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1、1Center for Pancreatic Care, Southern California Permanente Medical Group, Department of Gastroenterology, Kaiser Permanente Los Angeles Medical Center, Los Angeles, California （南加州,凯萨医疗机构） ; and 2 Center for Pancreatic Disease, Division of Gastroenterology, Hepatology and Endoscopy, Brigham and Wom
2、ens Hospital, Harvard Medical School, Boston, Massachusetts（波士顿，哈佛医学院),Keywords: Clinical Management; Fluid Resuscitation; Necrosis; Quality Improvement.,Abstract,Acute pancreatitis is the leading cause of hospitalization for gastrointestinal disorders in the US, with more than 280,000 hospitalizati
3、ons each year. The average length of stay at US hospitals in 2010 was estimated to be 5 days, at an aggregate cost of $2.9billion. 高发病率；平均住院时间：5天；治疗费用高昂 Mortality ranges from 3% for patients with interstitial (edematous) pancreatitis to 15% for patients who develop necrosis. 死亡率：3%（间质水肿性AP）-15%(坏死性A
4、P) As the rate of hospitalization for acute pancreatitis continues to increase, so does the demand for effective management. This demand has resulted in publication of at least 14 clinical practice guidelines in the past decade. An update to the American Pancreas Association and International Associ
5、ation of Pancreatology guidelines is forthcoming. 急性胰腺炎诊治指南需进一步规范,1. Peery AF, Dellon ES, Lund J, et al. Burden of gastrointestinal disease in the United States: 2012 update. Gastroenterology 2012;143:11791187. 2. Singh VK, Bollen TL, Wu BU, et al. An assessment of the severity of interstitial pancr
6、eatitis. Clin Gastroenterol Hepatol 2011;9:10981103. 3. van Santvoort HC, Bakker OJ, Bollen TL, et al. A conservative and minimally invasive approach to necrotizing pancreatitis improves outcome. Gastroenterology 2011;141:12541263,Contents,Diagnosis,The diagnosis of acute pancreatitis requires at le
7、ast 2 of the following: 1.typical upper abdominal pain 典型的上腹部疼痛 2.serum levels of amylase or lipase 3 times the upper limit of normal, 胰腺酶水平3倍正常值的上限 3.conrmatory ndings from crosssectional imaging analysis. 影像学支持,A recently completed revision of the Atlanta Classication provides a more detailed syst
8、em that emphasizes disease severity and includes comprehensive denitions of pancreatic and peripancreatic collections. There are also more complete denitions of local and systemic complications.,Disease Denitions: The Revised Atlanta Classication,The Atlanta Classication system was developed at a co
9、nsensus conference in 1992 to establish standard denitions for classication of acute pancreatitis.,最新修订版的亚特兰大分类标准提供了一个更加详细的分类标准，它着重于疾病的严重程度，及包括胰腺和胰周液体聚集的综合定义，而有更加完整的局部及系统性并发症的定义。,12. Banks PA, Bollen TL, Dervenis C, et al. Classication of acute pancreatitis2012: revision of the Atlanta classication
10、and denitions by international consensus. Gut 2013;62:102111. 13. Marshall JC, Cook DJ, Christou NV, et al. Multiple organ dysfunction score: a reliable descriptor of a complex clinical outcome.Crit Care Med 1995;23:16381652.,1,2,3,Denition of Local Complications 局部并发症的定义,Denition of Systemic Compli
11、cations and Organ Failure 全身并发症及器官衰竭的定义,Denition of Severity 严重程度分类,4,Roles of Advanced Imaging Techniques 影像学的作用,Diagnosis,Denition of Local Complications,急性胰腺炎,急性胰周液体积聚（APFC）,胰腺假性囊肿,坏死性胰腺炎,急性坏死物积聚（ANC） 包裹性坏死（WON）,A variety of local complications have been delineated. Interstitial pancreatitis invo
12、lves acute collection of peripancreatic uid（ACPF） and formation of pancreatic pseudocysts. 间质水肿性胰腺炎涉及急性胰周液体积聚和胰腺假性囊肿的形成 APFC develop during the early phase早期 of interstitial pancreatitis. They are homogeneous in appearance without a well-dened wall, usually remain sterile, and frequently resolve spo
