The treatment of people with pancreatic necrosis differs from that of people with oedematous pancreatitis. It is important to know the diagnostic accuracy of serum C-reactive protein (CRP), serum procalcitonin, and serum lactate dehydrogenase (LDH) as a triage test for the detection of pancreatic necrosis in people with acute pancreatitis, so that an informed decision can be made as to whether the person with pancreatic necrosis needs further investigations such as computed tomography (CT) scan or magnetic resonance imaging (MRI) scan and treatment for pancreatic necrosis started. There is currently no standard clinical practice, although CRP, particularly an increasing trend of CRP, is often used as a triage test to determine whether the person requires further imaging. There is also currently no systematic review of the diagnostic test accuracy of CRP, procalcitonin, and LDH for the diagnosis of pancreatic necrosis in people with acute pancreatitis.

To compare the diagnostic accuracy of CRP, procalcitonin, or LDH (index test), either alone or in combination, in the diagnosis of necrotising pancreatitis in people with acute pancreatitis and without organ failure.

We searched MEDLINE, Embase, Science Citation Index Expanded, National Institute for Health Research (NIHR HTA and DARE), and other databases until March 2017. We searched the references of the included studies to identify additional studies. We did not restrict studies based on language or publication status, or whether data were collected prospectively or retrospectively. We also performed a 'related search' and 'citing reference' search in MEDLINE and Embase.

We included all studies that evaluated the diagnostic test accuracy of CRP, procalcitonin, and LDH for the diagnosis of pancreatic necrosis in people with acute pancreatitis using the following reference standards, either alone or in combination: radiological features of pancreatic necrosis (contrast-enhanced CT or MRI), surgeon's judgement of pancreatic necrosis during surgery, or histological confirmation of pancreatic necrosis. Had we found case-control studies, we planned to exclude them because they are prone to bias; however, we did not locate any. Two review authors independently identified the relevant studies from the retrieved references.

Two review authors independently extracted data, including methodological quality assessment, from the included studies. As the included studies reported CRP, procalcitonin, and LDH on different days of admission and measured at different cut-off levels, it was not possible to perform a meta-analysis using the bivariate model as planned. We have reported the sensitivity, specificity, post-test probability of a positive and negative index test along with 95% confidence interval (CI) on each of the different days of admission and measured at different cut-off levels.

A total of three studies including 242 participants met the inclusion criteria for this review. One study reported the diagnostic performance of CRP for two threshold levels (> 200 mg/L and > 279 mg/L) without stating the day on which the CRP was measured. One study reported the diagnostic performance of procalcitonin on day 1 (1 day after admission) using a threshold level of 0.5 ng/mL. One study reported the diagnostic performance of CRP on day 3 (3 days after admission) using a threshold level of 140 mg/L and LDH on day 5 (5 days after admission) using a threshold level of 290 U/L. The sensitivities and specificities varied: the point estimate of the sensitivities ranged from 0.72 to 0.88, while the point estimate of the specificities ranged from 0.75 to 1.00 for the different index tests on different days of hospital admission. However, the confidence intervals were wide: confidence intervals of sensitivities ranged from 0.51 to 0.97, while those of specificities ranged from 0.18 to 1.00 for the different tests on different days of hospital admission. Overall, none of the tests assessed in this review were sufficiently accurate to suggest that they could be useful in clinical practice.

The paucity of data and methodological deficiencies in the studies meant that it was not possible to arrive at any conclusions regarding the diagnostic test accuracy of the index test because of the uncertainty of the results. Further well-designed diagnostic test accuracy studies with prespecified index test thresholds of CRP, procalcitonin, LDH; appropriate follow-up (for at least two weeks to ensure that the person does not have pancreatic necrosis, as early scans may not indicate pancreatic necrosis); and clearly defined reference standards (of surgical or radiological confirmation of pancreatic necrosis) are important to reliably determine the diagnostic accuracy of CRP, procalcitonin, and LDH.

Japanese (JPN) guidelines for the management of acute pancreatitis were published in 2006. The severity assessment criteria for acute pancreatitis were later revised by the Japanese Ministry of Health, Labour and Welfare (MHLW) in 2008, leading to their publication as the JPN Guidelines 2010. Following the 2012 revision of the Atlanta Classifications of Acute Pancreatitis, in which the classifications of regional complications of pancreatitis were revised, the development of a minimally invasive method for local complications of pancreatitis spread, and emerging evidence was gathered and revised into the JPN Guidelines.

A comprehensive evaluation was carried out on the evidence for epidemiology, diagnosis, severity, treatment, post-endoscopic retrograde cholangiopancreatography (ERCP) pancreatitis and clinical indicators, based on the concepts of the GRADE system (Grading of Recommendations Assessment, Development and Evaluation). With the graded recommendations, where the evidence was unclear, Meta-Analysis team for JPN Guidelines 2015 conducted an additional new meta-analysis, the results of which were included in the guidelines.

Thirty-nine questions were prepared in 17 subject areas, for which 43 recommendations were made. The 17 subject areas were: Diagnosis, Diagnostic imaging, Etiology, Severity assessment, Transfer indication, Fluid therapy, Nasogastric tube, Pain control, Antibiotics prophylaxis, Protease inhibitor, Nutritional support, Intensive care, management of Biliary Pancreatitis, management of Abdominal Compartment Syndrome, Interventions for the local complications, Post-ERCP pancreatitis and Clinical Indicator (Pancreatitis Bundles 2015). Meta-analysis was conducted in the following four subject areas based on randomized controlled trials: (1) prophylactic antibiotics use; (2) prophylactic pancreatic stent placement for the prevention of post-ERCP pancreatitis; (3) prophylactic non-steroidal anti-inflammatory drugs (NSAIDs) for the prevention of post-ERCP pancreatitis; and (4) peritoneal lavage. Using the results of the meta-analysis, recommendations were graded to create useful information. In addition, a mobile application was developed, which made it possible to diagnose, assess severity and check pancreatitis bundles.

The JPN Guidelines 2015 were prepared using the most up-to-date methods, and including the latest recommended medical treatments, and we are confident that this will make them easy for many clinicians to use, and will provide a useful tool in the decision-making process for the treatment of patients, and optimal medical support. The free mobile application and calculator for the JPN Guidelines 2015 is available via http://www.jshbps.jp/en/guideline/jpn-guideline2015.html.

