To evaluate the risk factors, Atlanta severity score, Balthazar-CTSI score, and disease course in patients of varying weight with acute pancreatitis (AP).

A retrospective evaluation was made of normal weight (NW), overweight (OW), and obese (OB) patients (n:1134) with respect to demographic findings, diabetes (DM)/hypertension, smoking/alcohol use, etiologies, laboratory findings, Balthazar/Atlanta severity scores, and disease outcomes. After consistency and associations among the BMI, Balthazar, and Atlanta groups were evaluated, combined effects of risk factors on mortality, hospital and ICU stays were re-examined statistically.

In the OB group, mean age (p < 0.001), female gender (p < 0.001), increased BUN(p < 0.027) and Hct (p = 0.039), DM(p < 0.024), and mortality (p < 0.011) were statistically significant. In the non-NW groups, the rates of complications (40.6%/38.6%), mortality (3.7%/4.9%), interventional procedures (36%/39%), and length of hospital stay (11.6%/9.8%) were increased. Obesity constituted 23.7% of severe AP(SAP) and 50% of mortality. There was no significant relationship between Atlanta and Balthazar groups and BMI, nor between Balthazar and moderate AP (MSAP) to SAP. Old age (p = 0.000), male sex (p = 0.05), obesity (p = 0.046), alcohol (p = 0.014), low Hct (p = 0.044), high CRP (p = 0.024), MSAP/SAP (p = 0.02/(p < 0.001), and any complications (p < 0.001) increased the mortality risk. Female gender (p = 0.024), smoking (p = 0.021), hypertriglyceridemia (p = 0.047), idiopathic etiology (p = 0.023), and MSAP/SAP (p < 0.001) associations increased ICU admission. Co-occurrences of higher Balthazar score (p < 0.001), MSAP/SAP (p < 0.001), all kinds of complications (p < 0.001), and recurrence (p = 0.040) increased the hospital stay (≥11 days).

Although complications, mortality, longer hospitalization, and interventional procedures were observed more in the overweight and obese, successful prediction of Atlanta severity and Balthazar-CTSI scores based on BMI does not appear to be accurate. OB carries an increased risk for morbidity and mortality. The combined effects of risk factors increased mortality, longer hospital stays, and ICU admission.

To develop and validate a prediction model for predicting in-hospital mortality in patients with acute pancreatitis (AP).

A retrospective observational cohort study based on a large multicentre critical care database.

All subject data were collected from the eICU Collaborative Research Database (eICU-CRD), which covers 200 859 intensive care unit admissions of 139 367 patients in 208 US hospitals between 2014 and 2015.

A total of 746 patients with AP were drawn from eICU-CRD. Due to loss to follow-up (four patients) or incomplete data (364 patients), 378 patients were enrolled in the primary cohort to establish a nomogram model and to conduct internal validation.

The outcome of the prediction model was in-hospital mortality. All risk factors found significant in the univariate analysis were considered for multivariate analysis to adjust for confounding factors. Then a nomogram model was established. The performance of the nomogram model was evaluated by the concordance index (C-index) and the calibration plot. The nomogram model was internally validated using the bootstrap resampling method. The predictive accuracy of the nomogram model was compared with that of Acute Physiology, Age, and Chronic Health Evaluation (APACHE) IV. Decision curve analysis (DCA) was performed to evaluate and compare the potential net benefit using of different predictive models.

The overall in-hospital mortality rate is 4.447%. Age, BUN (blood urea nitrogen) and lactate (ABL) were the independent risk factors determined by multivariate analysis. The C-index of nomogram model ABL (0.896 (95% CI 0.825 to 0.967)) was similar to that of APACHE IV (p=0.086), showing a comparable discriminating power. Calibration plot demonstrated good agreement between the predicted and the actual in-hospital mortality. DCA showed that the nomogram model ABL was clinically useful.

Nomogram model ABL, which used readily available data, exhibited high predictive value for predicting in-hospital mortality in AP.

Introduction: Acute pancreatitis (AP) incidence in the elderly population has increased in the last years. However, the role of age as influencing factor on the AP clinical course is still debated. Methods: We reviewed clinical records of consecutive patients admitted with diagnosis of AP. Patients were divided in elderly (≥65 years) and non-elderly  (<65 years). Primary endpoint was comparison of overall mortality. Secondary endpoint included ICU admission, in-hospital length of stay (LOS) and surgical procedures. Results: We enrolled 352 elderly and 532 non-elderly patients. A higher mortality rate (7.4% vs 1.9%; p < .001), ICU admission rate (18.9% vs 6.3%; p < .001) and prolonged length of hospital stay (9 (6-14) vs 7 (5-11.7) days; p = .01) were registered in the ≥65 years group. Multivariate analysis identified age (OR: 3.5; 95% CI:1.645-7.555; p = .001), a higher Ranson score at admission (OR: 5.52; 95% CI:1.11-27.41; p<.001) and necrotic pancreatitis (OR: 8.6; 95% CI:2.46-30.27; p = .001) as independent predictors of mortality. Conversely age and necrotic pancreatitis were independent risk factors for higher LOS and ICU admission. Conclusions: Patients with AP and age ≥65 years have a higher mortality, ICU admission and prolonged LOS. Early recognition and prompt treatment are key elements to improve outcomes in this population.

Severe acute pancreatitis (SAP) is characterised by two distinct clinical phases. Organ dysfunction and death is initially as a result of a systemic inflammatory response syndrome (SIRS). Systemic sepsis from infected pancreatic necrosis characterises the second phase, the so called 'second hit' of acute pancreatitis (AP). An immune imbalance during the second hit is postulated to contribute to the formation of the septic complications that occur in these patients. The pro-inflammatory T-helper (Th) 17 pathway has been shown to be an initiator of early SIRS in AP, however to date its role has not been established in the second hit in AP.

Thirty-six patients with mild (n = 16), moderate (n = 10) and severe (n = 10) acute pancreatitis were enrolled. Peripheral blood samples were drawn on days 7, 9, 11 and 13 of illness for analysis of routine clinical markers as well as cytokine analysis. Flow cytometry and a IL-17A ELISA was performed to determine cytokine concentrations.

