重症急性胰腺炎微循环障碍的治疗现状

胰腺微循环障碍是导致急性胰腺炎发展的重要因素,其在重症急性胰腺炎发病中的作用越来越引起人们的重视,针对改善胰腺微循环的治疗方法会减少胰腺组织的坏死程度和病变的演进。本文针对重症急性胰腺炎微循环障碍提出相关的治疗策略。     

磺达肝癸钠对高脂血症急性坏死性胰腺炎大鼠微循环及炎症因子影响

目的探讨磺达肝癸钠对高脂血症急性坏死性胰腺炎大鼠微循环及炎症因子影响。方法以健康SD雄性大鼠30只为研究对象,抽签法随机分为治疗组(n=15)和高脂血症组(n=15),两组均通过喂养高脂饲料建立高脂血症大鼠模型,此外治疗组通过将0.1 m L/100 g体重的5%的牛黄胆酸钠溶液注入胰胆管内制成急性坏死性胰腺炎模型,并在建模后0 h、6 h、12 h、18 h注射0.2 m L/100 g次璜达肝癸钠。两组建模后均禁食、禁饮并行2 m L/100 g生理盐水补液。治疗组分别于治疗前和治疗24 h取静脉血用于血清IFN-γ、TNF-α,IL-6和IL-10等炎症因子水平检测,并在治疗前、治疗6 h、12 h和24 h检查比较两组胰体头部和尾部微区血流量。两组建模24 h后均处死剖腹,观察腹腔内组织和胰腺情况,并切除十二指肠内侧胰腺组织行病理检查。结果与高脂血症组比较,治疗组治疗前血清IFN-γ、TNF-α,IL-6和IL-10等炎症因子水平均升高(P0.05)。与治疗前比较,治疗组治疗24 h血清炎症因子水平均降低(P0.05)。与高脂血症组比较,治疗组治疗6 h、12 h和24 h胰体头部和尾部微区血流量均升高(P0.05)。与治疗前比较,治疗组治疗前、治疗6 h、12 h和24 h胰体头部和尾部微区血流量则升高(P0.05)。治疗组水肿、坏死、炎性细胞浸润等胰腺组织病理学评分均高于高脂血症组(P0.05)。结论磺达肝癸钠可改善大鼠微循环及炎症状态。     

Pancreatic pseudocyst complicating treatment of acute lymphoblastic leukemia

In the management of children with acute lymphoblastic leukemia, L-asparaginase has become established as an effective drug in the usual multi-agent therapy; and the significance of pancreatitis as a complication of this drug is well recognized. Less well appreciated, however, is the progression of such pancreatitis in some patients to pseudocyst formation and the possible necessity for surgical management. Two adolescent girls who developed pancreatic pseudocysts while being treated with L-asparaginase are described in this report. Both were being treated for acute lymphoblastic leukemia for periods of 18 and 4 months, respectively, prior to the onset of pancreatitis. Both were in remission of their leukemic disease when typical clinical and laboratory manifestations of acute pancreatitis developed. In one girl, a pancreatic pseudocyst became apparent 2 weeks following the diagnosis of acute pancreatitis and in the other girl, this complication developed over a period of 8 weeks. The usual nonsurgical management of pancreatitis over protracted periods of time was ineffective in the treatment of the pseudocysts. Surgical drainage (internal in one and external in the other) was successful in both in eradicating the pseudocyst, and in neither did further evidence of pancreatic disease subsequently occur. In both resumption of chemotherapy, omitting L-asparaginase, was well tolerated. One has been in remission of leukemia and in good health for a 3-year period of follow-up observation, while the other subsequently had a relapse of leukemia and died 18 months following the onset of pancreatitis.     