Persistent organ failure and infected pancreatic necrosis are major determinants of mortality in acute pancreatitis, but there is a gap in the literature assessing the best available predictors of these two determinants. The purpose of this review was to investigate the utility of predictors of persistent organ failure and infected pancreatic necrosis in patients with acute pancreatitis, both alone and in combination.

We performed a systematic search of the literature in 3 databases for prospective studies evaluating predictors of persistent organ failure, infected pancreatic necrosis, or both, with strict eligibility criteria.

The best predictors of persistent organ failure were the Japanese Severity Score and Bedside Index of Severity in Acute Pancreatitis when the evaluation was performed within 48h of admission, and blood urea nitrogen and Japanese Severity Score after 48h of admission. Systemic Inflammation Response Syndrome was a poor predictor of persistent organ failure. The best predictor of infected pancreatic necrosis was procalcitonin.

Based on the best available data, it is justifiable to use blood urea nitrogen for prediction of persistent organ failure after 48h of admission and procalcitonin for prediction of infected pancreatic necrosis in patients with confirmed pancreatic necrosis. There is no predictor of persistent organ failure that can be justifiably used in clinical practice within 48h of admission.

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.

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.

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.

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.

The early identification of clinically severe acute pancreatitis (AP) is critical for the triage and treatment of patients. The aim of this study was to compare the accuracy of computed tomography (CT) and clinical scoring systems for predicting the severity of AP on admission.

Demographic, clinical, and laboratory data of all consecutive patients with a primary diagnosis of AP during a two-and-half-year period was prospectively collected for this study. A retrospective analysis of the abdominal CT data was performed. Seven CT scoring systems (CT severity index (CTSI), modified CT severity index (MCTSI), pancreatic size index (PSI), extrapancreatic score (EP), ''extrapancreatic inflammation on CT'' score (EPIC), ''mesenteric oedema and peritoneal fluid'' score (MOP), and Balthazar grade) as well as two clinical scoring systems: Acute Physiology, Age, and Chronic Health Evaluation (APACHE)-II and Bedside Index for Severity in AP (BISAP) were comparatively evaluated with regard to their ability to predict the severity of AP on admission (first 24 h of hospitalization). Clinically severe AP was defined as one or more of the following: mortality, persistent organ failure and/or the presence of local pancreatic complications that require intervention. All CT scans were reviewed in consensus by two radiologists, each blinded to patient outcome. The accuracy of each imaging and clinical scoring system for predicting the severity of AP was assessed using receiver operating curve analysis.

Of 346 consecutive episodes of AP, there were 159 (46%) episodes in 150 patients (84 men, 66 women; mean age, 54 years; age range, 21-91 years) who were evaluated with a contrast-enhanced CT scan (n = 131 episodes) or an unenhanced CT scan (n = 28 episodes) on the first day of admission. Clinically severe AP was diagnosed in 29/159 (18%) episodes; 9 (6%) patients died. Overall, the Balthazar grading system (any CT technique) and CTSI (contrast-enhanced CT only) demonstrated the highest accuracy among the CT scoring systems for predicting severity, but this was not statistically significant. There were no statistically significant differences between the predictive accuracies of CT and clinical scoring systems.

The predictive accuracy of CT scoring systems for severity of AP is similar to clinical scoring systems. Hence, a CT on admission solely for severity assessment in AP is not recommended.

The assessment of severity at the initial medical examination plays an important role in introducing adequate early treatment and the transfer of patients to a medical facility that can cope with severe acute pancreatitis. Under these circumstances, "criteria for severity assessment" have been prepared in various countries, including Japan, and these criteria are now being evaluated. The criteria for severity assessment of acute pancreatitis in Japan were determined in 1990 (of which a partial revision was made in 1999). In 2008, an overall revision was made and the new Japanese criteria for severity assessment of acute pancreatitis were prepared. In the new criteria for severity assessment, the diagnosis of severe acute pancreatitis can be made according to 9 prognostic factors and/or the computed tomography (CT) grades based on contrast-enhanced CT. Patients with severe acute pancreatitis are expected to be transferred to a specialist medical center or to an intensive care unit to receive adequate treatment there. In Japan, severe acute pancreatitis is recognized as being a specified intractable disease on the basis of these criteria, so medical expenses associated with severe acute pancreatitis are covered by Government payment.

To determine prognostic factors for arterial injury and gastrointestinal perforation in patients with severe acute pancreatitis (AP).

A prospective cohort study was performed in 39 patients with AP whose Ranson scores were > or =3. The following parameters were assessed: Ranson score, APACHE II score, C-reactive protein (CRP) concentration on admission and on day 7, and contrast-enhanced computed tomography (CT) scans on admission (first CT) and between days 6 and 8 (second CT). The Balthazar CT severity index was calculated.

Six patients developed seven vascular and/or gastrointestinal complications (duodenal perforations in 3 and arterial pseudoaneurysm in 4). CRP on day 7 and the CT severity indices at the second CT were significantly higher in the complication group than in the noncomplication group. A stepwise logistic regression analysis demonstrated that CRP > or =15 mg/dl on day 7 and CT severity index > or =7 at the second CT were independent risk factors (p = 0.02 and 0.04, respectively). The odds ratio for CRP > or =15 mg/dl was 23.0 and 15.7 for a CT severity index of > or =7.

A persistent elevation of the CRP concentration and a high CT severity index are independent risk factors for local complications associated with AP.

Necrotizing pancreatitis is the most severe form of acute pancreatitis associated with high morbidity and mortality. Percutaneous CT-guided catheter drainage is an important treatment option that can be effective whether used alone, or as an adjunct to operation. Existing literature describing the role of percutaneous catheter drainage of necrotizing pancreatitis is limited. This update reviews techniques, indications, outcomes, and complications of CT-guided percutaneous treatment of acute necrotizing pancreatitis.

The aim of the study was to compare Acute Physiology and Chronic Health Evaluation II score and C-reactive protein as a clinical index and computed tomography-based severity index (CTSI) in predicting the course of acute pancreatitis.

One hundred forty-eight patients with acute pancreatitis were enrolled in the study during a 2-year period. All data concerning etiology, Atlanta classification, CT findings, Acute Physiology and Chronic Health Evaluation score, C-reactive protein levels, stay in the intensive care unit, length of hospital stay, treatment, complications, and deaths were analyzed with Mann-Whitney U, Wilcoxon, Pearson, and Spearman statistical tests. The CT was performed on a spiral unit after intravenous administration of contrast material. Images were graded according to the Balthazar-CTSI scoring system.

