血液标志物与胰腺外炎症CT评分对急性胰腺炎严重性早期预测的比较

目的:比较血液标志物及胰腺外炎症CT评分(extrapancreatic inflammation on CT score,EPIC)对急性胰腺炎(acute pancreatitis,AP)严重性的早期预测价值.方法:对2010-09/2011-09住院的96例AP患者首个24h内的临床、实验室及CT资料进行分析.临床上重症急性胰腺炎(severe acute pancreatitis,SAP)的标准为:死亡或持续器官衰竭及/或入住ICU,及/或手术治疗.对重症急性胰腺炎组及轻症急性胰腺炎(mild acute pancreatitis,MAP)组患者血液标志物及胰腺外炎症CT评分进行t检验,血液标志物及EPIC预测AP严重性的相关性检验及预测AP严重性的ROC分析,并计算预测敏感性、阳性预测值及准确度.结果:MAP76例,SAP20例.重症患者的血液标志物及胰腺外炎症CT评分均明显较轻症患者的大[白细胞:(15.16±5.06)×109/Lvs(11.05±1.76)×109/L,中性粒细胞与淋巴细胞比值:18.95±12.13vs6.63±3.44,高敏C-反应蛋白:58.35mg/L±20.47mg/Lvs28.59mg/L±12.92mg/L,D-二聚体:1596.95μg/L±1409.05μg/Lvs412.52μg/L±316.66μg/L,胰腺外炎症CT评分:3.30±0.86vs1.50±0.96,P=0.000].白细胞、中性粒细胞与淋巴细胞比值、高敏C-反应蛋白、D-二聚体及胰腺外炎症CT评分与AP严重性的Spearman相关系数(rs)分别为0.419、0.571、0.568、0.434及0.61(P=0.000).白细胞、中性粒细胞与淋巴细胞比值、高敏C-反应蛋白、D-二聚体及胰腺外炎症CT评分对AP严重性预测的曲线下面积分别为0.798(0.670-0.925)、0.906(0.830-0.981)、0.904(0.838-0.970)、0.808(0.638-0.938)以及0.917(0.851-0.983);预测敏感性分别为70.00%、85.00%、85.00%、75.00%及85.00%;阳性预测值分别为58.33%、73.91%、51.52%、48.39%及72.00%;预测准确度分别为83.33%、90.63%、80.21%、78.13%及90.63%.结论:白细胞及D-二聚体对AP严重性的预测价值中等,中性粒细胞与淋巴细胞比值、高敏C-反应蛋白及胰腺外炎症CT评分的预测价值较高,其中中性粒细胞与淋巴细胞比值和胰腺外炎症CT评分预测的准确度最高,胰腺外炎症CT评分与AP严重性的相关系数最大,其预测AP严重性的受试者曲线下面积最大.     

急性胰腺炎微循环障碍的发生机制及其治疗进展

近年来,越来越多的研究表明,血管收缩、血液分流、灌注不足、血液黏滞度增加以及血液凝固等微循环障碍与急性胰腺炎(AP)的发病机制密切相关。缺血再灌注损伤及氧自由基的不断产生亦可加速AP的进程。介绍了胰腺微循环的解剖学特征、胰腺微循环障碍的病理生理学机制及相关的炎症介质,以及AP微循环障碍的治疗进展,提示胰腺及全身微循环障碍可能在AP发生发展中起着重要的作用。     

急性胰腺炎相关腹腔积液的研究进展

急性胰腺炎(AP)相关腹腔积液是AP患者常见的并发症，与患者疾病严重程度、局部及全身并发症的发生及预后密切相关。胰腺炎相关腹腔积液产生可能来源于腹腔内血管、淋巴管及胰管的渗漏等。近年来，研究发现通过腹腔穿刺引流早期积极清除胰腺炎相关腹腔积液有助于降低全身炎症水平及缓解胰腺炎相关器官损伤，从而改善重症AP患者病情及降低病死率。但胰腺炎相关腹腔积液如何加重全身炎症反应、参与胰腺和远处器官损害，以及如何导致AP患者病情恶化，尚不完全清楚。因而，本文就AP相关腹腔积液的概况及近年来的研究做一综述，为AP病理生理过程及治疗的探索提供一些方向。     

