Severe acute pancreatitis： pathogenesis, diagnosis and surgical management

BACKGROUND： Severe acute pancreatitis is a subtype of acute pancreatitis, associated with multiple organ failure and systemic inflammatory response syndrome. In this qualitative review we looked at the principles of pathogenesis, classification and surgical management of severe acute pancreatitis. We also looked at the current shift in paradigm in the management of severe acute pancreatitis since the guideline developed by the British Society of Gastroenterology.DATA SOURCES： Studies published between 1st January 1991 and 31st December 2015 were identified with Pub Med, MEDLINE, EMBASE and Google Scholar online search engines using the following Medical Subject Headings： “acute pancreatitis, necrosis, mortality, pathogenesis, incidence” and the terms “open necrosectomy and minimally invasive necrosectomy”.The National Institute of Clinical Excellence（NICE） Guidelines were also included in our study. Inclusion criteria for our clinical review included established guidelines, randomized controlled trials and non-randomized controlled trials with a follow-up duration of more than 6 weeks.RESULTS： The incidence of severe acute pancreatitis within the UK is significantly rising and pathogenetic theories are still controversial. In developed countries, the most common cause is biliary calculi. The British Society of Gastroenterology,acknowledges the Revised Atlanta criteria for prediction of severity. A newer Determinant-based system has been developed.The principle of surgical management of acute necrotizing pancreatitis requires intensive care management, identifying infection and if indicated, debridement of any infected necrotic area. The current procedures opted for include standard surgical open necrosectomy, endoscopic necrosectomy and minimally invasive necrosectomy. The current paradigm is shifting towards a step-up approach.CONCLUSIONS： Severe acute pancreatitis is still a subject of grey areas in its surgical management even though new studies have been recorded since the origin of the latest UK guidelines for management of severe acute pancreatitis.

Acute pancreatitis:Etiology and common pathogenesis

Acute pancreatitis is an inflammatory disease of the pancreas.The etiology and pathogenesis of acute pancreatitis have been intensively investigated for centuries worldwide.Many causes of acute pancreatitis have been discovered,but the pathogenetic theories are controversial.The most common cause of acute pancreatitis is gallstone impacting the distal common bile-pancreatic duct.The majority ofinvestigators accept that the main factors for acute billiary pancreatitis are pancreatic hyperstimulation and bile-pancreatic duct obstruction which increase pancreatic duct pressure and active trypsin reflux.Acute pancreatitis occurs when intracellular protective mechanisms to prevent trypsinogen activation or reduce trypsin activity are overwhelmed.However,little is known about the other acute pancreatitis.We hypothesize that acute biliary pancreatitis and other causes of acute pancreatitis possess a common pathogenesis.Pancreatic hyperstimulation and pancreatic duct obstruction increase pancreatic duct pressure,active trypsin reflux,and subsequent unregulated activation of trypsin within pancreatic acinar cells.Enzyme activation within the pancreas leads to auto-digestion of the gland and local inflammation.Once the hypothesis is confirmed,traditional therapeutic strategies against acute pancreatitis may be improved.Decompression of pancreatic duct pressure should be advocated in the treatment of acute pancreatitits which may greatly improve its outcome.

Pathogenesis of pancreatic encephalopathy in severe acute pancreatitis

BACKGROUND: Pancreatic encephalopathy (PE) is a serious complication of severe acute pancreatitis (SAP). In recent years, more and more PE cases have been reported worldwide, and the onset PE in the early stage was regarded as a poor prognosis sign of SAP, but the pathogenesis of PE in SAP still has not been clarified in the past decade. The purpose of this review is to elucidate the possible pathogenesis of PE in SAP. DATA SOURCES: The English-language literature concerning PE in this review came from the Database of MEDLINE (period of 1991-2005), and the keywords of severe acute pancreatitis and pancreatic encephalopathy were used in the searching. RESULTS: Many factors were involved in the pathogenesis of PE in SAP. Pancreatin activation, excessive release of cytokines and oxygen free radicals, microcirculation abnormalities of hemodynamic disturbance, ET-1/NO ratio, hypoxemia, bacterial infection, water and electrolyte imbalance, and vitamin B1 deficiency participated in the development of PE in SAP. CONCLUSIONS: The pathogenesis of PE in SAP has not yet been fully understood. The development of PE in SAP may be a multi-factor process. To find out the possible inducing factor is essential to the clinical management of PE in SAP.

