JPN Guidelines for the management of acute pancreatitis: cutting-edge information

The JPN Guidelines for the Management of Acute Pancreatitis are organized under the subject headings: epidemiology, diagnosis, management strategy, severity assessment and transfer criteria, management of gallstone pancreatitis, nonsurgical management, and surgical management. The Guidelines contain cutting-edge information on each of these subjects, as well as a section on the Japanese medical insurance system which provides information that should prove useful to physicians in other countries. The quality of the evidence was evaluated by the evidence-based classification method used at the Cochrane Library. The levels of recommendation of the individual management methods contained in the Guidelines were determined on the basis of the evaluation of evidence by the consensus of the members of the Working Group (see below). The Japanese Society for Abdominal Emergency Medicine, the Japan Pancreas Society, and the Research Group for Intractable Diseases and Refractory Pancreatic Diseases (which is sponsored by the Japanese Ministry of Health, Labour, and Welfare) were commissioned to produce the JPN Guidelines for the Management of Acute Pancreatitis. A Working Group of 20 physicians specializing in pancreatic diseases and emergency medicine investigated and analyzed 14821 cases retrieved by means of a Medline (1960–2004) search and discussed the available literature on acute pancreatitis (limited to human pancreatitis). The Working Group held many general discussions in order to reach a consensus on the content of the Guidelines. After producing a draft, the Publishing Committee of the JPN Guidelines for the Management of Acute Pancreatitis posted it on a website and asked for comments and criticisms. Subsequently, a final version of the Guidelines was published in Japanese in 2003. The Publishing Committee is now making the Guidelines available to a much wider readership by bringing out an English version.     

Evidence-based clinical practice guidelines for acute pancreatitis: proposals

Background/Purpose: To provide a framework for clinicians to manage acute pancreatitis, evidence-based guidelines have been developed by the Japanese Society of Abdominal Emergency Medicine. Methods: Evidence was collected by a systematic search of MEDLINE and Japana Centra Revuo Medicina. A total of 1348 papers were reviewed and levels of evidence were assessed. Practical recommendations were also graded. Results: The present guidelines consist of introductions, a summary of recommendations, practice algorithms, definitions, epidemiology, diagnosis, severity assessment, and therapy. The main points of recommendation in these guidelines are: (1) measuring lipase for the diagnosis of acute pancreatitis (recommendation grade [RG], A). (2) The Severity of acute pancreatitis should be assessed using a scoring system, such as that of the Japanese Ministry of Health and Welfare or Acute Physiology and Chronic Health Evaluation (APACHE) II (RG, A). (3) Enhanced computed tomography (CT) should be used for assessment of degree of pancreatic necrosis and inflammation (RG, B). (4) Prophylactic antibiotic administration should be used for severe pancreatitis (RG, A), but not for mild to moderate pancreatitis (RG, D). (5) Gabexate mesilate should be used for severe pancreatitis (RG, B). (6) Enteral feeding should be used for all pancreatitis (RG, B). (7) Continuous hemodiafiltration and continuous arterial infusion of proteinase inhibitor and antibiotics may be of benefit (RG, C). (8) Fine-needle aspiration should be done for the diagnosis of infectious pancreatic necrosis, and if positive, necrosectomy is indicated (RG, A). Conclusions: These guidelines provide useful information for physicians to manage this troublesome disease. Received: May 6, 2002 / Accepted: May 17, 2002 RID="*" ID="*"  Working Group for the Practical Guidelines for Acute Pancreatitis of the Japanese Society of Emergency Abdominal Medicine RID="*" RID="*" RID="*" RID="*" RID="*" RID="*" RID="*" RID="*" RID="*" RID="*" RID="*" RID="**" ID="**"  President of the Japanese Society of Emergency Abdominal Medicine, Tokyo, Japan Offprint requests to: T. Mayumi     

Evaluation of prognostic score based on the Japanese criteria for the severity of acute pancreatitis. Part I. Retrospective study

We used the Japanese Ministry of Health and Welfare criteria for acute pancreatitis to obtain a “prognosis score” for disease severity in 63 individuals with severe pancreatitis and we assessed the usefulness of these scores. To convert the Japanese criteria into a score, we excluded the CT grade classification, assigned a value of 1 point to the prognostic factors designated (1), and a value of 0.5 points to the prognostic factors designated (2), and added the number of points to obtain the “prognosis score”. The results showed a clear difference in prognosis between patients who had scores of 1.5 or less and those whose scores were 2.0 or more. These prognosis scores were useful both in rating the efficacy of treatment and in selecting the method of treatment in the early stage. To confirm the value of these scores, it will be necessary to accumulate more cases prospectively and to conduct additional assessments.     

