In experiment 1, the diet was replaced
with a control enteral formula, and mice were sacrificed at 24-hour intervals for 96 hours. In experiment 2, mice were randomized into control and IMF groups and received the control formula or the IMF respectively for
72 hr or 96 hr. In experiment 1, pancreatitis was induced by the CDE diet, and inflammatory mediators were elevated for several days. Remote organ injuries such as splenomegaly, hepatomegaly, and elevation of the hepatic
enzymes developed. A significant strong positive correlation was observed between plasma MCP-1 and hepatic enzymes. In experiment 2, the IMF significantly improved splenomegaly, hepatomegaly, and the elevation of hepatic
enzymes. Plasma MCP-1 levels were significantly lower in the IMF group than in the control group. Nutrition management with the IMF may be useful for alleviating remote organ injuries after AP.
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Affiliation(s)
- Kentaro Nakamura
- Nutrition Research Department, Food Science & Technology Research Laboratories, Meiji Co., Ltd., 1-29-1 Nanakuni, Hachiouji, Tokyo 192-0919, Japan
| | | | - Akina Sasayama
- Nutrition Research Department, Food Science & Technology Research Laboratories, Meiji Co., Ltd., 1-29-1 Nanakuni, Hachiouji, Tokyo 192-0919, Japan
| | - Taketo Yamaji
- Nutrition Research Department, Food Science & Technology Research Laboratories, Meiji Co., Ltd., 1-29-1 Nanakuni, Hachiouji, Tokyo 192-0919, Japan
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Komolafe O, Pereira SP, Davidson BR, Gurusamy KS. Serum C-reactive protein, procalcitonin, and lactate dehydrogenase for the diagnosis of pancreatic necrosis. Cochrane Database Syst Rev 2017; 4:CD012645. [PMID: 28431197 PMCID: PMC6478063 DOI: 10.1002/14651858.cd012645] [Citation(s) in RCA: 28] [Impact Index Per Article: 3.5] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 01/30/2023]
Abstract
BACKGROUND The treatment of people with pancreatic necrosis differs from that of people with oedematous pancreatitis. It is important to know the diagnostic accuracy of serum C-reactive protein (CRP), serum procalcitonin, and serum lactate dehydrogenase (LDH) as a triage test for the detection of pancreatic necrosis in people with acute pancreatitis, so that an informed decision can be made as to whether the person with pancreatic necrosis needs further investigations such as computed tomography (CT) scan or magnetic resonance imaging (MRI) scan and treatment for pancreatic necrosis started. There is currently no standard clinical practice, although CRP, particularly an increasing trend of CRP, is often used as a triage test to determine whether the person requires further imaging. There is also currently no systematic review of the diagnostic test accuracy of CRP, procalcitonin, and LDH for the diagnosis of pancreatic necrosis in people with acute pancreatitis. OBJECTIVES To compare the diagnostic accuracy of CRP, procalcitonin, or LDH (index test), either alone or in combination, in the diagnosis of necrotising pancreatitis in people with acute pancreatitis and without organ failure. SEARCH METHODS We searched MEDLINE, Embase, Science Citation Index Expanded, National Institute for Health Research (NIHR HTA and DARE), and other databases until March 2017. We searched the references of the included studies to identify additional studies. We did not restrict studies based on language or publication status, or whether data were collected prospectively or retrospectively. We also performed a 'related search' and 'citing reference' search in MEDLINE and Embase. SELECTION CRITERIA We included all studies that evaluated the diagnostic test accuracy of CRP, procalcitonin, and LDH for the diagnosis of pancreatic necrosis in people with acute pancreatitis using the following reference standards, either alone or in combination: radiological features of pancreatic necrosis (contrast-enhanced CT or MRI), surgeon's judgement of pancreatic necrosis during surgery, or histological confirmation of pancreatic necrosis. Had we found case-control studies, we planned to exclude them because they are prone to bias; however, we did not locate any. Two review authors independently identified the relevant studies from the retrieved references. DATA COLLECTION AND ANALYSIS Two review authors independently extracted data, including methodological quality assessment, from the included studies. As the included studies reported CRP, procalcitonin, and LDH on different days of admission and measured at different cut-off levels, it was not possible to perform a meta-analysis using the bivariate model as planned. We have reported the sensitivity, specificity, post-test probability of a positive and negative index test along with 95% confidence interval (CI) on each of the different days of admission and measured at different cut-off levels. MAIN RESULTS A total of three studies including 242 participants met the inclusion criteria for this review. One study reported the diagnostic performance of CRP for two threshold levels (> 200 mg/L and > 279 mg/L) without stating the day on which the CRP was measured. One study reported the diagnostic performance of procalcitonin on day 1 (1 day after admission) using a threshold level of 0.5 ng/mL. One study reported the diagnostic performance of CRP on day 3 (3 days after admission) using a threshold level of 140 mg/L and LDH on day 5 (5 days after admission) using a threshold level of 290 U/L. The sensitivities and specificities varied: the point estimate of the sensitivities ranged from 0.72 to 0.88, while the point estimate of the specificities ranged from 0.75 to 1.00 for the different index tests on different days of hospital admission. However, the confidence intervals were wide: confidence intervals of sensitivities ranged from 0.51 to 0.97, while those of specificities ranged from 0.18 to 1.00 for the different tests on different days of hospital admission. Overall, none of the tests assessed in this review were sufficiently accurate to suggest that they could be useful in clinical practice. AUTHORS' CONCLUSIONS The paucity of data and methodological deficiencies in the studies meant that it was not possible to arrive at any conclusions regarding the diagnostic test accuracy of the index test because of the uncertainty of the results. Further well-designed diagnostic test accuracy studies with prespecified index test thresholds of CRP, procalcitonin, LDH; appropriate follow-up (for at least two weeks to ensure that the person does not have pancreatic necrosis, as early scans may not indicate pancreatic necrosis); and clearly defined reference standards (of surgical or radiological confirmation of pancreatic necrosis) are important to reliably determine the diagnostic accuracy of CRP, procalcitonin, and LDH.
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Affiliation(s)
| | - Stephen P Pereira
- Royal Free Hospital CampusUCL Institute for Liver and Digestive HealthUpper 3rd FloorLondonUKNW3 2PF
| | - Brian R Davidson
- Royal Free Campus, UCL Medical SchoolDepartment of SurgeryPond StreetLondonUKNW3 2QG
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Parekh PJ, Majithia R, Sikka SK, Baron TH. The "Scope" of Post-ERCP Pancreatitis. Mayo Clin Proc 2017; 92:434-448. [PMID: 28160947 DOI: 10.1016/j.mayocp.2016.10.028] [Citation(s) in RCA: 25] [Impact Index Per Article: 3.1] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/01/2016] [Revised: 10/22/2016] [Accepted: 10/31/2016] [Indexed: 12/14/2022]
Abstract
Pancreatitis is the most common adverse event of endoscopic retrograde cholangiopancreatography, with the potential for clinically significant morbidity and mortality. Several patient and procedural risk factors have been identified that increase the risk of post-endoscopic retrograde cholangiopancreatography pancreatitis (PEP). Considerable research efforts have identified several pharmacologic and procedural interventions that can drastically affect the incidence of PEP. This review article addresses the underlying mechanisms at play for the development of PEP, identifying patient and procedural risk factors and meaningful use of risk-stratification information, and details current interventions aimed at reducing the risk of this complication.
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Affiliation(s)
- Parth J Parekh
- Department of Internal Medicine, Division of Gastroenterology and Hepatology, Tulane University, New Orleans, LA
| | - Raj Majithia
- Division of Gastroenterology and Hepatology, University of North Carolina-Johnston Healthcare, Smithfield
| | - Sanjay K Sikka
- Department of Internal Medicine, Division of Gastroenterology and Hepatology, Tulane University, New Orleans, LA
| | - Todd H Baron
- Department of Internal Medicine, Division of Gastroenterology and Hepatology, University of North Carolina, Chapel Hill.
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11
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Gloor B, Reber HA. Effects of Cytokines and Other Inflammatory Mediators on Human Acute Pancreatitis. J Intensive Care Med 2016. [DOI: 10.1177/088506669801300604] [Citation(s) in RCA: 9] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/22/2022]
Abstract
Most episodes of acute pancreatitis are mild, but severe disease complicated by multiple system organ failure develops in up to 20% of cases. In all patients with pancreatitis, the accumulation of leukocytes in pancreatic and extrapancreatic tissue, and the release of various mediators from them and other sites are important determinants of disease severity. Proinflammatory mediators, whose initial job is to limit the local damage, are released early in the disease. However, these mediators can exacerbate the severity of the pancreatitis when they continue to be elaborated in greater amounts or for longer periods than normal. When their actions are blocked or their release is inhibited, the severity of experimental pancreatitis and its associated mortality rate are less. This suggests the possibility that agents that inhibit the release and/or action of these mediators could be beneficial clinically.