There were no significant differences between days 7, 9, 11 and 13 for either the mild/moderate or SAP groups for IL-17A (CBA assay or ELISA), IFN-γ, TNF-α, IL-2 or IL-4. For each of the study days, the mean IL-6 and IL-10 concentrations were significantly higher in the SAP group compared to the mild/moderate group. WCC, CRP and PCT were all significantly higher in severe acute pancreatitis over the study days.

An immune imbalance exists in patients with SAP, however secreted IL-17A is not responsible for the second hit in AP.

Acute severe pancreatitis caused high mortality, and several scoring systems for predicting mortality are available. We evaluated the effectiveness of serial measurement of several scoring systems in patients with acute severe pancreatitis.We retrospectively obtained serial measurements of Ranson, Acute Physiology and Chronic Health Assessment (APACHE) II, and Sequential Organ Failure Assessment (SOFA) scores of 159 patients with acute severe pancreatitis.The overall mortality rate was 20%, and early mortality (in the first 2 weeks) occurred in 10 (7.4%) patients, while late mortality occurred in 17 (12.6%).All scoring systems were reliable for predicting overall and intensive care unit mortality, while the SOFA score on day 7 presented the largest area under the receiver operator characteristic (ROC) curve (0.858, SE 0.055). Changes in scores over time were evaluated for predicting the progression of organ failure, and the change in SOFA score on hospital day 7 or no interval change in SOFA score was associated with higher mortality rates.APACHE II and SOFA scores are both sensitive for predicting mortality in acute pancreatitis. The serial SOFA scores showed reliable for predicting mortality. Hospital day 7 is a reasonable time for SOFA score reassessment to predict late mortality in acute severe pancreatitis.

Sepsis is an important complication and cause of morbidity and mortality in acute pancreatitis (AP). The source of sepsis may be infected pancreatic and peripancreatic collections and/or necrosis or extrapancreatic including infections in the bloodstream or respiratory and urinary tracts. We studied the implications of the source of sepsis on various outcome parameters in AP like persistent organ failure (POF), length of hospital (LOH) stay, and mortality.

A retrospective analysis of culture reports of AP patients was done, and the outcome parameters were recorded.

Three hundred fifty-seven patients (229 M; age: 40.3 ± 14.04 years) of AP who had detailed culture reports were included. Eighty-four (23.5%) patients had pancreatic (or peripancreatic) source (group 1), 52 (14.6%) patients had other (extrapancreatic) sources (group 2), 20 (5.6%) patients were noted to have positive cultures from sources, which were both pancreatic and extrapancreatic (combined) sources (group 3), while 201 patients had sterile cultures. POF was seen in 147 (48%) patients (group 1: 67.8%; group 2: 65%; group 3: 90%; group 4: 34% [P < 0.001]). The mean LOH stay was 22.1 ± 20.26 days (group 1: 30.2 ± 20.64 days; group 2: 26.4 ± 26.82 days; group 3: 47.3 ± 32.60 days; group 4: 15.2 ± 11.34 days [P < 0.001]). Seventy (19.7%) patients succumbed to their illness (group 1 [22.9%]; group 2 [36.5%]; group 3 [40%]; group 4 [12%] [P < 0.001]).

POF and LOH stay were more common in patients with combined pancreatic and extrapancreatic sources of sepsis. Mortality was significantly higher in patients with sepsis (groups 1, 2, 3) compared with sterile groups.

To assess the efficiency and safety of parenteral analgesics for pain relief in acute pancreatitis.

We carried out an electronic search of PubMed, Cochrane Library, EMBASE, WEIPU, CNKI and CBM and a manual search for eligible studies. The methodological quality of included trials and quality of evidence were examined by the Cochrane Collaboration's tool for assessing risk of bias and GRADE, respectively. The data were mainly analyzed descriptively and some were pooled by Review manager 5.

Eight randomized controlled trials with a total of 356 patients were finally included in this systematic review. Compared with procaine, pentazocine led to lower pain severity: day 1, Mean Difference (MD), 95%CI: 40.0 [35.3, 44.7]; day 2, MD, 95%CI: 24.00 [20.88, 27.12]; day 3, MD, 95%CI: 5.00 [2.17, 7.83], and it decreased the requirement for additional analgesics, Relative Risk, 95%CI: 2.23 [1.63, 3.05]. The combination of fentanyl, atropine, droperidol and lidocaine rendered lower pain score: day 1, MD, 95%CI: -5.46 [-6.95, -3.97]; day 2, MD, 95%CI: -5.78 [-7.39, -4.17]. Patients treated with metamizole tended to had lower pain than those treated with morphine, MD, 95%CI: -2.60 [-2.95, -2.25]. Nausea, emesis and vomiting were the common adverse events reported and there was almost no significant difference between different agents on safety.

The systemic review showed that the randomized controlled trials comparing different analgesics were of low quality and did not favor clearly any particular analgesic for pain relief in acute pancreatitis.

The pancreas is versatile in the diversity of disorders that it can exhibit. In this article, characteristics of disorders such as chronic, autoimmune, eosinophilic, hereditary, and infectious pancreatitis are described. With regard to autoimmune pancreatitis, the role of clinical evaluation, histologic examination, and IgG4 immunohistochemistry is discussed. The role of pancreatitis in the pathogenesis of diabetes is also mentioned. Some implications of pancreatitis are highlighted, including the neoplastic predisposition caused by inflammatory lesions of the pancreas. The goal of this article is to convey an appreciation of these disorders because their recognition can benefit patients tremendously, as inflammatory lesions of the pancreas can be mass-forming, giving rise to pseudotumors, and leading to surgical resection that may otherwise be unnecessary.

Early endoscopic retrograde cholangio-pancreatography with or without endoscopic sphincterotomy (ERCP+/-ES) has been advocated to reduce complications in patients presenting with a severe attack of gallstone-associated acute pancreatitis (GAP). However, a recent trial has reported contradictory results. Importantly, patients with acute cholangitis were excluded suggesting it may be a major confounding factor affecting previous studies.

To assess the effectiveness of early ERCP+/-ES compared to conservative management stratified according to severity of disease, concealment of randomisation, acute cholangitis and bilirubin level in the reduction of mortality, morbidity, length of hospitalisation and cost in adults suspected of having GAP.