Pancreatic capillary blood flow in an improved model of necrotizing pancreatitis in the rat

INTRODUCTION: The development of acute pancreatitis is characterized by profound changes in pancreatic microcirculation. Using in vivo microscopy with fluorescent-labeled erythrocytes as tracers we studied changes in pancreatic microcirculation in an improved rat model of necrotizing pancreatitis (NP) in comparison to edematous pancreatitis (EP) and healthy controls. METHODS: Twenty-one male Wistar rats had their pancreatae exteriorized in a temperature-controlled immersion chamber followed by intravenous administration of fluorescent-labeled autologous erythrocytes. EP was induced by intraductal saline and intravenous caerulein (5 microg/kg/h) for 6 h (n = 7) and NP by controlled intraductal infusion of glycodeoxycholic acid (10 mmol/L) followed by intravenous caerulein (n = 7). Control animals received intraductal and intravenous saline (n = 7). The determination of pancreatic microcirculation was performed before as well as 1, 3, and 6 h after intraductal infusion by correlating the number of passing labeled erythrocytes/capillary/min with their concentration per microliter of arterial blood. RESULTS: Pancreatic capillary flow in control animals remained constant over the 6-h observation period. Pancreatic capillary flow in the EP group rapidly increased to 188% of baseline after 3 h and remained significantly elevated throughout the experiments (P = 0.0001). In contrast, pancreatic capillary flow decreased significantly in the group suffering NP with values 46.7% of baseline after 6 h (P = 0.0001). Complete capillary stasis developed in 38% of investigated capillaries in the NP group compared to 0-1% in both other groups (P = 0.0001). CONCLUSION: Pancreatic microcirculation in mild edematous pancreatitis is significantly increased while the evolution of necrotizing pancreatitis in the model studied herein is characterized by a dramatic reduction in pancreatic capillary flow in conjunction with areas of capillary stasis. These results underline the pathophysiologic relevance of the model and of therapeutic measures aimed at an improvement of pancreatic microcirculation in clinical necrotizing pancreatitis.     

Pancreatographic findings in idiopathic acute pancreatitis

Background/purpose Despite extensive evaluation based on clinical history, biochemical tests, and noninvasive imaging studies, the cause of acute pancreatitis cannot be determined in 10 to 30% of patients, and a diagnosis of idiopathic acute pancreatitis is made. The purpose of this study was to clarify the pancreatographic findings in patients with idiopathic acute pancreatitis.Methods Endoscopic retrograde cholangiopancreatography (ERCP) was performed in 34 patients with idiopathic acute pancreatitis, and the pancreatographic findings were examined. Patency of the accessory pancreatic duct was examined by dye-injection endoscopic retrograde pancreatography (ERP) in 16 of the 34 patients.Results In 11 patients (32%), the following anatomic abnormalities of the pancreatic or biliary system were demonstrated: complete pancreas divisum (n = 5), incomplete pancreas divisum (n = 2), high confluence of pancreaticobiliary ducts (n = 2), choledochocele (n = 1), and giant periampullary diverticulum (n = 1). Pancreatographic findings were normal in 17 patients. Eleven of these patients were examined by dye-injection ERP, and all were found to have nonpatent accessory pancreatic duct.Conclusions Anatomic abnormality of the pancreatic or biliary system is one of the major causes of idiopathic acute pancreatitis. Closure of the accessory pancreatic duct may play a role in the development of idiopathic acute pancreatitis in patients with a normal pancreaticobiliary ductal system.     

Intestinal microcirculation and gut permeability in acute pancreatitis: Early changes and therapeutic implications