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Affiliation(s)
- Beat Gloor
- UCLA School of Medicine, Department of Surgery, Los Angeles, CA
| | - Howard A. Reber
- UCLA School of Medicine, Department of Surgery, Los Angeles, CA
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12
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Sato T, Ohno K, Tamamoto T, Oishi M, Kanemoto H, Fukushima K, Goto-Koshino Y, Takahashi M, Tsujimoto H. Assessment of severity and changes in C-reactive protein concentration and various biomarkers in dogs with pancreatitis. J Vet Med Sci 2016; 79:35-40. [PMID: 27666150 PMCID: PMC5289234 DOI: 10.1292/jvms.16-0009] [Citation(s) in RCA: 34] [Impact Index Per Article: 3.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/20/2022] Open
Abstract
Canine pancreatitis is a relatively common disorder, and its mortality rate remains high. However, prognostic factors for pancreatitis based on evidence are
limited. Moreover, the relationship between changes in C-reactive protein (CRP) concentration—an important prognostic factor for human patients with acute
pancreatitis—and the prognosis of dogs with pancreatitis has not been widely studied. Therefore, we examined prognostic factors for canine pancreatitis during
the first medical examination and evaluated the usefulness of serial CRP measurements during hospitalization. Sixty-five dogs met the inclusion criteria,
including 22 that were hospitalized and treated. In Study 1, a multivariate analysis revealed that three factors— decreased platelet count and a marked (greater
than 1,000 µg/l) elevation of specific canine pancreatic lipase (Spec cPL) concentration at the first medical examination, as
well as elevated blood urea nitrogen (BUN) and/or creatinine (CRE) level—were significantly different between the survivors and nonsurvivors. Moreover, CRP
concentrations on the third and fourth days were significantly different between the two groups in Study 2. An evaluation of the decreased platelet count,
remarkable elevation of Spec cPL concentration at the first medical examination, elevation of BUN and/or CRE as well as serial CRP concentration measurements
may be useful for predicting the prognosis of canine pancreatitis.
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Affiliation(s)
- Toru Sato
- Department of Veterinary Internal Medicine, Graduate School of Agricultural and Life Sciences, The University of Tokyo, 1-1-1 Yayoi, Bunkyo-ku, Tokyo 113-8657, Japan
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13
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Sun Z, Yang L, Chen KF, Chen GW, Peng YP, Chen JK, Suo G, Yu J, Wang WC, Lin CH. Nano zerovalent iron particles induce pulmonary and cardiovascular toxicity in an in vitro human co-culture model. Nanotoxicology 2016; 10:881-90. [DOI: 10.3109/17435390.2015.1133861] [Citation(s) in RCA: 25] [Impact Index Per Article: 2.8] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/10/2023]
Affiliation(s)
- Zhelin Sun
- Key Laboratory of Nano-Bio Interface, Division of Nanobiomedicine, Suzhou Institute of Nano-Tech and Nano-Bionics, Chinese Academy of Sciences, Suzhou, China,
- School of Life Sciences, Shanghai University, Shanghai, China,
| | - Lingyan Yang
- Key Laboratory of Nano-Bio Interface, Division of Nanobiomedicine, Suzhou Institute of Nano-Tech and Nano-Bionics, Chinese Academy of Sciences, Suzhou, China,
| | - Ku-Fan Chen
- Department of Civil Engineering, National Chi Nan University, Nantou, Taiwan,
| | - Guan-Wen Chen
- Department of Food and Beverage Management, Taipei College of Maritime Technology, Taipei, Taiwan,
| | - Yen-Ping Peng
- Department of Environmental Science and Engineering, Tunghai University, Taichung, Taiwan,
| | - Jen-Kun Chen
- Institute of Biomedical Engineering & Nanomedicine, National Health Research Institutes, Miaoli, Taiwan,
| | - Guangli Suo
- Key Laboratory of Nano-Bio Interface, Division of Nanobiomedicine, Suzhou Institute of Nano-Tech and Nano-Bionics, Chinese Academy of Sciences, Suzhou, China,
| | - Jiantao Yu
- Key Laboratory of Nano-Bio Interface, Division of Nanobiomedicine, Suzhou Institute of Nano-Tech and Nano-Bionics, Chinese Academy of Sciences, Suzhou, China,
| | - Wen-Cheng Wang
- Research Center for Environmental Changes, Academia Sinica, Taipei, Taiwan, and
| | - Chia-Hua Lin
- Department of Biotechnology, National Formosa University, Yunlin, Taiwan
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14
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Sinha A, Cader R, Akshintala VS, Hutfless SM, Zaheer A, Khan VN, Khashab MA, Lennon AM, Kalloo AN, Singh VK. Systemic inflammatory response syndrome between 24 and 48 h after ERCP predicts prolonged length of stay in patients with post-ERCP pancreatitis: a retrospective study. Pancreatology 2015; 15:105-10. [PMID: 25728146 DOI: 10.1016/j.pan.2015.02.005] [Citation(s) in RCA: 7] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/18/2014] [Revised: 02/05/2015] [Accepted: 02/06/2015] [Indexed: 12/11/2022]
Abstract
BACKGROUND Early systemic inflammatory response syndrome (SIRS) has been associated with severe non-iatrogenic acute pancreatitis. The aims of this study were to determine whether early SIRS could be used to predict severe post-ERCP pancreatitis (PEP) and to determine the effect of prophylactic-pancreatic stenting (PS) on SIRS and severe PEP. METHODS Between 1/2000 and 6/2012, all patients admitted for PEP after an outpatient ERCP and who had ≥1 abdominal CT scan during hospitalization were retrospectively evaluated. The presence of SIRS was assessed between 0 and 24 h and 24 and 48 h after the time of ERCP completion. SIRS was evaluated as a predictor of severe PEP using area under receiver operating characteristic (AUROC) curve analysis. RESULTS There were 113 patients with PEP of whom 22 (19.5%) had severe PEP. SIRS was present in 44 (38.9%) and 33 (29.2%) patients between 0 and 24 h and 24 and 48 h, respectively. SIRS between 24 and 48 h had a higher predictive accuracy for severe PEP compared to SIRS between 0 and 24 h (AUROC = 0.7 vs. 0.5, p = 0.002). The prevalence of SIRS between 24 and 48 h was significantly less among the 19 patients who underwent PS (11% vs. 37%, p = 0.03). There was no difference between the prophylactic stenting and no stenting groups with regards to acute fluid collection(s), pancreatic necrosis, organ failure or mortality during hospitalization. CONCLUSIONS SIRS between 24 and 48 h after ERCP is an accurate, easy to obtain, and inexpensive predictor of severe PEP. PS is associated with a decreased prevalence of SIRS between 24 and 48 h after ERCP.
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Affiliation(s)
- Amitasha Sinha
- Department of Internal Medicine, Division of Gastroenterology and Hepatology, Johns Hopkins Medical Institutions, Baltimore, MD, USA.
| | - Rukshana Cader
- Department of Internal Medicine, Division of Gastroenterology and Hepatology, Johns Hopkins Medical Institutions, Baltimore, MD, USA.
| | - Venkata S Akshintala
- Department of Internal Medicine, Division of Gastroenterology and Hepatology, Johns Hopkins Medical Institutions, Baltimore, MD, USA.
| | - Susan M Hutfless
- Department of Internal Medicine, Division of Gastroenterology and Hepatology, Johns Hopkins Medical Institutions, Baltimore, MD, USA.
| | - Atif Zaheer
- Pancreatitis Center, Johns Hopkins Medical Institutions, Baltimore, MD, USA; Department of Radiology and Radiological Science, Johns Hopkins Medical Institutions, Baltimore, MD, USA.
| | - Vinshi N Khan
- Department of Internal Medicine, Division of Gastroenterology and Hepatology, Johns Hopkins Medical Institutions, Baltimore, MD, USA.
| | - Mouen A Khashab
- Department of Internal Medicine, Division of Gastroenterology and Hepatology, Johns Hopkins Medical Institutions, Baltimore, MD, USA.
| | - Anne Marie Lennon
- Department of Internal Medicine, Division of Gastroenterology and Hepatology, Johns Hopkins Medical Institutions, Baltimore, MD, USA.
| | - Anthony N Kalloo
- Pancreatitis Center, Johns Hopkins Medical Institutions, Baltimore, MD, USA; Department of Internal Medicine, Division of Gastroenterology and Hepatology, Johns Hopkins Medical Institutions, Baltimore, MD, USA.
| | - Vikesh K Singh
- Pancreatitis Center, Johns Hopkins Medical Institutions, Baltimore, MD, USA; Department of Internal Medicine, Division of Gastroenterology and Hepatology, Johns Hopkins Medical Institutions, Baltimore, MD, USA.
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15
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Suzuki M, Saito N, Naritaka N, Nakano S, Minowa K, Honda Y, Ohtsuka Y, Yamataka A, Shimizu T. Scoring system for the prediction of severe acute pancreatitis in children. Pediatr Int 2015; 57:113-8. [PMID: 25040470 DOI: 10.1111/ped.12449] [Citation(s) in RCA: 32] [Impact Index Per Article: 3.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/08/2013] [Revised: 02/17/2014] [Accepted: 07/03/2014] [Indexed: 12/01/2022]
Abstract
BACKGROUND The lack of an accurate scoring system for pediatric acute pancreatitis could cause delays in appropriate clinical management and increase the risk of progressive life-threatening complications. We investigated a modified Ministry of Health, Labour and Welfare of Japan (JPN) scoring system that uses pediatric systemic inflammatory response syndrome (SIRS) score, age, and weight to establish a more useful scoring system for children. METHODS A retrospective chart review was conducted of pediatric patients with acute pancreatitis who were admitted to Juntendo University Hospital between 1985 and 2011. The sensitivity, specificity, and positive and negative predictive values of the pediatric JPN scoring system were calculated and then compared with those of previously developed scoring systems. RESULTS The patient group consisted of 145 patients (88 girls, 57 boys). The pediatric JPN score had greater sensitivity (80%) than the Ranson (60%), modified Glasgow (50%), and DeBanto (60%) scores. The specificity was 96% for the pediatric JPN score, 94% for the Ranson score, 99% for the modified Glasgow score, and 86% for the DeBanto score. CONCLUSION The pediatric JPN score can be used to predict severe acute pancreatitis during the initial medical assessment.