13、ntaneously (Figure A). 急性胰周液体积聚（APFC）发生胰腺炎病程早期，渗出液均匀地而边界模糊地分布于胰周，通常是无菌的，可以自行吸收 If an acute peripancreatic uid collection does not resolve spontaneously, it could develop into a pseudocyst with a welldened inammatory wall that contains uid with very little, if any, solid material (Figure B). 如果一旦胰周积液
14、不能自行吸收，它将可能发展为有完整炎症性包膜容纳少量渗出液及极少量坏死组织的假性囊肿(发生AP后4周),间质水肿性胰腺炎,Figure (A) Interstitial pancreatitis with acute peripancreatic uid collection. Peripancreatic uid collection (arrows) is poorly dened with homogeneous uid density. Figure(B) Resolving interstitial pancreatitis with pseudocyst. A pseudocyst
15、 (arrow) is typically a round or oval encapsulated collection with homogeneous uid density.,急性胰周液体积聚（APFC）,胰腺假性囊肿,Necrotizing pancreatitis involves acute collection of necrosis and walled-off necrosis. 坏死性胰腺炎包括急性坏死物积聚（ANC）及包裹性坏死（WON）。 An acute necrotic collection refers to the presence of necrotic t
16、issue involving pancreatic parenchyma and peripancreatic tissues (Figure 2). These collections can be sterile or infected. If infected,they are called infected necrosis. 急性坏死物积聚（ANC）指的是胰腺实质及胰周组织的坏死（如表格2），坏死物的积聚可是无菌性和感染性，其中感染性的又叫感染坏死。 After 4 or more weeks, an acute necrotic collection can become sma
17、ller but rarely disappears completely and usually evolves into walled-off necrosis. Walled-off necrosis has a well-dened inammatory wall that contains varying amounts of uid and necrotic debris (Figure 3). 在4周及之后，急性坏死物的积聚逐渐变小，但很少有被完全吸收，通常发展为有炎症性包膜容纳混合大量渗出液及少量坏死物碎片的包裹性坏死（WON）（如表格3）。,Figure 2. Pancrea
18、tic and peripancreatic necrosis. This image shows an acute necrotic collection involving both the pancreas (large arrow) and peripancreatic tissue. Figure 3. Walled-off pancreatic necrosis is an encapsulated collection of necrosis. This type of collection typically forms 4 to 6 weeks after disease o
19、nset. This image shows pancreatic and peripancreatic necrosis.,坏死性胰腺炎,急性坏死物积聚（ANC）,包裹性坏死（WON）,Denition of Systemic Complications and Organ Failure,In the revised Atlanta Classication, systemic complications are dened as exacerbations of preexisting comorbidities such as chronic lung disease, chronic
20、 liver disease, or congestive heart failure, recognizing the failure of respiratory, cardiovascular, and renal organ systems.,在修订版的亚特兰大分类标准，全身并发症被定义为，先前存在的疾病诸如慢性肺部疾病、慢性肝病、充血性心力衰竭等的突然恶化，这些被认为是呼吸系统、心血管系统、肾脏功能系统的损害加重而衰竭。,Denition of Systemic Complications and Organ Failure,The scoring system that has b
21、een chosen to characterize organ failure is the modied Marshall scoring system . The modied Marshall system classies disease severity on a scale from 0 to 4, so that the overall evaluation of organ dysfunction can be more completely delineated and characterized over time. In this system, organ failu
22、re is dened by a score of 2 for one or more of these organ systems.,改良的马歇尔评分系统用于器官衰竭的评分，该评分系统将急性胰腺炎的严重程度分为04级，以至于更能清晰及特征性地对器官功能障碍发展进行综合评价。在该评分系统中，器官衰竭定义为有任何1个及多个器官功能评分 2分。,13. Marshall JC, Cook DJ, Christou NV, et al. Multiple organ dysfunction score: a reliable descriptor of a complex clinical outc
23、ome.Crit Care Med 1995;23:16381652.,Denition of Severity,Most patients with mild acute pancreatitis do not require pancreatic imaging analysis and are usually discharged within 3 to 5 days of onset of illness . 轻型急性胰腺炎患者无需影像学检查，住院时间通常为3-5天,Patients with moderately severe acute pancreatitis frequentl
24、y require extended hospitalization but have lower mortality rates than patients with severe acute pancreatitis. 中度重症急性胰腺炎需延长住院时间，但病死率低于重症急性胰腺炎,A meta-analysis found patients with severe acute pancreatitis with persistent organ failure have a 30% mortality rate; the risk of in-hospital death doubles
25、when they have persistent organ failure and infected necrosis. 重症急性胰腺炎有高达30%的病死率，当出现持续性器官功能衰竭和感染坏死时，住院期间死亡的风险成倍增加。,15. Petrov MS, Shanbhag S, Chakraborty M, et al. Organ failure and infection of pancreatic necrosis as determinants of mortality in patients with acute pancreatitis. Gastroenterology 20