Identification of severe acute pancreatitis using an artificial neural network

BACKGROUND: The aim of this study was to construct and validate an artificial neural network (ANN) model to identify severe acute pancreatitis (AP) and predict fatal outcome. METHODS: All patients who presented with AP from January 2000 to September 2004 were reviewed. Presentation data on admission and at 48 hours were collected. Acute Physiology and Chronic Health Evaluation (APACHE) II and Glasgow severity (GS) score were calculated. A feed-forward ANN was created and trained to predict development of severe AP and mortality from AP; 25% of the data set was withheld from training and was used to evaluate the accuracy of the ANN. Accuracy of the ANN in predicting severity of AP was compared with APACHE II and GS scores. RESULTS: A total of 664 patients with AP were identified of whom 181 (27.3%) fulfilled the clinical and radiologic criteria for severe pancreatitis and 42 patients died (6.3%). Median APACHE II score at 48 hours was 4 (range, 0 to 23). ANN was more accurate than APACHE II or GS scoring systems at predicting progression to a severe course (P < .05 and P < .01, respectively), predicting development of multiorgan dysfunction syndrome (P < .05 and P < .01) and at predicting death from AP (P < .05). CONCLUSIONS: An ANN was able to predict progression to severe disease, development of organ failure and mortality from acute pancreatitis with considerable accuracy and outperformed other clinical risk scoring systems. Further studies are required to assess its utility in aiding management decisions in patients with AP.     

JPN Guidelines for the management of acute pancreatitis: diagnostic criteria for acute pancreatitis

The currently used diagnostic criteria for acute pancreatitis in Japan are presentation with at least two of the following three manifestations: (1) acute abdominal pain and tenderness in the upper abdomen; (2) elevated levels of pancreatic enzyme in the blood, urine, or ascitic fluid; and (3) abnormal imaging findings in the pancreas associated with acute pancreatitis. When a diagnosis is made on this basis, other pancreatic diseases and acute abdomen can be ruled out. The purpose of this article is to review the conventional criteria and, in particular, the various methods of diagnosis based on pancreatic enzyme values, with the aim of improving the quality of diagnosis of acute pancreatitis and formulating common internationally agreed criteria. The review considers the following recommendations: — Better even than the total blood amylase level, the blood lipase level is the best pancreatic enzyme for the diagnosis of acute pancreatitis and its differentiation from other diseases. — A pivotal factor in the diagnosis of acute pancreatitis is identifying an increase in pancreatic enzymes in the blood. — Ultrasonography (US) is also one of the procedures that should be performed in all patients with suspected acute pancreatitis. — Magnetic resonance imaging (MRI) is one of the most important imaging procedures for diagnosing acute pancreatitis and its intraperitoneal complications. — Computed tomography (CT) is also one of the most important imaging procedures for diagnosing acute pancreatitis and its intraabdominal complications. CT should be performed when a diagnosis of acute pancreatitis cannot be established on the basis of the clinical findings, results of blood and urine tests, or US, or when the etiology of the pancreatitis is unknown. — When acute pancreatitis is suspected, chest and abdominal X-ray examinations should be performed to determine whether any abnormal findings caused by acute pancreatitis are present. — Because the etiology of acute pancreatitis can have a crucial influence on both the treatment policy and severity assessment, it should be evaluated promptly and accurately. It is particularly important to differentiate between gallstone-induced acute pancreatitis, which requires treatment of the biliary system, and alcohol-induced acute pancreatitis, which requires a different form of treatment.     