A very good correlation was noticed between Balthazar-CTSI scores and local complications, whereas no statistically significant correlation was found between CT scores and stay in the intensive care unit. Among survivors and nonsurvivors, there were no statistically significant differences as far as CT scores were concerned.

Although the extent of necrosis as defined on contrast-enhanced CT examinations is considered as a risk factor for a negative prognosis, our findings suggest that the initially documented disease severity according only to imaging parameters is not highly important for the final patient outcome.

Markers of inflammation, such as C-reactive protein (CRP) and white blood cell count, have, because of their low specificity, proven far from ideal in identifying patients with sepsis. Procalcitonin (PCT) has been shown to be a useful marker for differentiating patients with bacterial infection from other acute inflammatory conditions. Corticosteroid therapy has been demonstrated to be effective for treating patients with septic shock, late-phase acute respiratory distress syndrome (ARDS), or functional adrenal insufficiency, and the use of corticosteroid in critical illness has recently increased. It is also well established that corticosteroid modulate inflammatory variables in acute inflammatory conditions. The purpose of this study was to evaluate the clinical usefulness of PCT measurement for assessing the severity of bacterial infection in patients requiring corticosteroid therapy.

Six patients with confirmed bacterial infectious diseases or suspected infectious diseases and requiring corticosteroid therapy were enrolled in the study. Levels of PCT and CRP were measured. The Sequential Organ Failure Assessment (SOFA) score and the Acute Physiology and Chronic Health Evaluation (APACHE) II score were calculated to evaluate the severity of sepsis.

1) There was no significant correlation between the serum concentration of PCT and the plasma level of CRP in patients requiring corticosteroid therapy. 2) The PCT concentration was significantly correlated with the SOFA score (R(2)=0.467, p<0.0001) and the APACHE II score (R(2)=0.308, p=0.0003). However, no significant correlations was found between the CRP concentration and the SOFA score (R(2)=0.054, p=0.15) or the APACHE II score (R(2)=0.043, p=0.20). 3) Data sets were divided into two groups: septic shock and non-septic shock. No significant differences were present in CRP levels between the groups. However, significant differences were apparent in PCT concentrations (p<0.001).

PCT can be a more sensitive and useful marker than CRP for evaluating the severity and progression of sepsis in patients requiring corticosteroid therapy. Further studies are needed to confirm these results in larger groups of patients.

Acute pancreatitis (AP) is a common disease that has a mild to moderate course in most cases. During the last decade, a change in diagnostic facilities as well as improved intensive care have influenced both morbidity and mortality in AP. Still, however, a number of controversies and unresolved questions remain regarding AP. These include prognostic factors and how these may be used to improve outcome, diagnostic possibilities, their indications and optimal timing, and the systemic inflammatory reaction (systemic inflammatory response syndrome--SIRS) and its effect on the concomitant course of the disease and potential development of organ failure. The role of the gut has been suggested to be important in severe AP, but has recently been somewhat questioned. Despite extensive research, pharmacological and medical intervention of proven clinical value is scarce. Various aspects on surgical interventions, including endoscopic sphincterotomy, cholecystectomy and necrosectomy, as regards indications and timing, will be reviewed. Last, but not least, are the management of late complications and long-term outcome for patients with especially severe AP.

Severe acute pancreatitis (SAP) is associated with a high morbidity and mortality. The aim was to evaluate treatment, risk factors and outcome in SAP in a centre with a restrictive attitude to surgery.

All cases of acute pancreatitis admitted 1994-2003 were analysed retrospectively. SAP was defined as organ failure and/or hospital stay >7 days together with one or more of: C-reactive protein >150 mg/l within 72 h after admission, necrosis on computed tomography and need for treatment in the intensive care unit.

185 (22%) of patients with acute pancreatitis fulfilled the criteria for SAP. 175 patients were included, mean age 61 +/- 17 years. Hospital stay was in median 13 days. Forty-six patients had some surgical intervention, in 14 cases directed at the pancreas (8%). Hospital mortality was 9% (n = 16), in 88% (n = 14) associated with multiple organ dysfunction and 50% (n = 8) of the deaths occurred within the first week after admission. Of the parameters registered on admission, age and hypotension (systolic blood pressure <100 mm Hg) were identified as risk factors for death.

The present treatment regime for SAP as defined above resulted in a 9% mortality rate, with age and hypotension at admission as predictive factors for death.

To investigate day-by-day changes in procalcitonin and maximum obtained levels as predictors of mortality in critically ill patients.

Prospective observational cohort study.

: Multidisciplinary intensive care unit at Rigshospitalet, Copenhagen University Hospital, a tertiary reference hospital in Denmark.

Four hundred seventy-two patients with diverse comorbidity and age admitted to this intensive care unit.

Equal in all patient groups: antimicrobial treatment adjusted according to the procalcitonin level.

Daily procalcitonin measurements were carried out during the study period as well as measurements of white blood cell count and C-reactive protein and registration of comorbidity. The primary end point was all-cause mortality in a 90-day follow-up period. Secondary end points were mortality during the stay in the intensive care unit and in a 30-day follow-up period. A total of 3,642 procalcitonin measurements were evaluated in 472 critically ill patients. We found that a high maximum procalcitonin level and a procalcitonin increase for 1 day were independent predictors of 90-day all-cause mortality in the multivariate Cox regression analysis model. C-reactive protein and leukocyte increases did not show these qualities. The adjusted hazard ratio for procalcitonin increase for 1 day was 1.8 (95% confidence interval 1.3-2.7). The relative risk for mortality in the intensive care unit for patients with an increasing procalcitonin was as follows: after 1 day increase, 1.8 (95% confidence interval 1.4-2.4); after 2 days increase, 2.2 (95% confidence interval 1.6-3.0); and after 3 days increase: 2.8 (95% confidence interval 2.0-3.8).

A high maximum procalcitonin level and a procalcitonin increase for 1 day are early independent predictors of all-cause mortality in a 90-day follow-up period after intensive care unit admission. Mortality risk increases for every day that procalcitonin increases. Levels or increases of C-reactive protein and white blood cell count do not seem to predict mortality.

This study was designed to determine the most important early CT parameters predictive of acute pancreatitis severity.