We searched - Cochrane Library (Issue 4 2003), Medline (1966-2004), EMBASE (1980-2004) and LILACS. 'Grey literature' was sought by looking at cited references and hand searched to identify further relevant trials. Conference proceedings of United European Gastroenterology Week (published in Gut) and Digestive Disease Week (published in Gastroenterology) were also hand searched.

Randomized controlled trials (RCT) of adult patients, from 15 years old or greater, presenting with gallstone-associated acute pancreatitis (GAP) comparing ERCP +/- ES versus Conservative management within 72 hours of admission.

Data were assessed for quality independently by two reviewers. Wherever appropriate, results were pooled together and sub-grouped by predicted severity of disease. Fixed and random effects models were applied. Sensitivity analysis was performed to test the fragility of results.

Three trials, involving 511 patients, met inclusion criteria. The test for heterogeneity yielded statistically non-significant results (p-value 0.1 to 0.63) suggesting all comparisons were above the established threshold for combinability (p<0.1). Fixed effect and random effect meta-analyses gave identical results. Early ERCP +/- ES was associated with non-significant effect on reduction of mortality in predicted mild (OR = 0.62, 95% CI = 0.27 to 1.41) and severe GAP (OR = 0.62, 95% CI = 0.27 to 1.41). Reduction in complications was non-significant in predicted mild (OR = 0.89, 95% CI = 0.53 to 1.49), but significant in severe GAP (OR = 0.27, 95% CI = 0.14 to 0.53). There was insufficient evidence to draw any conclusions about hospital stay and cost.

Odds of having complications are reduced in predicted severe disease by early ERCP +/- ES. This effect was however, non-significant in predicted mild disease and for reduction of mortality in either predicted mild or severe disease. These results are controlled for confounding due to associated acute cholangitis and are robust for clinical and statistical heterogeneity.

Little is known regarding the impact of hospital-acquired infection (HAI) in acute pancreatitis (AP). We conducted a population-based assessment of the impact of HAI on outcome in AP.

Patient data were obtained from the Cardinal Health Clinical Outcomes Research Database, a large population-based data set. Cases with principal diagnosis by International Classification of Diseases, ninth revision, clinical modification 577.0 (AP) between January 2004 and January 2005 were identified. These cases were linked with recently reported HAI data collected by the Pennsylvania Health Care Cost Containment Council. Identification of HAI was based on definitions set forth by the National Nosocomial Infection Surveillance System. We conducted a 5:1 multivariate propensity-matched cohort study to determine the independent contribution of HAI to in-hospital mortality, length of stay (LOS), and hospital charges.

From 177 participating hospitals, there were 11,046 AP cases identified. Eighty-two (0.7%) patients developed an HAI. Mortality in the overall AP population was 1.2% vs 11.4% among 405 matched non-HAI controls vs 28.4% among patients who developed HAI (chi(2) test, P < .0001). Fifteen percent of all deaths was associated with an HAI. Both average LOS and hospital charges were significantly increased among patients with HAI compared with matched non-HAI controls.

We determined that HAI had a major impact on mortality in AP. Patients who developed HAI also had significantly increased LOS and hospital charges. These differences were not explained by increased disease severity alone. Reducing HAI is an important step to improving outcome in AP.

Risk stratification of acute pancreatitis (AP) is important.

To characterize patients with early severe pancreatitis, identify risk factors of severity, and assess their outcome.

All consecutive patients with AP were included in the study. Severity assessment was done by APACHE II score, and presence and intensity of organ failure (OF). OF was graded from 1 to 4. Patients with severe pancreatitis were divided into early severe and late severe AP. The criterion for early severe AP (ESAP) was severe OF within 7 days of pancreatitis. Patients with ESAP were subdivided into fulminant and subfulminant AP based on timing of OF, i.e., <72 h and between 4 and 7 days of pancreatitis, respectively.

Of 282 patients with AP, 144 (51%) had mild AP, 32 (11.34%) had ESAP, and 106 (37.58%) had late severe AP. Of the ESAP patients (mean age 45.4 yr, 22 men), 10 patients had fulminant AP and 22 had subfulminant AP. Patients with ESAP had higher admission APACHE II compared to patients with late severe AP (14.9 vs 8.8, P<0.001). The proportion of patients with multiorgan failure was significantly higher in ESAP compared with late severe AP (75%vs 26%, P<0.001). The difference in mortality was significant in the fulminant, subfulminant, and late severe AP (90%, 72.7%, and 30%; P<0.001). Patients with ESAP accounted for 44% of all deaths. Predictors of mortality were development and early onset of organ failure.

We have characterized newer subgroups of patients with fulminant and subfulminant AP with important prognostic and management implications.

Many epidemiological studies have recently been published on acute pancreatitis; however, there is no known published report on pancreatitis in China. The present study aims to assess the etiology and mortality of severe acute pancreatitis in China.

Fifteen medical centers located throughout mainland China were involved in this retrospective study. The medical records of 1976 patients, who were admitted to these centers with the diagnosis of severe acute pancreatitis from December 1990 to December 2005, were reviewed. Epidemiological, laboratory, radiological, and therapeutic data for each case were collected on a standardized form for analysis. Severity of pancreatitis was graded according to established criteria.

Of the 1976 patients (1028 men, 948 women; mean age, 56.2 +/- 16.5 years; range, 9-94 years). Biliary tract disease (58.7%) was the main etiologic factor, whereas in 25.2%, the cause was identified as idiopathic. Endotherapy was performed in 9.1% of the severe biliary cases, but only in 33%, it was performed within 72 hours. The mean duration of hospitalization was 22.5 +/- 21.4 days, and the overall mortality rate was 11.8%.

In this retrospective study, biliary tract disease was the main etiologic factor of severe acute pancreatitis in China. The highest mortality occurred in severe idiopathic pancreatitis, and there was no clear relationship between mortality and age.