Evaluation of prognostic score based on the Japanese criteria for the severity of acute pancreatitis. Part II. Prospective study

From July 1994 to October 1995, a prospective study was conducted at the First Department of Surgery, Mie University School of Medicine, to assess the usefulness of a prognosis score based on the Japanese criteria for the severity of acute pancreatitis. Ten patients with severe acute pancreatitis were treated, and all had good outcomes there were no deaths. In selecting early treatment according to the scoring of severity, we suggest that when the prognosis score is 2 or more and the APACHE II score is 8 or more, gallstone pancreatitis should first be treated by biliary drainage, and non-gallstone pancreatitis by peritoneal lavage. When infected pancreatic necrosis is exhibited, surgery is indicated. Conservative therapy should be selected when the prognosis score is less than 2 and the APACHE II score is less than 8. We found that the prognosis score was useful for both determining the severity of acute pancreatitis and in selecting appropriate treatment.     

JPN Guidelines for the management of acute pancreatitis: treatment of gallstone-induced acute pancreatitis

Gallstones, along with alcohol, are one of the primary etiological factors of acute pancreatitis, and knowledge of the etiology as well as the diagnosis and management of gallstones, is crucial for managing acute pancreatitis. Because of this, evidence regarding the management of gallstone-induced pancreatitis in Japan was collected, and recommendation levels were established by comparing current clinical practices with optimal clinical practices. The JPN Guidelines for managing gallstone-induced acute pancreatitis recommend two procedures: (1) an urgent endoscopic procedure should be performed in patients in whom biliary duct obstruction is suspected and in patients complicated by cholangitis (Recommendation A); and (2) after the attack of gallstone pancreatitis has subsided, a laparoscopic cholecystectomy should be performed during the same hospital stay (Recommendation B).     

Calcitonin precursors in the prediction of severity of acute pancreatitis on the day of admission

BACKGROUND: Calcitonin precursors are sensitive markers of inflammation and infection. The aim of this study was to evaluate the role of plasma calcitonin precursor levels on the day of admission in the prediction of severity of acute pancreatitis, and to compare this with the Acute Physiology And Chronic Health Evaluation (APACHE) II scoring system. METHODS: Plasma concentrations of calcitonin precursors were determined on admission in 69 patients with acute pancreatitis. APACHE II scores were calculated on admission. Attacks were classified as mild (n = 55) or severe (n = 14) according to the Atlanta criteria. Plasma calcitonin precursor levels were determined with a sensitive radioimmunoassay. RESULTS: On the day of hospital admission, plasma levels of calcitonin precursors were significantly greater in patients with a severe attack compared with levels in those with a mild attack of pancreatitis (median 64 versus 25 fmol/ml; P = 0.014), but the APACHE II scores were no different (median 9 versus 8; P = 0.2). The sensitivity, specificity, positive predictive and negative predictive values, and accuracy for the prediction of severe acute pancreatitis were 67, 89, 57, 93 and 85 per cent respectively for plasma calcitonin precursor levels higher than 48 fmol/ml, and 69, 45, 23, 86 and 50 per cent respectively for an APACHE II score greater than 7. Differences in the specificity and accuracy of the two prognostic indicators were significant (P < 0.001 and P = 0.001 respectively). A plasma calcitonin precursor concentration of more than 160 fmol/ml on admission was highly accurate (94 per cent) in predicting the development of septic complications and death. CONCLUSION: The assay of plasma calcitonin precursors on the day of admission to hospital has the potential to provide a more accurate prediction of the severity of acute pancreatitis than the APACHE II scoring system.     

Sequential organ failure assessment score in predicting outcome in patients with acute pancreatitis

Aims/Objectives

To evaluate the sequential organ failure assessment (SOFA) score pertaining to the severity and outcome in acute pancreatitis, and compare its outcome with the APACHE II score in terms of accuracy and ease of operation with a view to establishing whether the SOFA scoring system can replace APACHE II in predicting severity and outcome of acute pancreatitis.

Methods

Fifty cases of acute pancreatitis were evaluated in this prospective study. These patients were treated as per standard protocols and followed up daily. Both SOFA and APACHE II scores were calculated at admission and thereafter at 48-hour intervals till discharge or death. Subsequently, the data were analysed, and receiver operating characteristic curves were made for SOFA, APACHE II and other biochemical parameters; a p-value < 0.05 was taken as significant.

Results

The SOFA score showed a significant association in predicting the severity of the disease, especially during the first week. Moreover, it decreased the predicted severity of APACHE II by 18% and mortality by 4.5%.

