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Podda M, Murzi V, Marongiu P, Di Martino M, De Simone B, Jayant K, Ortenzi M, Coccolini F, Sartelli M, Catena F, Ielpo B, Pisanu A. Effectiveness and safety of low molecular weight heparin in the management of acute pancreatitis: a systematic review and meta-analysis. World J Emerg Surg 2024; 19:30. [PMID: 39256790 PMCID: PMC11385836 DOI: 10.1186/s13017-024-00558-3] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/30/2024] [Accepted: 08/24/2024] [Indexed: 09/12/2024] Open
Abstract
BACKGROUND Recent studies suggest that low-molecular-weight heparin (LMWH) may play a role in mitigating the severity of acute pancreatitis (AP). This systematic review and meta-analysis aims to synthesise existing evidence on the effectiveness and safety of LMWH in the treatment of moderately-severe and severe AP. METHODS This systematic review and meta-analysis was conducted in accordance with the 2020 update of the PRISMA guidelines and the Cochrane Handbook for Systematic Reviews of Interventions. The systematic search was conducted in MEDLINE, the Cochrane Central Register of Controlled Trials, Scopus, and EMBASE, covering studies published up to February 2024. Randomised controlled trials (RCTs) and observational studies (n-RCTs) that reported the differences in the outcomes of AP for patients receiving LMWH in addition to the standard treatment (Intervention), compared to patients managed by standard treatment without LMWH (Control) were eligible. A random-effects model was used to calculate the pooled relative risk (RR) and mean differences (MD) with the corresponding 95% CI. RESULTS Thirteen studies were included in the meta-analysis, all published between 2004 and 2022. Eight studies were RCTs, and five were n-RCTs. Data from 13,709 patients (6.971 Interventions and 6.738 Controls) were analysed. The comparison of Intervention and Control groups showed the superiority of LMWH to standard treatments in terms of overall mortality (RR = 0.44, 95% CI = 0.31; 0.64, P < 0.0001, I2 = 51%), acute necrotic collections (RR = 0.24, 95% CI = 0.09; 0.62, P = 0.003, I2 = 0%), and organ failure (RR = 0.67, 95% CI = 0.48; 0.93, P = 0.02, I2 = 78%). The Intervention group showed superior outcomes compared with the Control group for gastrointestinal bleeding (RR = 0.64, 95% CI = 0.44; 0.94, P = 0.02, I2 = 0%), length of hospital stay (MD= - 6.08, 95% CI = - 10.08; - 2.07, P = 0.003, I2 = 98%), need for operative interventions (RR = 0.50, 95% CI = 0.29; 0.87, P = 0.01, I2 = 61%), and vascular thrombosis (RR = 0.43, 95% CI = 0.31; 0.61, P < 0.00001, I2 = 0%). CONCLUSIONS Moderate to high-quality evidence suggests that early intervention with LMWH could improve the prognosis of non-mild AP in terms of mortality, organ failure, and decreased incidence of vascular thrombosis. In light of our findings, integrating LMWH into the treatment regimen for moderate-severe to severe AP is advocated.
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Grants
- F53D23006530006 This research was funded by the University of Cagliari (Italy), Department of Surgical Science, Italian Ministry of University and Research (Ministero dell'Università e della Ricerca Italiano), PRIN (Progetti di Ricerca di Rilevante Interesse Nazionale) 2022, ID 202273A4YP, grant number F53D23006530006.
- F53D23006530006 This research was funded by the University of Cagliari (Italy), Department of Surgical Science, Italian Ministry of University and Research (Ministero dell'Università e della Ricerca Italiano), PRIN (Progetti di Ricerca di Rilevante Interesse Nazionale) 2022, ID 202273A4YP, grant number F53D23006530006.
- F53D23006530006 This research was funded by the University of Cagliari (Italy), Department of Surgical Science, Italian Ministry of University and Research (Ministero dell'Università e della Ricerca Italiano), PRIN (Progetti di Ricerca di Rilevante Interesse Nazionale) 2022, ID 202273A4YP, grant number F53D23006530006.
- F53D23006530006 This research was funded by the University of Cagliari (Italy), Department of Surgical Science, Italian Ministry of University and Research (Ministero dell'Università e della Ricerca Italiano), PRIN (Progetti di Ricerca di Rilevante Interesse Nazionale) 2022, ID 202273A4YP, grant number F53D23006530006.
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Affiliation(s)
- Mauro Podda
- Emergency Surgery Unit, Department of Surgical Science, University of Cagliari, SS 554, Km 4,500, 09042, Monserrato, Cagliari, Italy.
| | - Valentina Murzi
- Emergency Surgery Unit, Department of Surgical Science, University of Cagliari, SS 554, Km 4,500, 09042, Monserrato, Cagliari, Italy
| | - Paola Marongiu
- Emergency Surgery Unit, Department of Surgical Science, University of Cagliari, SS 554, Km 4,500, 09042, Monserrato, Cagliari, Italy
| | - Marcello Di Martino
- Department of Health Sciences, University of Piemonte Orientale, Novara, Italy
| | | | - Kumar Jayant
- Department of Surgery and Cancer, Hammersmith Hospital, Imperial College London, London, UK
| | - Monica Ortenzi
- Department of General and Emergency Surgery, Università Politecnica delle Marche, Ancona, Italy
| | - Federico Coccolini
- General, Emergency and Trauma Surgery Department, Pisa University Hospital, Pisa, Italy
| | | | - Fausto Catena
- Department of Emergency and Trauma Surgery, Bufalini Hospital, Cesena, Italy
| | - Benedetto Ielpo
- HPB Unit, Hospital del Mar, Pompeu Fabra University, Barcelona, Spain
| | - Adolfo Pisanu
- Emergency Surgery Unit, Department of Surgical Science, University of Cagliari, SS 554, Km 4,500, 09042, Monserrato, Cagliari, Italy
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Ca S, Gondesi K, K KP, Yarremsetty SV. Efficacy of Low-Molecular-Weight Heparin in the Treatment of Severe Acute Pancreatitis: A Comparative Study at a Tertiary Health Center. Cureus 2024; 16:e65736. [PMID: 39211724 PMCID: PMC11360274 DOI: 10.7759/cureus.65736] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 07/23/2024] [Indexed: 09/04/2024] Open
Abstract
Introduction Acute pancreatitis is caused by multiple factors. The disease can progress to severe acute pancreatitis (SAP) rapidly, which is a fatal condition. SAP is associated with systemic inflammatory response and disturbances in microcirculation, which are responsible for the high rate of mortality. Low-molecular-weight heparin (LMWH), apart from preventing thrombus formation, also has a property of reducing the release of cytokines and inflammatory mediators. This aids in the improvement of microcirculation of the pancreas. Materials and methods A prospective hospital-based study was conducted on 60 patients diagnosed with SAP. Patients were randomly divided into two groups: conventional treatment group (C group consisting of 30 patients) and LMWH in addition to conventional treatment (L group, consisting of 30 patients). Clinical and laboratory parameters and computed tomography (CT) scores of pancreatic necrosis (CTSPN) were compared in the two study groups. Results No significant difference (p > 0.05) was observed in the clinical and laboratory parameters and CTSPN among the two study groups at the time of admission. On initiation of treatment, the rate of improvement in symptoms and laboratory parameters were significantly higher in the L group compared with the C group (p < 0.05). Acute physiology and chronic health evaluation (APACHE) II score and development of complications were significantly lower in the L group compared with the C group (p< 0.05). CTSPN was found to be very low in the L group compared with the C group (p < 0.05). After two weeks of treatment, the recovery rate in response to treatment was observed to be higher in the L group compared to the C group, and the mortality rate was very low in the L group (p <0.05, significant). Conclusion The addition of LMWH to conventional treatment in SAP augments the effect and improves the clinical response, improving the recovery rate and decreasing mortality. LMWH is highly effective for the treatment of SAP, with a good safety profile and easy availability and without high financial burden.
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Affiliation(s)
- Shashirekha Ca
- General Surgery, Sri Devaraj Urs Medical College, Kolar, IND
| | - Kavitha Gondesi
- General Surgery, Sri Devaraj Urs Medical College, Kolar, IND
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Yan Z, Zang B, Gong X, Ren J, Wang R. MiR-214-3p exacerbates kidney damages and inflammation induced by hyperlipidemic pancreatitis complicated with acute renal injury. Life Sci 2020; 241:117118. [PMID: 31790686 DOI: 10.1016/j.lfs.2019.117118] [Citation(s) in RCA: 25] [Impact Index Per Article: 5.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/16/2019] [Revised: 11/15/2019] [Accepted: 11/27/2019] [Indexed: 12/11/2022]
Abstract
AIMS Acute pancreatitis (AP) is usually complicated with multiple organ insufficiency, including renal injury. Hyperlipidemia is regarded as a risk factor to induce AP. High-fat diet-induced hyperlipidemic pancreatitis (HP) increased nowadays and showed more severe symptoms and complications than other AP. However, detailed mechanisms or mediators involved in HP complicated with acute renal injury were less studied. Here, we aimed to study how miR-214 expresses in the HP and whether miR-214 has functions to regulate pathological kidney damages induced by HP. MAIN METHODS Sprague-Dawley rats were adopted to establish HP model complicated with acute renal injury through long-term high-fat diet and sodium taurocholic injection. Models were injected with LV-rno-miR-214-3p or LV-anti-rno-miR-214-3p to exogenously regulate miR-214-3p to study its impacts on HP via a series of molecular and histological experiments. KEY FINDINGS MiR-214-3p was found to be up-regulated in the kidney, pancreas and serum of HP rats and also could intensify the pathological alterations, kidney and pancreas damages and fibrosis induced by HP. Inflammatory response in HP was enhanced when miR-214-3p was overexpressed. Besides, miR-214-3p up-regulation was showed to inhibit PTEN expression but increased P-Akt levels in the HP kidney, which might be a possible mechanism to induce severe symptoms of pancreatitis. Knockdown of miR-214-3p showed opposite effects. SIGNIFICANCE MiR-214-3p is indicated to exacerbate the tissue damages and inflammatory response caused by HP complicated with acute renal injury, which may provide a novel therapeutic perspective targeting miR-214-3p to treat HP with acute renal injury.
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Affiliation(s)
- Zhaopeng Yan
- Department of General Surgery, Shengjing Hospital, China Medical University, Shenyang, Liaoning, China
| | - Bin Zang
- Department of Critical Care Medicine, Shengjing Hospital, China Medical University, Shenyang, Liaoning, China
| | - Xiaoying Gong
- Department of Critical Care Medicine, Shengjing Hospital, China Medical University, Shenyang, Liaoning, China
| | - Jiangyue Ren
- Department of Critical Care Medicine, Shengjing Hospital, China Medical University, Shenyang, Liaoning, China
| | - Rui Wang
- Department of Critical Care Medicine, Shengjing Hospital, China Medical University, Shenyang, Liaoning, China.