A small but significant percentage of patients with acute pancreatitis die within 2 weeks of hospitalization, usually with multiorgan system failure. To determine the effect of chronic medical comorbidities on early death, we conducted a retrospective analysis of all patients who were hospitalized in California with first-time pancreatitis between 1992 and 2002. Among 84,713 patients, 1514 (1.8%) died within 2 weeks. In a risk-adjusted multivariate model, the strongest predictors of early death were age 65 to 75 years (OR = 2.6, 95% CI: 2.2-3.1 versus <55 years), age over 75 years (OR = 5.2, 95% CI: 4.4-6.1), and the presence of either two chronic comorbid conditions (OR = 3.5, CI: 2.7-4.6) or three or more comorbidities (OR = 7.4, 95% CI: 5.7-9.5). Among the 14,280 patients younger than 55 years who had no chronic comorbid conditions, only 14 (0.1%) died in the first 14 days compared to 701 (5.9%) of 24,852 patients 64 years or older who had three or more comorbidities (RR = 29, 95% CI: 17-50). Comorbid conditions associated with early death included recent cancer, heart failure, renal disease, and liver disease. We conclude that advancing age and the number of chronic comorbid conditions are very strong predictors of early death among patients with acute pancreatitis.

To examine the epidemiology of hospital admissions for acute pancreatitis in the United States.

We compiled data from the 1988-2003 National Hospital Discharge Survey and analyzed it with respect to patient demographics, hospital type and region, procedures performed, length of hospital stay, and inpatient mortality.

Hospital admissions for acute pancreatitis increased from a 1988 low of 101,000 (95% confidence interval [CI]: 87,000-116,000) to a 2002 peak of 210,000 (95% CI: 186,000-234,000). The corresponding admission rate increased from 0.4 to 0.7 hospitalizations per 1000 U.S. population (p = 0.001). The patients' average age was 53 years, 51% were male, and 23% were black. The hospitalization rate was higher among blacks (0.9; 95% CI, 0.6-1.1) than among whites (0.4; 95% CI, 0.3-0.5). The mean length of stay was 6.9 days and decreased over the study period. Overall mortality was 2%, with increasing age and male gender comprising independent risk factors for death.

The hospitalization rate for acute pancreatitis in the United States is rising and is higher in blacks than in whites. Further research is necessary to identify the cause(s) of increasing pancreatitis admissions, the observed racial disparity, and the cost of these admissions.

To determine the timing of mortality after onset of severe acute pancreatitis (SAP) and the course of the disease in a large series of patients.

From July 1996 to June 2005, all patients diagnosed with acute pancreatitis at Chang Gung Memorial Hospital, Taipei, Taiwan were retrospectively studied. Three thousand two hundred and fifty episodes of acute pancreatitis were recorded in 2248 patients (1431 males and 817 females; median age, 55.6 years; range, 18-97 years). Mortality was divided into two groups: early death (<= 14 d after admission), and late death (> 14 d after admission). The clinical features of patients in these two groups were compared.

Although the overall mortality rate of acute pancreatitis was 3.8% (123/3250), mortality rate of SAP was as high as 16.3% (105/643). Of those 105 SAP mortalities, 44 (41.9%) deaths occurred within the first 14 d after admission and 61 (58.1%) occurred after14 d. Incidence of early death did not significantly differ from that of late death. The co-morbidities did not contribute to the timing of death. Early deaths mainly resulted from multiple organ failure. Late deaths were mainly caused by secondary complication of infected necrosis. Intra-abdominal bleeding significantly caused higher mortality in late death.

Approximately half (42%) of SAP deaths occur within 14 d and most were due to multiple organ failure. The late deaths of SAP were mostly due to infected necrosis.

Poly (ADP-ribose) polymerase (PARP), a nuclear enzyme activated by strand breaks in DNA, plays an important role in the colon injury associated with experimental colitis. The aim of the present study was to examine the effects of 3-aminobenzamide (3-AB), an inhibitor of PARP activity, in the development of acute pancreatitis caused by cerulein in mice. Intraperitoneal injection of cerulein in mice resulted in severe, acute pancreatitis characterized by oedema, neutrophil infiltration and necrosis and elevated serum levels of amylase and lipase. Infiltration of pancreatic and lung tissue with neutrophils (measured as increase in myeloperoxidase activity) was associated with enhanced expression of the intercellular adhesion molecule-1 (ICAM-1) and P-selectin. Immunohistochemical examination demonstrated a marked increase in the staining (immunoreactivity) for transforming growth factor-beta (TGF-beta) and vascular endothelial growth factor (VEGF) in the pancreas of cerulein-treated mice in comparison to sham-treated mice. Acute pancreatitis in vehicle-treated mice was also associated with a significant mortality (40% survival at 5 days after cerulein administration). In contrast, (1) the degree of pancreatic inflammation and tissue injury (histological score), (2) upregulation/formation of ICAM-1 and P-selectin, (4) neutrophils infiltration and (5) the expression of TGF-beta and VEGF was markedly reduced in pancreatic tissue obtained from cerulein-treated mice which have been treated with 3-AB. These findings provide the evidence that PARP inhibition reduce the degree of pancreas injury caused by acute pancreatitis induced by cerulein administration.

To better define the epidemiology of acute pancreatitis in a racially diverse population.

Analysis of all patients hospitalized in California with first-time acute pancreatitis for the period between January 1994 and September 2001. Subtypes were classified based on the presence or absence of predisposing conditions.

There were 70,231 patients hospitalized for first-time acute pancreatitis; 32.6% had biliary tract disease alone, 20.3% had alcohol abuse alone, and 36.6% were idiopathic. The age-standardized incidence increased by 32% from 33.2 to 43.8 cases per 100,000 adults for the period between 1994 and 2001, with the largest increase in the biliary group (52%). The standardized incidence rate of alcoholic and idiopathic pancreatitis was highest in African Americans, whereas biliary pancreatitis was highest in Hispanics. There was no change over time in the percentage of patients dying in the first 14 or 91 days; and in a risk-adjusted model, patients with alcoholic pancreatitis had the highest risk of dying.

The incidence rate of acute pancreatitis rose for the period between 1994 and 2001. However, there was no reduction in the 14- or 91-day case-fatality rate. Further research is needed to explain both the rise in the incidence rate of pancreatitis and the absence of any improvement in the early case-fatality rate.

Pancreatic resection for severe acute necrotizing pancreatitis has been associated with prohibitive mortality rates and has been hence replaced by piecemeal debridement, either by the open or the laparoscopic technique. We report the results of deliberate subtotal pancreatectomy with splenectomy for infected pancreatic necrosis.