Three hundred and seventy-one consecutive patients with acute abdominal pain and hyperamylasemia were enrolled. Three hundred and ten of the 371 patients met our inclusion criteria. Acute pancreatitis severity was evaluated using the 1992 Atlanta criteria. Different CT parameters were reported from the admission abdominal CT by two radiologists blinded from any clinical parameter, but the patients' age and gender. These variables were fitted in a binary logistic regression model.

Acute pancreatitis was mild in 80% cases, severe in 20% cases and lethal in 12.69% cases. The following CT parameters were significantly associated with the severity of acute pancreatitis: the objective size of the pancreas (P = 0.001), the peripancreatic fat abnormalities (P = 0.001) and the extent of necrosis (P = 0.007). Moreover, the age of the patient revealed itself a highly significant (P = 0.001) indicator of disease severity. The association of the four CT criteria eventually showed a sensitivity of 73% and a specificity of 81% to predict acute pancreatitis severity.

Although these criteria correlated with disease severity, our study identified that morphological CT criteria cannot be used to triage patients with severe and mild acute pancreatitis.

In severe acute pancreatitis (SAP), it is important clinically to predict the prognosis at the time of admission. Most scoring systems for severity of acute pancreatitis consist of multiple factors and are complicated. This investigation aimed to propose a simple scoring system for the prediction of the prognosis of SAP.

Prognostic factors were evaluated by receiver operator characteristic curve analyses and multivariate analysis from data that were obtained on admission of 137 patients with SAP. A simple scoring system with 3 most useful factors was made, and its usefulness was investigated in comparison with conventional scoring systems.

Three prognostic factors were selected: serum blood urea nitrogen > or = 25 mg/dL, serum lactate dehydrogenase > or = 900 IU/L, and contrast-enhanced computed tomography finding with pancreatic necrosis. On admission, 137 patients were classified from 0 to 3 by the number of positive items (simple prognostic score [SPS]). Mortality rates for patients whose SPS was 0, 1, 2, and 3 were 2% (1/42 patients), 18% (7/40 patients), 48% (12/25 patients), and 67% (20/30 patients), respectively. Furthermore, when usefulness of SPS was compared with conventional scoring systems, the area under the curve by receiver operator characteristic curve analyses in SPS was 0.83; the Ranson score was 0.83; the Japanese severity score was 0.83; the Acute Physiology and Chronic Health Evaluation II score was 0.81, and the Glasgow score was 0.75. After onset, SPS kept almost same levels from day 2 to day 6, and a significant difference was observed between survivors and nonsurvivors from day 1 to day 6.

This scoring system that comprised 3 items is simple, is feasible for the prediction of prognosis and conventional scoring systems, and is useful for the selection of the extremely severe patients with SAP on admission.

The objective of this study was to assess the efficacy of percutaneous catheter drainage, of early infected pancreatic fluid collections, in critically ill patients with severe acute pancreatitis. The patients in our series had a mean Ranson's score of 5.4. Nineteen (63.3%) of the 30 patients were cured with percutaneous drainage. In this group, the mean C-reactive protein value at the beginning of treatment was 172.8 U/l and 102.5 U/l at the end (P<.001). Cultures yielded multiple organisms in 23 patients (76.7%). The most frequently seen organisms were Escherichia coli, Staphylococcus aureus, and Enterococcus faecium.

This article addresses the criteria for severity assessment and the severity scoring system of the Ministry of Health and Welfare of Japan; now the Japanese Ministry of Health, Labour, and Welfare (the JPN score). It also presents data comparing the JPN score with the Acute Physiology and Chronic Health Evaluation (APACHE) II score and the Ranson score, which are the major measuring scales used in the United States and Europe. The goal of investigating these scoring systems is the achievement of earlier diagnosis and more appropriate and successful treatment of severe or moderate acute pancreatitis, which has a high mortality rate. This article makes the following recommendations in terms of assessing the severity of acute pancreatitis: (1) Severity assessment is indispensable to the selection of proper initial treatment in the management of acute pancreatitis (Recommendation A). (2) Assessment by a severity scoring system (JPN score, APACHE II score) is important for determining treatment policy and identifying the need for transfer to a specialist unit (Recommendation A). (3) C-reactive protein (CRP) is a useful indicator for assessing severity (Recommendation A). (4) Contrast-enhanced computed tomography (CT) scanning and contrast-enhanced magnetic resonance imaging (MRI) play an important role in severity assessment (Recommendation A). (5) A JPN score of 2 or more (severe acute pancreatitis) has been established as the criterion for hospital transfer (Recommendation A). (6) It is preferable to transfer patients with severe acute pancreatitis to a specialist medical institution where they can receive continuous monitoring and systemic management.

A considerable number of acute pancreatitis cases have been reported to be complicated by nonocclusive mesenteric ischemia. However, no reports have ever referred to the incidence of ischemic enterocolitis in patients with acute pancreatitis, using a series of autopsy cases. Here, we report our review of autopsy cases of patients with acute pancreatitis to examine the incidence of associated ischemic enterocolitis.

The intestinal and pancreatic slides of 48 autopsy cases of patients with acute pancreatitis were reviewed and the incidence of ischemic enterocolitis was determined. Clinical case records were also reviewed.

Thirteen (27%) of 48 autopsy cases of patients with acute pancreatitis were complicated by ischemic enterocolitis. The frequency of shock was significantly higher in patients with ischemic enterocolitis than in those without ischemic enterocolitis. The intestinal lesion was diffuse in many cases and gangrene was not an unusual finding.

The incidence of ischemic enterocolitis in patients with acute pancreatitis was much higher than that in the previous reports. Clinicians who treat patients with acute pancreatitis should consider ischemic enterocolitis as one of the frequent and severe complications of this condition.

Acute pancreatitis varies from a mild, self-limited disease to one with significant morbidity and mortality in its most severe forms. While clinical criteria abound, imaging has become indispensable to diagnose the extent of the disease and its complications, as well as to guide and monitor therapy. Percutaneous interventional techniques offer options that can be life-saving, surgery-sparing or important adjuncts to operation. Close cooperation and communication between the surgeon, gastroenterologist and interventional radiologist enhance the likelihood of successful patient care.

Non-occlusive mesenteric ischemia (NOMI) has been defined as diffuse intestinal ischemia that often results in intestinal gangrene in the presence of a patent arterial trunk. The prevalence and nature of NOMI in acute pancreatitis was investigated.

A total of 120 consecutive patients with acute pancreatitis managed in the Department of Surgery II, Kumamoto University Medical School, from April 1992 through December 2002, were investigated retrospectively. Among them, 60 patients had the severe form.