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Gu L, Liu J, Xu D, Lu Y. Reciprocal Feedback Loop of the MALAT1-MicroRNA-194-YAP1 Pathway Regulates Progression of Acute Pancreatitis. Med Sci Monit 2019; 25:6894-6904. [PMID: 31518341 PMCID: PMC6756034 DOI: 10.12659/msm.915598] [Citation(s) in RCA: 19] [Impact Index Per Article: 3.2] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/06/2023] Open
Abstract
Background Acute pancreatitis (AP) has a high mortality rate and often has serious complications. The Hippo-YAP signaling pathway is mainly involved in cell proliferation and stem cell self-renewal. Recent studies have reported that YAP1 plays a crucial role in pancreatic cancer initiation and acute and chronic pancreatitis (CP). However, the role of YAP1 in AP still needs to be clarified. Material/Methods To assess the role of YAP1 in the progression of AP, we established a cell model of AP in AR42J cells. AR42J, a rat pancreatic acinar cell line, was stimulated with caerulein to mimic AP-like acinar cell injury. Levels of interleukin (IL)-6 and tumor necrosis factor-α (TNF-α) were measured by ELISA to investigate the role of YAP1 in the progression of AP. Results The results showed that YAP1 and MALAT1 were the targets of miR-194 and were upregulated in caerulein-treated AR42J cells. Overexpression of MALAT1 or YAP1 can increase the levels of IL-6 and TNF-α secreted by AR42J cells, while miR-194 dramatically counteracts this enhancement effect. Conclusions Our results demonstrated a regulation loop among MATAL1, miR-194, and YAP1, which dynamically regulates the progression of AP, providing a new therapeutic target for treatment of this disease.
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Affiliation(s)
- Lina Gu
- Department of ICU (Intensive Care Unit), The First Hospital of Jilin University, Changchun, Jilin, China (mainland)
| | - Jingyao Liu
- Department of Neurology, The First Hospital of Jilin University, Changchun, Jilin, China (mainland)
| | - Dan Xu
- Department of Traditional Chinese Medicine, The First Hospital of Jilin University, Changchun, Jilin, China (mainland)
| | - Ying Lu
- Department of ICU (Intensive Care Unit), The First Hospital of Jilin University, Changchun, Jilin, China (mainland)
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Tozlu M, Kayar Y, İnce AT, Baysal B, Şentürk H. Low molecular weight heparin treatment of acute moderate and severe pancreatitis: A randomized, controlled,open-label study. TURKISH JOURNAL OF GASTROENTEROLOGY 2019; 30:81-87. [PMID: 30289392 DOI: 10.5152/tjg.2018.18583] [Citation(s) in RCA: 28] [Impact Index Per Article: 4.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 12/13/2022]
Abstract
BACKGROUND/AIMS Acute pancreatitis (AP) runs a moderately severe and severe course in 20%-30% of cases. The purpose of the present study was to determine the effect of low molecular weight heparin (LMWH) for the prevention of pancreatic necrosis (PN) in moderately severe and severe AP (MSAP). MATERIALS AND METHODS A total of 100 patients with MSAP were randomized to receive either standard care (SC) or SC plus LMWH. LMWH was administered at 1 mg/kg via subcutaneous injection twice a day between days 1 and 7. The revised Atlanta criteria were used in the diagnosis of MSAP. Patients with a Harmless AP Score of >1 and a Balthazar computed tomography (CT) score of D and E were included in the study. RESULTS The mean age±SD of the patients (46 male and 54 female) was 52±19 years (range, 17-100). There were 50 patients in each group. On admission, clinical and laboratory parameters and Balthazar CT scores were similar between the groups. Initially, PN was present in one patient in the LMWH group and two in the SC group. Over the course, PN developed in 3 (6.1%) patients in the LMWH group and 11 (22.9%) in the SC group (p<0.05). Local and systemic complications were significantly lower in the LMWH group (p<0.05). No hemorrhagic complication occurred. Mortality was not significantly different between the groups (p=0.056). CONCLUSION Low molecular weight heparin treatment is safe and provides better prognosis in MSAP.
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Affiliation(s)
- Mukaddes Tozlu
- Department of Gastroenterology, Sakarya University School of Medicine, Sakarya, Turkey
| | - Yusuf Kayar
- Department of Gastroenterology, Bezmialem Vakif University School of Medicine, İstanbul, Turkey
| | - Ali Tüzün İnce
- Department of Gastroenterology, Bezmialem Vakif University School of Medicine, İstanbul, Turkey
| | - Birol Baysal
- Department of Gastroenterology, Bezmialem Vakif University School of Medicine, İstanbul, Turkey
| | - Hakan Şentürk
- Department of Gastroenterology, Bezmialem Vakif University School of Medicine, İstanbul, Turkey
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Waller A, Long B, Koyfman A, Gottlieb M. Acute Pancreatitis: Updates for Emergency Clinicians. J Emerg Med 2018; 55:769-779. [PMID: 30268599 DOI: 10.1016/j.jemermed.2018.08.009] [Citation(s) in RCA: 39] [Impact Index Per Article: 5.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/22/2018] [Accepted: 08/03/2018] [Indexed: 12/12/2022]
Abstract
BACKGROUND Acute pancreatitis is a frequent reason for patient presentation to the emergency department (ED) and the most common gastrointestinal disease resulting in admission. Emergency clinicians are often responsible for the diagnosis and initial management of acute pancreatitis. OBJECTIVE This review article provides emergency clinicians with a focused overview of the diagnosis and management of pancreatitis. DISCUSSION Pancreatitis is an inflammatory process within the pancreas. While the disease is often mild, severe forms can have a mortality rate of up to 30%. The diagnosis of pancreatitis requires two of the following three criteria: epigastric abdominal pain, an elevated lipase, and imaging findings of pancreatic inflammation. The most common etiologies include gallbladder disease and alcohol use. After the diagnosis has been made, it is important to identify underlying etiologies requiring specific intervention, as well as obtain a right upper quadrant ultrasound. The initial management of choice is fluid resuscitation and pain control. Recent data have suggested that more cautious fluid resuscitation in the first 24 h might be more appropriate for some patients. Intravenous opiates are generally safe if used judiciously. Appropriate disposition is a multifactorial decision, which can be facilitated by using Ranson criteria or the Bedside Index of Severity in Acute Pancreatitis score. Complications, though rare, can be severe. CONCLUSIONS Pancreatitis is a potentially deadly disease that commonly presents to most emergency departments. It is important for clinicians to be aware of the current evidence regarding the diagnosis, treatment, and disposition of these patients.
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Affiliation(s)
- Anna Waller
- Department of Emergency Medicine, Brooke Army Medical Center, Fort Sam Houston, Texas
| | - Brit Long
- Department of Emergency Medicine, Brooke Army Medical Center, Fort Sam Houston, Texas
| | - Alex Koyfman
- Department of Emergency Medicine, The University of Texas Southwestern Medical Center, Dallas, Texas
| | - Michael Gottlieb
- Department of Emergency Medicine, Rush University Medical Center, Chicago, Illinois
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Gamma-enolase predicts lung damage in severe acute pancreatitis-induced acute lung injury. J Mol Histol 2018; 49:347-356. [PMID: 29728894 DOI: 10.1007/s10735-018-9774-3] [Citation(s) in RCA: 6] [Impact Index Per Article: 0.9] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/09/2018] [Accepted: 05/02/2018] [Indexed: 12/18/2022]
Abstract
Severe acute pancreatitis (SAP) associated acute lung injury (ALI) accounts for about 70% mortality of SAP patients. However, there are no precise biomarkers for the disease currently. Herein, we evaluated the potential of gamma-enolase (ENO2), against its universal isoform alpha-enolase (ENO1), as a marker of SAP-ALI in a rat model. Firstly, 16 male Sprague-Dawley rats were randomly divided into two groups, Sham (n = 8) and SAP-ALI (n = 8), for pancreatitis induction. Ultra-structure examination by electron microscopy and HE staining were used for lung injury assessment. Lung tissue expressions of alpha-enolase and gamma-enolase were evaluated by qRT-PCR and immunohistochemistry. In a prospective validation experiment, 28 rats were used: sham (n = 8), SAP-ALI at 3 h (3 h, n = 10), and SAP-ALI at 24 h (24 h, n = 10). Lung tissue damage, tissue expression and circulating alpha-enolase and gamma-enolase levels were evaluated. Elevated serum levels of α-amylase and TNF-α were observed in SAP rats but not in sham-operated rats. Histological examination of pancreatic and lung tissues indicated marked damage in SAP rats. While alpha-enolase was universally expressed, gamma-enolase was expressed only in damaged lung tissues. Gamma-enolase was detected in lung tissues, BALF, and serum as early as 3 h post-surgery when physical pathological damage was not apparent. Unlike alpha-enolase, secreted and/or circulating gamma-enolase level progressively increased, especially in serum, as lung damage progressed. Thus, gamma-enolase may signal and correlate lung tissue damage well before obvious physical pathological tissue damage and might be a candidate diagnostic and/or prognostic marker.
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Sun K, He SB, Qu JG, Dang SC, Chen JX, Gong AH, Xie R, Zhang JX. IRF5 regulates lung macrophages M2 polarization during severe acute pancreatitis in vitro. World J Gastroenterol 2016; 22:9368-9377. [PMID: 27895424 PMCID: PMC5107700 DOI: 10.3748/wjg.v22.i42.9368] [Citation(s) in RCA: 31] [Impact Index Per Article: 3.4] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/26/2016] [Revised: 08/13/2016] [Accepted: 08/23/2016] [Indexed: 02/06/2023] Open
Abstract
AIM To investigate the role of interferon regulatory factor 5 (IRF5) in reversing polarization of lung macrophages during severe acute pancreatitis (SAP) in vitro.
METHODS A mouse SAP model was established by intraperitoneal (ip) injections of 20 μg/kg body weight caerulein. Pathological changes in the lung were observed by hematoxylin and eosin staining. Lung macrophages were isolated from bronchoalveolar lavage fluid. The quantity and purity of lung macrophages were detected by fluorescence-activated cell sorting and evaluated by real-time polymerase chain reaction (RT-PCR). They were treated with IL-4/IRF5 specific siRNA (IRF5 siRNA) to reverse their polarization and were evaluated by detecting markers expression of M1/M2 using RT-PCR.
RESULTS SAP associated acute lung injury (ALI) was induced successfully by ip injections of caerulein, which was confirmed by histopathology. Lung macrophages expressed high levels of IRF5 as M1 phenotype during the early acute pancreatitis stages. Reduction of IRF5 expression by IRF5 siRNA reversed the action of macrophages from M1 to M2 phenotype in vitro. The expressions of M1 markers, including IRF5 (S + IRF5 siRNA vs S + PBS, 0.013 ± 0.01 vs 0.054 ± 0.047, P < 0.01), TNF-α (S + IRF5 siRNA vs S + PBS, 0.0003 ± 0.0002 vs 0.019 ± 0.018, P < 0.001), iNOS (S + IRF5 siRNA vs S + PBS, 0.0003 ± 0.0002 vs 0.026 ± 0.018, P < 0.001) and IL-12 (S + IRF5 siRNA vs S + PBS, 0.000005 ± 0.00004 vs 0.024 ± 0.016, P < 0.001), were decreased. In contrast, the expressions of M2 markers, including IL-10 (S + IRF5 siRNA vs S + PBS, 0.060 ± 0.055 vs 0.0230 ± 0.018, P < 0.01) and Arg-1 (S + IRF5 siRNA vs S + PBS, 0.910 ± 0.788 vs 0.0036 ± 0.0025, P < 0.001), were increased. IRF5 siRNA could reverse the lung macrophage polarization more effectively than IL-4.