26、10;139:813820.,Roles of Advanced Imaging Techniques,The role of CT in assessing patients with acute pancreatitis has changed with time. CT的作用是用于评价急性胰腺炎发病及治疗各阶段的变化 A contrast-enhanced CT scan obtained within the rst several days of illness cannot be used to determine whether a patient has necrotizing
27、 or severe interstitial pancreatitis. This might be because intrapancreatic uid causes heterogeneous enhancement, which can indicate necrosis. 在发病的前几天，不能通过CT检查判断出胰腺坏死的存在及其范围，这可能是由于胰腺内液体渗出导致了CT的不均匀增强。 Over a period of several days, the uid can be reabsorbed such that a subsequent CT scan clearly show
28、s the absence of necrosis. As such, patients should not be evaluated by CT within a few days after the onset of disease to establish the presence or extent of pancreatic necrosis. 胰腺积液被重吸收后，后来的CT检查才能够区分液体积聚或胰腺坏死范围。,The best use of an early-stage CT scan is to conrm a diagnosis of acute pancreatitis
29、when the clinical situation is unclear. 发病早期行CT检查仅能用于诊断不明时，以确诊急性胰腺炎。 The best use of a CT scan after the rst 5 to 7 days is to evaluate the presence of local complications in patients with moderately severe or severe pancreatitis to guide ongoing care. 发病的第一个5-7天后行CT检查最大好处，用以评价中度重症急性胰腺炎或重症急性胰腺炎病人的局部
30、并发症，并指导治疗。,MRCP has become a useful procedure for identifying retained common bile duct stones. Selective use of MRCP can reduce the need for ERCP for patients with suspected gallstone pancreatitis. MRCP对胆管结石敏感，能够减少因怀疑为胆源性胰腺炎而行ERCP检查。 MRI is helpful in distinguishing walled-off necrosis from a pseud
31、ocyst. For example, in walled-off necrosis, there are variable amounts of uid and solid debris that can be visualized using T2-weighted imaging. MRI能用于鉴别是包裹性坏死（WON）或是胰腺假性囊肿，因为T2加权像能很直观地看出含有大量渗液体及固体坏死物的包裹性坏死。 Endoscopic ultrasonography is a highly sensitive test for detecting cholelithiasis and chole
32、docholithiasis.19 It could be an alternative to MRCP, which has limited accuracy for detecting smaller gallstones or sludge. 超声内镜对胆石病高度敏感，可以代替对细小结石或淤泥样胆汁不敏感的MRCP检查。,1,2,3,Prognostic Factors 预后因素,Risk and Prognostic Factors,Clinical scoring systems 临床系统性评分,Risk factors 危险因素,Risk factors,？,Comorbid il
33、lnesses,Alcohol,60 years of age or older,cancer, heart failure, and chronic kidney and liver disease,BMI30 kg/m2,chronic alcohol consumption,increases the risk of severe pancreatitis 3-fold and mortality 2-fold,Clinical scoring systems,The initial 12 to 24 hours of hospitalization is critical during
34、 patient management, because the highest incidence of organ dysfunction occurs during this period. 发病第12-24h是临床处理非常重要，器官功能障碍多发生于这个时段。 A number of clinical scoring systems and biomarkers have been developed to facilitate risk stratication during this phase. Whereas previous scoring systems such as th
35、e Ranson or ImrieGlasgow scores required 48 hours to complete, 2 scoring systems were recently developed and involve a simplied approach that can be performed during the rst 24 hours of hospitalizationThe Bedside Index of Severity in Acute Pancreatitis . Ranson 评分系统、ImrieGlasgow评分系统对疾病的危险分层评分滞后， 最新的
36、AP严重程度床旁指数（BISAP） 可在发病24h内完成。,26. Harrison DA, DAmico G, Singer M. Case mix, outcome, and activity for admissions to UK critical care units with severe acute pancreatitis: a secondary analysis of the ICNARC Case Mix Programme Database. Crit Care 2007;11(Suppl 1):S1. 27. Wu BU, Conwell DL. Update in
37、acute pancreatitis. Curr Gastroenterol Rep 2010;12:8390.,Clinical scoring systems,AP严重程度床旁指数,BUN25 mg/dl(8.9mmol/L),Impaired mental status 精神状态受损,SIRS,age 60 years or older,pleural effusion 胸腔积液,Score 2 within 24 hours is associated with a 7-fold increase in risk of organ failure and 10-fold increas