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Affiliation(s)
- Mitsuyoshi Suzuki
- Department of Pediatrics, Juntendo University School of Medicine, Tokyo, Japan
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16
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Abstract
Post-procedure pancreatitis is the most common complication of endoscopic retrograde cholangio pancreatography (ERCP) and carries a high morbidity and mortality occurring in at least 3%-5% of all procedures. We reviewed the available literature searching for "ERCP" and "pancreatitis" and "post-ERCP pancreatitis". in PubMed and Medline. This review looks at the diagnosis, risk factors, causes and methods of preventing post-procedure pancreatitis. These include the evidence for patient selection, endoscopic techniques and pharmacological prophylaxis of ERCP induced pancreatitis. Selecting the right patient for the procedure by a risk benefits assessment is the best way of avoiding unnecessary ERCPs. Risk is particularly high in young women with sphincter of Oddi dysfunction (SOD). Many of the trials reviewed have rather few numbers of subjects and hence difficult to appraise. Meta-analyses have helped screen for promising modalities of prophylaxis. At present, evidence is emerging that pancreatic stenting of patients with SOD and rectally administered nonsteroidal anti-inflammatory drugs in a large unselected trial reduce the risk of post-procedure pancreatitis. A recent meta-analysis have demonstrated that rectally administered indomethecin, just before or after ERCP is associated with significantly lower rate of pancreatitis compared with placebo [OR = 0.49 (0.34-0.71); P = 0.0002]. Number needed to treat was 20. It is likely that one of these prophylactic measures will begin to be increasingly practised in high risk groups.
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Affiliation(s)
- Lin-Lee Wong
- Lin-Lee Wong, Her-Hsin Tsai, Department of Gastroenterology, Castle Hill Hospital, HEY NHS Trust and Hull York Medical School, Cottingham HU165JQ, United Kingdom
| | - Her-Hsin Tsai
- Lin-Lee Wong, Her-Hsin Tsai, Department of Gastroenterology, Castle Hill Hospital, HEY NHS Trust and Hull York Medical School, Cottingham HU165JQ, United Kingdom
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17
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Gomatos IP, Xiaodong X, Ghaneh P, Halloran C, Raraty M, Lane B, Sutton R, Neoptolemos JP. Prognostic markers in acute pancreatitis. Expert Rev Mol Diagn 2014; 14:333-46. [PMID: 24649820 DOI: 10.1586/14737159.2014.897608] [Citation(s) in RCA: 36] [Impact Index Per Article: 3.3] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/11/2024]
Abstract
Acute pancreatitis has a mortality rate of 5-10%. Early deaths are mainly due to multiorgan failure and late deaths are due to septic complications from pancreatic necrosis. The recently described 2012 Revised Atlanta Classification and the Determinant Classification both provide a more accurate description of edematous and necrotizing pancreatitis and local complications. The 2012 Revised Atlanta Classification uses the modified Marshall scoring system for assessing organ dysfunction. The Determinant Classification uses the sepsis-related organ failure assessment scoring system for organ dysfunction and, unlike the 2012 Revised Atlanta Classification, includes infected necrosis as a criterion of severity. These scoring systems are used to assess systemic complications requiring intensive therapy unit support and intra-abdominal complications requiring minimally invasive interventions. Numerous prognostic systems and markers have been evaluated but only the Glasgow system and serum CRP levels provide pragmatic prognostic accuracy early on. Novel concepts using genetic, transcriptomic and proteomic profiling and also functional imaging for the identification of specific disease patterns are now required.
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Affiliation(s)
- Ilias P Gomatos
- NIHR Pancreas Biomedical Research Unit, the Royal Liverpool University and Broadgreen Hospitals NHS Trust and the University of Liverpool, Liverpool L69 3GA, UK
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18
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Wong LL, Tsai HH. Prevention of post-ERCP pancreatitis. World J Gastrointest Pathophysiol 2014; 5:1-10. [PMID: 24891970 PMCID: PMC4024515 DOI: 10.4291/wjgp.v5.i1.1] [Citation(s) in RCA: 25] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/05/2013] [Revised: 10/26/2013] [Accepted: 01/14/2014] [Indexed: 02/06/2023] Open
Abstract
Post-procedure pancreatitis is the most common complication of endoscopic retrograde cholangio pancreatography (ERCP) and carries a high morbidity and mortality occurring in at least 3%-5% of all procedures. We reviewed the available literature searching for “ERCP” and “pancreatitis” and “post-ERCP pancreatitis”. in PubMed and Medline. This review looks at the diagnosis, risk factors, causes and methods of preventing post-procedure pancreatitis. These include the evidence for patient selection, endoscopic techniques and pharmacological prophylaxis of ERCP induced pancreatitis. Selecting the right patient for the procedure by a risk benefits assessment is the best way of avoiding unnecessary ERCPs. Risk is particularly high in young women with sphincter of Oddi dysfunction (SOD). Many of the trials reviewed have rather few numbers of subjects and hence difficult to appraise. Meta-analyses have helped screen for promising modalities of prophylaxis. At present, evidence is emerging that pancreatic stenting of patients with SOD and rectally administered nonsteroidal anti-inflammatory drugs in a large unselected trial reduce the risk of post-procedure pancreatitis. A recent meta-analysis have demonstrated that rectally administered indomethecin, just before or after ERCP is associated with significantly lower rate of pancreatitis compared with placebo [OR = 0.49 (0.34-0.71); P = 0.0002]. Number needed to treat was 20. It is likely that one of these prophylactic measures will begin to be increasingly practised in high risk groups.
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19
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Liang HY, Song ZM, Cui ZJ. Lasting inhibition of receptor-mediated calcium oscillations in pancreatic acini by neutrophil respiratory burst--a novel mechanism for secretory blockade in acute pancreatitis? Biochem Biophys Res Commun 2013; 437:361-367. [PMID: 23820383 DOI: 10.1016/j.bbrc.2013.06.081] [Citation(s) in RCA: 11] [Impact Index Per Article: 0.9] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/19/2013] [Accepted: 06/21/2013] [Indexed: 02/07/2023]
Abstract
Although overwhelming evidence indicates that neutrophil infiltration is an early event in acute pancreatitis, the effect of neutrophil respiratory burst on pancreatic acini has not been investigated. In the present work, effect of fMLP-induced neutrophil respiratory burst on pancreatic acini was examined. It was found that neutrophil respiratory burst blocked calcium oscillations induced by cholecystokinin or by acetylcholine. Such lasting inhibition was dependent on the density of bursting neutrophils and could be overcome by increased agonist concentration. Inhibition of cholecystokinin stimulation was also observed in AR4-2J cells. In sharp contrast, neutrophil respiratory burst had no effect on calcium oscillations induced by phenylephrine (PE), vasopressin, or by ATP in rat hepatocytes. These data together suggest that inhibition of receptor-mediated calcium oscillations in pancreatic acini by neutrophil respiratory burst would lead to secretory blockade, which is a hallmark of acute pancreatitis. The present work has important implications for clinical treatment and management of acute pancreatitis.
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Affiliation(s)
- Hui Yuan Liang
- Institute of Cell Biology, Beijing Normal University, Beijing 100875, China
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20
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Novovic S, Andersen AM, Nord M, Astrand M, Ottosson T, Jørgensen LN, Hansen MB. Activity of neutrophil elastase reflects the progression of acute pancreatitis. Scandinavian Journal of Clinical and Laboratory Investigation 2013; 73:485-93. [PMID: 23819644 DOI: 10.3109/00365513.2013.807935] [Citation(s) in RCA: 9] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 01/03/2023]
Abstract
OBJECTIVE Neutrophil elastase (NE) concentration is associated with progression of acute pancreatitis (AP), but measuring total NE concentration includes biologically inactive NE. This study aims to investigate the relationship between NE activity and the aetiology and severity of AP and associated organ failure. METHODS Seventy-five patients admitted to our surgery department with a first episode of AP during 2004-2005 were age- and sex-matched to 20 healthy volunteers (controls). NE activity was assessed using venous blood samples obtained on patient admission and after 1, 2 and 14 days. One sample was also taken from each control. ANOVA was used for statistical comparison between groups. RESULTS Baseline NE activity (geometric mean; 95% confidence intervals) differed between patients (58.6 nM of substrate 7-amino-4-methylcoumarin [AMC]/hour; 48.52-70.72) and controls (31.5 nM AMC/hour; 25.5-39.0) (p = 0.0003), and did not correlate with time between symptom onset and admission. Patients with alcohol-induced AP demonstrated higher mean activity (59.1 nM AMC/h; 44.7-78.2) than those with gallstone-induced AP (41.7 nM AMC/h; 33.9-51.4) (p = 0.0496). NE activity was higher overall in patients with predicted severe AP (60.9 nM AMC/h; 48.0-77.2) than in those with predicted mild AP (42.1 nM AMC/h; 34.9-50.8) (p = 0.027). Patients with respiratory failure had higher NE activity (82.5 nM AMC/h; 57.5-118.4) than those without (43.9 nM AMC/h; 37.6-51.3) (p = 0.0024). CONCLUSIONS NE activity was associated with predicted severity of AP and AP-associated respiratory failure. Specific NE inhibitors may have therapeutic potential in acute pancreatitis.