CONCLUSION Treatment with IRF5 siRNA can reverse the pancreatitis-induced activation of lung macrophages from M1 phenotype to M2 phenotype in SAP associated with ALI.
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Alexandrova ED, Sadchikov DV, Kuligin AV. [Optimization of antisecretory component of severe acute pancreatitis intensive management]. Khirurgiia (Mosk) 2016:83-85. [PMID: 27296128 DOI: 10.17116/hirurgia2016683-85] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/18/2022]
Abstract
AIM Improvement of complex intensive care of severe acute pancreatitis with use of continued intravenous infusion of octreotid. METHODS 85 patients with severe acute pancreatitis were involved into the investigation, were divided into 2 groups. Patients of the control group (44 patients) got an intensive care according to severe acute pancreatitis treatment. Complex intensive treatment of the group of comparison (41 patients) included injections of octreotid (300 mcg 3 times a day). RESULTS The change of octreotid usege scheme allowed to improve treatment resultes, wchis is the decrease of endotoxemia level and minimization of time spent at emergency department.
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Affiliation(s)
| | - D V Sadchikov
- V.I. Razumovsky Saratov State Medical University, Russia
| | - A V Kuligin
- V.I. Razumovsky Saratov State Medical University, Russia
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Golub AV, Kozlov RS, Pleshkov VG, Moskalev AP, Alibegov RA, Chelombitko MA. [Surgical Site Infections after Open Appendectomy and Effectiveness of Complex Approach to Their Prevention]. Khirurgiia (Mosk) 2016:68-76. [PMID: 27296126 DOI: 10.17116/hirurgia2016668-76] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/05/2023]
Abstract
AIM To assess an incidence rate of surgical site infections (SSI) after open appendectomy and effectiveness of combined preventive measures (CPM). MATERIAL AND METHODS This study was performed at three surgical departments of Smolensk hospitals. A total of 150 consecutive patients (50 at each department) hospitalized since January 2012 were included into the retrospective observation (period I). In order to perform prospective evaluation of CPM, a total of 66 consecutive patients (randomized 1:1) hospitalized since December 2012 (period II) were followed up at each of the departments. Antibiotic prophylaxis (AP) with IV amoxicillin/clavulanate (1.2 g) was planned for all patients from period II. The study group (group 1) included patients with surgical wound closure with triclosan-coated polyglactin 910 and additionally with a skin 2-octylcyanoacrylate-based adhesive. The control group (group 2) included patients with surgical wound closure with non-triclosan-coated polyglactin 910. Each patient from the period II was assigned to an "Individual SSI Prevention Package" (IPP), which included an antibiotic, sutures, skin adhesive (only in a package for CPM) and label "AP" for patients' medical records. Patients' medical records were reviewed by one expert. Exclusion criteria were: age <14 years; transition to midline laparotomy; drainage of the abdominal cavity through the surgical wound; simultaneous interventions; secondary appendicitis; refusal to use of sutures from the IPP. In order to determine signs of SSI presence/absence within 30 days after surgery, attempts to contact with patients by phone were made. The data obtained was recorded into case report forms and then entered into the study database. RESULTS A total of 322 patients were included into the final analysis (mean age: 34.8±17.1 years). The mean length of hospital stay was 8.2±2.5 days. The mean duration of hospital stay with or without SSI was 7.9±1.8 and 14.2±4.0 days, respectively (p<0.001). The AP during the periods I and II was performed in 56.1% (83/148) and 97.7% (170/174) of patients, respectively (p<0.00001). Cephalosporins I-IV were the most frequently used antibiotics during the period I (85.6%). During the period II, amoxicillin/clavulanate from IPP was used in 98.2% of patients. Percentage of IV antibiotic administration in different time periods was 57.3% and 98.2%, respectively (p<0.0001); frequency of the first administration before skin incision was 53.6% and 97.1%, respectively (p<0.0001). The telephone contact with patient was successful in 74.8% (both periods), 56.8% (period I) and 90.2% (period II) of cases, respectively. SSI was recorded only once per patient with the following priority: SSI was documented in the patient's medical record; patient developed SSI that was not documented (in the expert's opinion) in the patient's medical record; SSI signs were determined during the telephone contact or reported by the patient. The incidence of SSI in both study periods, period I and period II was 14.9%, 15.5% and 14.4%, respectively (p>0.05 for all comparisons). In the patient subgroup with successful telephone contact, the incidence of SSI in both study periods, period I and period II was 17.4%, 21.4% and 15.3%, respectively; the incidence of SSI in group 1 and group 2 of the period II was 12.0% and 18.9%, respectively (p>0.05 for all comparisons). CONCLUSION SSI after an open appendectomy remains an important problem. In order to determine a true incidence of SSI, it is necessary to improve the national nosocomial infection surveillance system. The CMP used in the study have showed a trend to significant SSI risk reduction and may be recommended to maximize patient protection. Further large studies are needed to confirm effectiveness of the proposed CMP.
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Affiliation(s)
- A V Golub
- Department of General Surgery, Smolensk State Medical University, Smolensk, Russia
| | - R S Kozlov
- Institute of Antimicrobial Chemotherapy, Smolensk, Russia
| | - V G Pleshkov
- Department of General Surgery, Smolensk State Medical University, Smolensk, Russia
| | - A P Moskalev
- Smolensk Regional Clinical Hospital, Smolensk, Russia
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Qiao YY, Liu XQ, Xu CQ, Zhang Z, Xu HW. Interleukin-22 ameliorates acute severe pancreatitis-associated lung injury in mice. World J Gastroenterol 2016; 22:5023-32. [PMID: 27275094 PMCID: PMC4886377 DOI: 10.3748/wjg.v22.i21.5023] [Citation(s) in RCA: 20] [Impact Index Per Article: 2.2] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/15/2016] [Revised: 04/11/2016] [Accepted: 05/04/2016] [Indexed: 02/06/2023] Open
Abstract
AIM To investigate the potential protective effect of exogenous recombinant interleukin-22 (rIL-22) on L-arginine-induced acute severe pancreatitis (SAP)-associated lung injury and the possible signaling pathway involved. METHODS Balb/c mice were injected intraperitoneally with L-arginine to induce SAP. Recombinant mouse IL-22 was then administered subcutaneously to mice. Serum amylase levels and myeloperoxidase (MPO) activity in the lung tissue were measured after the L-arginine administration. Histopathology of the pancreas and lung was evaluated by hematoxylin and eosin (HE) staining. Expression of B cell lymphoma/leukemia-2 (Bcl-2), Bcl-xL and IL-22RA1 mRNAs in the lung tissue was detected by real-time PCR. Expression and phosphorylation of STAT3 were analyzed by Western blot. RESULTS Serum amylase levels and MPO activity in the lung tissue in the SAP group were significantly higher than those in the normal control group (P < 0.05). In addition, the animals in the SAP group showed significant pancreatic and lung injuries. The expression of Bcl-2 and Bcl-xL mRNAs in the SAP group was decreased markedly, while the IL-22RA1 mRNA expression was increased significantly relative to the normal control group (P < 0.05). Pretreatment with PBS did not significantly affect the serum amylase levels, MPO activity or expression of Bcl-2, Bcl-xL or IL-22RA1 mRNA (P > 0.05). Moreover, no significant differences in the degrees of pancreatic and lung injuries were observed between the PBS and SAP groups. However, the serum amylase levels and lung tissue MPO activity in the rIL-22 group were significantly lower than those in the SAP group (P < 0.05), and the injuries in the pancreas and lung were also improved. Compared with the PBS group, rIL-22 stimulated the expression of Bcl-2, Bcl-xL and IL-22RA1 mRNAs in the lung (P < 0.05). In addition, the ratio of p-STAT3 to STAT3 protein in the rIL-22 group was significantly higher than that in the PBS group (P < 0.05). CONCLUSION Exogenous recombinant IL-22 protects mice against L-arginine-induced SAP-associated lung injury by enhancing the expression of anti-apoptosis genes through the STAT3 signaling pathway.
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Han X, Wang Y, Chen H, Zhang J, Xu C, Li J, Li M. Enhancement of ICAM-1 via the JAK2/STAT3 signaling pathway in a rat model of severe acute pancreatitis-associated lung injury. Exp Ther Med 2016; 11:788-796. [PMID: 26997994 PMCID: PMC4774378 DOI: 10.3892/etm.2016.2988] [Citation(s) in RCA: 26] [Impact Index Per Article: 2.9] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/12/2015] [Accepted: 10/09/2015] [Indexed: 12/14/2022] Open
Abstract
Acute lung injury (ALI), which is associated with severe acute pancreatitis (SAP), results from damage to the pulmonary microvascular endothelial cells (PMVECs), which in turn leads to high levels of inflammatory cytokines that destroy PMVECs. However, the molecular mechanisms underlying SAP-associated ALI (SAP-ALI) are currently not well understood. Intercellular adhesion molecule-1 (ICAM-1) has been implicated in the persistent migration and accumulation of neutrophils and macrophages, which in turn has been associated with the increased permeability of microvascular endothelial cells. Signal transduction via the Janus kinase-2 (JAK2)/signal transducer and activator of transcription-3 (STAT3) transcription factors has been shown to be involved in inflammation. The present study aimed to investigate the expression levels of ICAM-1 and JAK2/STAT3 signaling components in a rat model of SAP-ALI. SAP was induced in the rat model, and dexamethasone (DEX) was administered to the treatment group. Subsequently, ICAM-1, interleukin (IL)-6, IL-8, tumor necrosis factor (TNF)-α, JAK2, STAT3 and nuclear factor (NF)-κB mRNA expression levels were determined using reverse transcription-polymerase chain reaction; ICAM-1 protein expression levels were determined using western blotting; and IL-6, IL-8 and TNF-α levels were measured via an enzyme-linked immunosorbent assay. In addition, an immunohistochemical analysis of ICAM-1, NF-κB, JAK2 and STAT3 was conducted, and the protein expression and cell morphology of the lungs in all rats was analyzed. ICAM-1 mRNA and protein expression levels were significantly increased following induction of SAP, and were significantly decreased in the DEX-treated group. Furthermore, treatment with DEX significantly reduced serum expression levels of IL-6, IL-8 and TNF-α and decreased expression levels of NF-κB, JAK2 and STAT3 in the lung tissue, as compared with the untreated SAP group. The present study demonstrated that DEX treatment was able to suppress ICAM-1 mRNA and protein expression in a rat model of SAP-ALI via the inhibition of IL-6 and TNF-α-induced JAK2/STAT3 activation; thus suggesting that DEX treatment may be considered a potential strategy in the treatment of patients with SAP-ALI.