38、e in risk of mortality. 发病24小时内分数2分，发生器官衰竭的风险增加7倍，死亡的风险增加10倍。,Another scoring system, the Harmless Acute Pancreatitis Score, uses a different approach to risk stratication, identifying patients at the time of admission who are unlikely to experience complications related to acute pancreatitis. Speci
39、cally, patients with a normal hematocrit and normal serum level of creatinine without rebound tenderness or guarding, are unlikely to develop severe pancreatitis (positive predictive value of 98%). 轻症急性胰腺炎评分（HAPS）则注重于在入院时不会发生与急性胰腺炎相关并发症的病人的评分，特别是Hct、Cre正常，无反跳痛体征的病人，将不再发展为重症急性胰腺炎（阳性率高达98%）。 With resp
40、ect to scoring systems, the most widely validated remains the Acute Physiology and Chronic Health Examination II score. These scoring systems have comparable levels of overall accuracy. 最受到广泛认同的评分系统为急性生理功能和慢性健康状况评分系统 (APACHE II)， 这些评分系统具有相当的水平的整体精度。,Prognostic Factors,Additional approaches have been
41、 developed to monitor disease progression. Parameters that are easy to determine and have been validated for their ability to determine disease activity include the presence of SIRS, level of BUN or Cr, and hematocrit. SIRS、尿素氮水平、肌酐水平、红细胞压积的参数，用于监测疾病的进展。,Prospective studies have shown that the level
42、 of BUN at admission and during the initial 24 hours of hospitalization is a strong prognostic factor. For example, patients with a level of BUN at admission 20 mg/dL that increased during the initial 24 hours have 9% to 20% mortality. By contrast, patients with an increased level of BUN at admissio
43、n that decreased at least 5 mg/dL within 24 hours have 0% to 3% mortality. 入院时及入院后24小时内BUN水平的高低是一个非常重要的预后因素。例如，入院时患者BUN20 mg/dL（7.14mmol/L），在发病最初24小时内可增加9%- 20%的病死率，相反，高BUN水平在入院后24小时内至少下降5 mg/dL(1.8mmol/L)则有0% - 3% 病死率。,38. Wu BU, Bakker OJ, Papachristou GI, et al. Blood urea nitrogen in the early a
44、ssessment of acute pancreatitis: an international validation study. Arch Intern Med 2011;171:669676. 39. Wu BU, Johannes RS, Sun X, et al. Early changes in blood urea nitrogen predict mortality in acute pancreatitis. Gastroenterology 2009;137:129135.,An increasing number of SIRS criteria during the
45、initial 24 hours of hospitalization increases the risk of persistent organ failure and necrosis as well as mortality. Patients with persistent SIRS (beyond 48 hours) have 11% to 25% mortality. SIRS增加持续性器官衰竭、胰腺坏死、病死率（11-25%）的风险。,2 or more of the following criteria,T38.3C 或36C,脉搏90次/分,WBC12109/L 或 10%
46、,呼吸20次/分,A serum level of Cr 1.8 mg/dL（159umol/L） within the rst 24 hours of hospitalization is associated with a 35-fold increased risk of development of pancreatic necrosis. A persistent increase in HCT 44% has also been shown to increase the risk of necrosis and organ failure. 研究表明，在发病的最初的24小时内血肌
47、酐1.8 mg/dL，发展为胰腺坏死的风险增加35倍 红细胞压积持续44%也同样增加了胰腺坏死及器官衰竭的风险。,33. Muddana V, Whitcomb DC, Khalid A, et al. Elevated serum creatinine as a marker of pancreatic necrosis in acute pancreatitis.Am J Gastroenterol 2009;104:164170. 34. Brown A, Orav J, Banks PA. Hemoconcentration is an early marker for organ f
48、ailure and necrotizing pancreatitis. Pancreas 2000;20:367372.,Treatment,1,2,3,Initial Resuscitation and Management 早期治疗,Management of Local Complications 局部并发症的治疗,Management of Extrapancreatic Complications 胰腺外并发症的治疗,4,Special Considerations Based on Etiology 对因治疗,Initial Resuscitation and Managemen
49、t,Aggressive volume resuscitation has been a cornerstone of therapy, based on studies in animal models and observational data from clinical studies . However, approaches to uid resuscitation require optimization. Under-resuscitation during the early phase of acute pancreatitis has been associated with increased risk of necrosis and mortality. In contrast, over-resuscitation can lead to complications such as pulmonary sequestration（肺隔离症 ）. 积极的容量复苏已经成为治疗的里程碑，疾病早期液体复苏的容量不足会增加胰腺坏死及死亡的风险，相反，如过度补液可能