Conclusion

On the day of admission, SOFA scores were comparable with APACHE II in predicting the outcome with a higher area under the ROC curve, and displayed better predicting capability as compared to APACHE II.     

Scoring of human acute pancreatitis: state of the art

Background

Acute pancreatitis remains as one of the most difficult and challenging digestive disorder to predict in terms of clinical course and outcome. Every case has an individual course and therefore acute pancreatitis remains challenging and fascinating. Due to this variability, many different scoring systems have evolved during the last decades. Every scoring system has advantages and disadvantages. Not every scoring system is capable of assessing the clinical time course of the disease, some are only suitable for the time of initial presentation.

Aim

This paper will give an overview on the development of different widely used scoring systems and their performance in assessing severity and prognosis of acute pancreatitis.

Conclusion

Severity assessment means objective quantification of overall severity of illness. Early and reliable stratification of severity is required to decide best treatment of the individual patient, preparation for possible evolving complications or for referral to specialist centers. No single scoring system is able to cover the entire range of problems associated with treatment and assessment of acute pancreatitis. In our clinical experience, we recommend hematocrit upon admission, daily sequential organ failure assessment score and procalcitonin, C-reactive protein on day 3 and CT severity index beyond the first week. These scoring tools together with close clinical follow-up of the patient ultimately lead to an optimized treatment of this challenging disease.     

Management strategy for acute pancreatitis in the JPN Guidelines

The diagnosis of acute pancreatitis is based on the following findings: (1) acute attacks of abdominal pain and tenderness in the epigastric region, (2) elevated blood levels of pancreatic enzymes, and (3) abnormal diagnostic imaging findings in the pancreas associated with acute pancreatitis. In Japan, in accordance with criteria established by the Japanese Ministry of Health, Labour, and Welfare, the severity of acute pancreatitis is assessed based on the clinical signs, hematological findings, and imaging findings, including abdominal contrast-enhanced computed tomography (CT) and magnetic resonance imaging (MRI). Severity must be re-evaluated, especially in the period 24 to 48 h after the onset of acute pancreatitis, because even cases diagnosed as mild or moderate in the early stage may rapidly progress to severe. Management is selected according to the severity of acute pancreatitis, but it is imperative that an adequate infusion volume, vital-sign monitoring, and pain relief be instituted immediately after diagnosis in every patient. Patients with severe cases are treated with broad-spectrum antimicrobial agents, a continuous high-dose protease inhibitor, and continuous intraarterial infusion of protease inhibitors and antimicrobial agents; continuous hemodiafiltration may also be used to manage patients with severe cases. Whenever possible, transjejunal enteral nutrition should be administered, even in patients with severe cases, because it seems to decrease morbidity. Necrosectomy is performed when necrotizing pancreatitis is complicated by infection. In this case, continuous closed lavage or open drainage (planned necrosectomy) should be the selected procedure. Pancreatic abscesses are treated by surgical or percutaneous drainage. Emergency endoscopic procedures are given priority over other methods of management in patients with acute gallstone-associated pancreatitis, patients suspected of having bile duct obstruction, and patients with acute gallstone pancreatitis complicated by cholangitis. These strategies for the management of acute pancreatitis are shown in the algorithm in this article.     

重症急性胰腺炎早期目标治疗研究

目的 研究两种不同液体复苏目标在重症急性胰腺炎治疗中的差别.方法 选取2000年1月至2010年1月间80例重症急性胰腺炎患者,按时间顺序分为2组.A组治疗目标为24 h内:①血压控制在90/60 mm Hg(1 mm Hg=0.133 kPa)以上;②中心静脉压控制在8～12 mmHg;③尿量控制在0.5 ml·kg-1·h-1以上.B组治疗目标按照2004:年SSC早期目标治疗标准执行,6 h内:①平均动脉压大于65 mm Hg;②中心静脉压8～12 mm Hg;③尿量大于0.5 ml·kg-1·h-1以上;④中心静脉血氧饱和度大于70%.观察患者液体治疗3 d后的Marshall评分、APACHEⅡ评分及患者胰周感染率和病死率.结果 治疗3 d后,Marshall评分A组为6.82±4.69,B组为4.48±3.78,两者之间差异有统计学意义(P=0.02);APACHEⅡ评分A组为11.35±5.96,B组为8.22±4.53,两者之间差异有统计学意义(P=0.01).A组胰周感染率和病死率分别为44%和24%,B组胰周感染率和病死率分别为37%和17%,两者之间差异无统计学意义(P值分别为0.65和0.57).结论 按照SSC指南早期目标治疗标准对重症胰腺炎患者行液体复苏可以改善治疗3 d患者脏器功能,但不能显著改善患者的胰周感染率和病死率.