The overall mortality of acute pancreatitis patients was 8.3% (10/120). The prevalence and mortality of acute pancreatitis associated with NOMI were 6.7% (8/120) and 63% (5/8), respectively, while those of patients with NOMI-associated intestinal gangrene were 4.2% (5/120) and 100% (5/5), respectively. The mortality of patients with severe acute pancreatitis who did not develop NOMI was 10% (5/52). All patients with NOMI-associated intestinal gangrene quickly progressed and subsequently died of multiple organ failure. Plasma creatine phosphokinase (CPK) and lactate levels were elevated significantly in patients with NOMI.

Acute pancreatitis associated with NOMI was extremely severe. If the plasma CPK and lactate levels are extremely high, NOMI should be suspected.

The aim of this study was to identify factors associated with death after surgery in patients with extensive pancreatic necrosis.

Sixty-four patients who underwent pancreatic necrosectomy between 1996 and 2002 were studied.

The median age was 60.5 (95 per cent confidence interval (c.i.) 57 to 64) years and 40 patients (62.5 per cent) were tertiary referrals. The initial median Acute Physiology And Chronic Health Evaluation (APACHE) II score was 9 (95 per cent c.i. 7.9 to 10.1) and there were 21 deaths (32.8 per cent). Twenty-eight patients (43.8 per cent) underwent minimally invasive retroperitoneal pancreatic necrosectomy (MIRP) and the remainder had open pancreatic necrosectomy (OPN); 44 (72.1 per cent) of 61 patients had infected pancreatic necrosis at the time of the first procedure. Seven patients who underwent MIRP died compared with 14 after OPN (P = 0.240). Patients who died were older than those who survived, with higher APACHE II scores at presentation, and before and after surgery (P = 0.001). Survivors had significantly longer times to surgery than those who died (P = 0.038). All 21 patients who died required intensive care compared with 26 of 43 survivors (P < 0.001). Thirty of 36 patients who had the OPN procedure required intensive care compared with only 17 of 28 patients who had MIRP (P = 0.042). Logistic regression analysis showed that only postoperative APACHE II score was an independent predictor of increased mortality (P = 0.031).

Advanced age and increasing APACHE II score, and a need for postoperative intensive care, were the most important predictors of outcome after pancreatic necrosectomy.

Severe acute pancreatitis is occasionally associated with pancreatic and intestinal necrosis. Mesenteric vasoconstriction is one of the most probable types of pathogenesis of these complications.

To investigate the involvement of endothelin-1 (ET-1), a potent vasoconstrictor.

Plasma ET-1 concentrations were extremely high in patients with pancreatic and/or diffuse intestinal necrosis. ET-1 mRNA was demonstrated in the rat pancreas, and the production of ET-1 protein by human umbilical vein endothelial cells was enhanced by tumor necrosis factor-alpha, thrombin, and protease-activated receptor-2-activating peptide. Administration of ET-1 in vivo induced mesenteric arterial spasm and decreased pancreatic and intestinal blood flow.

These results suggest the following: ET-1 is produced in and around the pancreas, mainly by endothelial cells, in severe acute pancreatitis; in the inflammatory setting, cytokines, activated thrombin and trypsin, may stimulate ET-1 production in a paracrine fashion; produced ET-1 may exaggerate the splanchnic microcirculation; and progressive ischemia may lead to necrosis of the pancreas and intestine.

Acute pancreatitis (AP) is a common disease with wide variation of severity. The diagnosis of AP is usually based on high serum amylase or lipase values but the accuracy of these methods is considered unsatisfactory. One in five of the patients develops a severe disease and carries a considerable risk of development of organ failure and high mortality. Early detection of patients with severe AP and especially those with increased risk of organ failure is importance since such patients seem to benefit from treatment in an intensive care unit started as soon as possible after presentation. In addition to enzymological methods, increasing interest has been focused on laboratory markers reflecting the level of inflammatory response in AP. At present, in routine clinical work the most commonly used severity marker is serum C-reactive protein, the concentration of which rises too slowly to be used for early prediction of severity. New therapies aiming at modifying the course of systemic inflammation in AP are being developed and therefore monitoring the patient's immune inflammatory status is needed. In this review article we present the current knowledge of laboratory tests, which has been evaluated for diagnostic and prognostic purposes in AP.

Necrotizing pancreatitis still remains a life-threatening disease despite several improvements in diagnosis, prevention and treatment. In recent years, some important questions have been answered such as the need for early intensive medical treatment rather than early surgery, but others are still strongly debated. The aim of this paper is to present an up-to-date assessment of current challenges in the management of necrotizing pancreatitis in order to prevent infection.

CT has proved to be helpful in patients with acute pancreatitis for differentiating between mild and severe forms. Followup of acute pancreatitis with CT has been advocated but rarely studied. The aim of this study was to determine if late CT performed at day 7 might be helpful in establishing the prognosis or the type of complications, and to select a subgroup of patients in whom CT could be beneficial.

Contrast-enhanced CT was performed at the admission day and 7 days after admission in 102 patients admitted for acute pancreatitis. The extent of pancreatic inflammation was classified according to Balthazar grade, and intrapancreatic necrosis on these examinations was prospectively assessed and compared with clinical and biologic data and with patient outcomes.

Among 102 patients, complications developed in 24 (23%). Complications developed in only 8% of patients with Ranson score <2, making routine early CT unnecessary. For the patients with Ranson score <2 and Balthazar grades A and B at day 1 CT, late CT seemed to be useless. Complication was suspected by clinical and biologic tests before day 7 in 22 of 24 complicated patients (92%), suggesting that CT could be proposed only in cases of clinical or biologic deterioration. Late CT was correlated with a complicated course in patients with Balthazar grades D and E or intrapancreatic necrosis >50%. Late CT was predictive of complications in cases of intrapancreatic necrosis enlarging since the first examination.

Our study showed that in acute pancreatitis: 1) there is little justification for systematic early CT, especially in patients with Ranson score <2, and 2) late CT does not need to be performed routinely, but only in cases of clinical or biologic worsening.

Studies done in the early 1970s came to the conclusion that antibiotic prophylaxis was not useful in the management of acute pancreatitis. However, these studies suffered from the drawback of using antibiotics that had poor penetration into the pancreas. In addition, the design of these trials were faulty. With the advent of new information and the availability of better antibiotics, the picture is changing. Recent studies have suggested that antibiotic prophylaxis is useful in decreasing the incidence of infection in patients with severe pancreatitis. Of the antibiotics that have been tested, imipenem appears to be the most promising.