Six-year prospective audit of patients treated by a single surgeon, with an interest in pancreatic disease, within a Low Volume Hospital (LVH) setting. Results are presented as median (IQR).

During the study period 18 patients (9 males) with complicated severe acute pancreatitis underwent radical pancreatic resection. The median age was 61 years (range 36-69). The median time to operation after presentation was 27 days (range 2-74). Microbiological culture confirmed infection in 14 (78%) patients. Three patients (17%) died within 30 days of operation. Twelve of the 15 survivors (80%) underwent a single operative procedure. Three patients required a further laparotomy, of whom 2 required colectomy for ischemia. Median hospital and ICU stays were 43 (range 30-57) and 5 (range 4-6) days respectively. Six patients (40% of survivors) developed an infection of the left half of the chevron incision; however, all wounds were fully healed within 3 months. Long-term follow-up of survivors (n=14) revealed 8 (57%) to need at least occasional pancreatic enzyme supplementation and 5 (36%) to have diabetes mellitus. Two patients (14%) developed an incisional hernia.

Radical resection of pancreas and spleen, combined with postoperative irrigation, was associated with comparatively low rates of morbidity and mortality for patients with infected pancreatic necrosis in a LVH setting.

Acute pancreatitis is a disease of increasing prevalence, unchanged mortality over many decades, and limited treatment strategies. Progress has been made in developing therapies that reduce the rate of endoscopic retrograde cholangiopancreatography (ERCP)-associated pancreatitis and in preventing infected pancreatic necrosis with intravenous carbapenems. Attempts at reducing pancreatic enzyme output or inhibiting the activity of digestive enzyme proteases have not yielded encouraging results - nor have anti-inflammatory strategies for the treatment of acute pancreatitis been found to be effective so far. Future therapeutic options that are presently being developed or under investigation attempt to restore pancreatic secretory function, interfere with inflammatory pathways in a more effective manner, or inhibit digestive enzyme proteases more selectively.

Acute pancreatitis is a common disease with an annual incidence of between 5 and 80 people per 100,000 of the population. The two major etiological factors responsible for acute pancreatitis are alcohol and cholelithiasis (gallstones). The proportion of patients with pancreatitis caused by alcohol or gallstones varies markedly in different countries and regions. The incidence of acute alcoholic pancreatitis is considered to be associated with high alcohol consumption. Although the incidence of alcoholic pancreatitis is much higher in men than in women, there is no difference in sexes in the risk involved after adjusting for alcohol intake. Other risk factors include endoscopic retrograde cholangiopancreatography, surgery, therapeutic drugs, HIV infection, hyperlipidemia, and biliary tract anomalies. Idiopathic acute pancreatitis is defined as acute pancreatitis in which the etiological factor cannot be specified. However, several studies have suggested that this entity includes cases caused by other specific disorders such as microlithiasis. Acute pancreatitis is a potentially fatal disease with an overall mortality of 2.1%-7.8%. The outcome of acute pancreatitis is determined by two factors that reflect the severity of the illness: organ failure and pancreatic necrosis. About half of the deaths in patients with acute pancreatitis occur within the first 1-2 weeks and are mainly attributable to multiple organ dysfunction syndrome (MODS). Depending on patient selection, necrotizing pancreatitis develops in approximately 10%-20% of patients and the mortality is high, ranging from 14% to 25% of these patients. Infected pancreatic necrosis develops in 30%-40% of patients with necrotizing pancreatitis and the incidence of MODS in such patients is high. The recurrence rate of acute pancreatitis is relatively high: almost half the patients with acute alcoholic pancreatitis experience a recurrence. When the gallstones are not treated, the risk of recurrence in gallstone pancreatitis ranges from 32% to 61%. After recovering from acute pancreatitis, about one-third to one-half of acute pancreatitis patients develop functional disorders, such as diabetes mellitus and fatty stool; the incidence of chronic pancreatitis after acute pancreatitis ranges from 3% to 13%. Nevertheless, many reports have shown that most patients who recover from acute pancreatitis regain good general health and return to their usual daily routine. Some authors have emphasized that endocrine function disorders are a common complication after severe acute pancreatitis has been treated by pancreatic resection.

Oxidative stress plays an important role in the early stage of acute pancreatitis, as well as in the associated multiple organ injury. This study tests the hypothesis that M40401, a new superoxide dismutase mimetic, attenuates experimental acute pancreatitis. Intraperitoneal injection of cerulein in mice resulted in a severe, acute pancreatitis that was characterized by edema, neutrophil infiltration, tissue hemorrhage, and cell necrosis, as well as increases in the serum levels of amylase and/or lipase. The infiltration of the pancreatic tissue of these animals with neutrophils (measured as an increase in myeloperoxidase activity) was associated with expression of intercellular adhesion molecule-1, as well as signs of enhanced lipid peroxidation (e.g., increased tissue levels of malondialdehyde). Immunohistochemical examination demonstrated a marked increase in the staining (immunoreactivity) for nitrotyrosine and poly (ADP-ribose) polymerase in the pancreas of cerulein-treated mice. In contrast, the degree of pancreatic inflammation and tissue injury (histological score), the expression of intercellular adhesion molecule-1, the staining for nitrotyrosine and poly (ADP-ribose) polymerase, and lipid peroxidation were markedly reduced in pancreatic tissue sections obtained from cerulein-treated mice administered with M40401. These results confirm our hypothesis that superoxide anions play an important role in cerulein-mediated acute pancreatitis and support the possible clinical use of low-molecular-weight synthetic superoxide dismutase mimetics in those conditions that are associated with overproduction of superoxide.

Acute pancreatitis is a relatively common acute abdominal emergency but there is no specific therapy for it. Traditional Chinese medicinal herbs have been used widely for many years in China to treat acute pancreatitis, and several controlled trials have been carried out to investigate their efficacy.

To assess the efficacy and safety of traditional Chinese medicinal herbs for acute pancreatitis.

The following electronic databases were searched, in September 2002: the Cochrane Central Register of Controlled Trials (CENTRAL) in The Cochrane Library Issue 3, 2002, MEDLINE, EMBASE, AHMED (Allied and Complementary Medicine Database) and SIGLE (System for Information on Grey Literature). Four Chinese journals and conference proceedings were handsearched. No language restriction was used. The searches were updated in October 2003 (The Cochrane Library Issue 3, 2003).