Translocation of bacteria from the intestine causes local and systemic infection in severe acute pancreatitis. Increased intestinal permeability is considered a promoter of bacterial translocation. The mechanism leading to increased gut permeability may involve impaired intestinal capillary blood flow. The aim of this study was to evaluate and correlate early changes in capillary blood flow and permeability of the colon in acute rodent pancreatitis of graded severity. Edematous pancreatitis was induced by intravenous cerulein; necrotizing pancreatitis by intravenous cerulein and intraductal glycodeoxycholic acid. Six hours after induction of pancreatitis, the permeability of the ascending colon was assessed by the Ussing chamber technique; capillary perfusion of the pancreas and colon (mucosal and subserosal) was determined by intravital microscopy. In mild pancreatitis, pancreatic capillary perfusion remained unchanged (2.13 ± 0.06 vs. 1.98 ± 0.04 nl-min^−l.cap ⁻¹ [control]; P = NS), whereas mucosal (1.59 _± 0.03 vs. 2.28 ± 0.03 nl.min^−l.cap ⁻¹ [control]; P <0.01) and subserosal (2.47 ± 0.04 vs. 3.74 ± 0.05 nl-min^−l.cap ^-1 [control]; P <0.01) colonic capillary blood flow was significantly reduced. Severe pancreatitis was associated with a marked reduction in both pancreatic (1.06 = 0.03 vs. 1.98 ± 0.04 nl’min^-1.cap ^-1 [control]; P <0.01) and colonic (mucosal: 0.59 = 0.01 vs. 2.28 ± 0.03 nl.min^−l.cap ^-1 [control], P < 0.01; subserosal: 1.96 ± 0.05 vs. 3.74 ± 0.05 nl.min^−l.cap ^-1 [control], P <0.01) capillary perfusion. Colon permeability tended to increase with the severity of the disease (control: 147 ±19 nmol.hr^−l.cm {−2}2; mild pancreatitis: 158±23 nmol-hr^−l.cm^-2; severe pancreatitis: 181 ±33 nmol.hr^−l.cm^-2; P = NS). Impairment of colonic capillary perfusion correlates with the severity of pancreatitis. A decrease in capillary blood flow in the colon, even in mild pancreatitis not associated with significant protease activation and acinar cell necrosis or impairment of pancreatic capillary perfusion, suggests that colonic microcirculation is especially susceptible to inflammatory injury. There was no significant change in intestinal permeability in the early stage of pancreatitis, suggesting a window of opportunity for therapeutic interventions to prevent the later-observed increase in gut permeability, which could result in improved intestinal microcirculation. Presented at the Thirty-Seventh Annual Meeting of The Society for Surgery of the Alimentary Tract, San Diego, Calif., May 19–22, 1996. Supported in part by Deutsche Forschungsgemeinschaft (DFG Fo 197/3).     

Pancreatic microcirculation in acute pancreatitis of dogs

Pancreatic microcirculation in acute pancreatitis and the effect of dopamine and pancreatic protease inhibitor were investigated in 35 mongrel dogs. Acute pancreatitis was induced by the injection of autologous bile added trypsin into pancreatic duct. In acute pancreatitis dogs femoral artery pressure and pulse pressure gradually decreased and pancreatic microflow in basal state temporarily increased immediately after bile injection, however, thereafter continuously decreased during the experiments. Portal flow severely decreased just after onset of acute pancreatitis. By administration of dopamine femoral artery pressure was maintained during the first 90 minutes of experiments, however, thereafter decreased until the end of experiments. Pancreatic microflow, 56.1 +/- 15.3 ml/min/100g in basal level was shown 66.1 +/- 13.7 and 60.3 +/- 10.3 ml/min/100g at 1 and 2 hours, respectively, after bile injection, which were significantly high values as compared with those of non dopamine administration. However those values decreased at 5 hours of both experiments. Portal flow whose basal level was 237 +/- 67 ml/min was maintained during the first 1 hour however it decreased to 139 +/- 25 ml/min at 5 hours. By administration of pancreatic protease inhibitor femoral artery pressure and pulse pressure, temporarily decreased immediately after bile injection, however, they were maintained thereafter. Pancreatic microflow, 57.1 +/- 18.3 ml/min/100g in basal level, was maintained during the first 2 hours, however significantly decreased to 27.6 +/- 9.7 ml/min/100g at 5 hours. Portal flow significantly increased to 442 +/- 115 ml/min at 2 hours, however, thereafter decreased 219 +/- 93 ml/min at 5 hours.(ABSTRACT TRUNCATED AT 250 WORDS)     