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Affiliation(s)
- Srdan Novovic
- Department of Surgery K, Bispebjerg Hospital, University of Copenhagen , Denmark
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21
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Tammaro S, Caruso R, Pallone F, Monteleone G. Post-endoscopic retrograde cholangio-pancreatography pancreatitis: Is time for a new preventive approach? World J Gastroenterol 2012; 18:4635-8. [PMID: 23002332 PMCID: PMC3442201 DOI: 10.3748/wjg.v18.i34.4635] [Citation(s) in RCA: 13] [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: 06/06/2012] [Revised: 07/17/2012] [Accepted: 07/28/2012] [Indexed: 02/06/2023] Open
Abstract
Acute pancreatitis is the most common serious complication of endoscopic retrograde cholangio-pancreatography (ERCP) and its incidence may exceed 25% in some high-risk patient subsets. In some patients, pancreatitis may follow a severe course with pancreatic necrosis, multiorgan failure, permanent disability and even death. Hence, approaches which minimize both the incidence and severity of post-ERCP pancreatitis are worth pursuing. Pancreatic stents have been used with some success in the prevention of post-ERCP, while so far pharmacological trials have yielded disappointing results. A recent multicenter, randomized, placebo-controlled, double-blind trial has shown that rectally administered indomethacin is effective in reducing the incidence of post-ERCP pancreatitis, the occurrence of episodes of moderate-to-severe pancreatitis and the length of hospital stay in high-risk patients. These results together with the demonstration that rectal administration of indomethacin is not associated with enhanced risk of bleeding strongly support the use of this drug in the prophylaxis of post-ERCP pancreatitis.
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22
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Abstract
Pancreatitis is the most common complication of ERCP. It can be associated with substantial morbidity. Hence, the minimization of both the incidence and severity of post-ERCP pancreatitis is paramount. Considerable efforts have been made to identify factors that may be associated with an increased risk of this complication. In addition, both procedure- and pharmacological-related interventions have been proposed that may prevent this complication. This paper outlines these interventions and presents the evidence to support their use in the prevention of post-ERCP pancreatitis.
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23
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Abstract
Acute pancreatitis (AP) is an important cause of morbidity and mortality worldwide and the annual incidence appears to be increasing. It presents as a mild self-limiting illness in 80% of patients. However, one-fifth of these develop a severe complicated life-threatening disease requiring intensive and prolonged therapeutic intervention. Alcohol and gallstone disease remain the commonest causes of AP but metabolic abnormalities, obesity and genetic susceptibility are thought be increasingly important aetiological factors. The prompt diagnosis of AP and stratification of disease severity is essential in directing rapid delivery of appropriate therapeutic measures. In this review, the range of diagnostic and prognostic assays, severity scoring systems and radiological investigations used in current clinical practice are described, highlighting their strengths and weaknesses. Increased understanding of the complex pathophysiology of AP has generated an array of new potential diagnostic assays and these are discussed. The multidisciplinary approach to management of severe pancreatitis is outlined, including areas of controversy and novel treatments.
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Affiliation(s)
- Simon J F Harper
- Department of Pancreaticobiliar Surgery, Luton & Dunstable NHS Foundation Trust, Lewsey Road, Luton, LU4 0DZ, UK.
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24
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Assessment of severity of acute pancreatitis according to new prognostic factors and CT grading. JOURNAL OF HEPATO-BILIARY-PANCREATIC SCIENCES 2009; 17:37-44. [PMID: 20012329 DOI: 10.1007/s00534-009-0213-4] [Citation(s) in RCA: 65] [Impact Index Per Article: 4.1] [Reference Citation Analysis] [Abstract] [Track Full Text] [Subscribe] [Scholar Register] [Received: 08/01/2009] [Accepted: 09/01/2009] [Indexed: 12/17/2022]
Abstract
The assessment of severity at the initial medical examination plays an important role in introducing adequate early treatment and the transfer of patients to a medical facility that can cope with severe acute pancreatitis. Under these circumstances, "criteria for severity assessment" have been prepared in various countries, including Japan, and these criteria are now being evaluated. The criteria for severity assessment of acute pancreatitis in Japan were determined in 1990 (of which a partial revision was made in 1999). In 2008, an overall revision was made and the new Japanese criteria for severity assessment of acute pancreatitis were prepared. In the new criteria for severity assessment, the diagnosis of severe acute pancreatitis can be made according to 9 prognostic factors and/or the computed tomography (CT) grades based on contrast-enhanced CT. Patients with severe acute pancreatitis are expected to be transferred to a specialist medical center or to an intensive care unit to receive adequate treatment there. In Japan, severe acute pancreatitis is recognized as being a specified intractable disease on the basis of these criteria, so medical expenses associated with severe acute pancreatitis are covered by Government payment.
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25
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Schütte K, Malfertheiner P. Markers for predicting severity and progression of acute pancreatitis. Best Pract Res Clin Gastroenterol 2008; 22:75-90. [PMID: 18206814 DOI: 10.1016/j.bpg.2007.10.013] [Citation(s) in RCA: 65] [Impact Index Per Article: 3.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/07/2023]
Abstract
Several tools have been developed for severity stratification in acute pancreatitis. They include single biochemical markers, imaging methods, and complex scoring systems, all of which aim at an early detection of severe acute pancreatitis to optimise monitoring and treatment of patients as early as possible. Among single biochemical markers, C-reactive protein (CRP) remains the most useful. Despite its delayed increase, peaking not earlier than 72 h after the onset of symptoms, it is accurate and widely available. Many other markers have been evaluated for their usefulness, and for some of them very promising data could be shown. Among them interleukin 6 seems to be the most promising parameter for use in clinical routine. For the detection of pancreatic infection, procalcitonin is the most sensitive, and can be used as an indicator for the need for fine-needle aspiration of pancreatic necrosis. Regarding imaging, contrast-enhanced computed tomography is still the reference method for the detection of necrotising acute pancreatitis. Pancreatitis-specific scoring systems have been shown to be of value for the prediction of severity and progression of acute pancreatitis, but cannot be applied any earlier than 48 h after admission to hospital. The APACHE-II score has not been developed specifically for acute pancreatitis and is rather complex to assess, but has been proven to be an early and reliable tool. Indication, timing and consequences of the methods applied need to be carefully considered and incorporated into clinical assessments to avoid costs and harm to the patient.
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Affiliation(s)
- Kerstin Schütte
- Department of Gastroenterology, Hepatology and Infectious Diseases, Otto-von-Guericke University, Leipziger Str. 44, 39120 Magdeburg, Germany
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26
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Abstract
Severity stratification is a critical issue in acute pancreatitis that strongly influences diagnostic and therapeutic decision making. According to the widely used Atlanta classification, "severe" disease comprises various local and systemic complications that are associated with an increased risk of mortality. However, results from recent clinical studies indicate that these complications vary in their effect on outcome, and many are not necessarily life threatening on their own. Therefore, "severe," as defined by Atlanta, must be distinguished from "prognostic," aiming at nonsurvival. In the first week after disease onset, pancreatitis-related organ failure is the preferred variable for predicting severity and prognosis because it outweighs morphologic complications. Contrast-enhanced CT and MRI allow for accurate stratification of local severity beyond the first week after symptom onset. Among the biochemical markers, C-reactive protein is still the parameter of choice to assess attack severity, although prognostic estimation is not possible. Other markers, including pancreatic protease activation peptides, interleukins-6 and -8, and polymorphonuclear elastase are useful early indicators of severity. Procalcitonin is one of the most promising single markers for assessment of major complications and prognosis throughout the disease course.
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Affiliation(s)
- Bettina M Rau
- Department of General, Visceral, and Vascular Surgery, University of the Saarland, Kirrberger Strasse, Building 57, 66421 Homburg/Saar, Germany.
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27
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Papachristou GI, Clermont G, Sharma A, Yadav D, Whitcomb DC. Risk and markers of severe acute pancreatitis. Gastroenterol Clin North Am 2007; 36:277-96, viii. [PMID: 17533079 DOI: 10.1016/j.gtc.2007.03.003] [Citation(s) in RCA: 73] [Impact Index Per Article: 4.1] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/07/2023]
Abstract
Acute pancreatitis begins with pancreatic injury, elicits an acute inflammatory response, and encompasses a variety of potential complications in a subset of patients. Early determination of severity and risk of complications is crucial for instituting immediate interventions to improve outcome. The severity of acute pancreatitis is a function of the amount of pancreas that is injured and the intensity of the inflammatory response. Early death is mainly linked to an overwhelming inflammatory response leading to cardiovascular collapse or acute respiratory distress syndrome, whereas late death is associated with infected pancreatic necrosis and sepsis. This article reviews recent advancements in understanding the pathogenesis, immunology, and genetics of severe acute pancreatitis, and the literature on laboratory-based markers, which predict a severe clinical course and pancreatic necrosis.