环氧合酶-2对重症急性胰腺炎大鼠模型的实验研究

胰腺细胞内胰蛋白酶原激活是引起急性胰腺炎(AP)的起始因素，然而决定病程转归及严重程度的机制并未明确。研究显示，胰酶激活后的炎症反应与AP严重程度密切相关。环氧合酶-2(COX-2)受各种炎症因子调节，在炎症发生发展中起重要作用。已有研究证实，AP时胰腺细胞中COX-2表达增加。我们在5％牛磺胆酸钠诱导大鼠重症急性胰腺炎(SAP)模型中，用特异性COX-2抑制剂(NS-398)干预，观察胰腺组织COX-2变化及这一变化与胰腺组织学之间的关系，探讨COX-2在AP中的可能作用机制。     

SOCS3在大鼠急性胰腺炎早期炎症反应过程中对NF-κB的影响

目的探讨SOCS3在急性胰腺炎(alute pancreatitis,AP)早期炎症反应过程中与NF-κB的关系,为AP早期炎症反应过程的治疗提供理论依据。方法 48只雄性Sprague-Dawley(SD)大鼠随机分为2组:假手术组(8只)、AP造模组(40只)。假手术组开腹后翻动肠管;AP造模组以4%牛磺胆酸钠胰胆管逆行注射诱导模型。各组分别于术后3 h、6 h、12 h、18 h、24 h抽血检测血清淀粉酶(AMY),并测定腹水量;光镜下观察胰腺病理形态学改变;采用免疫组化法和Western blotting法检测SOCS3和NF-κBp65在胰腺中定位和蛋白表达水平。结果与假手术组比较,AP各组胰腺病理损伤程度随病情进展逐渐加重,淀粉酶(AMY)水平均明显升高,腹水量明显增多(P0.05);在AP病程进展的不同时段,SOCS3和NF-κBp65表达水平均明显高于假手术组,且各组间比较,差异有统计学意义(P0.05)。结论 SOCS3和NF-κB均参与AP早期胰腺损伤及炎症反应过程,并与AP严重程度、持续时间密切相关,可能在胰腺局部及全身炎症反应的调节中起重要作用。     

大黄对急性胰腺炎多靶点的治疗作用

急性胰腺炎(AP)是临床常见的急腹症之一,病情轻重不等。轻者以胰腺水肿为主,病情自限;约10％～20％的患者将进展为重症胰腺炎,表现为胰腺出血、坏死,可引起全身性炎症反应综合征(SIRS)和多脏器功能衰竭(MOF),死亡率高达10％～50％。 AP的发病机制至今尚未能完全阐明,大量研究表明胰酶激活和胰腺自身消化是AP发病初期的细胞内事件,而促使AP重症化的因素是胰腺缺血、微循环紊乱、肠道细菌易位和胰腺感染以及氧自由基损伤等。由于目前对AP的发病机制有了更深层次的了解,已明确胰酶一旦被激活,药     

急性胰腺炎流行病学及严重性预测评估研究进展

流行病学显示急性胰腺炎(acute pancreatitis,AP)的发病率有所增加。依据修订的Atlanta分类标准,分为轻、中、重型AP,其严重性的预测方法有急性胰腺炎床旁严重性指标评分(BISAP)、急性胰腺炎胰腺外炎症CT评分(EPIC)及外周血中性粒细胞与淋巴细胞比值(NLR)等。     

三种不同造模方法建立大鼠急性胰腺炎模型的对比

目的采用雨蛙肽、L-精氨酸、牛磺胆酸钠作为诱导剂建立大鼠急性胰腺炎(AP)动物模型,通过大鼠病理评分、血清生化及炎症细胞因子指标检测,找出一种操作简单、重复性好的大鼠AP造模方法。方法采用不用造模方法处理后的大鼠在不同时间点采集血液及胰腺标本。检测指标有淀粉酶(AMY)、谷丙转氨酶(ALT)、尿素氮(BUN)、肌酐(Cr)、Ca~(2+)、超氧化物歧化酶(SOD)、白介素(IL)-6、IL-10、肿瘤坏死因子(TNF)-α及胰腺组织病理评分。结果雨蛙肽组大鼠血清检查结果及胰腺病理均符合轻型AP改变,L-精氨酸及牛磺胆酸钠组血清检查结果及胰腺病理均符合重症AP改变。结论三种方法均可成模,大鼠AP模型病情最重的是牛磺胆酸钠诱导组,其次为L-精氨酸诱导组,病情最轻为雨蛙肽诱导组。     