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Affiliation(s)
- Xiao Han
- Department of General Surgery, The First Affiliated Hospital of Dalian Medical University, Dalian, Liaoning 116011, P.R. China
| | - Yuxi Wang
- Department of General Surgery, The Second Affiliated Hospital of Dalian Medical University, Dalian, Liaoning 116023, P.R. China
| | - Hailong Chen
- Department of General Surgery, The First Affiliated Hospital of Dalian Medical University, Dalian, Liaoning 116011, P.R. China
| | - Jingwen Zhang
- Department of General Surgery, The First Affiliated Hospital of Dalian Medical University, Dalian, Liaoning 116011, P.R. China
| | - Caiming Xu
- Department of General Surgery, The First Affiliated Hospital of Dalian Medical University, Dalian, Liaoning 116011, P.R. China
| | - Jian Li
- Department of General Surgery, The First Affiliated Hospital of Dalian Medical University, Dalian, Liaoning 116011, P.R. China
| | - Mingyue Li
- Department of General Surgery, The First Affiliated Hospital of Dalian Medical University, Dalian, Liaoning 116011, P.R. China
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13
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Hu YY, Zhou CH, Dou WH, Tang W, Hu CY, Hu DM, Feng H, Wang JZ, Qian MJ, Cheng GL, Wang SF. Improved autophagic flux is correlated with mTOR activation in the later recovery stage of experimental acute pancreatitis. Pancreatology 2015; 15:470-477. [PMID: 26164831 DOI: 10.1016/j.pan.2015.06.004] [Citation(s) in RCA: 11] [Impact Index Per Article: 1.1] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/24/2015] [Revised: 05/20/2015] [Accepted: 06/15/2015] [Indexed: 12/11/2022]
Abstract
BACKGROUND/OBJECTIVES Lysosomal/autophagic pathway plays important role in the early onset of acute pancreatitis (AP). However, its role in the later recovery phase of AP is unknown. This study aims to investigate the role of lysosomal/autophagic pathway in the self-limited program of AP and elucidate the underlying mechanisms. METHODS AP was induced in the rat by 3% sodium taurocholate injection in the pancreaticobiliary duct. Serum amylase activity assay, histological examination, and cell death detection were used to assess the time course of AP severity. Meanwhile, the expression of LC3-II, p62 and Lamp-2 was measured to evaluate the status of autophagic flux. S6RP phosphorylation was detected to determine the time course of mTOR activation. Rapamycin was administered to block mTOR activity. RESULTS AP developed in the rats to the most severe at 24 h but tended to self-restore at 36 and 48 h. The impairment of autophagic flux characterized by the accumulation of LC3-II and p62 and the depletion of Lamp-2 occurred at 24 h after AP induction followed by the restoration over the following 24 h. Furthermore, the phosphorylation of S6RP was increased at 36 and 48 h after AP induction despite the initial inhibition. Rapamycin treatment reduced the level of phospho-S6RP and inhibited the restoration of autophagic homeostasis and pancreatic tissue injury. CONCLUSIONS Activation of mTOR is correlated with the improvement of autophagic flux and pancreatic injury, suggesting that mTOR activation plays a potential protective role in the later recovery of AP.
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Affiliation(s)
- Yang-Yang Hu
- Department of Gastroenterology, The Second Affiliated Hospital of Soochow University, Soochow 215004, China
| | - Chun-Hua Zhou
- Department of Gastroenterology, The Second Affiliated Hospital of Soochow University, Soochow 215004, China
| | - Wen-Huan Dou
- Department of Gastroenterology, The Second Affiliated Hospital of Soochow University, Soochow 215004, China
| | - Wen Tang
- Department of Gastroenterology, The Second Affiliated Hospital of Soochow University, Soochow 215004, China
| | - Chuang-Ying Hu
- Department of Gastroenterology, The Second Affiliated Hospital of Soochow University, Soochow 215004, China
| | - Duan-Min Hu
- Department of Gastroenterology, The Second Affiliated Hospital of Soochow University, Soochow 215004, China
| | - Hui Feng
- Department of Gastroenterology, The Second Affiliated Hospital of Soochow University, Soochow 215004, China
| | - Jian-Zong Wang
- Department of Gastroenterology, The Second Affiliated Hospital of Soochow University, Soochow 215004, China
| | - Ming-Jie Qian
- Department of Gastroenterology, The Second Affiliated Hospital of Soochow University, Soochow 215004, China
| | - Gui-Lian Cheng
- Department of Gastroenterology, The Second Affiliated Hospital of Soochow University, Soochow 215004, China
| | - Shao-Feng Wang
- Department of Gastroenterology, The Second Affiliated Hospital of Soochow University, Soochow 215004, China.
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Qi B, Chen HL, Shang D, Dong Y, Zhang GX, Yu L. Effects of hypoxia-inducible factor-1α and matrix metalloproteinase-9 on alveolar-capillary barrier disruption and lung edema in rat models of severe acute pancreatitis-associated lung injury. Exp Ther Med 2014; 8:899-906. [PMID: 25120621 PMCID: PMC4113543 DOI: 10.3892/etm.2014.1810] [Citation(s) in RCA: 8] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/19/2013] [Accepted: 06/03/2014] [Indexed: 02/06/2023] Open
Abstract
The aim of this study was to investigate the effects of hypoxia-inducible factor-1α (HIF-1α) and matrix metalloproteinase-9 (MMP-9) on alveolar-capillary barrier disruption and lung edema in rat models of severe acute pancreatitis-associated lung injury (PALI). A total of 40 male Sprague-Dawley rats were randomly divided into a sham surgery group (n=10) and three PALI groups, in which acute pancreatitis was induced by the retrograde infusion of 5% sodium taurocholate (1 ml/kg). The PALI groups were as follows: i) Untreated PALI group (n=10); ii) 2-methoxyestradiol (2ME2) group (5 mg/kg body mass; n=10); and iii) 2ME2 group (15 mg/kg body mass; n=10). In the two 2ME2 groups, the HIF-1α inhibitor 2ME2 was administered intraperitoneally 1 h after the induction of AP. The severity of the pancreatitis was evaluated by the serum amylase levels and pathology. The severity of the lung injury was evaluated by the wet/dry ratio, blood gas analysis and pathology. The alveolar-capillary barrier disruption was assessed by Evans blue dye extravasation. The protein and mRNA expression levels of HIF-1α and MMP-9 were studied using enzyme-linked immunosorbent assays (ELISAs), western blot analysis and reverse transcription-polymerase chain reaction. The active tumor necrosis factor-α levels were measured using an ELISA. The HIF-1α inhibitor 2ME2 attenuated the severity of the pancreatitis and PALI, while the lung edema and alveolar-capillary barrier disruption were significantly ameliorated compared with those in the untreated PALI group. Administration of the higher dose of 2ME2 significantly suppressed the protein expression of MMP-9 in the lung tissues. The results indicate that HIF-1α has a major function in alveolar-capillary barrier disruption and lung edema in PALI via a molecular pathway cascade involving MMP-9. Inhibition of HIF-1α by 2ME2 attenuates alveolar-capillary barrier disruption and lung edema. Pharmacological blockade of this pathway in patients with PALI may provide a novel therapeutic strategy.
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Affiliation(s)
- Bing Qi
- Dalian Medical University, Dalian, Liaoning 116044, P.R. China ; Department of Acute Abdominal Surgery, First Affiliated Hospital of Dalian Medical University, Dalian, Liaoning 116011, P.R. China
| | - Hai-Long Chen
- Department of Acute Abdominal Surgery, First Affiliated Hospital of Dalian Medical University, Dalian, Liaoning 116011, P.R. China
| | - Dong Shang
- Department of Acute Abdominal Surgery, First Affiliated Hospital of Dalian Medical University, Dalian, Liaoning 116011, P.R. China
| | - Ying Dong
- Department of Gastroenterology and Hepatology, The Second Affiliated Hospital of Dalian Medical University, Dalian, Liaoning 116021, P.R. China
| | - Gui-Xin Zhang
- Department of Acute Abdominal Surgery, First Affiliated Hospital of Dalian Medical University, Dalian, Liaoning 116011, P.R. China
| | - Lei Yu
- Dalian Medical University, Dalian, Liaoning 116044, P.R. China
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15
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LIU ZHIYONG, LIU JIAO, ZHAO KAILIANG, WANG LIKUN, SHI QIAO, ZUO TENG, LIU TIANYI, ZHAO LIANG, WANG WEIXING. Protective effects of daphnetin on sodium taurocholate-induced severe acute pancreatitis in rats. Mol Med Rep 2014; 9:1709-14. [DOI: 10.3892/mmr.2014.1995] [Citation(s) in RCA: 10] [Impact Index Per Article: 0.9] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/17/2013] [Accepted: 02/11/2014] [Indexed: 11/05/2022] Open
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16
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Luan ZG, Zhang J, Yin XH, Ma XC, Guo RX. Ethyl pyruvate significantly inhibits tumour necrosis factor-α, interleukin-1β and high mobility group box 1 releasing and attenuates sodium taurocholate-induced severe acute pancreatitis associated with acute lung injury. Clin Exp Immunol 2013; 172:417-26. [PMID: 23600830 DOI: 10.1111/cei.12062] [Citation(s) in RCA: 37] [Impact Index Per Article: 3.1] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 01/02/2013] [Indexed: 12/16/2022] Open
Abstract
In this study, we examined the effect of ethyl pyruvate (EP) on pulmonary inflammation in rats with severe pancreatitis-associated acute lung injury (ALI). Severe acute pancreatitis (SAP) was induced in rats by the retrograde injection of 5% sodium taurocholate into the pancreatic duct. Rats were randomly divided into the following experimental groups: control group, SAP group and EP-treated group. The tissue specimens were harvested for morphological studies, Streptavidin-peroxidase immunohistochemistry examination. Pancreatic or lung tissue oedema was evaluated by tissue water content. Serum amylase and lung tissue malondialdehyde (MDA) and myeloperoxidase (MPO) were measured. Meanwhile, the nuclear factor-κB (NF-κB) activation, tumour necrosis factor-α (TNF-α), interleukin-1β (IL-1β) levels and HMGB1 protein expression levels in the lung were studied. In the present study, we demonstrated that treatment with EP after SAP was associated with a reduction in the severity of SAP and lung injury. Treatment with EP significantly decreased the expression of TNF-α, IL-1β, HMGB1 and ameliorated MDA concentration, MPO activity in the lung in SAP rats. Compared to SAP group, administration of EP prevented pancreatitis-induced increases in nuclear translocation of NF-κB in the lung. Similarly, treatment with EP significantly decreased the accumulation of neutrophils and markedly reduced the enhanced lung permeability. In conclusion, these results demonstrate that EP might play a therapeutic role in pulmonary inflammation in this SAP model.