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Affiliation(s)
- Georgios I Papachristou
- Division of Gastroenterology, Hepatology and Nutrition, University of Pittsburgh School of Medicine, Pittsburgh, PA, USA.
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28
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Spitzer AL, Barcia AM, Schell MT, Barber A, Norman J, Grendell J, Harris HW. Applying Ockham's razor to pancreatitis prognostication: a four-variable predictive model. Ann Surg 2006; 243:380-8. [PMID: 16495704 PMCID: PMC1448950 DOI: 10.1097/01.sla.0000202213.22389.36] [Citation(s) in RCA: 38] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/31/2022]
Abstract
OBJECTIVE We sought to develop a simple yet accurate prognostic scoring system to determine the severity of acute pancreatitis at admission. SUMMARY BACKGROUND DATA Because acute pancreatitis has a variable and frequently unpredictable course, identifying individuals at greatest risk for significant, life-threatening complications and stratifying their care appropriately remain a concern. Previous prognostic scoring systems predict severity reasonably well but are limited by time constraints, are unwieldy to use, or both. METHODS Data from the international phase III trial of the platelet-activating factor receptor-antagonist Lexipafant were used to develop a 4-variable prognostic model. We then compared the model's ability to predict the severity of acute pancreatitis with the Ranson, Glasgow, and APACHE II systems. RESULTS The model (BALI), which included BUN >or=25 mg/dL, Age >or=65 years, LDH >or=300 IU/L, and IL-6 >or=300 pg/mL, measured at admission, was similar to the Ranson, Glasgow, and APACHE II systems in its ability to identify increased mortality from acute pancreatitis. The receiver operating characteristic curve area for the BALI model was >or=0.82 +/- 0.03 (mean +/- SD) versus 0.75 +/- 0.04 (Ranson), 0.80 +/- 0.03 (Glasgow), and 0.79 +/- 0.03 (APACHE II). Furthermore, at a prevalence of 15%, the positive and negative predictive values for increased mortality were similar for all systems. CONCLUSION The prognostic ability of the BALI 4-variable model was similar to the Ranson, Glasgow, and APACHE II systems but is unique in its simplicity and ability to accurately predict disease severity when used at admission or anytime during the first 48 hours of hospitalization.
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Affiliation(s)
- Austin L Spitzer
- Department of Surgery, University of California-San Francisco, 94143-0104, USA
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Hirota M, Takada T, Kawarada Y, Hirata K, Mayumi T, Yoshida M, Sekimoto M, Kimura Y, Takeda K, Isaji S, Koizumi M, Otsuki M, Matsuno S. JPN Guidelines for the management of acute pancreatitis: severity assessment of acute pancreatitis. JOURNAL OF HEPATO-BILIARY-PANCREATIC SURGERY 2006; 13:33-41. [PMID: 16463209 PMCID: PMC2779364 DOI: 10.1007/s00534-005-1049-1] [Citation(s) in RCA: 55] [Impact Index Per Article: 2.9] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Subscribe] [Scholar Register] [Indexed: 12/19/2022]
Abstract
This article addresses the criteria for severity assessment and the severity scoring system of the Ministry of Health and Welfare of Japan; now the Japanese Ministry of Health, Labour, and Welfare (the JPN score). It also presents data comparing the JPN score with the Acute Physiology and Chronic Health Evaluation (APACHE) II score and the Ranson score, which are the major measuring scales used in the United States and Europe. The goal of investigating these scoring systems is the achievement of earlier diagnosis and more appropriate and successful treatment of severe or moderate acute pancreatitis, which has a high mortality rate. This article makes the following recommendations in terms of assessing the severity of acute pancreatitis: (1) Severity assessment is indispensable to the selection of proper initial treatment in the management of acute pancreatitis (Recommendation A). (2) Assessment by a severity scoring system (JPN score, APACHE II score) is important for determining treatment policy and identifying the need for transfer to a specialist unit (Recommendation A). (3) C-reactive protein (CRP) is a useful indicator for assessing severity (Recommendation A). (4) Contrast-enhanced computed tomography (CT) scanning and contrast-enhanced magnetic resonance imaging (MRI) play an important role in severity assessment (Recommendation A). (5) A JPN score of 2 or more (severe acute pancreatitis) has been established as the criterion for hospital transfer (Recommendation A). (6) It is preferable to transfer patients with severe acute pancreatitis to a specialist medical institution where they can receive continuous monitoring and systemic management.
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Affiliation(s)
- Masahiko Hirota
- Department of Gastroenterological Surgery, Kumamoto University Graduate School of Medical Sciences, 1-1-1 Honjo, Kumamoto 860-0811, Japan
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Chen HM, Chen JC, Ng CJ, Chiu DF, Chen MF. Melatonin reduces pancreatic prostaglandins production and protects against caerulein-induced pancreatitis in rats. J Pineal Res 2006; 40:34-9. [PMID: 16313496 DOI: 10.1111/j.1600-079x.2005.00271.x] [Citation(s) in RCA: 18] [Impact Index Per Article: 0.9] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 01/23/2023]
Abstract
Melatonin has been used to treat experimental pancreatitis, although not all the drug's therapeutic mechanisms of melatonin have been defined. Prostaglandins (PGs) are proinflammatory mediators that exert their effects mainly locally during inflammatory diseases. The present study was undertaken to examine whether treatment with melatonin influences local PG production. An acute pancreatitis model in male Sprague-Dawley rats (225-275 g) was established by continuously infusing caerulein (15 mg/kg/hr). Mean arterial pressure and pancreatic perfusion were monitored continuously. Melatonin was delivered via the intraperitoneal route at doses of either 2 or 10 mg/kg, 30 min after caerulein injection. Malondialdehyde and glutathione levels of the pancreas and liver and the trypsinogen activation peptide levels in the serum were measured at the end of the experiment (8 hr after infusion of caerulein). Intraperitoneal injection of melatonin (2 and 10 mg/kg) reduced the reduction in systemic arterial pressure and decreased pancreatic perfusion in the rat model of caerulein pancreatitis. Moreover, melatonin treatment changed local PG production toward control level. Higher dose of melatonin was somewhat more effective in preventing the caerulein-induced alterations than was the lower dose.
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Affiliation(s)
- Han-Ming Chen
- Department of Surgery, Chang Gung Memorial Hospital, Chang Gung University College of Medicine, Taipei, Taiwan.
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Domínguez-Muñoz JE, Villanueva A, Lariño J, Mora T, Barreiro M, Iglesias-Canle J, Iglesias-García J. Accuracy of plasma levels of polymorphonuclear elastase as early prognostic marker of acute pancreatitis in routine clinical conditions. Eur J Gastroenterol Hepatol 2006; 18:79-83. [PMID: 16357624 DOI: 10.1097/00042737-200601000-00014] [Citation(s) in RCA: 13] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/10/2022]
Abstract
OBJECTIVES The early prognostic evaluation of acute pancreatitis (AP) is a key step in the appropriate management of the disease. Plasma levels of polymorphonuclear elastase have proved to be an accurate early prognostic marker of AP in research conditions. Whether the test remains sufficiently accurate in routine clinical conditions has been questioned. The aim of our study was to evaluate the accuracy of plasma polymorphonuclear-elastase levels for the early prognostic evaluation of AP in the clinical setting. METHODS A total of 224 consecutive patients with AP admitted to our Gastroenterology Department were included. A blood sample for polymorphonuclear-elastase quantification was obtained from all of them in the first morning of hospital stay, together with samples for routine haematological and biochemical analysis. Blood samples for polymorphonuclear-elastase evaluation were sent to the laboratory and managed there according to routine protocols. AP was classified as mild or severe according to the Atlanta classification, whereas polymorphonuclear-elastase results were kept blind. Results were shown as mean+/-SD and compared using Student's t-test for unrelated samples. The accuracy of the test for the prognostic evaluation of AP was calculated after drawing the corresponding receiver operator curve. RESULTS Fifty patients (23%) suffered from severe AP. The plasma levels of polymorphonuclear elastase were 217.8+/-93.5 microg/l in patients with severe AP and 68.1+/-32.7 microg/l in those with mild disease (P<0.001). The sensitivity and specificity of the test for the detection of severe AP were 92 and 91%, respectively, for an optimal cut-off value of 110 microg/l. The positive and negative predictive values for a prevalence of severe disease of 20% were 78 and 96%, respectively. The area under the receiver operator curve was 0.956. CONCLUSION Quantification of plasma polymorphonuclear-elastase levels is a very accurate method for the early prognostic evaluation of AP, and is easily applicable in the clinical setting.
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Affiliation(s)
- J Enrique Domínguez-Muñoz
- Department of Gastroenterology, University Hospital of Santiago de Compostela, Santiago de Compostela, Spain.