Pathogenesis of acute lung injury in rats with severe acute pancreatitis

BACKGROUND: Acute lung injury (ALI) is the most common and severe complication of severe acute pancreatitis (SAP). The elucidation of the mechanism of ALI contributes to the diagnosis and treatment of the illness. In this study, we studied the pathogenesis of ALI in rats with severe acute pancreatitis. METHODS: The rats were sacrificed at 1, 3, 5, 6, 9 and 12 hours after the establishment of the model of SAP. Pancreas and lung tissues were obtained for pathological study, and examination of microvascular permeability and myeloperoxidase (MPO) examination. The gene expressions of tumor necrosis factor-α (TNF-α) and intercellular adhesion molecule-1 (ICAM-1) in the pancreas and lung tissues were detected by reverse transcriptase-polymerase chain reaction (RT-PCR). RESULTS: After the establishment of the SAP model, the degree of pancreatic and lung injury increased gradually along with the gradual increase of MPO activity and micro-vascular permeability. Gene expressions of TNF-α and ICAM-1 in the pancreas rose at 1 hour and peaked at 7 hours. In contrast, their gene expression in the lungs rose slightly at 1 hour and peaked at 9-12 hours. CONCLUSION: An obvious time window existed between SAP and lung injury, which is beneficial to the early prevention of the development of ALI.

Role of phosphoinositide 3-kinase in the pathogenesis of acute pancreatitis

A large body of experimental and clinical data supports the notion that inflammation in acute pancreatitis has a crucial role in the pathogenesis of local and systemic damage and is a major determinant of clinical severity. Thus, research has recently focused on molecules that can regulate the inflammatory processes, such as phosphoinositide 3-kinases (PI3Ks), a family of lipid and protein kinases involved in intracellular signal transduction. Studies using genetic ablation or pharmacologic inhibitors of different PI3K isoforms, in particular the class I PI3Kδ and PI3Kγ, have contributed to a greater understanding of the roles of these kinases in the modulation of inflammatory and immune responses. Recent data suggest that PI3Ks are also involved in the pathogenesis of acute pancreatitis. Activation of the PI3K signaling pathway, and in particular of the class IB PI3Kγ isoform, has a significant role in those events which are necessary for the initiation of acute pancreatic injury, namely calcium signaling alteration, trypsinogen activation, and nuclear factor-κB transcription. Moreover, PI3Kγ is instrumental in modulating acinar cell apoptosis, and regulating local neutrophil infiltration and systemic inflammatory responses during the course of experimental acute pancreatitis. The availability of PI3K inhibitors selective for specific isoforms may provide new valuable therapeutic strategies to improve the clinical course of this disease. This article presents a brief summary of PI3K structure and function, and highlights recent advances that implicate PI3Ks in the pathogenesis of acute pancreatitis.

Integrity of the pancreatic duct-acinar system in the pathogenesis of acute pancreatitis

BACKGROUND: Acute pancreatitis is an acute inflammatory process of the pancreas that frequently involves peripancreatic tissues and at times remote organ systems. For a long time, the etiology and pathogenesis of acute pancreatitis has been intensively investigated worldwide, but the pathogenetic theories are controversial. The integrity of the pancreatic duct-acinar system might play an important role in the pathogenesis of this disease. DATA SOURCES: Web of Science and PubMed databases were searched for published studies (between January 1966 and June 2009) to identify relevant articles using the keywords 'acinar hyperstimulation', 'pathogenesis', 'acute pancreatitis', 'pancreatic duct-acinar system', and 'pancreatic duct pressure'. Most of the relevant articles were reviewed. RESULTS: From critical reading of the relevant articles, we found that the underlying mechanisms involved in the pathogenesis of acute pancreatitis are still under debate and ill-understood. On the basis of the relevant studies, we propose a hypothesis for the pathogenesis of acute pancreatitis, in which the integrity of the pancreatic duct-acinar system plays an essential role in the onset and progression of various forms of the disease. CONCLUSIONS: In our hypothesis, pancreatic duct obstruction and hyperstimulation of the exocrine pancreas are preconditions for the onset of acute pancreatitis; under the common conditions of pancreatic duct obstruction and acinar hyperstimulation, acute pancreatitis arises and develops. This may be an important common pathophysiological mechanism causing various forms of acute pancreatitis. (Hepntobiliary Pancreat Dis Int 2010; 9: 242-247)