All randomized controlled trials involving traditional Chinese medicinal herbs in the treatment of acute pancreatitis and published in any language, regardless of whether they were single-blinded, double-blinded, or not blinded.

Data were extracted independently by two reviewers. The methodological quality of trials was evaluated using the Jadad scale plus allocation concealment.

Eleven randomized clinical trials (including a total of 658 participants) were identified in which Chinese medicinal herbs or Chinese medicinal herbs plus routine treatment were compared with routine treatment. All of these trials were published in Chinese and all included inpatients. None of the articles described the method of randomisation. The large heterogeneity of the intervention prevented us from doing a meaningful subgroup analysis. There appeared to be some benefit from Chinese medicinal herbs over control for mortality rates, length of hospital stay and operative intervention but the trials were of low quality and this benefit did not reach statistical significance.

Some Chinese medicinal herbs may work in acute pancreatitis. However, the evidence is too weak to recommend any single herb. Rigorously designed, randomized, double-blind, placebo-controlled trials are required.

Early endoscopic retrograde cholangio-pancreatography with or without endoscopic sphincterotomy (ERCP+/-ES) has been advocated to reduce complications in patients presenting with a severe attack of gallstone-associated acute pancreatitis (GAP). However, a recent trial has reported contradictory results. Importantly, patients with acute cholangitis were excluded suggesting it may be a major confounding factor affecting previous studies.

To assess the effectiveness of early ERCP+/-ES compared to conservative management stratified according to severity of disease, concealment of randomisation, acute cholangitis and bilirubin level in the reduction of mortality, morbidity, length of hospitalisation and cost in adults suspected of having GAP.

We searched - Cochrane Library (Issue 4 2003), Medline (1966-2004), EMBASE (1980-2004) and LILACS. 'Grey literature' was sought by looking at cited references and hand searched to identify further relevant trials. Conference proceedings of United European Gastroenterology Week (published in Gut) and Digestive Disease Week (published in Gastroenterology) were also hand searched.

Randomized controlled trials (RCT) of adult patients, from 15 years old or greater, presenting with gallstone-associated acute pancreatitis (GAP) comparing ERCP +/- ES versus Conservative management within 72 hours of admission.

Data were assessed for quality independently by two reviewers. Wherever appropriate, results were pooled together and sub-grouped by predicted severity of disease. Fixed and random effects models were applied. Sensitivity analysis was performed to test the fragility of results.

Three trials, involving 511 patients, met inclusion criteria. The test for heterogeneity yielded statistically non-significant results (p-value 0.1 to 0.63) suggesting all comparisons were above the established threshold for combinability (p<0.1). Fixed effect and random effect meta-analyses gave identical results. Early ERCP +/- ES was associated with non-significant effect on reduction of mortality in predicted mild (OR = 0.62, 95% CI = 0.27 to 1.41) and severe GAP (OR = 0.62, 95% CI = 0.27 to 1.41). Reduction in complications was non-significant in predicted mild (OR = 0.89, 95% CI = 0.53 to 1.49), but significant in severe GAP (OR = 0.27, 95% CI = 0.14 to 0.53). There was insufficient evidence to draw any conclusions about hospital stay and cost.

Odds of having complications are reduced in predicted severe disease by early ERCP +/- ES. This effect was however, non-significant in predicted mild disease and for reduction of mortality in either predicted mild or severe disease. These results are controlled for confounding due to associated acute cholangitis and are robust for clinical and statistical heterogeneity.

The nuclear factor-kappaB (NF-kappaB) is a transcription factor that plays a pivotal role in the induction of genes involved in the response to injury and inflammation. Dithiocarbamates are antioxidants that are potent inhibitors of NF-kappaB. This study tested the hypothesis that pyrrolidine dithiocarbamate (PDTC) attenuates experimental acute pancreatitis. Intraperitoneal injection of cerulein in mice resulted in severe, acute pancreatitis characterized by edema, neutrophil infiltration, tissue hemorrhage and necrosis, and elevated serum levels of amylase and lipase. Infiltration of pancreatic and lung tissue with neutrophils (measured as increase in myeloperoxidase activity) was associated with enhanced lipid peroxidation (increased tissue levels of malondialdehyde). Immunohistochemical examination demonstrated a marked increase in immunoreactivity for nitrotyrosine and intracellular adhesion molecule-1 in the pancreas and lung of cerulein-treated mice. In contrast, the degree of 1) pancreas and lung injury, 2) upregulation/expression of intracellular adhesion molecule-1, 3) staining for nitrotyrosine, and 4) lipid peroxidation was markedly reduced by pretreatment with PDTC. This study demonstrates that prevention of the activation of NF-kappaB by PDTC ameliorates the tissue injury associated with experimental murine acute pancreatitis and provides an important insight into the molecular biology of acute pancreatitis.

The fate of a patient with acute pancreatitis largely depends on early recognition of the severity of the disease. Acute pancreatitis is severe when organ failure and/or pancreatic necrosis occur. Whereas simple and low cost parameters are available for the detection of organ failure, the detection and extent of pancreatic necrosis requires a costly contrast-enhanced computed tomography. This is not always available in all institutions. This review article which considers when the clinician should be concerned about his patient diagnosed with acute pancreatitis, summarizes possibilities for diagnosing clinical severe (that is organ failure) and radiological severe (that is the necrotizing form of the disease) pancreatitis using simple and inexpensive parameters which are available everywhere. At present, a CT scan should be performed in those patients with alcohol etiology, those admitted to hospital early (time interval between the onset of symptoms and admission to hospital of less than 24 h, those presenting with rebound tenderness and/or guarding, a lipase >1,000 U/l, as well as a raised hematocrit and blood glucose. The evaluation, furthermore, shows that some parameters have a sufficiently high negative predictive value of >90%, which may render a contrast-enhanced CT scan unnecessary in the early stages, unless the patient fails to improve. These parameters include non-alcohol etiology, time interval between onset and admission to hospital longer than 24 h, no guarding or rebound tenderness on admission, low or normal hematocrit and nonelevated blood glucose. It is necessary to look further on simple low cost and more valid parameters on admission in order to reliably distinguish between necrotizing pancreatitis and interstitial pancreatitis.