In a previous retrospective case-control study, hemoconcentration was associated with the development of pancreatic necrosis. The aim of the present study was to determine in a cohort study whether hemoconcentration is a marker for both organ failure and necrotizing pancreatitis. A cohort study was performed on patients admitted with acute pancreatitis from February 1996 to April 1997. Pancreatic necrosis was defined by findings on dynamic contrast-enhanced computed tomography scan or magnetic resonance imaging. Of 128 total patients with acute pancreatitis, 53 underwent computed tomography or magnetic resonance imaging. Eighteen of 53 had necrotizing pancreatitis. Logistic regression identified an admission hematocrit > or = 44% and a failure of admission hematocrit to decrease at 24 hours as the best binary predictors of necrotizing pancreatitis and organ failure. By 24 hours, 17 of 18 patients with necrotizing pancreatitis versus 11 of 35 with interstitial pancreatitis met one or the other criterion for necrosis (p < 0.001). By 24 hours, 13 of 15 with organ failure versus 36 of 104 without organ failure met one or the other criterion (p < 0.001). The negative predictive value by 24 hours was 96% for necrotizing pancreatitis and 97% for organ failure. Hemoconcentration with an admission hematocrit > or = 44% and/or failure of admission hematocrit to decrease at approximately 24 hours was associated with the development of necrotizing pancreatitis and organ failure. Patients who did not experience hemoconcentration were very unlikely to develop pancreatic necrosis or organ failure.

The diagnosis, early assessment, and management of severe acute pancreatitis remain difficult clinical problems. This article presents the consensus obtained at a meeting convened to consider the evidence in these areas. The aim of the article is to provide outcome statements to guide clinical practice, with an assessment of the supporting evidence for each statement.

Working groups considered the published evidence in the areas of diagnosis, assessment of severity, nonoperative treatment, and surgical treatment of severe acute pancreatitis. Outcome statements were defined to summarize the conclusions on each point considered. The findings were discussed and agreed on by all participants. A careful assessment was made of the strength of the available evidence (proven, probable, possible, unproven, or inappropriate).

There is reliable evidence to support much current practice. Clear guidance can be given in most areas examined, and several areas were identified where further investigation would be helpful. Diagnosis using plasma concentrations of pancreatic enzymes is reliable. Rapid advances are taking place in the assessment of severity. Several new therapeutic strategies show real promise for the reduction of morbidity and mortality rates. Surgical debridement is required for infected pancreatic necrosis, but is less often necessary for sterile necrosis.

Antibiotic prophylaxis in severe pancreatitis has recently yielded promising clinical results, with imipenem significantly reducing the incidence of infected necrosis compared with an untreated control group. On the bases of pefloxacin's spectrum of action and pancreatic penetration, we investigated whether such drugs represent a valid alternative to imipenem.

In a multicenter study, 60 patients with severe acute pancreatitis with necrosis affecting at least 50% of the pancreas were randomly allocated to receive intravenous treatment for 2 weeks with pefloxacin, 400 mg twice daily (30 patients), or imipenem, 500 mg three times daily (30 patients), within 120 hours of onset of symptoms. Age, sex, body weight, Ranson and Apache II scores, C-reactive protein, etiology, and time from onset of symptoms to treatment were well matched in the two groups.

The incidences of infected necrosis and extrapancreatic infections were 34% and 44%, respectively, in the pefloxacin group and 10% and 20% in the imipenem group. Imipenem proved significantly more effective in prevention of pancreatic infections (P </= 0.05). Mortality was not significantly different in the two groups.

Despite its theoretical potential, pefloxacin is inferior to imipenem in the prevention of infections associated with severe pancreatitis.

In the Emergency Department it is mandatory to establish the diagnosis and the prognosis of acute pancreatitis as soon as possible. To evaluate whether the association of serum lipase either with serum beta2-microglobulin or with C-reactive protein allows simultaneously to establish the diagnosis and the prognosis of acute pancreatitis, 96 patients with acute abdomen were studied. Fifty-eight patients had non-pancreatic acute abdomen and the remaining 38 had acute pancreatitis: 23 mild acute pancreatitis, and 15 severe acute pancreatitis. Forty healthy subjects were studied as controls. Lipase, beta2-microglobulin and C-reactive protein were determined in the serum of all subjects, using commercial kits. One patient with acute pancreatitis was not correctly classified when lipase was used to discriminate between patients with non-pancreatic acute abdomen and those with acute pancreatitis. For the discrimination of patients with severe acute pancreatitis from those with the mild form of the disease in the remaining 37 acute pancreatitis patients, beta2-microglobulin had a sensitivity of 53.3 %, specificity of 81.8%, and prognostic accuracy of 70.3 % (27 of the 37 patients correctly classified); 87.5 % of the 96 cases were correctly classified. C-reactive protein showed a lower prognostic accuracy than beta2-microglobulin: sensitivity 86.7%, specificity 45.5%, accuracy 62.2 %; 84.4 % of the cases were correctly classified. Using the polychotomous logistic regression analysis we found the same accuracy in discriminating between patients with acute pancreatitis and those with non-pancreatic acute abdomen (99.0%) but a lower accuracy (54.1%) between patients with severe acute pancreatitis and those with the mild form of the disease. Our study shows that the association of serum lipase with beta2-microglobulin or with C-reactive protein is not useful in simultaneously establishing the diagnosis and prognosis of acute pancreatitis.

To evaluate the results of débridement and closed packing for necrotizing pancreatitis and to determine the optimal timing of surgical intervention based on patient outcomes.

Between February 1990 and November 1996, 64 consecutive patients with necrotizing pancreatitis were treated with necrosectomy followed by closed packing of the cavity with stuffed Penrose and closed suction drains. The mean APACHE II score immediately before surgery was 9, and 31% of the patients had organ failure. Patients were stratified with an outcome score based on death and major complications; this was correlated with the timing of surgical intervention. The data were then subjected to cut-point analysis by sequential group comparison.

Patients underwent surgery a median of 31 days after diagnosis. Fifty-six percent had infected necrosis. The mortality rate was 6.2% and was no different in infected or sterile necrosis. Eleven patients required a second surgical procedure and 13 required percutaneous drainage; a single surgical procedure sufficed in 69%. Enteric fistulae occurred in 16% of patients. The mean hospital stay after surgery was 41 days, and the interval until return to regular activities was 147 days. A significant negative correlation between duration of pancreatitis and outcome scores was found, and sequential group comparison demonstrated that the change point at which significantly better outcomes were encountered was day 27.