急性胰腺炎外周循环和胰腺微循环血小板内皮细胞粘附分子-1的表达

目的　探讨急性胰腺炎 (AP)外周循环和胰腺微循环中血小板内皮细胞粘附分子 1(PECAM 1)表达的变化规律。方法　Wistar大鼠 48只 ,诱发AP动物模型 ,用流式细胞仪分析脾静脉和下腔静脉血中多形核白细胞 (PMN )PECAM 1的表达。结果　 ( 1)在急性水肿性胰腺炎(AEP)动物模型中 ,外周循环和胰腺微循环PMNPECAM 1的表达水平在AEP 2、4h组相近 ,自 4h开始 ,外周循环PMNPECAM 1的表达上调直至 8h ;胰腺微循环PMNPECAM 1的表达下调直至 8h ,在AEP 8h组 ,差异有显著性 ( P <0 .0 5 )。 ( 2 )在急性坏死性胰腺炎 (ANP)模型中 ,胰腺微循环PMNPECAM 1的表达下调 ;外周循环组PMNPECAM 1的表达未见明显变化 ,在ANP 4、6h组 ,差异有显著性 (P <0 .0 5 )。结论　AEP胰腺微循环和外周循环PMNPECAM 1的表达呈逆向性 ,在胰腺微循环呈下调趋势 ,在外周循环呈上调趋势 ;ANP胰腺微循环PMNPECAM 1的表达呈加速性下调 ,该结果显示 ,在ANP早期 ,抑制PMNPECAM 1的过度表达可能有助于改善AP病理改变。     

肥大细胞在重症急性胰腺炎发病机制中的作用

重症急性胰腺炎是外科是常见的急腹症，迄今尚无特异性治疗。肥大细胞是重要炎症效应细胞，在重症急性胰腺炎发病机制中发挥重要作用，引起胰腺、肺、肠道等器官损害。肥大细胞稳定剂通过抑制其炎症反应，对重症急性胰腺炎时上述器官有重要的保护作用。     

Intestinal hypoperfusion contributes to gut barrier failure in severe acute pancreatitis

Intestinal barrier failure and subsequent bacterial translocation have been implicated in the development of organ dysfunction and septic complications associated with severe acute pancreatitis. Splanchnic hypoperfusion and ischemia/reperfusion injury have been postulated as a cause of increased intestinal permeability. The urinary concentration of intestinal fatty acid binding protein (IFABP) has been shown to be a sensitive marker of intestinal ischemia, with increased levels being associated with ischemia/reperfusion. The aim of the current study was to assess the relationship between excretion of IFABP in urine, gut mucosal barrier failure (intestinal hyperpermeability and systemic exposure to endotoxemia), and clinical severity. Patients with a clinical and biochemical diagnosis of acute pancreatitis were studied within 72 hours of onset of pain. Polyethylene glycol probes of 3350 kDa and 400 kDa were administered enterally, and the ratio of the percentage of retrieval of each probe after renal excretion was used as a measure of intestinal macromolecular permeability. Collected urine was also used to determine the IFABP concentration (IFABP-c) and total IFABP (IFABP-t) excreted over the 24-hour period, using an enzyme-linked immun-osorbent assay technique. The systemic inflammatory response was estimated from peak 0 to 72-hour plasma C-reactive protein levels, and systemic exposure to endotoxins was measured using serum IgM en-dotoxin cytoplasmic antibody (EndoCAb) levels. The severity of the attack was assessed on the basis of the Atlanta criteria. Sixty-one patients with acute pancreatitis (severe in 19) and 12 healthy control subjects were studied. Compared to mild attacks, severe attacks were associated with significantly higher urinary IFABP-c (median 1092 pg/ml vs. 84 pg/ml; P < 0.001) and IFABP-t (median 1.14 μg vs. 0.21 |μg; P = 0.003). Furthermore, the control group had significantly lower IFABP-c (median 37 pg/ml; P = 0.029) and IFABP-t (median 0.06 μg; P = 0.005) than patients with mild attacks. IFABP correlated positively with the polyethylene glycol 3350 percentage retrieval (r = 0.50; P < 0.001), CRP (r = 0.51; P < 0.001), and inversely with serum IgM EndoCAb levels (r = —0.32; P = 0.02). The results of this study support the hypothesis that splanchnic hypoperfusion contributes to the loss of intestinal mucosal integrity associated with a severe attack of pancreatitis. Presented at the Forty-Third Annual Meeting of The Society for Surgery of the Alimentary Tract, San Francisco, California, May 19–22, 2002 (oral presentation).     