人重组血管生成素-1对小鼠急性胰腺炎的治疗作用及机制

目的观察血管生成素-1(Ang-1)对小鼠急性胰腺炎(AP)的治疗作用,并探讨其作用机制。方法BALB/c小鼠54只,随机分为对照组、AP组、Ang-1治疗组(各18只)。AP组:腹腔注射雨蛙素50μg/kg,1次/h,共7次,制成AP模型;Ang-1治疗组:同法制作AP模型,之后腹腔注射100μg/kg的Ang-1;对照组:腹腔注射等量生理盐水。上述各组小鼠在作相应处理后分别于9、18、24 h各取6只,摘眼球取血处死,取胰腺组织观察其病理变化并评分(Schmidt法),检测小鼠血清淀粉酶(AMY)、TNF-α、IL-6。结果 AP组胰腺组织病理学评分及血清AMY、TNF-α、IL-6水平较对照组明显升高(P均<0.01),Ang-1治疗组胰腺组织病理学评分及血清AMY、TNF-α、IL-6水平较AP组下降(P均<0.05)。结论 Ang-1可明显减轻雨蛙素诱导的小鼠AP的炎症反应及胰腺损伤,其作用机制与降低炎症因子TNF-α、IL-6的水平有关。     

新CT评分系统预测急性胰腺炎病情严重程度的临床研究

目的 在综合急性胰腺炎(AP)患者胰腺外炎症征象及胰腺坏死程度基础上,建立一种新CT评分系统--胰腺外炎症和胰腺坏死CT指数(EPIPN)评分系统.以初步探讨其预测AP病情严重程度和预后的诊断价值.方法 回顾分析2006年8月至2007年12月住院确诊的77例AP患者的临床资料,包括年龄、性别、病因、起病72 h C反应蛋白(CRP)水平、Ranson评分、人院48 h时APACHEⅡ评分,器官衰竭发生情况、腹痛消失时间、住院时间等.所有患者人院后2～3 d行增强CT检查,获得CT严重指数(CTSI)评分和EPIPN评分,CTSI≥7分为重症AP(SAP),EPIPN>5分为SAP.应用ROC曲线比较EPIPN和CTSI预测AP病情严重程度的诊断效力,初步分析EPlPN和CTSI与AP临床预后指标的相关性.结果 77例患者中男34例,女43例,平均年龄51.79岁(22～92岁).胆源性63例,高血脂6例,酒精性1例,原因不明7例.14例(18.2%)患者曾发生器官衰竭.EPIPN和CTSI预测SAP的ROC曲线下面积分别为0.82(95%可信区间0.73～0.91)、0.72(95%可信区间0.59～0.86),CTSI≥7预测SAP的灵敏度、特异度分别为80.4%和55%,EPIPN>5预测SAP的灵敏度、特异度分别为91.3%和63%.EPIPN与AP患者住院时间、APACHEⅡ评分、CRP有良好的相关性.结论 EPIPN可准确预测和评估AP病情严重程度和预后,其诊断效力优于CTSI.EPIPN简便实用,具有良好的临床应用价值.     