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Chen HM, Hsu JT, Chen JC, Ng CJ, Chiu DF, Chen MF. Delayed neutrophil apoptosis attenuated by melatonin in human acute pancreatitis. Pancreas 2005; 31:360-364. [PMID: 16258371 DOI: 10.1097/01.mpa.0000180905.05494.9a] [Citation(s) in RCA: 17] [Impact Index Per Article: 0.9] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/17/2022]
Abstract
OBJECTIVES This study evaluated the expression of neutrophil apoptosis and the effects of melatonin at different concentrations on delayed neutrophil apoptosis in different severities of acute pancreatitis in patients. METHODS The study population was comprised of 10 patients with severe acute pancreatitis (SAP) and 10 with mild acute pancreatitis (MAP). A total of 10 mL of blood was drawn 24 hours after the onset of the clinical disease for isolation and incubation of the human neutrophils with 4 different concentrations of melatonin. Neutrophil apoptosis activity, CD18 expression, and respiratory burst activity were assessed with flow cytometry 12 hours after incubation. Another group of neutrophils from a healthy control group was used (n = 6) for comparison. RESULTS Neutrophil apoptosis in patients with SAP is delayed compared with that of patients with MAP. Neutrophils from patients with SAP or MAP are functionally activated. Melatonin at concentrations of 10(-8), 10(-7), or 10(-6) M reverses the delayed process and enhances apoptosis activity in neutrophils in patients with MAP. Melatonin at concentrations of 10(-7) and 10(-6) M reverses the delayed process and increases apoptosis activity in neutrophils in patients with SAP. Neutrophils from patients with SAP and MAP showed significantly increased CD18 expression and respiratory burst activity. Melatonin at concentrations of 10(-7) or 10(-6) M reverses CD18 expression and respiratory burst activity in neutrophils in patients with SAP. CONCLUSIONS This study highlights the importance of neutrophil apoptosis in patients with SAP and raises the possibility of a therapeutic strategy. Study data show that melatonin promotes neutrophil apoptosis in human acute pancreatitis.
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Affiliation(s)
- Han-Ming Chen
- Department of Surgery, Chang Gung Memorial Hospital, Kwei-Shan, Taoyuan, Taiwan.
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de Madaria E, Martínez J, Lozano B, Sempere L, Benlloch S, Such J, Uceda F, Francés R, Pérez-Mateo M. Detection and identification of bacterial DNA in serum from patients with acute pancreatitis. Gut 2005; 54:1293-7. [PMID: 16099797 PMCID: PMC1774656 DOI: 10.1136/gut.2004.047514] [Citation(s) in RCA: 44] [Impact Index Per Article: 2.2] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 01/14/2023]
Abstract
BACKGROUND AND AIMS Bacterial infections are common complications in patients with acute pancreatitis, and translocation of bacteria from the intestinal lumen is probably the first step in the pathogenesis of these infections. As blood cultures in afebrile patients are usually negative, more sensitive methods to investigate this hypothesis in patients are needed. Our group has recently developed a method to detect the presence of bacterial DNA in biological fluids, and we aimed to detect bacterial DNA in patients with acute pancreatitis, as molecular evidences of bacterial translocation. METHODS Samples of blood were obtained on three consecutive days within the first six days after admission. Bacterial DNA was detected using a polymerase chain reaction based method, and an automated DNA nucleotide sequencing process allowed identification of bacteria species. RESULTS Thirty one consecutively admitted patients with acute pancreatitis were studied. Bacterial DNA was detected in six patients (19.3%), and the sequencing process allowed identification of Citrobacter freundii and Pseudomonas aeruginosa. In two patients the same bacteria detected at admission was detected 24 hours later (above 99.9% homology of nucleotide sequence). Basic clinical and biochemical characteristics were similar among patients with or without the presence of bacterial DNA. CONCLUSION Detection of gram negative bacteria derived bacterial DNA in our series supports the contention that bacterial translocation is a systemic process in approximately 20% of patients with acute pancreatitis that does not seem to be related to the severity of the episode or immediate development of infection.
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Affiliation(s)
- E de Madaria
- Sección Aparato Digestivo, Hospital General Universitario de Alicante, Pintor Baeza s/n 03010 Alicante, Spain
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Al-Bahrani AZ, Ammori BJ. Clinical laboratory assessment of acute pancreatitis. Clin Chim Acta 2005; 362:26-48. [PMID: 16024009 DOI: 10.1016/j.cccn.2005.06.008] [Citation(s) in RCA: 68] [Impact Index Per Article: 3.4] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/03/2005] [Revised: 06/13/2005] [Accepted: 06/14/2005] [Indexed: 12/20/2022]
Abstract
BACKGROUND Several biochemical markers in blood and urine have been investigated to establish their clinical application in patients with acute pancreatitis (AP). The relevant studies are reviewed and critically appraised. METHODS Medline and the World Wide Web were searched and the relevant literature was classified under the following categories: (1) diagnosis of AP and (2) prediction of: a) disease severity, b) pancreatic necrosis and its secondary infection, c) organ failure and death, and d) disease etiology. RESULTS AND CONCLUSIONS Serum lipase is a more reliable diagnostic marker of AP than serum amylase. Urinary strip tests for trypsinogen activation peptide (TAP) and trypsinogen-2 provide a reliable early diagnosis of AP. Useful predictors of severity may include serum procalcitonin and urinary TAP and trypsinogen-2 on admission, serum interleukins-6 and -8 and polymorphonuclear elastase at 24 h, and serum C-reactive protein (CRP) at 48 h. Other markers such as amyloid A and carboxypeptidase B activation peptide (CAPAP) need further investigation. Biochemical prediction of pancreatic necrosis requires 72 h to reach reliability and is impractical. However, the daily monitoring of serum procalcitonin provides a non-invasive detection of infected necrosis; the promising role of phospholipase A(2) in this regard requires further investigation. Early transient hypertransaminasemia reliably predicts biliary etiology, while serum carbohydrate-deficient transferrin and trypsin may predict an alcoholic etiology.
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Maraví Poma E, Jiménez Urra I, Gener Raxarch J, Zubia Olascoaga F, Pérez Mateo M, Casas Curto J, Montejo González J, García de Lorenzo A, López Camps V, Fernández Mondéjar E, Álvarez Lerma F, Vallés Daunis J, Olaechea Astigarraga P, Domínguez Muñoz E, Tellado Rodríguez J, Landa García I, Lafuente Martínez J, Villalba Martín C, Sesma Sánchez J. Recomendaciones de la 7ª Conferencia de Consenso de la SEMICYUC. Pancreatitis aguda grave en Medicina Intensiva. Med Intensiva 2005. [DOI: 10.1016/s0210-5691(05)74245-5] [Citation(s) in RCA: 7] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/11/2022]
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Abstract
To date, CRP remains the single standard biochemical marker for predicting the severity of AP. Because the combination of clinico-physiological scores and CRP provides good information at 48 hours, research has focused on the predictive ability of various markers when applied in the initial 24 hours after admission to the hospital. After detailed review of the literature, the authors conclude that there is no single tool that serves as the optimal predictor of severity. There are, however, data supporting the use of certain tests to improve upon the clinician's early predictive ability on the subsequent course of AP. These include an APACHE II score greater than seven, IL-6 at the time of admission, and urine TAP, urine trypsinogen-2,and serum PMN-elastase at 24 hours (Box 1). These markers will only be able to help the clinician's predictive ability if they can be performed locally and if the results can be available in a timely manner. Future research should focus on markers such as procalcitonin, IL-8, IL-I ra, sTNFR,CAPAP, PLA-2, novel markers, and the combined use of more than one marker. The conventional research approach in predicting severity used in the last15 years has limitations and appears to have reached its maximal potential. Novel conceptions and approaches, such as identification of genetic polymorphisms that predispose to severe course and complications of AP, are needed for a quantum step forward.
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Affiliation(s)
- Georgios I Papachristou
- Division of Gastroenterology, Hepatology and Nutrition, Department of Medicine, University of Pittsburgh, 200 Lothrop Street, Pittsburgh, PA 15213, USA
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Papachristou GI, Whitcomb DC. Predictors of severity and necrosis in acute pancreatitis. Gastroenterol Clin North Am 2004; 33:871-90. [PMID: 15528023 DOI: 10.1016/j.gtc.2004.07.004] [Citation(s) in RCA: 53] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/21/2023]
Abstract
C-reactive protein remains the single standard biochemical marker for predicting the severity of AP. Because the combination of clinical-physiological scores and CRP provide good information at 48 hours, research has focused on the predictive ability of various markers when applied in the initial 24 hours after admission to the hospital. After detailed review of the literature, the authors conclude that there is no single tool that serves as the optimal predictor of severity. There are, however, data that support the use of certain tests to improve upon the clinician's early predictive ability on the subsequent course of AP. These include an APACHE II score greater than 7 and IL-6 at the time of admission, and urine TAP, urine trypsinogen-2, and serum PMN elastase at 24 hours (Table 4). These markers only will be able to help the clinician's predictive ability if they can be performed locally and if the results can be available ina timely manner. Future research should focus on promising markers such as procalcitonin, IL-8, IL-I ra, sTNFR, CAPAP, PLA-2, novel markers, and the combined use of more than one marker. The conventional research approach in predicting severity used in the last 15 years has limitations and appears to have reached its maximal potential. Novel conceptions and approaches, such as identification of genetic polymorphisms that predispose to severe course and complications of AP or other approaches are needed for a quantum step forward.