脾脏与急性胰腺炎

急性胰腺炎是个多因素、多步骤的病理过程,炎症因子级联瀑布反应与急性胰腺炎的发生发展关系密切。脾脏是人体最大的免疫器官,含有多种免疫活性细胞和免疫因子,在机体炎症反应中发挥一定的作用。动物实验表明,预先切除脾脏对于缓解急性胰腺炎的病情有一定作用,但需进一步的研究来证实。急性胰腺炎发病后脾脏对病情进展有无影响以及如何影响,有待深入探讨。     

细胞信号通路在重症急性胰腺炎发病机制中的研究进展

重症急性胰腺炎是一种预后凶险的疾病,常导致全身炎性介质反应综合征及多器官功能衰竭.重症急性胰腺炎全身炎性介质反应的基础是由许多细胞因子通过细胞信号通路介导构成的复杂的炎性介质反应网络.本文通过综合分析和归纳近年来国内外有关文献,就细胞信号通路在重症急性胰腺炎发病机制中的研究现状作一综述.     

Necrotizing pancreatitis

Acute pancreatitis is primarily caused by gallstone disease and excessive alcohol use. The clinical course is varied and those with severe disease may develop pancreatic necrosis and localized collections. Up to 30% of patients with pancreatic necrosis develop infection. This is difficult to diagnose but requires prompt treatment with antibiotics and often percutaneous, endoscopic or surgical intervention. The imprudent use of antibiotics risks the overgrowth of antibiotic-resistant organisms and makes the treatment of subsequent infections more challenging. Advances in biomarkers and imaging may improve the detection of infection, but the optimal timing of antibacterial and antifungal initiation and duration remain unresolved. Clinical trials are required to address these questions.     

中度急性胰腺炎临床特征分析

目的探讨中度急性胰腺炎的临床特征。方法回顾性分析2013年1月至12月,青海省交通医院普通外科收治的103例急性胰腺炎（acute pancreatitis,AP）患者临床资料,根据国际AP专题研讨会最新修订的诊断和分类标准（2012年,美国亚特兰大）诊断为轻度急性胰腺炎（mildacutepancreatitis,MAP）61例、中度急性胰腺炎（moderately severe acute pancreatitis,MSAP）25例、重度急性胰腺炎（severe acute pancreatitis,SAP）17例,对比三组患者一般资料、局部并发症发生此例、器官功能衰竭发生比例、入住ICU比例和天数、干预措施、住院天数、病死率。结果三组患者性别、年龄和病因学情况差异均无统计学意义,但MSAP组APACHEⅡ评分显著高于MAP组,同时低于SAP组（均P〈0．05）。MAP、MSAP和SAP三组出现局部并发症的比例分别为0、92．0％（23125）和76．5％（13／17）（P〈0．05）。MAP组无器官功能表竭发生,MSAP组5例出现一过性（〈48h）器官功能表竭,SAP组均出观特续性（〉48h）器官功能衰竭,SAP组器官功能衰竭比例显著高于MSAP组（P〈0．05）。MAP组无入住ICU病例,均无需介入、内镜或外科干预,无死亡病例。MSAP组入住ICU此例、ICU时间、住院时间和病死率显著低于SAP组（P〈0．05）。结论中度急性胰腺炎为有别于轻度和重度急性胰腺炎的独立类型,伴有局部并发症或一过性（48h内）器官功能表竭,但病死率较低,预后明显好于重度急性胰腺炎。     

Operative treatment of severe acute pancreatitis

Summary BACKGROUND: Operative treatment of severe acute pancreatitis is still related to high mortality rates. By avoiding early surgical intervention patient survival may be significantly improved. METHODS: Review both of the literature as well as of own results has led to a conservative approach in severe acute pancreatitis at the surgical department of the Medical University Vienna. RESULTS: Delaying surgery up to the third week after onset of disease improves patient survival significantly. Moreover, surgical control of pancreatic necrosis can be achieved by a single operation. CONCLUSIONS: The conservative approach in severe acute pancreatitis is a promising therapeutic conception. Organ failure during the early phase of disease can be successfully managed by means of intensive care treatment.      