Mortality of acute pancreatitis is dependent on the development of potentially lethal complications that can coexist and occur at any time following an acute attack. The nature and clinical relevance of these complications differ, contingent on the time of occurrence following a severe episode of pancreatitis. They can be divided into (1), early complications that manifest at the onset or within the first 2 to 3 days, (2) intermediate complications that occur predominantly during the second to fifth week, and (3) late complications that usually manifest months or years following the resolution of an acute attack. Early complications are systemic in nature with diverse clinical manifestations of the cardiovascular, pulmonary, renal, and/or metabolic systems. Intermediate complications are abdominal, pancreatic, and retroperitoneal, and are mostly septic in nature, associated with pancreatic or peripancreatic fat necrosis and pseudocysts. Late, life-threatening complications are mainly vascular or hemorrhagic in nature or involve the development of chronic pancreatic ascites. The early detection and objective evaluation of these complications by clinical and imaging methods leads to specific treatment options in the continuous attempt to decrease mortality rates in acute pancreatitis.

This study aims to determine predictability of death in acute pancreatitis at a secondary-care hospital in Germany.

This study is part of an ongoing study on the epidemiology of acute pancreatitis and covers 368 patients with a first attack of acute pancreatitis in Lüneburg county from 1988 to 1999. Early and late mortality were defined as < or = 1 weeks and > 1 week after admission. The following parameters were used to establish on admission likelihood of death: admission within 24 h or later with an acute attack, abdominal tenderness, signs of peritonitis, amylase and lipase in serum, leukocytes, hematocrit, potassium, sodium, calcium, creatinine after rehydration, blood glucose, bilirubin, serum glutamate-oxalacetate transaminase (SGOT), serum lactate dehydrogenase (SLDH), arterial pO2, APACHE II score, Ranson and Imrie scores.

Of the 368 patients 17 (5%) died, 7 early because of multiple organ failure and 10 late because of septic complications. Mortality rates in interstitial and necrotising pancreatitis were 3 and 17%, respectively. Only an elevated serum creatinine (> 2.0 mg/dl) and a blood glucose > 250 mg significantly correlated with mortality. Ranson and Imrie scores were also significantly correlated with mortality; however, they were not obtained on admission, but only after 48 h. In univariate analysis, APACHE II score > or = 6 on admission and lipase > 1,000 U/l on admission provided a high sensitivity and negative predictive value for early and late mortality patients.

Approximately half of the deaths in acute pancreatitis occur because of multiple organ failure or septic complications. New approaches have to be found to counteract these severe complications. A fatal outcome may be predicted by simple laboratory parameters such as a high serum creatinine and blood glucose. An APACHE II score > or = 6 and a lipase level on admission > or = 1,000 U/l indicate severe pancreatitis.

Pancreatic diseases occur in patients of every age. Older individuals suffer more often from gallstone related acute pancreatitis, ischaemic and idiopathic acute pancreatitis, whereas alcohol-induced acute pancreatitis occurs only in a minority of cases. Similarly, alcohol-related chronic pancreatitis in elderly people is rare and late-onset idiopathic chronic pancreatitis is the most common form of the disease. This form of chronic pancreatitis is characterized by faster progression to endocrine and exocrine pancreatic insufficiency and less severe pain compared to the clinical picture found in younger patients. Ductal pancreatic adenocarcinomas, which are responsible for more than 90% of exocrine pancreatic tumours, are typically a disease of the elderly patient. Today pancreatic resection still offers the only hope for cure and also can be performed safely in elderly patients. Age, by itself, is not a reason for withholding surgical intervention from an individual patient. Today, denial of pancreatic resection is much more likely to be based on severe co-morbidity.

We recently demonstrated that pancreatitis-associated ascitic fluid (PAAF) contains cytotoxic factor(s), inducing apoptosis in hepatocytes, and that PAAF induces hepatic adenosine triphosphate depletion, hepatocellular acidosis, and accumulation of hepatic intracellular sodium. Because ascitic fluid and serum from patients with hemorrhagic pancreatitis contain a lot of hematin, we aimed to test the hypothesis that hematin can induce hepatocellular injury, and then we compared its cytotoxicity with that of PAAF.

In vivo effects of intraperitoneal injection of hematin into the liver of healthy rats were evaluated with in situ nick-end labeling, blood biochemical analysis, and nuclear magnetic resonance spectroscopy. In vitro cytotoxic and apoptosis-inducing activities of hematin on rat primary culture hepatocytes were investigated with a cellular proliferation assay kit and DNA fragmentation enzyme-linked immunosorbent assay, respectively. Furthermore, PAAF was fractionated with Sephacryl S-300 gel column chromatography, and cytotoxic activities of its fractions on a human hepatoma cell line (HuH-7) were compared with those of hematin.

Intraperitoneal injection of hematin into healthy rats caused apoptosis in the hepatocytes and elevated serum glutamate oxaloacetic transaminase and lactate dehydrogenase levels. Intraperitoneal injection of hematin also caused a significant decrease in the hepatic beta-adenosine triphosphate/inorganic phosphate ratio, severe hepatic intracellular acidosis, and a significant increase of hepatic intracellular sodium (Na(+)) concentration, similar to the effects of PAAF. In vitro, hematin decreased hepatocyte viability and increased the DNA fragmentation of hepatocytes, similar to the effects of 10% PAAF. Albumin reversed the cytotoxic effects of hematin and PAAF on HuH-7 cells nearly completely and partially, respectively. Fractionation of PAAF and hematin by gel column chromatography revealed that the first peak of cytotoxic activity of PAAF corresponded to that of hematin and that the cytotoxic activity was reversed by albumin nearly completely.

These results suggest that hematin is one of the cytotoxic factors in PAAF that causes hepatocellular injury and that cellular injuries caused by hematin may be involved in the development of multiple organ failure associated with severe acute pancreatitis.

Mortality due to severe or necrotizing acute pancreatitis most often results from multiorgan dysfunction syndrome (MODS) occurring either early (within the first 14 days) or 2 weeks or more after the onset of symptoms due to septic complications. The aim of this study was to analyse the course of the disease in patients who died from severe acute pancreatitis.