Pathogenesis of acute lung injury in severe acute pancreatitis

Objective:To study the pathogenesis of acute lung injury in severe acute pancreatitis (SAP). Methods:Rats were sacrificed at 1, 3, 5, 6, 9 and 12 h after establishment of inducing model. Pancreas and lung tissues were obtained for pathological study, microvascular permeability and MPO examination. Gene expressions of TNF-α and ICAM-1 in pancreas and lung tissues were detected by RT-PCR. Results:After inducing SAP model, the injury degree of the pancreas and the lung increased gradually, accompanied with gradually increased MPO activity and microvascular permeability. Gene expressions of TNF-α and ICAM-1 in pancreas rose at 1 h and reached peak at 7 h. Relatively, their gene expressions in the lungs only rose slightly at 1 h and reached peak at 9-12 h gradually. Conclusion:There is an obvious time window between SAP and lung injury, when earlier protection is beneficial to prevent development of acute lung injury.

Severe acute pancreatitis: Pathogenetic aspects and prognostic factors

Approximately 20% of patients with acute pancreatitis develop a severe disease associated with complications and high risk of mortality. The purpose of this study is to review pathogenesis and prognostic factors of severe acute pancreatitis （SAP）. An extensive medline search was undertaken with focusing on pathogenesis, complications and prognostic evaluation of SAP. Cytokines and other inflammatory markers play a major role in the pathogenesis and course of SAP and can be used as prognostic markers in its early phase. Other markers such as simple prognostic scores have been found to be as e^ective as multifactorial scoring systems （MFSS） at 48 h with the advantage of simplicity, efficacy, low cost, accuracy and early prediction of SAP. Recently, several laboratory markers including hematocrit, blood urea nitrogen （BUN）, creatinine, matrix metalloproteinase-9 （MMP-9） and serum amyloid A （SAA） have been used as early predictors of severity within the first 24 h. The last few years have witnessed a tremendous progress in understanding the pathogenesis and predicting the outcome of SAP. In this review we classified the prognostic markers into predictors of severity, pancreatic necrosis （PN）, infected PN （IPN） and mortality.

Protective effects of MCP-1 inhibitor on a rat model of severe acute pancreatitis

BACKGROUND: Chemokines and their receptors play key roles in the pathogenesis of acute pancreatitis. This study aimed to establish a rat model of severe acute pancreatitis (SAP) for investigating monocyte chemotactic protein-1 (MCP-1) expression in the pathogenesis of the disease. We assessed the effects of the inhibitor of MCP-1, Bindarit, on SAP and explored the mechanisms underlying SAP. METHODS: Seventy-two Sprague-Dawley rats were randomly divided into a saline control group (group S), an SAP group (group P), and a Bindarit group (group T). The SAP model was induced by retrograde infusion of 4% sodium taurocholate into the bilio-pancreatic duct. Based on the SAP model, Bindarit was injected intraperitoneally in group T, and 0.5% methyl cellulose was injected intraperitoneally in groups S and P. In group S, saline was retrogradely infused into the bilpancreatic duct. Serum amylase levels and the histological changes in the pancreas were assessed at different time-points in each group. Expression of MCP-1 in serum was measured by enzyme-linked immunoadsorbent assay (ELISA). MCP-1 protein and mRNA expression levels were detected by immunohistochemistry, Western blotting, and semi-quantitative reverse transcriptase-polymerase chain reaction (RT-PCR). RESULTS: Serum amylase levels in groups P and T were higher than those in group S. Serum amylase levels were significantly lower in group T than in group P at 6 and 12 hours after operation. The levels of MCP-1 in serum at 6 and 12 hours after operation in group P were significantly higher than in group S, and significantly lower in group T than in group P at 6 and 12 hours after operation. The pathological damage in the pancreas was milder in group T than in group P. MCP-1 protein and mRNA expression levels in the pancreas were higher in groups P and T than in group S. These expression levels were positively correlated with the pathological damage of pancreatic tissues. The activity of MCP-1 in group T was significantly lower than in group P. CONCLUSION: MCP-1 may play important roles in the pathogenesis of SAP. The data suggest that Bindarit ameliorates SAP by inhibiting the activity of MCP-1 in vivo. (Hepatobiliary Pancreat Dis Int 2010; 9: 201-207)

The role of predictive and prognostic values of inflammatory markers in acute pancreatitis:a narrative review