Inflammatory bowel disease does not alter the clinical features and the management of acute pancreatitis: A prospective,multicentre, exact-matched cohort analysis

Objective and aimsAcute pancreatitis in inflammatory bowel disease occurs mainly as an extraintestinal manifestation or a side effect of medications. We aimed to investigate the prognostic factors and severity indicators of acute pancreatitis and the treatment of patients with both diseases.DesignWe performed a matched case-control registry analysis of a multicentre, prospective, international acute pancreatitis registry. Patients with both diseases were matched to patients with acute pancreatitis only in a 1:3 ratio by age and gender. Subgroup analyses were also carried out based on disease type, activity, and treatment of inflammatory bowel disease.ResultsNo difference in prognostic factors (laboratory parameters, bedside index of severity in acute pancreatitis, imaging results) and outcomes of acute pancreatitis (length of hospitalization, severity, and local or systemic complications) were detected between groups. Significantly lower analgesic use was observed in the inflammatory bowel disease population. Antibiotic use during acute pancreatitis was significantly more common in the immunosuppressed group than in the non-immunosuppressed group (p = 0.017). However, none of the prognostic parameters or the severity indicators showed a significant difference between any subgroup of patients with inflammatory bowel disease.ConclusionNo significant differences in the prognosis and severity of acute pancreatitis could be detected between patients with both diseases and with pancreatitis only. The need for different acute pancreatitis management is not justified in the coexistence of inflammatory bowel disease, and antibiotic overuse should be avoided.     

Early prediction of severity in acute pancreatitis. Is this possible?

One out of ten cases of acute pancreatitis develops into severe acute pancreatitis which is a life threatening disorder with a high mortality rate. The other nine cases are self limiting and need very little therapy. The specificity of good clinical judgement on admission, concerning the prognosis of the attack, is high (high specificity) but misses a lot of severe cases (low sensitivity). The prediction of severity in acute pancreatitis was first suggested by John HC Ranson in 1974. Much effort has been put into finding a simple scoring system or a good biochemical marker for selecting the severe cases of acute pancreatitis immediately on admission. Today C-reactive protein is the method of choice although this marker is not valid until 48-72 hours after the onset of pain. Inflammatory mediators upstream from CRP like interleukin-6 and other cytokines are likely to react faster and preliminary results for some of these mediators look promising. Another successful approach has been to study markers for the activation of trypsinogen such as TAP and CAPAP. This is based on studies showing that active trypsin is the initial motor of the inflammatory process in acute pancreatitis. In the near future a combined clinical and laboratory approach for early severity prediction will be the most reliable. Clinical judgement predicts 1/3 of the severe cases on admission and early markers for either inflammation or trypsinogen activation should accurately identify 50-60% of the mild cases among the rest, thus missing only 2-4% of the remaining severe cases. One problem is that there is no simple and fast method to analyze any of these parameters.     

Clinical significance of the neutrophil-lymphocyte ratio as an early predictive marker for adverse outcomes in patients with acute pancreatitis

AIM To investigated the prognostic value of the neutrophillymphocyte ratio(NLR) in patients with acute pancreatitis and determined an optimal cut-off value for the prediction of adverse outcomes in these patients.METHODS We retrospectively analyzed 490 patients with acute pancreatitis diagnosed between March 2007 and December 2012. NLRs were calculated at admission and 24, 48, and 72 h after admission. Patients were grouped according to acute pancreatitis severity and organ failure occurrence, and a comparative analysis was performed to compare the NLR between groups. RESULTS Among the 490 patients, 70 had severe acute pancreatitis with 31 experiencing organ failure. The severe acute pancreatitis group had a significantly higher NLR than the mild acute pancreatitis group on all 4 d(median, 6.14, 6.71, 5.70, and 4.00 vs 4.74, 4.47, 3.20, and 3.30, respectively, P 0.05). The organ failure group had a significantly higher NLR than the group without organ failure on all 4 d(median, 7.09, 6.72, 6.27, and 6.24 vs 4.85, 4.49, 3.35, and 2.34, respectively, P 0.05). The optimal cut-off value for baseline NLR was 4.76 in predicting severity and 4.88in predicting organ failure in acute pancreatitis. CONCLUSION Elevated baseline NLR correlates with severe acute pancreatitis and organ failure.     