Débridement of pancreatic necrosis followed by closed packing and drainage is accomplished with a low mortality rate and reduced rates of complications and second surgical procedures. Although intervention is best deferred until the demarcation of necrosis is complete, delay beyond the fourth week confers no additional advantage.

The aim of our study was to determine whether measurement of serum hematocrit during the first 24 h helps in distinguishing necrotizing from mild pancreatitis.

From May 1992 to June 1996, a case-control study was performed with cases of patients with necrotizing pancreatitis. We selected as a control the next patient admitted with mild pancreatitis.

There were 32 patients in each group. Logistic regression identified an admission hematocrit of > or = 47% and a failure of admission hematocrit to decrease at 24 h as the best binary risk factors for necrotizing pancreatitis. At admission, more patients with necrotizing pancreatitis than with mild pancreatitis had a hematocrit > or = 47% (11/32 vs 3/32; p = 0.03). At 24 h, 15 additional patients with necrotizing pancreatitis versus only one with mild pancreatitis showed no decrease in admission hematocrit (p < 0.01). Thus, by 24 h, 26 of 32 patients with necrotizing pancreatitis versus only four of 32 patients with mild pancreatitis met one or the other criterion (p < 0.01). The sensitivity and specificity at admission were 34% and 91%; at 24 h, 81% and 88%.

Hemoconcentration with an admission hematocrit > or = 47% or failure of admission hematocrit to decrease at approximately 24 h were strong risk factors for the development of pancreatic necrosis.

Alcoholic pancreatitis may be one of the most serious adverse consequences of alcohol abuse. Its diagnosis, as it has for many years, depends primarily on clinical acumen in interpreting properly the symptoms and signs of abdominal distress, buttressed by elevated pancreatic enzymes (amylase and lipase). More recently, the use of computerized tomography (CT) in selected situations has been both of confirmatory and prognostic value. Severity of abnormality by CT correlates reasonably well with a variety of clinical-laboratory clusters (APACHE system, Ranson's criteria, etc.) and aids in therapy. The pathogenesis of alcoholic pancreatitis is not fully defined. The ultimate picture is one of tissue autolysis by activated proteolytic enzymes. The triggers for such activation, however, are still not known. They are represented by three main theories: (1) large duct obstruction and/or increased permeability relative to pancreatic secretion, (2) small duct obstruction due to proteinaceous precipitates, and (3) a direct toxic-metabolic effect of ethanol on pancreatic acinar cells. While not mutually exclusive, we favor the last hypothesis as being most consistent with the effects of ethanol on other organ systems. The direct effects of ethanol and/or its metabolites may be mediated, at least in part, via oxidative stress or the generation of fatty acid ethyl esters. Autolysis (regardless of proximate mechanism(s)) leads to inflammation likely mediated via release of various cytokines. It also should be appreciated that "acute" pancreatitis (the topic of this chapter) likely represents an acute process within a chronic pancreatic exposure and injury from alcoholic abuse. The key question of why pancreatitis develops in only a small number of alcohol abusers is not resolved. Therapy depends on the severity of alcoholic pancreatitis, which is defined by clinical-laboratory and often CT criteria. Mild pancreatitis usually resolves acutely with alcohol abstention and supportive therapy. Severe pancreatitis has a significant morbidity and mortality, mainly related to the degree of pancreatic necrosis and infection. It requires meticulous combined medical-surgical care.

Early evaluation of the severity of acute pancreatitis (AP) requires measurement of many variables within 48 h after admission. Septic complications (SC) are frequent, and preliminary studies have highlighted the value of prophylactic antibiotherapy; however, single and reliable predictive markers of sepsis are not yet available. The aim of this study was to assess the value of determining early blood Th-1 cytokines and their natural antagonists (interleukin-6 (IL-6), IL-1, IL-1ra, and the soluble form of tumor necrosis factor (sTNF) receptors RI and RII) to predict the severity and SC during AP.

Thirty-seven patients with AP were prospectively included; 25 of them had severe AP, including 8 with SC. Serum cytokines were measured 48 h and 72 h after the onset of AP with an enzyme-linked immunosorbent assay. The optimal severity or SC diagnostic thresholds was determined using receiver operative curves.

Severe AP in accordance with the Atlanta criteria were better predicted by C-reactive protein and IL-6 serum determination, albeit these levels could not predict absolutely the death of two patients. In severe AP cases (n = 25) the IL-1 to IL-1-ra ratio was lower in cases further complicated by sepsis ((6+/-4) 10(-3) versus (34+/-13) 10(-3), P < 0.05); moreover, sTNF RI (2497+/-270 pg/ml versus 2133+/-611 pg/ml, P < 0.05) and RII (3751+/-400 pg/ml versus 3045+/-509 pg/ml, P < 0.05) were higher in AP characterized by further SC. The IL-1 to IL-1-ra ratio and IL-1 concentration were dramatically decreased within the first 48 h ((0.4+/-0.4) 10(-3) versus (30+/-11) 10(-3), P < 0.05, and 0.3+/-0.3 versus 15+/-3 ng/l, P < 0.05) in patients with further infection of the pancreatic necrosis (n = 3). The SC diagnosis was better anticipated by an IL-1 to IL-1-ra ratio lower than 5 x 10(-3) or by an sTNF RI higher than 1750 pg/ml and sTNF RII higher than 2750 pg/ml, and the infection of the pancreatic necrosis by an IL-1 concentration <2 ng/l or an IL-1 to IL-1-ra ratio <2 x 10(-3).

Besides severity markers, IL-1, IL-1-ra, and sTNF RI and RII should be considered in base-line AP assays and, if confirmed by larger studies, could help to screen patients at risk for SC and candidates for prophylactic antibiotherapy with a good negative predictive value.

Early detection of infected pancreatic necrosis has a major impact on further management and outcome in acute pancreatitis. The aim of this study was to evaluate the clinical value of ultrasonographically guided fine-needle aspiration cytology (FNAC) in patients with necrotizing pancreatitis over an 8-year period.

From January 1988 to September 1996 193 (mean 2.0 (range 1-9) aspirations per patient) prospectively assessed FNACs guided ultrasonographically were performed in 98 patients with necrotizing pancreatitis proven by contrast-enhanced computed tomography. Aspirates were considered infected if either Gram stain and/or culture revealed micro-organisms.