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Affiliation(s)
- Georgios I Papachristou
- Division of Gastroenterology, Hepatology and Nutrition, Department of Medicine, University of Pittsburgh, 200 Lothrop Street, Pittsburgh, PA 15213, USA
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Frasquet JL, Sáez J, Trigo C, Martínez J, Pérez-Mateo M. [Proteinuria and urinary beta 2-microglobulin as markers of tubular malfunction in the assessment of severity of acute pancreatitis]. GASTROENTEROLOGIA Y HEPATOLOGIA 2004; 27:295-9. [PMID: 15117607 DOI: 10.1016/s0210-5705(03)70463-4] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 11/30/2022]
Abstract
INTRODUCTION Proteinuria is a common finding in acute pancreatitis (AP). Increased urinary beta 2-microglobulin can be explained by renal tubular malfunction induced by substances released from the pancreas. The degree of renal tubular malfunction may reflect the severity of AP. AIM To assess proteinuria and urinary beta 2-microglobulin as prognostic factors in AP. PATIENTS AND METHODS We retrospectively studied patients with AP with symptom onset within 24 hours before admission. Random urine specimens were obtained on days 1, 2 and 3 after admission. In a subgroup of 25 patients, urine samples could be obtained within 24 hours of symptom onset on day 1. The severity of AP was established using the Atlanta criteria. Proteinuria and beta 2-microglobulin were determined and were adjusted by urinary creatinine concentrations. RESULTS We studied 51 patients with AP (26 men and 25 women; age: 59.6 (+/-16.7 years). Fifteen cases of AP were severe and 36 were mild. The most frequent etiology was gallstones (60.1%). Levels of proteinuria were (median and interquartile range) in mg/g creatinine: day 1: 180.5 (84.0-250.9), day 2: 164.3 (16.7-421.7), and day 3: 136.7 (24.0-371.29). Differences between severe and mild AP were significant on day 2 of admission: 339.7 (191.7-471.8) versus 120,1 (11.0-382.6); p = 0.04. Levels of urinary beta 2-microglobulin in AP on days 1 to 3 postadmission were: 9.7 (1.1-93.3), 27.6 (4.7-421.4) and 88.3 (7.3-415.2) microg/mg of creatinine, respectively. When urinary beta 2-microglobulin was compared between severe and mild AP, no significant differences were found among days 1, 2 and 3. Selection of only the subgroup of patients whose urine samples were obtained within 24 h of symptom onset, did not improve the results of these urine markers for the group as a whole. CONCLUSIONS 1) Proteinuria was slightly increased in severe AP and was able to discriminate between mild and severe episodes on day 2 of admission. 2) Urinary beta 2-microglobulin as a tubular malfunction marker did not discriminate between mild and severe AP in patients in our study.
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Affiliation(s)
- J L Frasquet
- Laboratorio de Bioquímica, Servicio de Análisis Clínicos, Hospital General Universitario de Alicante, Universidad Miguel Hernández, Alicante, Spain
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Sáez J, Martínez J, Trigo C, Sánchez-Payá J, Griñó P, Compañy L, Laveda R, Penalva JC, García C, Pérez-Mateo M. A comparative study of the activation peptide of carboxypeptidase B and trypsinogen as early predictors of the severity of acute pancreatitis. Pancreas 2004; 29:e9-14. [PMID: 15211118 DOI: 10.1097/00006676-200407000-00062] [Citation(s) in RCA: 14] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 01/31/2023]
Abstract
BACKGROUND Serum and urine concentrations of the activation peptide of carboxypeptidase B (CAPAP) and urinary trypsinogen activation peptide (TAP) as prognostic markers in acute pancreatitis were compared. METHOD Fifty-two patients with acute pancreatitis hospitalized within 24 hours after symptom onset were prospectively studied. Blood and urine samples were obtained during the first 3 days of the hospital stay. RESULTS Pancreatitis was severe in 17 patients and mild in 35 (Atlanta criteria). Median serum CAPAP levels on days 1 and 2 and of urine CAPAP and TAP on days 1, 2, and 3 were significantly higher in severe pancreatitis than in mild disease. On the first day of admission, TAP was the most accurate predictor of severity (sensitivity, 92.3%; specificity, 80%; positive and negative predictive values, 63.2% and 96.6%, respectively), with a 4.61 positive likelihood ratio for a cutoff value of 18.10 nmol/L, whereas within 24 hours after symptom onset, urinary CAPAP was superior (sensitivity, 88.9%; specificity, 81.3%; positive and negative predictive values 72.7% and 92.9%, respectively), with a 4.72 positive likelihood ratio for a cutoff value of 15.45 nmol/L. CONCLUSION Serum and urine CAPAP levels and urinary TAP are accurate in the early assessment of severity in acute pancreatitis. Urine CAPAP levels was the most accurate marker 24 hours after onset of symptoms.
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Affiliation(s)
- J Sáez
- Section of Gastroenterology and Department of Internal Medicine, Hospital General Universitario de Alicante, Alicante, Spain
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Affiliation(s)
- Evan L Fogel
- Division of Gastroenterology/Hepatology, Indiana University Medical Center, Indaianpolis, 46202-5280, USA.
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Rettally CA, Skarda S, Garza MA, Schenker S. The usefulness of laboratory tests in the early assessment of severity of acute pancreatitis. Crit Rev Clin Lab Sci 2003; 40:117-49. [PMID: 12755453 DOI: 10.1080/713609331] [Citation(s) in RCA: 18] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/22/2022]
Abstract
Acute pancreatitis is a disorder that affects approximately 200,000 individuals in the U.S. annually. While most cases are mild, up to 30% of patients will have a complicated course with prolonged hospitalization and significant morbidity and mortality. Early institution of several therapeutic interventions, such as enteral nutrition, prophylactic antibiotics, endoscopic retrograde cholangiopancreatography (ERCP) and intensive care monitoring, have been shown to decrease the morbidity associated with severe acute pancreatitis. However, the ability of clinicians to predict, upon presentation, which patient will have mild or severe pancreatitis has remained poor over the years, thus leading to a delay in the institution of such treatments. Researchers have focused on markers that might improve upon clinical prediction alone. While data have shown the predictive value of tools such as Ranson's and Glasgow's criteria, C-reactive protein (CRP) and the APACHE score, their application in clinical practice has been limited by a time delay of at least 48 h in the former two and by being cumbersome in the latter. Thus, our focus is to critically appraise the evidence available for various biochemical markers in their ability to distinguish mild and severe acute pancreatitis early and more accurately than currently available tools.
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Affiliation(s)
- Carlos A Rettally
- Department of Gastroenterology and Nutrition, University of Texas Health Science Center at San Antonio, 78229-3900, USA
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Abstract
BACKGROUND Acute pancreatitis is still associated with significant morbidity and mortality. Current management guidelines are sometimes equivocal, particularly in relation to the surgical treatment of severe disease. This review assesses available investigative and treatment strategies to allow the development of a formalized management approach. METHODS A literature review of diagnosis, staging and management of acute pancreatitis was performed. RESULTS AND CONCLUSION Recent evidence has helped to clarify the roles of computed tomography, endoscopic retrograde cholangiopancreatography, prophylactic antibiotics, enteral feeding and fine-needle aspiration for bacteriology in the management of acute pancreatitis. Despite a relative shortage of prospective randomized trials there has been a significant change in the surgical management of acute pancreatitis over the past 20 years. This change has been away from early aggressive surgical intervention towards more conservative management, except when infected necrosis is confirmed. A formalized approach, with appropriate use of the various non-surgical and surgical options, is feasible in the management of severe acute pancreatitis.
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Affiliation(s)
- M Yousaf
- Department of Surgery, Mater Hospital Trust, Crumlin Road, Belfast BT14 6AB, UK
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Salomone T, Tosi P, Raiti C, Guariento A, Tomassetti P, Migliori M, Saieva C, Romboli M, Gullo L. Apoptosis in the peripheral blood mononuclear cells as a self-limitation process in human acute pancreatitis. Pancreatology 2003; 2:204-10. [PMID: 12138725 DOI: 10.1159/000058034] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/11/2022]
Abstract
BACKGROUND/AIM Acute pancreatitis is primed and sustained by a chain of immuno-inflammatory factors. In this study, we investigated the possible existence of peripheral blood mononuclear cell apoptosis as a self-limitation mechanism in acute pancreatitis. METHODS Peripheral blood mononuclear cell apoptosis was determined cytofluorometrically daily for 10 days from the onset of the illness in 27 consecutive patients (18 having mild uncomplicated acute pancreatitis and 9 having pancreatitis with complications) and was related to peripheral blood counts, including reticulocytes and reticulocyte fractions, and albumin, fibrinogen, and C-reactive protein levels. RESULTS In the 18 patients with uncomplicated acute pancreatitis, the rate of peripheral blood apoptosis increased progressively until days 5-6 and then decreased. The 9 patients who developed complications showed levels of peripheral blood apoptosis stable across the five periods and lower than those with uncomplicated disease during the first four periods. This difference was statistically significant (p = 0.002) only on days 7-8. On days 9-10, the patients with complications showed higher levels of peripheral blood apoptosis than those with mild uncomplicated acute pancreatitis (p = 0.0005). Peripheral blood apoptosis was not significantly related to the other laboratory parameters, but there was a trend towards an inverse relation to reticulocytes and total leucocytes (p < 0.09). CONCLUSIONS Peripheral blood apoptosis may act as a mechanism of self-limitation of the process of acute pancreatitis. Its effects, however, seem to be hampered and delayed by the presence of complications.