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Affiliation(s)
- Z-G Luan
- Department of Intensive Care Unit, The First Hospital, China Medical University, Shenyang, China
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17
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Luan ZG, Ma XC, Zhang H, Zhang C, Guo RX. Protective effect of ethyl pyruvate on pancreas injury in rats with severe acute pancreatitis. J Surg Res 2013; 181:76-84. [DOI: 10.1016/j.jss.2012.05.066] [Citation(s) in RCA: 21] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/25/2012] [Revised: 04/20/2012] [Accepted: 05/22/2012] [Indexed: 12/22/2022]
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18
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Luan ZG, Zhang XJ, Yin XH, Ma XC, Zhang H, Zhang C, Guo RX. Downregulation of HMGB1 protects against the development of acute lung injury after severe acute pancreatitis. Immunobiology 2013; 218:1261-70. [PMID: 23706497 DOI: 10.1016/j.imbio.2013.04.013] [Citation(s) in RCA: 38] [Impact Index Per Article: 3.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/03/2012] [Accepted: 04/21/2013] [Indexed: 01/02/2023]
Abstract
OBJECTIVE To examine the effect of downregulation of high mobility group box 1 (HMGB1) on severe acute pancreatitis (SAP) associated with acute lung injury (ALI), and its subsequent effect on disease severity. METHODS Wistar rats were given an IV injection of pRNA-U6.1/Neo-HMGB1, pRNA-U6.1/Neo-vector or saline before induction of SAP. Then, SAP was induced in rats by the retrograde injection of 5% sodium taurocholate into the pancreatic duct. The control group received only a sham operation. Lung and pancreas samples were harvested after induction of SAP. The protein levels of HMGB1, matrix metalloproteinase-9 (MMP-9) and intercellular adhesion molecule-1 (ICAM-1) in lung tissue were investigated. The severity of pancreatic injury was determined by a histological score of pancreatic injury, serum amylase, and pancreatic water content. The lung injury was evaluated by measurement of pulmonary microvascular permeability, lung myeloperoxidase activity and malondialdehyde levels. RESULTS The results found that in pRNA-U6.1/Neo-HMGB1 treated rats, serum tumor necrosis factor-α (TNF-α) and interleukin-1β (IL-1β) levels were decreased and the severity of pancreatic tissue injury was less compared with either untreated SAP or pRNA-U6.1/Neo-vector treated rats (P<0.05). The administration of pRNA-U6.1/Neo-HMGB1 in SAP-induced rats downregulated the DNA binding activity of the nuclear factor-kappa B (NF-κB) and the expressions of MMP-9 and ICAM-1 in lung. Thus, compared with the untreated SAP rats, the inflammatory response and the severity of ALI decreased (P<0.05). CONCLUSIONS These results demonstrate that HMGB1 could augment Inflammation by inducing nuclear translocation of NF-κB, thus aggratating the severity of SAP associated with ALI.
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Affiliation(s)
- Zheng-Gang Luan
- Department of Intensive Care Unit, The First Hospital, China Medical University, Shenyang, China.
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19
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Huang L, Wang MH, Cheng ZY, Xue P, Jin T, Yang XN, Xia Q. Effects of Chai-Qin-Cheng-Qi decoction () on acute pancreatitis-associated lung injury in mice with acute necrotizing pancreatitis. Chin J Integr Med 2012. [PMID: 23001459 DOI: 10.1007/s11655-012-1207-7] [Citation(s) in RCA: 6] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/06/2011] [Indexed: 02/05/2023]
Abstract
OBJECTIVE: To investigate the effects of Chai-Qin-Cheng-Qi Decoction (, CQCQD) on acute pancreatitis-associated lung injury in mice with acute necrotizing pancreatitis (ANP). METHODS: Thirty healthy mice were randomly divided into three groups: an ANP group (ANP+placebo, n=10); a treatment group (ANP+CQCQD, n=10); and a control group (normal mice+placebo, n=10). ANP was induced by intraperitoneal injection with 8% L-arginine (4 μg/kg), and the control group was injected with normal saline. The treatment group received CQCQD (20 mL/kg), and the ANP and control groups received placebo (sucrose and starch) intragastrically at 2 h intervals. After the third intragastric administration, blood, pancreatic tissues and right lung tissues were collected for measurement of serum interleukin-6 (IL-6) and interleukin-10 (IL-10) by enzyme-linked immunosorbent assay, and the expression of heat shock protein 70 (HSP70) in lung tissue was determined by Western blot analysis. Pathological changes of pancreatic tissue and lung tissue were examined. RESULTS: Serum IL-6 was significantly higher in the ANP group compared with the control and the treatment groups (1589.63±377.28 vs. 927.46±210.42 pg/mL, P<0.05, and 1589.63±377.28 vs. 1107.73±351.62 pg/mL, P<0.05, respectively). The IL-10 concentration was significantly lower in the ANP group compared with the treatment group (920.64±101.68 vs. 1177.84±201.72 pg/mL, P<0.05), but no signififi cant difference was found between the ANP and control groups and between the treatment and control groups. The expression level of HSP70 in the ANP and control groups was signififi cantly lower than in the treatment group (0.93±0.03 vs. 1.42±0.21, P<0.01, and 0.81±0.09 vs. 1.42±0.21, P<0.01, respectively). There was no signififi cant difference in HSP70 levels between the ANP and control groups. Histological scores of pancreatic and lung tissue were significantly decreased in the treatment group compared with the ANP groups (4.50±0.54 vs. 6.20±1.65, P<0.05, and 3.00±0.63 vs. 3.87±0.83, P<0.05, respectively). CONCLUSIONS: The incidence of acute pancreatitisassociated lung injury in ANP mice correlates positively with serum IL-6 concentration. CQCQD may inhibit IL-6 induction and increase IL-10 concentration and HSP70 expression, effectively reducing lung injury.
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Affiliation(s)
- Lei Huang
- Department of Integrated Traditional Chinese and Western Medicine, West China Hospital, Sichuan University, Chengdu, 610041, China
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Barreto SG, Saccone GTP. Pancreatic nociception--revisiting the physiology and pathophysiology. Pancreatology 2012; 12:104-112. [PMID: 22487519 DOI: 10.1016/j.pan.2012.02.010] [Citation(s) in RCA: 30] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/02/2011] [Revised: 01/23/2012] [Accepted: 02/19/2012] [Indexed: 12/11/2022]
Abstract
BACKGROUND Pain management of many pancreatic diseases remains a major clinical concern. This problem reflects our poor understanding of pain signaling from the pancreas. OBJECTIVES This review provides an overview of our current knowledge, with emphasis on current pain management strategies and recent experimental findings. METHODS A systematic search of the scientific literature was carried out using EMBASE, PubMed/MEDLINE, and the Cochrane Central Register of Controlled Trials for the years 1965-2011 to obtain access to all publications, especially randomized controlled trials, systematic reviews, and meta-analyses exploring pain and its management in disease states such as acute pancreatitis (AP), chronic pancreatitis (CP) and pancreatic cancer (PC). RESULTS Over the last decade, numerous molecular mediators such as nerve growth factor and the transient receptor potential (TRP) cation channel family have been implicated in afferent nerve signaling. More recent animal studies have indicated the location of the receptive fields for the afferent nerves in the pancreas and shown that these are activated by agents including cholecystokinin octapeptide, 5-hydroxytryptamine and bradykinin. Studies with PC specimens have shown that neuro-immune interactions occur and numerous agents including TRP cation channel V1, artemin and fractalkine have been implicated. Experimental studies in the clinical setting have demonstrated impairment of inhibitory pain modulation from supraspinal structures and implicated neuropathic pain mechanisms. CONCLUSIONS Our knowledge in this area remains incomplete. Characterization of the mediators and receptors/ion channels on the sensory nerve terminals are required in order to facilitate the development of new pharmaceutical treatments for AP and CP.
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Affiliation(s)
- Savio G Barreto
- Department of Surgery, Modbury Hospital, South Australia, Australia
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Kan SH, Huang F, Tang J, Gao Y, Yu CL. Role of intrapulmonary expression of inducible nitric oxide synthase gene and nuclear factor kappaB activation in severe pancreatitis-associated lung injury. Inflammation 2010; 33:287-94. [PMID: 20143141 DOI: 10.1007/s10753-010-9184-5] [Citation(s) in RCA: 17] [Impact Index Per Article: 1.1] [Reference Citation Analysis] [Abstract] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/29/2022]
Abstract
The aim of this study is to explore the relationship of intrapulmonary activation of nuclear factor-kappaB (NF-kappaB) and the expression of inducible nitric oxide synthase (iNOS) mRNA with pulmonary injury in rats with severe acute pancreatitis (SAP). Fifty-four Sprague Dawley rats were randomly divided into three groups: sham operation (control) group (n = 18), SAP group (n = 18), and pyrrolindine dithiocarbamate (PDTC) pretreated group (n = 18). A SAP model was induced by retrograde injected 5% sodium taurocholate into the bile-pancreatic duct (1 ml/kg). PDTC-pretreated SAP rats were given 100 mg/kg body weight PDTC intraperitoneally before pancreatitis was induced. Six rats from each group were sacrificed at 3, 6, and 12 h after modeling. Activation of NF-kappaB in pulmonary tissues and pancreas tissues was detected by immunohistochemical methods. Intrapulmonary expression of iNOSmRNA was assayed by fluorogenic quantitative reverse transcription polymerize chain reaction. The expression of NF-kappaB in the SAP group in pulmonary tissues was enhanced significantly at any measure point compared with control group (58.4 +/- 10.8 vs. 3.8 +/- 1.8, 119.8 +/- 17.8 vs. 5.2 +/- 2.4, and 90.2 +/- 14.4 vs. 4.7 +/- 2.2, P < 0.01). But the expressions of NF-kappaB in the PDTC group were significantly lower than those in SAP group (54.3 +/- 9.6 vs. 58.4 +/- 10.8, 93.9 +/- 7.9 vs. 119.8 +/- 17.8, and 82.2 +/- 13.3 vs. 90.2 +/- 14.4, P < 0.05). The number of positive cells in SAP group and PDTC group reached its peak at 6 h and then declined. The expression of iNOSmRNA in PDTC groups was significantly weaker than that in SAP group (2.0 +/- 0.8 vs. 2.2 +/- 1.9, 2.4 +/- 1.2 vs. 4.6 +/- 1.8, and 1.5 +/- 0.8 vs. 3.2 +/- 1.5, P < 0.05). The activation of NF-kappaB may be involved in the SAP lung injury through regulating the expression of iNOSmRNA. PDTC might inhibit the activation of NF-kappaB and then reduce the expression of iNOSmRNA and effectively alleviate the severity of lung injury.
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Affiliation(s)
- Shi-hai Kan
- Department of Human Anatomy, Binzhou Medical University, No. 346 Guanhai Road, Yantai, 264003, China
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22
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Szentkereszty Z, Kotán R, Damjanovich L, Sápy P. Surgical treatment of acute pancreatitis today. Orv Hetil 2010; 151:1697-701. [DOI: 10.1556/oh.2010.28956] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/16/2022]
Abstract
Az enyhe akut pancreatitis kezelése alapvetően konzervatív, míg súlyos esetekben a sebészi kezelésnek jelentős szerepe van.
Módszer:
A szerzők az utóbbi 10 évben megjelent, a műtét kérdéseit taglaló közlemények alapján elemzik a sebészi kezelés indikációit, időzítését és a műtét technikai kérdéseit.
Eredmények/következtetések:
A steril pancreasnecrosis csak ritkán, a szeptikus necrosis azonban műtéti indikációt képez, ha a konzervatív kezelés eredménytelen. A terápiarezisztens sokszervi elégtelenség, a súlyos hasi kompartmentszindróma és egyéb sebészi szövődmény, mint a vérzés, perforáció is műtéti beavatkozást tesz szükségessé. Pancreatitist okozó epekövesség talaján kialakult cholestasis esetén sürgős endoszkópos sphincterotomia és később cholecystectomia javasolt. Pancreasnecrosis esetén a műtét ideális időpontja a betegség kezdetétől számított 21. nap utánra tehető, mivel a „korai” műtétek szövődmény- és halálozási aránya magas. Fontos a gondos necrectomia, amelynek a retrocolicus és retroduodenalis terekre is ki kell terjednie. A nyitott has kezelésének több a szövődménye, ezért csak válogatott esetekben javasolják. A műtétet posztoperatív bursa omentalis lavage-zsal érdemes kiegészíteni. Orv. Hetil., 2010,
41,
1697–1701.