中度重症-重症急性胰腺炎发病28天内继发胰腺/胰周感染的相关因素分析

目的 分析中度重症-重症急性胰腺炎（MSAP-SAP）发病28 d内继发胰腺/胰周感染的相关因素。方法 回顾2014年1月至2018年3月上海交通大学医学院附属瑞金医院急诊科与重症医学科收治并符合研究条件的患者,以发病28 d内继发胰腺/胰周感染与否分为感染组和非感染组,分析感染的特点和感染的相关因素。结果 共纳入243例MSAP-SAP患者,感染组81例（33.3%）,非感染组162例（66.7%）。81例感染患者中共检出病原菌83株,革兰阳性菌20株（24.10%）,革兰阴性菌62株（74.70%）,真菌1株（1.20%）。两组对比分析发现,感染组中酶抑制剂复合制剂类使用率和经皮穿刺引流（PCD）发生率显著高于非感染组（16.05 vs 7.45%,P=0.038和64.20% vs 39.20%,P＜0.001）。进一步多因素分析发现,仅PCD是胰腺/胰周感染的独立危险因素（OR 4.21,P＜0.001）。在PCD患者中,继发感染组中小网膜囊与肝肾间隙/脾肾间隙穿刺、猪尾管使用和生理盐水/甲硝唑冲管的比例高（P≤0.001）,而盆腔穿刺比例低（P＜0.001）,导管留置时间则较长（P＜0.001）。对上述与PCD相关性感染呈正相关的多个因素进行Logistic回归分析发现,肝肾间隙/脾肾间隙穿刺和使用猪尾管与感染的相关性并不显著（P=0.064和P=0.215）,而小网膜囊穿刺、生理盐水/甲硝唑冲管、导管留置时间延长与PCD相关性感染密切相关（P=0.010,P=0.015和P=0.004）。结论 PCD是MSAP-SAP发病28 d内继发胰腺/胰周感染的独立危险因素,其感染的高发主要与小网膜囊穿刺、生理盐水/甲硝唑冲管、导管留置时间延长密切相关。     

活血化瘀注射液对大鼠肠系膜活体微循环作用的观察

目的：观察血活化瘀注射液（HHI-I）对大鼠肠系膜活体微循环的影响。方法：将观察到的毛细血管后静脉微循环现象记录于录象带留作分析。观察指标包括白细胞滚动数、粘附数、平均血流速度和壁切率。结果：HHI-I及丹参注射液对生理状态下的肠系膜微循环无作用,急性胰腺炎（AP）使微循环各指标明显恶化,于AP造模的同时给予HHI-I可防止微循环障碍,丹参注射液无类似作用。结论：HHI-I降低AP时的白细胞滚动及粘附数增加,能增加血流速及壁切率。     

E-Cadherin在急性胰腺炎中的检测及其意义

目的 探讨E-Cadherin在急性胰腺炎（AP）患者中的变化及其对预测AP严重程度的价值。方法 收集我院2011年11月至2013年5月急性胰腺炎和其他腹部炎症性疾病患者44例,检测患者血sE-Cadherin的变化,分析其在轻型急性胰腺炎（MAP,15例）、重症急性胰腺炎（SAP,13例）和其他腹部炎症患者（16例）的差别及意义。结果 SAP组在起病12 h、24 h、48 h血sE-Cadherin浓度均高于MAP组以及其他腹部炎症组（P＜0.01）。MAP组在起病12 h、24 h、48 h血sE-Cadherin浓度与其他腹部炎症组比较无明显差异（P＞0.01）。结论 本研究提示在AP早期血sE-Cadherin在SAP患者显著升高,是早期判断AP严重程度的一个有效方法。     

急性胰腺炎患者血浆内皮素和一氧化氮水平变化及其意义

目的：了解急性胰腺炎患者血浆内皮素（ＥＴ）和一氧化氮（ＮＯ）与胰腺微循环的关系。方法：采用放免法和反相高效液相色谱法,分别检测血浆总ＥＴ和ＮＯ的稳定代谢产物ＮＯ２＾－／ＮＯ３＾－,以ＮＯ２＾－／ＮＯ３＾－,以ＮＯ２＾－与ＮＯ３＾－之和代表ＮＯ水平。结果：治疗前ＥＴ和ＮＯ均增高,前者显著大于后者,ＥＴ／ＮＯ比值显著增大。治疗后各值随病情好转渐恢复正常。ＥＴ和ＮＯ呈正相关关系。结论：ＥＴ／ＮＯ比值失衡