Balthazar computed tomography severity index is superior to Ranson criteria and APACHE II and III scoring systems in predicting acute pancreatitis outcome

BACKGROUND AND GOALS: Acute pancreatitis runs an unpredictable course. We prospectively analyzed the prognostic usefulness of four different scoring systems in separately assessing three variables; acute pancreatitis severity, development of organ failure and pancreatic necrosis. STUDY: 78 patients with acute pancreatitis were studied prospectively. Data pertinent to scoring systems were recorded 24 hours (APACHE II and III scores), 48 hours (Ranson score) and 72 hours (Balthazar computed tomography severity index) after admission. Statistical analysis was performed by using receiver operating characteristic curves and by comparing likelihood ratios of positive test (LRPT) for all three outcome variables. RESULTS: 44 patients were classified as mild and 34 as severe pancreatitis. When we compared LRPT, only that for the Balthazar score (11.2157) was able to generate large and conclusive changes from pretest to post-test probability in acute pancreatitis severity prediction. LRPT were 2.4157 for Ranson, 4.0980 for APACHE II and 3.6670 for APACHE III score. The APACHE II and III scores and Ranson criteria performed slightly better than the Balthazar score in predicting organ failure (LRPT: 4.0667, 3.2892, 3.0362 and 1.7941 respectively), while when predicting pancreatic necrosis the APACHE II and III performed slightly better than the Ranson score (LRPT: 2.0769, 2.7500 and 1.7813 respectively). CONCLUSIONS: In all outcome measures the APACHE scores generate small and of similar extent changes in probability. The Balthazar score is superior to other scoring systems in predicting acute pancreatitis severity and pancreatic necrosis. However the Ranson and APACHE scores perform slightly better with respect to organ failure prediction.     

Laboratory diagnostic tests in acute pancreatitis

The diagnosis of acute pancreatitis depends on a combination of clinical assessment and laboratory testing. Although the serum amylase is the cornerstone laboratory test used in establishing the diagnosis of acute pancreatitis, there are limitations in the sensitivity and specificity that may be important for the clinician to recognize. The serum lipase level may be especially useful in patients with alcohol-induced acute pancreatitis. A new urinary test strip that uses trypsinogen-2 may have a role in establishing the diagnosis of acute pancreatitis. In addition, several new laboratory tests and new interpretations of old laboratory tests may assist in establishing the etiology and severity of acute pancreatitis. This review summarizes important aspects of standard laboratory tests and novel laboratory approaches in establishing the diagnosis, etiology, and severity of acute pancreatitis.     

Criteria for the diagnosis and severity stratification of acute pancreatitis

Recent diagnostic and therapeutic progress for severe acute pancreatitis(SAP)remarkably decreased the casemortality rate.To further decrease the mortality rate of SAP,it is important to precisely evaluate the severity at an early stage,and initiate appropriate treatment as early as possible.Research Committee of Intractable Diseases of the Pancreas in Japan developed simpler criteria combining routinely available data with clinical signs.Severity can be evaluated by laboratory examinations or by clinical signs,reducing the defect values of the severity factors.Moreover,the severity criteria considered laboratory/clinical severity scores and contrastenhanced computed tomography(CE-CT)findings as independent risk factors.Thus,CE-CT scans are not necessarily required to evaluate the severity of acute pancreatitis.There was no fatal case in mild AP diagnosed by the CE-CT severity score,whereas case-mortality rate in those with SAP was 14.8%.Case-mortality of SAP that fulfilled both the laboratory/clinical and the CE-CT severity criteria was 30.8%.It is recommended,therefore,to perform CE-CT examination to clarify the prognosis in those patients who were diagnosed as SAP by laboratory/clinical severity criteria.Because the mortality rate of these patients with SAP is high,such patients should be transferred to advanced medical units.     

Immune-manipulation of the inflammatory response in acute pancreatitis. What can be expected?

Severe acute pancreatitis still has a high mortality rate and multiple organ failure is considered to be a severe complication of the disease. Activated polymorphonuclear leukocytes have an important role in the development of multiple organ failure which may result from acute pancreatitis and they are an important pathogenetic factor in the severity of this disease. Therefore, a logical therapeutic approach is to limit the organ damage by selective suppression of inflammatory mediators involved in the systemic inflammatory response syndrome and protect against systemic complication. In this paper, we review the recent literature data on the possible manipulation of the immune response in acute pancreatitis.     