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Affiliation(s)
- Zsolt Szentkereszty
- 1 Debreceni Egyetem, Orvos- és Egészségtudományi Centrum, Általános Orvostudományi Kar Sebészeti Intézet Debrecen Móricz Zs. krt. 22. 4032
| | - Róbert Kotán
- 1 Debreceni Egyetem, Orvos- és Egészségtudományi Centrum, Általános Orvostudományi Kar Sebészeti Intézet Debrecen Móricz Zs. krt. 22. 4032
| | - László Damjanovich
- 1 Debreceni Egyetem, Orvos- és Egészségtudományi Centrum, Általános Orvostudományi Kar Sebészeti Intézet Debrecen Móricz Zs. krt. 22. 4032
| | - Péter Sápy
- 1 Debreceni Egyetem, Orvos- és Egészségtudományi Centrum, Általános Orvostudományi Kar Sebészeti Intézet Debrecen Móricz Zs. krt. 22. 4032
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Kotán R, Pósán J, Sápy P, Damjanovich L, Szentkereszty Z. Analysis of clinical course of severe acute biliary and non biliary pancreatitis: a comparative study. Orv Hetil 2010; 151:265-8. [DOI: 10.1556/oh.2010.28760] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/17/2022]
Abstract
Az akut pancreatitis viszonylag gyakran előforduló betegség. Évenként 5 és 80 közötti új megbetegedés esik 100 000 lakosra, és ez a szám az utóbbi években növekedést mutat a különböző tanulmányok szerint. A két fő etiológiai faktor az alkohol és az epekövesség. Az alkoholos eredetű hasnyálmirigy-gyulladás a férfiak körében, a biliaris pancreatitis a nők körében gyakoribb.
Célkitűzés:
a szerzők súlyos akut pancreatitis miatt kezelt betegek adatait elemezik, arra keresve a választ, hogy milyen eltérő sajátságokkal rendelkezik a biliaris és a más etiológiájú pancreatitis.
Betegek és módszer:
a szerzők 139, súlyos akut pancreatitisben szenvedő beteget kezeltek, akiket etiológiai szempontból két csoportra osztottak: az epeköves (A csoport) és a nem epeköves (B csoport) talajon kialakult súlyos hasnyálmirigy-gyulladásban szenvedők csoportjára. Összehasonlították a két csoport nem és kor szerinti sajátosságait, a mortalitási és a morbiditási adatokat, a műtétek és az ápolási napok számát. A statisztikai analízishez a χ
2
-tesztet alkalmazták.
Eredmények:
a szövődmények az epés (A) csoportban súlyosabbak voltak, mint a nem epés (B) csoportban. A halálozás az A csoportban 17,8%-nak, a B csoportban 13,8%-nak bizonyult, míg az átlagos 15,1% volt. A mortalitás a nők körében az A csoportban szignifikánsan magasabb volt.
Következtetések:
a súlyos epés akut pancreatitisben szenvedő nőbetegek esetében súlyosabb lefolyással, magasabb halálozási aránnyal kell számolnunk. A szerzők az idős, egyéb betegségekkel terhelt epeköves nőknél még a szövődmények jelentkezése előtt elektív cholecystectomiát javasolnak.
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Affiliation(s)
- Róbert Kotán
- 1 Debreceni Egyetem, Orvos- és Egészségtudományi Centrum, Általános Orvostudományi Kar Sebészeti Intézet Debrecen Nagyerdei krt. 98. 4028
| | - János Pósán
- 1 Debreceni Egyetem, Orvos- és Egészségtudományi Centrum, Általános Orvostudományi Kar Sebészeti Intézet Debrecen Nagyerdei krt. 98. 4028
| | - Péter Sápy
- 1 Debreceni Egyetem, Orvos- és Egészségtudományi Centrum, Általános Orvostudományi Kar Sebészeti Intézet Debrecen Nagyerdei krt. 98. 4028
| | - László Damjanovich
- 1 Debreceni Egyetem, Orvos- és Egészségtudományi Centrum, Általános Orvostudományi Kar Sebészeti Intézet Debrecen Nagyerdei krt. 98. 4028
| | - Zsolt Szentkereszty
- 1 Debreceni Egyetem, Orvos- és Egészségtudományi Centrum, Általános Orvostudományi Kar Sebészeti Intézet Debrecen Nagyerdei krt. 98. 4028
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Abstract
OBJECTIVES Systemic inflammatory mediators, including the protein high-mobility group box 1 (HMGB1), play an important role in the development of acute pancreatitis. Anticoagulants, such as antithrombin III (AT III), inhibit inflammation resulting from various causes, but their mechanism of action is not well understood. Because acute pancreatitis is a severe inflammatory disease, we hypothesized that AT III would inhibit inflammation and prevent cerulein-induced acute pancreatitis. METHODS Experimental animals received or were saline injected with a bolus of 250 IU/kg of AT III followed by intraperitoneal injections of 50 mg/kg of cerulein. Levels of cytokines (interleukin 6 and tumor necrosis factor alpha), nitric oxide (NO), and HMGB1 were measured in serum and pancreatic tissue at regular intervals for 12 hours after the cerulein injection. RESULTS Pancreas histopathology and wet-dry ratio significantly improved in the AT III-injected (250 IU/kg) animals compared with the saline-injected rats. Serum and pancreas HMGB1 levels decreased over time in AT III-treated animals. Antithrombin III also decreased cytokine, NO, and HMGB1 levels during cerulein-induced inflammation. As a result, AT III ameliorated the pathologic pancreas in the rat model of cerulein-induced acute pancreatitis. CONCLUSIONS Antithrombin III treatment inhibited the secretion of cytokines, NO, and HMGB1 and prevented cerulein-induced acute pancreatitis in the rat model.
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25
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Lu XS, Qiu F, Li JQ, Fan QQ, Zhou RG, Ai YH, Zhang KC, Li YX. Low molecular weight heparin in the treatment of severe acute pancreatitis: a multiple centre prospective clinical study. Asian J Surg 2009; 32:89-94. [PMID: 19423455 DOI: 10.1016/s1015-9584(09)60017-8] [Citation(s) in RCA: 19] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Abstract] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/16/2023] Open
Abstract
OBJECTIVE To study the effect of low molecular weight heparin (LMWH) in the treatment of severe acute pancreatitis (SAP). METHODS A total of 265 SAP patients were randomly divided into two groups: firstly, the conventional treatment group (C group, n = 130; and secondly the conventional treatment plus the LMWH treatment group (LT group, n = 135). The clinical parameters, laboratory parameters and computed tomography (CT) score of pancreatic necrosis (CTSPN) in the two groups were compared. RESULTS On admission, all the clinical parameters, laboratory parameters and CTSPN in the two groups were not significantly different (p > 0.05). However, after treatment, in LT group, the clinical presentation improvement rate and laboratory parameters improvement were significantly higher than those in C group (p < 0.05-0.01), and the acute physiology and chronic health evaluation (APACHE) II score, complication rate, mortality and mean hospital stay in LT group were obviously lower than those in C group (p < 0.05-0.01). The CT score in LT group was much lower than that in C group (p < 0.05). Two weeks after treatment FBI decreased obviously in C group, but not in LT group, and no haemorrhagic complications occurred. CONCLUSIONS LMWH can enhance the effect of conventional treatment for SAP, and can markedly decrease the mortality of SAP. LMWH is a simple, safe, economic and effective method for treatment of SAP. It is can be used in every hospital.
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Affiliation(s)
- Xin-Sheng Lu
- Department of General Surgery, Xiangya Hospital, Central South University, Changsha, China.
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26
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27
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Babu BI, Siriwardena AK. Current status of minimally invasive necrosectomy for post-inflammatory pancreatic necrosis. HPB (Oxford) 2009; 11:96-102. [PMID: 19590631 PMCID: PMC2697887 DOI: 10.1111/j.1477-2574.2009.00041.x] [Citation(s) in RCA: 22] [Impact Index Per Article: 1.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/31/2008] [Accepted: 01/27/2009] [Indexed: 12/12/2022]
Abstract
OBJECTIVE This paper reviews current knowledge on minimally invasive pancreatic necrosectomy. BACKGROUND Blunt (non-anatomical) debridement of necrotic tissue at laparotomy is the standard method of treatment of infected post-inflammatory pancreatic necrosis. Recognition that laparotomy may add to morbidity by increasing postoperative organ dysfunction has led to the development of alternative, minimally invasive methods for debridement. This study reports the status of minimally invasive necrosectomy by different approaches. METHODS Searches of MEDLINE and EMBASE for the period 1996-2008 were undertaken. Only studies with original data and information on outcome were included. This produced a final population of 28 studies reporting on 344 patients undergoing minimally invasive necrosectomy, with a median (range) number of patients per study of nine (1-53). Procedures were categorized as retroperitoneal, endoscopic or laparoscopic. RESULTS A total of 141 patients underwent retroperitoneal necrosectomy, of whom 58 (41%) had complications and 18 (13%) required laparotomy. There were 22 (16%) deaths. Overall, 157 patients underwent endoscopic necrosectomy; major complications were reported in 31 (20%) and death in seven (5%). Laparoscopic necrosectomy was carried out in 46 patients, of whom five (11%) required laparotomy and three (7%) died. CONCLUSIONS Minimally invasive necrosectomy is technically feasible and a body of evidence now suggests that acceptable outcomes can be achieved. There are no comparisons of results, either with open surgery or among different minimally invasive techniques.
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28
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Chen C, Xu S, Wang WX, Ding YM, Yu KH, Wang B, Chen XY. Rosiglitazone attenuates the severity of sodium taurocholate-induced acute pancreatitis and pancreatitis-associated lung injury. Arch Med Res 2009; 40:79-88. [PMID: 19237016 DOI: 10.1016/j.arcmed.2008.11.004] [Citation(s) in RCA: 32] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/29/2008] [Accepted: 11/10/2008] [Indexed: 01/22/2023]
Abstract
BACKGROUND AND AIMS In addition to the effect of regulating adipocyte differentiation and insulin sensitivity, peroxisome proliferator activated receptor-gamma (PPAR-gamma) ligands also exhibit anti-inflammatory effect. However, the mechanisms concerning how PPAR-gamma ligands affect acute pancreatitis and pancreatitis-associated lung injury have not been fully elucidated. This study investigated the effect of rosiglitazone, a PPAR-gamma ligand, on acute pancreatitis and pancreatitis-associated lung injury in the rat pancreatitis model induced by sodium taurocholate. METHODS Acute pancreatitis was induced by retrograde infusion of 5% sodium taurocholate (1 mL/kg) into the bile-pancreatic duct. Rosiglitazone (6 mg/kg) was administered via the femoral vein 30 min prior to the infusion of sodium taurocholate. The severity of pancreatitis was evaluated by serum amylase level, myeloperoxidase activity, and pathology. Pancreatitis-associated lung injury was evaluated by myeloperoxidase activity, the magnitude of pulmonary edema and pathology. Intercellular adhesion molecule-1 (ICAM-1) and tumor necrosis factor-alpha mRNA expression were studied using reverse transcriptase polymerase chain reaction. ICAM-1 protein expression was studied using Western blot analysis. RESULTS Prophylactic administration of rosiglitazone attenuated (1) serum amylase level; (2) myeloperoxidase activity of pancreatic and pulmonary tissue; (3) expression of tumor necrosis factor-alpha and ICAM-1 in pancreas and lung; (4) pancreas and lung pathological damage. CONCLUSIONS Our study demonstrated that rosiglitazone exerts a protective effect against sodium taurocholate-induced pancreatic and pulmonary injury.