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Robert JH, Frossard JL, Mermillod B, Soravia C, Mensi N, Roth M, Rohner A, Hadengue A, Morel P. Early prediction of acute pancreatitis: prospective study comparing computed tomography scans, Ranson, Glascow, Acute Physiology and Chronic Health Evaluation II scores, and various serum markers. World J Surg 2002; 26:612-9. [PMID: 12098056 DOI: 10.1007/s00268-001-0278-y] [Citation(s) in RCA: 68] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/13/2022]
Abstract
The aim of this study was to assess the predictability of the outcome of acute pancreatitis using the Ranson, Glascow, and Acute Physiology and Chronic Health Evaluation (APACHE) II scores, the computed tomography (CT) scan, and several serum markers. Altogether, 137 consecutive patients with acute pancreatitis confirmed by CT scan were prospectively included. Blood samples were obtained daily for 6 days. The predictive value of each parameter was studied by univariate and multivariate analyses comparing mild and severe pancreatitis. A total of 111 attacks were graded as mild (81%) and 26 as severe (19%). Ranson (p = 0.3) and APACHE II (p = 0.049) scores appeared insufficiently predictive in the univariate analysis. Pancreatic imaging by CT scan was insufficiently predictive (p > 0.05), whereas the presence of extrapancreatic fluid collections was more indicative of outcome (p <0.05). With the univariate analysis, the four most reliable serum markers were pancreatic amylase (p <0.001), neutrophil elastase (p <0.05), albumin (p <0.002), and C-reactive protein (p <0.001). Results became homogeneous when the CT results were added; serum albumin plus extrapancreatic fluid collections (negative predictive value 92%-96% and positive predictive value 67%-100%) comprised the best indicator of severity. None of the parameters tested achieved sufficient predictability when used alone. Serum albumin plus extrapancreatic fluid collections comprise the best indicator of severity at the time of admission.
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Affiliation(s)
- John H Robert
- Department of Digestive Surgery, Geneva University Hospitals, Rue Micheli du Crest, 1211 Geneva 14, Switzerland
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Abstract
Acute pancreatitis (AP) is a common disease with wide variation of severity. The diagnosis of AP is usually based on high serum amylase or lipase values but the accuracy of these methods is considered unsatisfactory. One in five of the patients develops a severe disease and carries a considerable risk of development of organ failure and high mortality. Early detection of patients with severe AP and especially those with increased risk of organ failure is importance since such patients seem to benefit from treatment in an intensive care unit started as soon as possible after presentation. In addition to enzymological methods, increasing interest has been focused on laboratory markers reflecting the level of inflammatory response in AP. At present, in routine clinical work the most commonly used severity marker is serum C-reactive protein, the concentration of which rises too slowly to be used for early prediction of severity. New therapies aiming at modifying the course of systemic inflammation in AP are being developed and therefore monitoring the patient's immune inflammatory status is needed. In this review article we present the current knowledge of laboratory tests, which has been evaluated for diagnostic and prognostic purposes in AP.
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de Las Heras Castaño G, Castro Senosiain B. [Prognostic factors for acute pancreatitis]. GASTROENTEROLOGIA Y HEPATOLOGIA 2001; 24:357-64. [PMID: 11481073 DOI: 10.1016/s0210-5705(01)70194-x] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 11/26/2022]
Affiliation(s)
- G de Las Heras Castaño
- Servicio de Aparato Digestivo, Hospital Universitario Marqués de Valdecilla, Santander, Spain
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Zaninovic V, Gukovskaya AS, Gukovsky I, Mouria M, Pandol SJ. Cerulein upregulates ICAM-1 in pancreatic acinar cells, which mediates neutrophil adhesion to these cells. Am J Physiol Gastrointest Liver Physiol 2000; 279:G666-76. [PMID: 11005752 DOI: 10.1152/ajpgi.2000.279.4.g666] [Citation(s) in RCA: 64] [Impact Index Per Article: 2.6] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 01/31/2023]
Abstract
Neutrophil infiltration into the pancreas is a key event in pancreatitis. Here we show that intercellular adhesion molecule-1 (ICAM-1), which regulates neutrophil adhesion, is present on rat pancreatic acinar cells, is upregulated by a hormone (cerulein) and mediates direct binding of neutrophils to acinar cells. ICAM-1 was upregulated in pancreas of rats with experimental pancreatitis induced by supramaximal doses of cerulein. Furthermore, cerulein time and dose dependently stimulated expression of ICAM-1 mRNA and protein in isolated pancreatic acinar cells. Inhibitory analysis showed that activation of transcription factor nuclear factor-kappaB (NF-kappaB) was involved in ICAM-1 upregulation by cerulein, but NF-kappaB did not mediate basal expression of ICAM-1 mRNA in acinar cells. With an adhesion assay, we found that neutrophils bind to isolated pancreatic acinar cells and that cerulein upregulates the extent of adhesion. Neutralizing ICAM-1 antibody blocked neutrophil binding to both control and cerulein-stimulated acinar cells, suggesting ICAM-1 involvement in this adhesion. Thus the acinar cell is capable of targeting neutrophils to its surface, a process that may be important for inflammatory and cell death responses in pancreatitis and other pancreatic disorders.
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Affiliation(s)
- V Zaninovic
- Department of Medicine, Veterans Affairs Greater Los Angeles Healthcare System and University of California, Los Angeles, California 90073, USA
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Chen HM, Shyr MH, Chi CP, Chi TY, Lo CC, Chen MF. Effects of timing of diatrizoate (water-soluble contrast medium) administration on pancreatic microcirculatory derangement in cerulein pancreatitis in rats. THE JOURNAL OF TRAUMA 2000; 48:689-94. [PMID: 10780603 DOI: 10.1097/00005373-200004000-00017] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 11/25/2022]
Abstract
OBJECTIVE We investigated whether the timing of administration of contrast medium after onset of acute pancreatitis is critical in determining the magnitude of microcirculatory derangement. METHODS An acute pancreatitis model in male Sprague-Dawley rats (225-275 g) was established by continuous infusion of cerulein (15 mg/kg per hour). The mean arterial pressure was monitored continuously by means of a femoral artery catheter. Diatrizoate (Hypaque-76), a water-soluble contrast medium, was delivered through a femoral vein catheter at doses corresponding to those given to humans, either 1, 2, or 3 hours after pancreatitis induction. In vivo microscopy and laser-Doppler flowmetry were used to investigate microcirculatory derangement. The water contents of the pancreas and lung, the malondialdehyde levels of the pancreas, and the trypsinogen activation peptide levels in the serum were measured at the end of the experiment (8 hours after infusion of cerulein). RESULTS Early administration of contrast medium (1 hour after pancreatitis induction) resulted in significantly greater changes in microcirculation and mean arterial pressure than did late administration (2 or 3 hours after pancreatitis induction). Rats given contrast medium 1 hour after induction also had highest pancreas and lung water contents, the highest pancreas malondialdehyde levels, and the highest serum trypsinogen activation peptide levels. CONCLUSION These results show that a water soluble contrast medium that is often used for computed tomographic imaging of the pancreas can adversely affect the pancreatic microcirculatory parameters, such as tissue perfusion and leukocyte sticking, and hemodynamics in a cerulein-induced model of acute pancreatitis. Early administration seems to cause more severe derangement of the pancreatic microcirculation.
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Affiliation(s)
- H M Chen
- Department of Surgery, Chang Gung Memorial Hospital, Chang Gung University School of Medicine, Taipei, Taiwan, Republic of China.
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García de Lorenzo A, Mateos, López Martínez J, Sánchez Castilla M. Respuesta inflamatoria sistémica: definiciones, marcadores inflamatorios y posibilidades terapéuticas. Med Intensiva 2000. [DOI: 10.1016/s0210-5691(00)79623-9] [Citation(s) in RCA: 6] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/17/2022]
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Abstract
Acute pancreatitis is a disease that has many causes. Each cause seems to affect the acinar cell in some way that results in the premature activation and retention of potent proteolytic enzymes. These activated enzymes then injure the acinar cell and cause the immediate release of cytokines and activate the complement system. Together, these molecules attract and sequester inflammatory cells, in particular neutrophils, which causes further secretion of cytokines, free radicals, and other vasoactive molecules, such as nitric oxide. We propose that the released inflammatory molecules induce local effects, such as pancreatic edema and necrosis, and systemic complications, such as hypotension, tachycardia, fever, capillary leak syndrome, and hypoxia. The cytokines released in the pancreas also stimulate apoptosis, further enhancing the cell death response in pancreatitis. Much of the current research is aimed at understanding the links between these series of events and finding agents that can modulate the cascade of events involved in pancreatitis. What is promising in this endeavor is that the response produced with pancreatitis is nearly identical with all etiologies, suggesting that therapy may not have to be specific to a particular cause. The mechanistic models of AP presented herein are supported by preliminary clinical studies that suggest that protease and cytokine inhibitors may improve the course of AP in specific clinical settings.
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Affiliation(s)
- S Karne
- Department of Internal Medicine, Yale University School of Medicine, New Haven, Connecticut, USA
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