Between January 1994 and August 2000 details of 263 consecutive patients with acute pancreatitis were entered prospectively into a database. All patients were treated in an intermediate or intensive care unit.

The overall mortality rate was 4 per cent (ten of 263 patients). The mortality rate was 9 per cent (ten of 106) in patients with necrotizing disease. No patient died within the first 2 weeks of disease onset. The median day of death was 91 (range 15-209). Six patients died from septic MODS. Ranson score, Acute Physiology and Chronic Health Evaluation (APACHE) II score during the first week of disease, pre-existing co-morbidity, body mass index, infection and extent of necrosis were significantly associated with death (P < 0.01 for all parameters). However, only infection of the necrotic pancreas was an independent risk factor in the multivariate analysis.

Early deaths in patients with severe acute pancreatitis are rare, mainly as a result of modern intensive care treatment. Nine of the ten deaths occurred more than 3 weeks after disease onset. Infection of pancreatic necrosis was the main risk factor for death.

Several prior studies have suggested that 80% of deaths in acute pancreatitis occur late as a result of pan-creatic infection. Others have suggested that approx half of deaths occur early as a result of multisystem organ failure. The aim of the present study was to determine the timing of mortality of acute pancreatitis at a large tertiary-care hospital in the United States.

Patients with a diagnosis of acute pancreatitis (ICD-9 code 577.0) admitted to Brigham and Women's Hospital from October 1, 1982 to June 30, 1995 were retrospectively studied to determine total mortality, frequency of early vs late deaths, and clinical features of patients with early (< or = 14 d after admission) or late deaths (> 14 d after admission).

The overall mortality of acute pancreatitis was 2.1% (17 deaths among 805 patients). Eight deaths (47%) occurred within the first 14 d of hospitalization (median d 8, range 1-11 d), whereas 9 occurred after 14 d (median d 56, range 19-81). Early deaths resulted primarily from organ failure. Late deaths occurred postoperatively in 8 patients with infected or sterile necrosis and 1 patient with infected necrosis treated medically.

Approximately half of deaths in acute pancreatitis occur within the first 14 d owing to organ failure and the remainder of deaths occur later because of complications associated with necrotizing pancreatitis. Improvement in mortality in the future will require innovative approaches to counteract early organ failure and late complications of necrotizing pancreatitis.

We have reported that pancreatitis-associated ascitic fluid (PAAF) contains a cytotoxic factor(s) inducing apoptosis on renal tubular cells and hepatocytes. It has been suggested that elevation of intracellular Ca(2+) concentration ([Ca(2+)](i)) is associated with the development of cell damage and apoptosis.

To clarify the mechanism of hepatocellular injury in acute pancreatitis, the effect of PAAF on hepatocyte [Ca(2+)](i) was investigated. Primary cultures of rat hepatocytes were loaded with Fura-2/acetoxymethyl, and the changes of [Ca(2+)](i) were measured using spectrofluorometer.

The baseline of hepatocyte [Ca(2+)](i) was 172 +/- 17 nM. [Ca(2+)](i) increased from 1 min after the addition of PAAF in a dose-dependent manner. Fractionation of PAAF revealed only one fraction (molecular weight >/= 5 x 10(4)) possessed both [Ca(2+)](i) elevation activity and cytotoxic activity. Neither 8-(N,N-diethyl-amino) octyl-3,4,5-trimethoxybenzoate (TMB-8) nor thapsigargin inhibited the PAAF-evoked [Ca(2+)](i) elevation. Chelation of extracellular Ca(2+) by ethylene glycol bis-(beta-aminoethyl ether) N,N,N',N'-tetraacetic acid (EGTA) prevented the elevation of [Ca(2+)](i), but verapamil did not prevent it. Platelet-activating factor antagonist (TCV-309) blocked the PAAF-elicited [Ca(2+)](i) elevation. Pancreatitis-associated serum also increased hepatocyte [Ca(2+)](i). Moreover, PAAF increased [Ca(2+)](i) on Madin-Darby canine kidney cells in a dose-dependent manner.

These results suggest that the dramatic elevation of hepatocyte [Ca(2+)](i) due to PAAF may be closely related to the hepatocellular injury in severe acute pancreatitis and that platelet-activating factor may play a pivotal role in increasing hepatocyte [Ca(2+)](i). Elevation of [Ca(2+)](i) in various cells may be involved in the mechanism of multiple organ failure in this disease.

Acute pancreatitis is a disease with a variety of symptoms. In patients in whom the disease takes a more severe course, stabilization is mandatory, often in a high dependency unit or intensive care unit. When the pancreatitis is of biliary origin and cholangitis and cholestatic changes are proven or suspected, an endoscopic cholangiopancreaticography is indicated. Aggressive organ support and continuation of the prophylactic antibiotics are the mainstay of treatment. When infected necrosis has been proven by CT-guided fine needle biopsy, surgical necrotectomy and debridement with drainage are necessary. Enteral feeding is superior to parenteral feeding even in situations of severe pancreatitis. Further investigation into the role of selective digestive tract decontamination, by controlled randomized trials, is needed.

In acute pancreatitis, pancreatic inflammation may be complicated by the development of pancreatic infection with a high associated mortality. Pancreatic infection is related to the extent of pancreatic inflammation and necrosis and typically occurs in the second or third week of severe disease. It may be associated with a wide range of Gram-positive and Gram-negative bacteria, notably enterobacteria and also with Candida spp. Current surgical practice in the UK is to use prophylactic antimicrobial therapy in patients with severe disease, with the aim of preventing secondary pancreatic infection. Experimental evidence demonstrates that prophylactic antibacterial therapy prevents pancreatic infection and reduces mortality. Furthermore, studies of antibacterial prophylaxis in patients with acute pancreatitis suggest that prophylactic antibacterial therapy is associated with a reduction in mortality, particularly in those with severe disease. In general, broad-spectrum antibiotics have been used in animal and human studies. However, current evidence does not allow comparisons to be made between different antimicrobial agents. Nutritional strategies may also be important in the prevention of pancreatic infection. Enteral, rather than parenteral, nutrition has been associated with an improved clinical outcome in severe pancreatitis.