Abstract：

Objective To study the difference in outcomes between two treatment regimens of goal-directed fluid therapy in patients with severe acute pancreatitis. Methods From January 2000 to January 2010, 80 patients with severe acute pancreatitis were assigned into 2 groups. In group A,patients received fluid therapy aiming at the following goals in 24 hours: (1) Blood pressure >90/60 mm Hg;(2) CVP between 8-12 mm Hg;(3) Urine output >0. 5 ml · kg-1 · h-1. In group B, patients received fluid therapy aiming at the following goals in 6 hours (according to SSC guideline,2004): (1) mean arterial blood pressure >65 mm Hg;(2) CVP between 8-12 mm Hg;(3) Urine output >0. 5 ml · kg-1 · h-1 ;(4) central venous oxygen saturation >70%. After therapy for 3 days we measured the Marshall score, APACHE Ⅱ score, and the peri-pancreatic infection and mortality rates. Results The Marshall score was 6. 82±4. 69 and 4. 48±3. 78 in group A and B, respectively (P=0. 02). The APACHE Ⅱ score was 11. 35±5. 96 and 8. 22±4. 53 in group A and B, respectively (P=0. 01). The peri-pancreatic infection rate was 44% and 37% in group A and B, respectively, and there was no significant difference between the 2 groups (P = 0. 65). The mortality rate was 24% and 17% in group A and B. There was no significant difference between the 2 groups(P=0. 57). Conclusion Goal-directed fluid therapy in patients with severe acute pancreatitis according to the SSC guideline improved organ function but it did not reduce peri-pancreatic infection and mortality rates.     

Early warning scores predict outcome in acute pancreatitis

The Early Warning Score (EWS) is a widely used general scoring system to monitor patient progress with a varying score of 0-20 in critically unwell patients. This study evaluated the EWS system compared with other established scoring systems in patients with acute pancreatitis. EWS scores were compared with APACHE scores, Imrie scores, computed tomography grading scores, and Ranson criteria for 110 admissions with acute pancreatitis. A favorable outcome was considered to be survival without intensive therapy unit admission or surgery. Nonsurvivors, necrosectomy, and critical care admission were considered adverse outcomes. EWS was the best predictor of adverse outcome in the first 24 hours of admission (receiver operating curve, 0.768). The most accurate predictor of mortality overall was EWS on day 3 of admission (receiver operating curve, 0.920). EWS correlated with duration of intensive therapy unit stay and number of ventilated days (P<0.05) and selected those who went on to develop pancreas-specific complications such as pseudocyst or ascites. EWS of 3 or above is an indicator of adverse outcome in patients with acute pancreatitis. EWS can accurately and reliably select both patients with severe acute pancreatitis and those at risk of local complications.     

Scoring systems for predicting outcome in acute hemorrhagic necrotizing pancreatitis.

Five scoring systems for predicting the severity and outcome of acute haemorrhagic necrotizing pancreatitis were retrospectively evaluated in 39 patients. The respective scores were Ranson, Imrie, APACHE II, multiple organ failure (MOF) and Sepsis Sensitivity Score (SSS). Twenty-two (56%) of the patients died. The survivors were significantly younger than the non-survivors, 68% of whom died within 3 weeks of admission to the intensive care unit. Stay in the unit was significantly longer in the former group. Sensitivity in prediction of death was best with APACHE II score greater than 9 (96%) and Ranson score greater than or equal to 3 (95%). Of the five scores, MOF greater than or equal to 4 gave the best equilibration between sensitivity (73%) and specificity (76%) and the strongest prediction of lethal outcome (80%). Although the independent factor age had low sensitivity (55%), it showed the highest values for specificity (88%) and prediction of death (86%). APACHE II scoring is concluded to be best for grading the severity of disease on admission to intensive care, while the MOF score is best for monitoring the degree of organ dysfunction and the intensity of supportive treatment.     