Pancreatitis is an inflammatory condition affecting the pancreas and is classified into 2 types,acute and chronic,which can manifest in various forms.This review article summarizes the role of predictive and prognostic values of inflammatory markers in the pathogenesis of acute pancreatitis,mainly focused on preclinical and clinical studies.It includes serum amyloid A(SAA),monocyte chemotactic protein-1(MCP-1),erythrocyte sedimentation rate(ESR),interleukin-6(IL-6),C-reactive protein(CRP),IL-10,myeloperoxidase,pentraxin 3,and plasminogen activator inhibitor 1.SAA3 plays a crucial role in developing acute pancreatitis by triggering a receptor-interacting protein 3-dependent necroptosis pathway in acinar cells.Targeting SAA3 could be a potential strategy for treating acute pancreatitis.The recruitment of monocytes/macrophages and the activation of the systemic MCP-1 signaling pathway play a role in the progression of pancreatitis,and blocking MCP-1 may have a suppressive effect on the development of pancreatic fibrosis.The ESR can predict severe acute pancreatitis with slightly lower accuracy than CRP.When ESR and CRP levels are combined at 24 hours,they predict severe acute pancreatitis accurately.IL-6 plays a crucial role in activating the Janus kinase/signal transducers and activators of the transcription pathway,exacerbating pancreatitis and contributing to the initiation and progression of pancreatic cancer.Endogenous IL-10 plays a crucial role in controlling the regenerative phase and limiting the severity of fibrosis and glandular atrophy induced by repeated episodes of acute pancreatitis in mice.The predictive and diagnostic roles of these inflammatory factors in pancreatitis were introduced in detail in this review.

急性胰腺炎的急诊救治新进展

急性胰腺炎(acute pancreatitis,AP)是引起急性腹痛的常见病因之一,其病情可分为轻症急性胰腺炎(MAP)、中重度急性胰腺炎(MSAP)及重症急性胰腺炎(SAP),其中SAP的发病率约为25%。SAP病情危重,常合并多脏器功能障碍,病死率高达30%。AP的病因在我国以胆源性、高脂性和酒精性居多,其发病机制主要包括胰蛋白酶原的异常激活、病理性钙离子(Ca 2+)信号、线粒体功能紊乱等。AP的治疗目前以补液、抗炎等内科综合治疗和内镜、穿刺等微创治疗为主。与传统手术治疗相比,近年来出现的如升阶梯治疗策略等新的治疗方法具有显著优势。因此,充分了解AP患者的相关危险因素及发病机制,应用不同方法对患者严重程度进行评估,以采取有效方式进行治疗,能明显改善患者预后。

猫胰腺炎成因及其营养调控

胰腺炎是猫的一种常见病,其发病原因复杂,临床症状比较严重,死亡率高,但目前还没有针对猫胰腺炎的特效治疗方法。胰腺炎患病动物的试验和临床数据都证明营养管理措施对治疗猫胰腺炎的重要意义,营养调控不仅有助于预防营养不良,也是降低全身炎症、并发症和死亡率的关键。猫胰腺炎营养调控的研究主要是添加营养素如蛋白质、脂肪、维生素和矿物质等。本文综述了关于猫急性与慢性胰腺炎的发病原因及其营养调控的相关研究,旨在为猫胰腺炎的临床治疗提供参考。

急性胰腺炎的发病机制研究进展及未来展望

急性胰腺炎(acute pancreatitis,AP)是消化系统常见急腹症之一,发病率在我国和欧美各国均呈逐年上升趋势。尽管病因多种多样,但均遵循特定的病理生理学过程且其中的关键调控分子具有相似性。近年来,一方面以胰腺腺泡和导管上皮细胞为主要研究对象,聚焦钙信号通路、自噬流受损、线粒体等细胞器功能障碍、内质网应激失衡取得了不少重要进展;另一方面聚焦免疫细胞的早期募集和过度活化参与调控全身炎症反应的发生及胰腺坏死和胰腺炎相关器官功能不全开展了不少前沿研究。上述研究发现大大增进了我们对AP发病机制和干预策略的理解和认识。本文将重点讨论近年来AP发病机制的基础研究进展,以期对AP的早期治疗提供临床指导。

复发性急性胰腺炎病因的研究进展

近年来,急性胰腺炎(AP)发病率逐年稳步上升,约21%的初发AP患者会发展为复发性AP(RAP)。RAP的病因包括胆源性、高甘油三酯血症(HTG)、酒精性及其他较少见因素。对于RAP患者,早期明确病因并给予相应的治疗可明显降低复发率并改善预后。本文将从RAP的定义、病因进行综述。