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Affiliation(s)
- Chen Chen
- Department of General Surgery, Renmin Hospital of Wuhan University, PR China
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29
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Babu BI, Siriwardena AK. Practical strategies for case selection in minimally invasive necrosectomy. Pancreatology 2008; 9:9-12. [PMID: 19077450 DOI: 10.1159/000178861] [Citation(s) in RCA: 6] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/11/2022]
Abstract
BACKGROUND Minimally invasive necrosectomy is an umbrella term encapsulating the retroperitoneal, endoscopic and laparoscopic approaches. However, current evidence is unclear in terms of which approach to select in any particular setting. METHODS/RESULTS This leading article provides a pragmatic guide to approach selection in treating pancreatic necrosis with particular reference to the use of minimally invasive approaches. Current evidence in relation to timing of surgery, use of fine-needle aspiration and detailed imaging by magnetic resonance scanning is incorporated into a modern treatment algorithm. CONCLUSION The era of minimally invasive necrosectomy has arrived. In the absence of randomised trial evidence, the keys to contemporary management of pancreatic necrosis are good multidisciplinary care, adequate high-quality imaging and careful consideration of all available treatment options including traditional open approaches.
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30
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Schrover IM, Weusten BLAM, Besselink MGH, Bollen TL, van Ramshorst B, Timmer R. EUS-guided endoscopic transgastric necrosectomy in patients with infected necrosis in acute pancreatitis. Pancreatology 2008; 8:271-6. [PMID: 18497540 DOI: 10.1159/000134275] [Citation(s) in RCA: 48] [Impact Index Per Article: 2.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/11/2007] [Accepted: 01/15/2008] [Indexed: 12/11/2022]
Abstract
BACKGROUND Infected pancreatic and peripancreatic necrosis in acute pancreatitis is potentially lethal, with mortality rates up to 35%. Therefore, there is growing interest in minimally invasive treatment options, such as (EUS-guided) endoscopic transgastric necrosectomy. METHODS Retrospective cohort study on EUS-guided endoscopic transgastric necrosectomy in patients with infected necrosis in acute pancreatitis. RESULTS 8 patients (age 38-75, mean 50 years) with documented infected peripancreatic or pancreatic necrosis were included. Median time to first intervention was 33 days (range 17-62) after onset of symptoms. At the time of first intervention 2 patients had organ failure. All patients were managed on the patient ward. Initial endoscopic drainage was successful in all patients, a median of 4 (range 2-6) subsequent endoscopic necrosectomies were needed to remove all necrotic tissue. Two patients needed additional surgical intervention because of pneumoperitoneum (n = 1) and insufficient endoscopic drainage (n = 1). Six patients recovered, with 1 mild relapse during follow-up (median 12, range 8-60 months). One patient died. CONCLUSION EUS-guided endoscopic transgastric necrosectomy of infected necrosis in acute pancreatitis appears to be a feasible and relatively safe treatment option in patients who are not critically ill. Further randomized comparison with the current 'gold standard' is warranted to determine the place of this treatment modality.
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Affiliation(s)
- Ilse M Schrover
- Department of Gastroenterology, St Antonius Hospital, Nieuwegein, The Netherlands
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31
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Sempere L, Martinez J, de Madaria E, Lozano B, Sanchez-Paya J, Jover R, Perez-Mateo M. Obesity and fat distribution imply a greater systemic inflammatory response and a worse prognosis in acute pancreatitis. Pancreatology 2008; 8:257-64. [PMID: 18497538 DOI: 10.1159/000134273] [Citation(s) in RCA: 73] [Impact Index Per Article: 4.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/26/2007] [Accepted: 12/12/2007] [Indexed: 12/11/2022]
Abstract
BACKGROUND AND AIMS Acute pancreatitis (AP) is a systemic inflammatory disease. It is already known that obesity and central fat distribution are related to the severity of AP, but the intimate mechanism of this relationship remains unknown. Obesity and central fat distribution are associated with an inflammatory state that could amplify the systemic inflammatory response (SIR) in AP. The aim of this study was to investigate how obesity and body fat distribution correlate with the SIR and severity of AP. METHODS 85 consecutive patients with AP were studied. Body mass index, body fat distribution and previous comorbidity were obtained at admission. The SIR was assessed by the serum levels of interleukin (IL)-1beta, IL-1ra, IL-6, IL-8, IL-10, IL-12p70, tumor necrosis factor-alpha (TNF-alpha) and C-reactive protein. Serum concentrations of the previously mentioned cytokines were also determined in a control group of 40 healthy volunteers. RESULTS 63 patients (74%) had mild AP and 22 patients (26%) had severe AP. All the cytokines except IL-12p70 and TNF-alpha were increased in the AP group in comparison with the control group. The SIR was significantly increased in patients with severe AP. Obese patients and patients with central fat distribution had significantly more comorbidity, a higher proportion of severe AP and more intense SIR. Patients with comorbidity had a significantly higher proportion of severe AP and more SIR. CONCLUSION The severity of AP in obese patients and in patients with central fat distribution seems to be related to the comorbidity and the amplification of SIR. and IAP.
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Affiliation(s)
- Laura Sempere
- Department of Gastroenterology, Hospital General Universitario de Alicante, Alicante, Spain
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Dabrowski A, Osada J, Dabrowska MI, Wereszczynska-Siemiatkowska U. Monocyte subsets and natural killer cells in acute pancreatitis. Pancreatology 2008; 8:126-134. [PMID: 18382098 DOI: 10.1159/000123605] [Citation(s) in RCA: 30] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/15/2007] [Accepted: 09/02/2007] [Indexed: 12/11/2022]
Abstract
BACKGROUND Alteration of the immune system is one of the major mechanisms responsible for complications in severe acute pancreatitis (AP). The aim of our study was to provide a complex evaluation of peripheral blood monocyte subsets, natural killer cells (NK cells) and cytotoxic T lymphocytes in patients with different severity forms of AP. METHODS 20 patients with mild AP and 15 with severe AP (S-AP) were included in our study. Peripheral blood mononuclear cells were studied on days 1-3, 5, 10 and 30, by means of flow cytometry. RESULTS In peripheral blood of patients with pancreatitis, we found a marked increase in total monocyte count. In S-AP, circulating monocytes were significantly activated, which was presumed from increased expression of HLA-DR, CD54, CD69 and CD25. Concurrent increased expression of CD95 (FasR) may indicate enhanced susceptibility of these cells to apoptosis. In patients with S-AP, a dramatic depletion of circulating NK cells (CD16/56 and CD3- CD8+) was found along with a reduction of circulating CD3+ CD8+ lymphocytes (cytotoxic T lymphocytes). CONCLUSION Our findings suggest profound disturbances of innate cellular immunity in patients with S-AP.
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Affiliation(s)
- Andrzej Dabrowski
- Department of Gastroenterology and Internal Medicine, Medical University of Bialystok, Bialystok, Poland.
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Mohamed SR, Siriwardena AK. Understanding the colonic complications of pancreatitis. Pancreatology 2008; 8:153-8. [PMID: 18382101 DOI: 10.1159/000123607] [Citation(s) in RCA: 52] [Impact Index Per Article: 3.1] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/17/2007] [Accepted: 11/06/2007] [Indexed: 12/11/2022]
Abstract
BACKGROUND Colonic necrosis, fistula and stricture are infrequent but potentially lethal complications of pancreatitis. As any individual unit will have only limited experience, this study aims to provide a structured, systematic appraisal of published experience to identify any consistent trends and disease patterns that may help in practical management. METHODS A computerized search of the MEDLINE databases for the period January 1950 through January 2006 yielded 43 articles. Pooled extracted data were examined for type of pancreatitis and colonic complications, method and time of diagnosis, treatment and outcome. RESULTS 43 reports provided pooled data on 97 patients. Colonic complications were more frequent in severe disease, occurring in 15%. The principal presentations were necrosis, fistula and stricture. All episodes of colonic necrosis complicated severe acute pancreatitis, were diagnosed operatively, presented at a median of 25 (1-55) days into the episode and were associated with a mortality of 54%. In contrast, stricture presented at a median of 50 (10-270) days. Surgical resection without anastomosis is the mainstay of management of necrosis. Trial of conservative management in a stable patient with a fistula may facilitate spontaneous closure. CONCLUSIONS This study highlights several consistent trends: preoperative diagnosis is difficult, colonic necrosis and fistula are rare complications principally of severe acute pancreatitis and they present either as ongoing abdominal sepsis or rectal bleeding. Surgical resection remains the mainstay of management. A high index of suspicion should be maintained in patients with severe acute pancreatitis, with ongoing sepsis and evidence of gastrointestinal blood loss.
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Affiliation(s)
- Samy R Mohamed
- Hepatobiliary Surgical Unit, Department of Surgery, Manchester Royal Infirmary, Manchester, UK
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Abstract
OBJECTIVES Infected necrotizing pancreatitis represents a serious and therapeutically challenging complication. Percutaneous drainage of infected pancreatic necrosis is often unsuccessful. Alternatively, open necrosectomies are associated with high morbidity. Recently, minimally invasive necrosectomy techniques have been tried with satisfying results; however, they frequently necessitate multiple sessions for definitive necrosectomy. To evaluate results of single large-port laparoscopic necrosectomy for proven infected necrotizing pancreatitis. METHODS Eight patients presenting proven infected pancreatic necrosis during course of acute pancreatitis and not responding to radiological drainage were prospectively offered minimally invasive necrosectomy. Laparoscopic necrosectomy were performed using a single large port placed along the drain tract directly into the infected necrosis. In all patients, drainage was placed during laparoscopic necrosectomy for continuous postoperative lavage. RESULTS No perioperative complications were recorded with a median operative time of 87 +/- 42 minutes. No blood transfusions were needed. No surgical postoperative morbidity and mortality were recorded. In all cases, except for one patient with multiple abscesses, only one session of necrosectomy was sufficient to completely clear the necrotic abscess. Laparoscopic necrosectomy was successful in all patients, and none required complementary surgical or radiological treatment. CONCLUSIONS Minimally invasive necrosectomy has been safe and highly efficient through single large-port laparoscopy for infected pancreatic necrosis in our series of patients. Minimally invasive necrosectomy is a promising technique for infected necrotizing pancreatitis and should be regarded as a valid therapeutic option for necrotizing pancreatitis.