Severe acute pancreatitis in Japan

The status of severe acute pancreatitis in Japan has been clarified by a series of surveys of the disease carried out by the Research Committee of Intractable Diseases of the Pancreas under the aegis of the Japanese Ministry of Health and Welfare. The severity of disease classification systems, consisting of: clinical signs and symptoms, laboratory data, and computed tomographic grading, have led to early detection of severe disease with precise assessment and the potential to screen for local complications. Early mortality has been markedly reduced by intensive care, with specific treatment modalities, while there has been an increase in late mortality caused by severe infection. Indications for surgery have been changed: to debridement for infected pancreatic necrosis and drainage of abscess although the timing of surgery is still controversial.     

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重症急性胰腺炎治疗过程中面临的一个主要难题是在疾病的变化过程中预测其严重程度和潜在并发症。常见的评分标准包括Ranson、APACHEⅡ和序贯器官衰竭评分(SOFA)等。单一的预测指标除白细胞、血氧分压、血糖、血钙外,更有价值的有降钙素原、腹腔内压、BalthazarCT评分等。重症急性胰腺炎两个最重要标志是器官衰竭和胰腺坏死,预后评价应同时考虑器官衰竭和胰腺坏死因素,将形态学和生理学指标相结合,以提高预测的准确性。     

动态检测血清白介素-18对急性胰腺炎病情及预后评价的意义

目的 探索急性胰腺炎患者血清中自介素-18(IL-18)水平变化情况,及其与患者入院时APACHE Ⅱ评分及患者预后之间的关系.方法 按照急性胰腺炎的临床诊断及分级标准分组选择AP患者34例,其中重症胰腺炎(SAP)患者12例,轻型急性胰腺炎(MAP)患者22例,正常对照组16例.用ELISA法检测血清IL-18浓度.结果 血清中IL-18浓度在MAP和SAP两组患者之间均存在统计学差异(P<0.01),SAP组明显高于MAP组,且IL-18水平动态变化与APACHEⅡ评分呈正相关.结论 血清IL-18参与了急性胰腺炎的炎症反应过程,可以作为预测急性胰腺炎严重程度的指标.     

肠型脂肪酸结合蛋白应用于重症急性胰腺炎胃肠道功能及病情评估的研究

目的探讨肠型脂肪酸结合蛋白（I-FABP）在重症急性胰腺炎（SAP）患者胃肠道功能障碍严重程度以及病情评估中的意义。 方法选取2016年12月至2018年12月青岛市第八人民医院收治的34例SAP患者，收集入院时患者血清I-FABP、降钙素原（PCT）、C反应蛋白（CRP）浓度以及白细胞计数等临床资料，并进行胃肠功能障碍程度评分以及急性生理与慢性健康状况（APACHEⅡ）评分，将以上指标与I-FABP质量浓度进行相关性分析。 结果入院时I-FABP浓度为（551±204）ng/L，PCT浓度为（3.36±1.79）μg/L，CRP浓度为（171±73）mg/L，白细胞计数为（14.47±4.09）×10⁹/L，APACHE Ⅱ评分为（12±5）分，胃肠道功能障碍评分为（10±2）分。患者血清I-FABP浓度和入院时PCT、CRP浓度、白细胞计数、APACHEⅡ评分、胃肠道功能评分均呈正相关关系（P<0.01），r分别为0.537、0.662、0.730、0.716、0.686。 结论血清I-FABP与血清炎性指标、APACHEⅡ评分和胃肠道功能评分存在相关性，有助于评估SAP患者的胃肠功能障碍及疾病严重程度。     

Staging of acute pancreatitis. Is it important?

Staging of acute pancreatitis is important for selection of patients for clinical trials, comparison of results between centers, and the early identification of patients who may benefit from therapeutic intervention or transfer to a specialist unit. The APACHE-II score and other multiple-factor scoring systems are widely used for the first two indications, and of these, the APACHE-II score provides the best accuracy at an early stage in the course of the illness. Presently, however, no system provides sufficient predictive power to facilitate clinical decision making. At a time of increasing pressure to involve specialist units at an early stage in the management of these complex patients, a pressing need to identify a system for accurate early staging of acute pancreatitis remains.