Predictors of adverse outcomes in acute pancreatitis: new horizons

Acute pancreatitis (AP) continues to be a clinical challenge. The mortality of patients with AP with adverse outcomes like organ failure and infected necrosis can be as high as 43 %. Highly accurate predictors of adverse outcomes are necessary to identify the high-risk patients so that they can be meticulously monitored and managed. However, there are no ideal predictors till date. Over the past several years, a number of single- and multi-parameter predictors have been identified and tested for prediction of adverse outcomes in AP. Out of the different tools tested, blood urea nitrogen and the harmless acute pancreatitis score appears to be useful and feasible in the management of AP under Indian conditions. Other single-parameter predictors like serum creatinine, hematocrit, erythrocyte sedimentation rate, C-reactive protein, and D-dimer need to be put to further tests in high-quality prospective studies with large sample size at the community level. Multi-parameter prediction tools like the bedside index of severity of acute pancreatitis may not be appealing in day-to-day clinical practice.     

Early laboratory biomarkers for severity in acute pancreatitis; A systematic review and meta-analysis

Background/ObjectivesAcute pancreatitis is complicated by local and systemic complications in 20–30% of the patients. Accurate prediction of severity may be important for clinical decision making. Our aim is to identify and compare the accuracy of laboratory biomarkers that predict severity and complications in adult patients.MethodsMedline, EMBASE, Web of Science and Cochrane Library (1993 to August 2020) were searched for studies with an unselected population of patients with acute pancreatitis, that contains accuracy data for ≥1 laboratory biomarker(s) and/or APACHE-II score for the prediction of a patient outcomes of interest during the first 48 h of admission. The primary outcome is moderate severe or severe acute pancreatitis (MSAP/SAP). Secondary outcomes are severe acute pancreatitis, pancreatic necrosis and organ failure. Risk of bias was assed using QUADAS-2. Biomarkers extracted from ≥3 unique sources, were analyzed using hierarchical summary receiver operating characteristic (HSROC) and bivariate model analysis.ResultsIn total, 181 studies were included in the qualitative analysis reporting on 29 biomarkers. For the primary outcome at admission, summary sensitivities and specificities were, respectively, 87% (95% CI 69–95%) and 88% (95% CI 80–93%) for IL-6 at a threshold of >50 pg/ml, 72% (95% CI 64–79%) and 76% (95% CI 67–84%) for an APACHE-II score of ≥8, and 53% (95% CI 35–71%) and 82% (95% CI 74–88%) for CRP >150 mg/l. HSROC curve analysis confirmed these results.ConclusionThis study indicates superiority of IL-6 for the early prediction of MSAP/SAP and may be used for to guide clinical decision making.     

Laboratory markers of severe acute pancreatitis

BACKGROUND: A large array of parameters has been proposed for the biochemical stratification of severity and prediction of complications in acute pancreatitis. However, the number of accurate and readily available variables for routine application is still limited. METHODS: The literature was reviewed for laboratory markers of acute pancreatitis with special regard to their clinical usefulness and test performance for stratifying severity and monitoring disease progression. RESULTS: Several parameters, such as trypsinogen and procarboxypeptidase B activation peptide, PMN-elastase, interleukin-6 (IL-6) and 8 (IL-8), serum amyloid A (SAA), and procalcitonin (PCT), can differentiate between mild and severe acute pancreatitis within 48 h of disease onset with favorable diagnostic accuracy. Because fully automated assays have become available, IL-6, IL-8, PCT, and SAA are the most interesting parameters in this respect. For monitoring disease progression beyond 48 h, acute-phase proteins, IL-6, IL-8, and PCT are valuable markers. PCT is the first biochemical variable for predicting severe pancreatic infections and overall prognosis throughout the course of acute pancreatitis with high sensitivity and specificity. CONCLUSIONS: Among all the biochemical variables available, C-reactive protein is still the standard for a fast, reliable, and cost-effective assessment of severity in acute pancreatitis. PCT substantially contributes to an improved stratification of patients at risk to develop major complications and deserves routine application.