Ultrasonographically guided FNAC correctly diagnosed infection in 29 of 33 patients with infected necrosis a median of 13 days after onset of symptoms. Of 61 patients with sterile necrosis 55 were identified correctly as sterile by FNAC. There were six false-positive and four false-negative aspirates of which nine occurred during the first week of the disease. In four patients who did not undergo operation FNAC revealed Gram-negative organisms; however, in the absence of repeated aspirations, the positive results remained unconfirmed. An overall sensitivity of 88 per cent and a specificity of 90 per cent was obtained. No difference was found in biochemical and clinical parameters indicating systemic inflammatory response syndrome before each FNAC between patients with proven sterile or infected necrosis. All patients tolerated the procedure well and no major complications were observed.

Ultrasonographically guided FNAC is a fast and reliable technique for the diagnosis of infected necrosis. As complication rates are very low, the procedure can be repeated at short intervals to improve the diagnostic accuracy. Ultrasonographically guided FNAC is recommended for all patients with necrotizing pancreatitis in whom systemic inflammatory response syndrome persists beyond the first week after onset of symptoms.

The close association between infection and poor outcome in severe pancreatitis has led many investigators to hypothesize that antibiotic prophylaxis might reduce infection and thereby reduce mortality. However, despite this possible relationship, few studies of good quality have been performed in humans. Comprehensive searches using Medline and reviewing relevant published bibliographies of English-language human and experimental literature concerning acute pancreatitis or pancreatic tissue and antibiotic therapy or pharmacokinetics were conducted. Ample experimental evidence indicates that aminoglycosides penetrate pancreatic tissue poorly and that penetration of penicillins is variable, although the relevance of this is debatable, because most tissue that requires debridement in severe pancreatitis is necrotic peripancreatic retroperitoneal fat, not the pancreas itself. Although several animal studies suggest that antibiotic prophylaxis would be beneficial in severe pancreatitis, two recent randomized studies of intravenous antibiotics in humans provide conflicting data. There are insufficient data to recommend the use of selective digestive decontamination. Some justification exists for the use of intravenous antibiotic prophylaxis in severe pancreatitis, but the data are insufficient to mandate prophylaxis or to elevate it to the standard of care. If chosen, prophylaxis with the combination of a fluoroquinolone plus metronidazole, or monotherapy with a carbapenem antibiotic, would be most appropriate. Several other questions-including the minimum degree of severity that will benefit, the validity of endpoints other than mortality, and reduction of the need for surgical drainage-require additional trials.

A total of 161 primary contrast-enhanced computed tomography (CT) scans of patients with acute necrotizing pancreatitis taken between 1982 and 1994 were analysed retrospectively. The aim was to assess the prognostic significance of the extent and anatomical site of pancreatic tissue necrosis in the first contrast-enhanced CT scan. The scans were obtained a mean of 2.9 days after the onset of symptoms. The pancreatic head was affected in 107 patients, the body in 119 and the tail in 138. Pancreatic tissue necrosis, when divided into four groups according to anatomical site, correlated with overall clinical outcome. The anatomical site of necrosis was clearly better than its crude extent in predicting the risk of complications. For patients with necrosis in the head of the pancreas, the outcome was as severe as when the entire pancreas was affected. In contrast, for patients with necrosis only in the distal part of the pancreas, the outcome was favourable with few complications. The exact site of pancreatic tissue necrosis should be known when early contrast-enhanced CT is used in prognostic scoring.

The analysis of all the data available in 192 patients at 24 h from admission shows that only serum glucose above 250 mg/dL (13.88 mmol/L) and serum creatinine above 2 mg/dL (176.8 mumol/L) are prognostic factors of death (P < 0.0001). When, however, pathological chest X-rays are also considered in a subset of 149 patients, these and serum creatinine are prognostic factors of death with odd ratios of 2.9 (95% CL 1.3-6.3) and 9.4 (95% CL 2.2-40.7), respectively (P < 0.0001).

In patients suffering from acute pancreatitis, neither Ranson scores nor Glasgow criteria evaluation at 24 h yield a sufficiently reliable prognosis of the risk of death from the first acute attack.

After excluding posttraumatic, postsurgical, and post-ERCP acute pancreatitis, we selected 192 consecutive patients admitted in the first instance to our center for a first attack, distinguishing between patients who died and patients who survived. We used Cox's model to analyze the prognostic weight of variables available within 24 h of admission (sex, age, alcohol intake, smoking habits, 17 biochemical tests, body mass index, chest X-rays, body temperature, and shock status).

Seventeen (8.8%) patients died; mortality showed a decreasing trend over the period of years considered and was correlated, among other things, with necrotizing type of pancreatitis, idiopathic etiology, and shock status on admission.

The aims of the study were to determine whether the platelet-activating factor antagonist Lexipafant could alter the clinical course and suppress the inflammatory response of human acute pancreatitis. In a double-blind, placebo-controlled study 83 patients were randomized to receive Lexipafant 60 mg intravenously for 3 days, or placebo. Clinical progression was assessed by daily Acute Physiology And Chronic Health Evaluation (APACHE) II score and organ failure score (OFS). The magnitude of the inflammatory response on days 1-5 was assessed by serial measurement of interleukin (IL) 8, IL-6, E-selectin, polymorphonuclear elastase-alpha1-antitrypsin (PMNE-alpha 1-AT), and C-reactive protein (CRP). At entry, patients receiving Lexipafant (n = 42) or placebo (n = 41) were matched for age and sex, aetiology, APACHE II score and OFS. The disease was classified as severe in 29 patients (APACHE II score eight or more). There was a significant reduction in the incidence of organ failure (P = 0.041) and in total OFS (P = 0.048) at the end of medication (72 h). During this time seven of 12 patients with severe acute pancreatitis who had Lexipafant recovered from an organ failure; only two of 11 with severe acute pancreatitis who had placebo recovered from an organ failure and two others developed new organ failure. Lexipafant treatment significantly reduced serum IL-8 (P = 0.038), and IL-6 declined on day 1. Plasma PMNE-alpha 1-AT complexes peaked on day 1; the gradual fall to baseline over 5 days observed in controls did not occur in patients given Lexipafant. No effect was observed on serum CRP. This study provides a rationale for further clinical trials with the potent PAF antagonist Lexipafant in human acute pancreatitis.