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35
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Effect of low molecular weight heparin on pancreatic microcirculation in severe acute pancreatitis in a rodent model. Chin Med J (Engl) 2007. [DOI: 10.1097/00029330-200712020-00020] [Citation(s) in RCA: 17] [Impact Index Per Article: 0.9] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/30/2022] Open
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36
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Abstract
Acute pancreatitis represents a spectrum of disease, ranging from a mild, transitory illness to a severe, rapidly progressive hemorrhagic form, with massive necrosis and mortality rates of up to 24%. The reported incidence of acute pancreatitis diagnosed first at clinicopathologic autopsy ranges between 30% and 42%. To better describe outpatient fatalities due to acute pancreatitis that present as sudden, unexpected death, we retrospectively reviewed the autopsy files at the Institute of Legal Medicine, University of Hamburg, Germany, from 2000-2004. Individual cases were analyzed for sex, age, race, circumstances of death, social background of the deceased and previous medical history, seasonal occurrence of the disease, blood alcohol concentration at the time of death, body mass index, autopsy findings, histopathology, and etiology of acute pancreatitis. Among the 6178 autopsies carried out during the 5-year period evaluated, there were 27 cases of acute pancreatitis that presented as sudden, unexpected death. In all cases, the diagnosis was first made at autopsy. The male:female ratio was 1.7:1 and the mean age was 52 years (range, 30-91 years). Etiologies of acute pancreatitis included alcohol (n=19), gall stones (n=2), other identified etiologic factors (n=3), and idiopathic (n=3). Complications of acute pancreatitis included lung edema and/or acute respiratory distress syndrome, peritonitis, disseminated intravascular coagulation, and sepsis. At least 20 subjects (74%) had lived isolated, with no social contacts. Contrary to the clinical observations of a clear seasonal variation in the onset of acute pancreatitis, we found no correlation between death due to acute pancreatitis and a specific month or season. Many prior studies have suggested that the majority of deaths in severe acute pancreatitis occur in the late phase of the disease as a result of pancreatic sepsis. Conversely, in the present study, the majority of affected individuals died during the very early phase of the disease. While gallstones represent the main etiologic factor in most larger clinical series, biliary etiology seems to play only a minor role in outpatient deaths undergoing medicolegal autopsies. Data derived from medicolegal autopsy studies should be included in future population-based studies of acute pancreatitis.
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Affiliation(s)
- Michael Tsokos
- Institute of Legal Medicine and Forensic Sciences, Berlin, Germany.
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Mäkelä JT, Eila H, Kiviniemi H, Laurila J, Laitinen S. Computed tomography severity index and C-reactive protein values predicting mortality in emergency and intensive care units for patients with severe acute pancreatitis. Am J Surg 2007; 194:30-4. [PMID: 17560905 DOI: 10.1016/j.amjsurg.2006.08.089] [Citation(s) in RCA: 16] [Impact Index Per Article: 0.9] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/08/2006] [Revised: 08/16/2006] [Accepted: 08/16/2006] [Indexed: 01/23/2023]
Abstract
BACKGROUND Severe acute pancreatitis is a multisystem disease in which various local and systemic complications lead to high mortality. We retrospectively examined the clinical and biochemical factors that may influence the risk of mortality on admission to emergency and intensive care units (ICUs). METHODS Sixty-eight patients were admitted into our hospital for acute pancreatitis and treated in our ICU for computed tomography-proven severe acute pancreatitis during the years 1997 to 2004. The clinical, biochemical, and radiologic data were reviewed from the computerized database, radiologic films, and patient records. RESULTS The mortality rate during the ICU stay was 18% (12/68) and that during the whole period of hospitalization 26% (18/68). A C-reactive protein (CRP) value over 150 was the only independent predictor of mortality on admission into the emergency unit, whereas the computed tomography severity index and the elevated CRP value over 150 predicted significantly and independently mortality on admission into the ICU. Linear backward regression analysis showed that high CRP values and respiratory failure on ICU admission correlate with longer ICU stay. Men's ICU stays were longer than those of women. CONCLUSIONS A high computed tomography severity index and CRP values over 150 on admission into the ICU are valuable predictors of the mortality risk. High CRP, renal and respiratory failure, and male gender are associated with longer ICU stay.
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Affiliation(s)
- Jyrki T Mäkelä
- Department of Surgery, Division of Gastroenterology, PO Box 5000, 90014 University of Oulu, Oulu, Finland.
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Zhang XP, Zhang L, Chen LJ, Cheng QH, Wang JM, Cai W, Shen HP, Cai J. Influence of dexamethasone on inflammatory mediators and NF-kappaB expression in multiple organs of rats with severe acute pancreatitis. World J Gastroenterol 2007; 13:548-56. [PMID: 17278220 PMCID: PMC4065976 DOI: 10.3748/wjg.v13.i4.548] [Citation(s) in RCA: 49] [Impact Index Per Article: 2.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/23/2006] [Revised: 09/27/2006] [Accepted: 12/12/2006] [Indexed: 02/06/2023] Open
Abstract
AIM To observe the therapeutic effects of dexamethasone on rats with severe acute pancreatitis (SAP) and investigate the influences of dexamethasone on the inflammatory mediators and NF-kappaB expression in multiple organs of SAP rats as well as the mechanisms involved. METHODS Ninety Sprague-Dawley (SD) rats with SAP were randomly divided into the model group (n = 45) and dexamethasone treatment group (n = 45), and another 45 rats were selected for the sham operation group. All groups were randomly subdivided into the 3 h, 6 h and 12 h groups, each group containing 15 rats. The survival of all groups and pathological changes of multiple organs (liver, kidney and lung) were observed at different time points after the operation. The pathological score of multiple organs was carried out, followed by the determination of amylase, endotoxin and TNF-alpha contents in blood. The tissue microarray was used to detect the expression levels of NF-kappaB p65 protein in multiple organs. RESULTS There was no marked difference between the model group and treatment group in the survival rate. The amylase content of the treatment group was significantly lower compared to the model group at 12 h (P < 0.01, 7791.00 vs 9195.00). Moreover, the endotoxin and TNF-alpha levels of the treatment group were significantly lower than that of the model group at 6 h and 12 h (P < 0.01, 0.040 vs 0.055, 0.042 vs 0.059 and P < 0.05, 58.30 vs 77.54, 38.70 vs 67.30, respectively). Regarding the changes in liver NF-kappaB expression, the model group significantly exceeded the sham operation group at 3 h (P < 0.01, 1.00 vs 0.00), and the treatment group significantly exceeded the sham operation group at 12 h (P < 0.01, 1.00 vs 0.00), whereas no marked difference was observed between the model group and treatment group at all time points. The kidney NF-kappaB expression level in the treatment group significantly exceeded the model group (P < 0.05, 2.00 vs 0.00) and the sham operation group (P < 0.01, 2.00 vs 0.00) at 12 h. No NF-kappaB expression in the lung was found in any group. CONCLUSION Dexamethasone can lower the amylase, endotoxin and TNF-alpha levels as well as mortality of SAP rats. NF-kappaB plays an important role in multiple organ injury. Further studies should be conducted to determine whether dexamethasone can ameliorate the pathological changes of multiple organs by reducing the NF-kappaB expression in the liver and kidney. The advantages of tissue microarrays in pancreatitis pathological examination include time- and energy- saving, and are highly efficient and representative. The restriction of tissue microarrays on the representation of tissues to various extents due to small diameter may lead to the deviation of analysis.
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Affiliation(s)
- Xi-Ping Zhang
- Department of General Surgery, Hangzhou First People's Hospital, 261 Huansha Road, Hangzhou 310006, Zhejiang Province, China.
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Andersson R, Andersson B, Andersson E, Axelsson J, Eckerwall G, Tingstedt B. Acute pancreatitis--from cellular signalling to complicated clinical course. HPB (Oxford) 2007; 9:414-420. [PMID: 18345287 PMCID: PMC2215353 DOI: 10.1080/13651820701713766] [Citation(s) in RCA: 12] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/13/2007] [Indexed: 12/12/2022]
Abstract
Acute pancreatitis (AP) is a common disease that has a mild to moderate course in most cases. During the last decade, a change in diagnostic facilities as well as improved intensive care have influenced both morbidity and mortality in AP. Still, however, a number of controversies and unresolved questions remain regarding AP. These include prognostic factors and how these may be used to improve outcome, diagnostic possibilities, their indications and optimal timing, and the systemic inflammatory reaction (systemic inflammatory response syndrome--SIRS) and its effect on the concomitant course of the disease and potential development of organ failure. The role of the gut has been suggested to be important in severe AP, but has recently been somewhat questioned. Despite extensive research, pharmacological and medical intervention of proven clinical value is scarce. Various aspects on surgical interventions, including endoscopic sphincterotomy, cholecystectomy and necrosectomy, as regards indications and timing, will be reviewed. Last, but not least, are the management of late complications and long-term outcome for patients with especially severe AP.
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Affiliation(s)
- Roland Andersson
- Department of Surgery, Clinical Sciences Lund, Lund University Hospital, Lund, Sweden.
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Recombinant Human Activated Protein C Administered Twice to The Same Patient with Shock Caused by the Acute Pancreatitis and With Septic Shock As Iatrogenic Complication. POLISH JOURNAL OF SURGERY 2007. [DOI: 10.2478/v10035-007-0008-8] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/21/2022]
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Kohli RS, Bleibel W, Shetty A, Dhanjal U. Plasmapheresis in the treatment of hypertriglyceridemic pancreatitis with ARDS. Dig Dis Sci 2006; 51:2287-91. [PMID: 17120148 DOI: 10.1007/s10620-006-9315-x] [Citation(s) in RCA: 19] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/19/2005] [Accepted: 03/14/2006] [Indexed: 12/14/2022]
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Sakaguchi Y, Inaba M, Kusafuka K, Okazaki K, Ikehara S. Establishment of animal models for three types of pancreatitis and analyses of regeneration mechanisms. Pancreas 2006; 33:371-81. [PMID: 17079942 DOI: 10.1097/01.mpa.0000236734.39241.99] [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: 12/17/2022]
Abstract
OBJECTIVES To investigate the mechanisms underlying the onset and progress of pancreatitis, 3 animal models (chronic, acute, and severe pancreatitis) were established by double ligature of the pancreatic duct, injection with cerulein, or injection with cerulein + double ligature of the pancreatic duct. METHODS We prepared a control and 3 experimental groups: group 1 (untreated control), group 2 (a chronic pancreatitis model; the pancreatic tail was exposed through a midline incision, and the pancreatic duct from this part was double-ligated), group 3 (an acute pancreatitis model; cerulein was intraperitoneally injected 7 times on day 0), and group 4 (a severe pancreatitis model; the double ligature of the pancreatic duct plus injection of cerulein). RESULTS Kinetic observations of survival rate, relative pancreatic weight, and the macroscopical and microscopical diagnoses and observations of the changes in endocrine function clearly show that these 3 murine models of pancreatitis can serve as human models for chronic, acute, and severe pancreatitis. Furthermore, pancreas duodenum homeobox 1, cytokeratin 19, and Ki67 are expressed at the site of injury in the pancreas, resulting from the injection with cerulein and/or double ligature of the pancreatic ducts and indicating that there remains a tissue-regenerative capacity. CONCLUSIONS These 3 mouse models could serve as human models for chronic, acute, and severe pancreatitis. Furthermore, cells of the epithelial lineage might participate in tissue regeneration in chronic, acute, and severe pancreatitis.
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Affiliation(s)
- Yutaku Sakaguchi
- First Department of Pathology, Kansai Medical University, Moriguchi City, Osaka, Japan
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