急性胰腺炎并发急性呼吸窘迫综合征的发病机制研究进展

急性胰腺炎(acute pancreatitis,AP)是消化系统中常见的急性腹痛疾病之一。导致AP疾病进展及致命的主要因素包括全身炎症反应综合征(SIRS)和多器官功能衰竭(MOF)。急性呼吸窘迫综合征(ARDS)作为AP最常见、最严重的早期并发症之一,与高病死率密切相关。然而,重症急性胰腺炎(SAP)并发ARDS的发病机制尚未完全阐明,可能与初始腺泡细胞损伤后核转录因子-κB(NF-κB)的激活、大量炎症介质释放以及免疫细胞介入等复杂因素相关,形成全身炎症瀑布反应。因此,本研究详细阐述NF-κB在AP发展早期的关键作用,揭示了NF-κB如何将初始腺泡损伤与全身炎症相关联,并导致肺泡弥漫性损伤。这不仅深化了临床医师对AP并发ARDS的理解,还为临床治疗提供潜在治疗靶点和理论依据。

基于伏气温病理论探析慢性胰腺炎急性发作期诊疗思路

伏气温病是一类特殊的温病,与反复发作的慢性炎症性疾病关系密切。慢性胰腺炎急性发作期具有邪气伏藏,因时而发的特点,与中医学伏气温病发病特点相似。从伏气温病理论探析慢性胰腺炎急性发作,饮酒、暴饮暴食、胆胰自身病变是其主要病因,饮食不节引动伏火,伏火内发,湿热瘀阻,腑气不通,并随发病部位不一、气血阴阳亏虚的不同而表现各异,发为本病。慢性胰腺炎急性发作期以定震源、清里热、辨虚实、透伏邪、护津液为主要辨治原则。从伏气温病角度探析慢性胰腺炎急性发作的病因、病机、辨证与治疗,以期为中医治疗慢性胰腺炎急性发作提供新的思路和方法。

重症急性胰腺炎并发胰性脑病的诊疗进展

胰性脑病(PE)是重症急性胰腺炎(SAP)罕见的并发症,临床多表现为定向力障碍、意识模糊、妄想或出现幻觉等精神神经症状,并伴有弥漫性脱髓鞘和脑白质改变,其病情凶险,病死率高,临床诊断易延误、混淆。目前关于PE的研究尚少,本文就PE的发病机制、诊断要点、治疗研究进展进行综述,旨在为临床及科研实践提供帮助。

高脂血症性急性胰腺炎病因、发病机制及严重程度评估研究新进展

近年来,高脂血症引发的急性胰腺炎日益流行,其发病年轻化,病情重且反复,预后差,引起了临床医生的普遍关注和重视。急性胰腺炎主要是由高甘油三酯所致,发病机制可能主要与游离脂肪酸损害腺泡细胞、胰腺微循环障碍、胰腺炎性介质加速激活等有关,在严重程度上目前有几种比较常用的评分系统。本文就高脂血症性急性胰腺炎的发病原因、发病机制及严重程度评估进行综述,重点阐述其严重程度评估。

重症急性胰腺炎“腑气不通”的中医病机本质探讨

重症急性胰腺炎(severe acute pancreatitis,SAP)是临床消化内科、胃肠外科常见的危急重症,其发病急、进展快、并发症多、病情凶险、病死率高,对临床诊疗考验巨大。随着中、西医学科交融日趋频繁,发挥现代医学的优势,使中医对疾病的认知更加具体化、客观化、精准化成为了当下的研究热点。现代医学从微循环障碍、炎症激活、免疫失调、肠道屏障异常等多角度揭示SAP的病理机制,而“腑气不通”做为中医对SAP的病机认识,得到了普遍认同,且中医以“通下”为法治疗收效甚佳,由此探讨中医“腑气不通”的病机与现代医学发病机制之间的联系。本文基于中、西医两种医学从不同角度对SAP的探究,试整合二者在对SAP认知上的契合点,寻求SAP中医“腑气不通”的病机本质,使得SAP的中医病机更加客观化,并拓宽临床运用通下中药治疗SAP的诊治思路。

代谢综合征与急性胰腺炎

代谢综合征与急性胰腺炎的发病、严重程度及预后密切相关,且代谢综合征合并急性胰腺炎的发病率呈逐渐上升的趋势,但其具体发病机制及相关性目前尚未完全阐明,本文将近年来代谢综合征合并急性胰腺炎的相关进展进行了总结,以期为后续临床工作提供参考。