Outcome In Severe Acute Pancreatitis Research Articles

Binge Drinking Aggravates the Outcomes of First-Attack Severe Acute Pancreatitis

To study the association of binge drinking and the outcomes of severe acute pancreatitis (SAP). This retrospective study included 347 patients with first-attack SAP from January 2001 to February 2004. On the basis of the history of binge drinking or not, the patients were divided into the alcohol (n = 77) and the control groups (n = 270). Clinical data of the 2 groups were compared. Patient age and comorbidity were similar between the 2 groups. There were more men (64, 83.1%) than women (13, 16.9%; P < 0.05) in the alcohol and the control groups (111, 41.1%; P < 0.05). The 2 groups had significant differences in admission serum triglyceride levels (5.0 +/- 5.0 vs 3.0 +/- 3.5, P < 0.05), Balthazar computed tomographic score (6.3 +/- 5.4 vs 4.2 +/- 4.5, P < 0.05), and Acute Physiology and Chronic Heath Evaluation II score (19.1 +/- 5.1 vs 16.2 +/- 6.0, P < 0.05). Total mortality and the incidences of complications were higher in the alcohol group than in the control group (P < 0.05). Binge drinking might be a contributor to the aggravation of first-attack SAP.

Effects of early parenteral supplementation with omega-3 fish oil emulsion on clinical outcome in severe acute pancreatitis

Effects of early parenteral supplementation with omega-3 fish oil emulsion on clinical outcome in severe acute pancreatitis

Severe acute pancreatitis in intensive care in 2008 – experts review

Az akut pancreatitis dinamikusan változó, gyakran progresszív kórkép, amelynek 14–20%-a az intenzív terápiás ellátást igénylő súlyos heveny hasnyálmirigy-gyulladás csoportjába tartozik, az akutan vagy több fázisban, elhúzódóan kialakuló többszervi elégtelenség, illetve többszervi diszfunkció miatt. Szisztémás irodalomkereséssel áttekintettük az elmúlt öt évben e tárgykörben megjelent közleményeket. A prognózis felállításában elsősorban a szisztémás gyulladásos válaszreakciónak, a többszervi elégtelenségnek és a többszervi diszfunkciónak van szerepe, amelyre az állapotfelmérő skálák alkalmasak (Acute Physiology and Chronic Health Evaluation, Glasgow Prognostic Index, Sepsis-related Organ Failure Assessment, Multi Organ Dysfunction Syndrome Scale, Ranson Scale). Ezek mellett a klinikai jeleknek [életkor, társbetegség(ek), tudatzavar, elhízás] és a laboratóriumi vizsgálatoknak (szérumamiláz, -lipáz, C-reaktív protein, -prokalcitonin, -kreatinin, karbamid-nitrogén, -kalcium) fontos kiegészítő prognosztikai jelentősége van. A korai szervi elégtelenség fennállásával növekszik a késői lokális szövődmények és a halálozás aránya. Az intenzív osztályos kezelés lehetővé teszi a megfelelő klinikai észlelés és eszközös monitorozás mellett a szövődmények korai felismerését és ennek alapján a célzott terápia bevezetését. A kezelés célja a szisztémás gyulladásos válaszreakció, a többszervi elégtelenség és diszfunkció progressziójának gátlása és a szervezet kompenzatorikus gyulladásellenes válaszreakciójának beindítása. A pancreas exokrin működésének csökkentése a teljes per os táplálás 24–48 órás megszüntetésével javasolt, a proteázgátlók hatásossága vitatott. Lényeges a szervi elégtelenségek korai felismerése és kezelése, valamint az intravascularis volumen rendezése, fenntartása, a folyadékresuscitatio, ezzel a stabil hemodinamika biztosítása és a mikrocirkuláció javítása. Alapvető az adekvát oxigenizáció fenntartása, korai oxigénadagolás, szükség esetén korai intenzív lélegeztetés bevezetése, emellett az elektrolit- (szérumkalcium) és sav-bázis, valamint cukorháztartás szoros kontrollja, illetve a megfelelő fájdalomcsillapítás (szisztémás, epiduralis). A mesterséges táplálás kulcspontja a korai enteralis táplálás és immunonutríció. Az inflammációs mediátor etiológiai szerepének ismeretében a kezelésben szerepet kap a gyulladásos reakció csökkentése és a koagulációs kaszkád modulációja (aktivált protein C). A komplex terápia lényeges része megfelelő javallat alapján az aktivált enzimek és toxinok eltávolítása (hemofiltráció, plazmaferézis) és az antimikrobás profilaxis, illetve kezelés, valamint a thromboembolia-profilaxis. Az akut fázisban szükségessé válhat a megnövekedett intraabdominalis nyomás csökkentése. Intenzív protokoll alkalmazásával és interdiszciplináris együttműködéssel a súlyos heveny hasnyálmirigy mortalitása 30%-ról 10%-ra csökkenthető.

Long-term outcome of severe acute pancreatitis

This study was undertaken to evaluate the post-discharge outcome of severe acute pancreatitis (SAP) and to clarify the prognostic factors for poor outcome. In 45 patients, recurrence of acute pancreatitis (AP), transition to chronic pancreatitis (CP), and development of diabetes mellitus (DM) were evaluated. Relationships of the outcome with the findings on admission and the presence/absence of alcohol intake were analyzed. The mean follow-up period was 56+/-6 months. Recurrence of AP was noted in 19% of the patients. The recurrence rate was higher in patients with necrotizing pancreatitis than in those without this feature. C-reactive protein and white blood cell (WBC) count were higher in patients with recurrence of AP. Transition to CP was noted in 22% of patients. The transition rate was higher in those with alcoholic SAP than in those with biliary SAP. In patients with transition to CP, the WBC count, hematocrit, Ranson score, and Japanese severity score were higher, and base excess (BE) was lower, compared with these features in patients without this transition. Development of DM was noted in 39% of patients. Blood glucose and BE were higher in patients who developed DM than in those who did not. The degree of inflammation and pancreatic necrosis found on admission for SAP may be related to the recurrence of AP. Alcoholic SAP in which the disease is very severe may contribute to the transition to CP. Patients with impaired glucose tolerance readily develop DM after SAP.

The Effect of Age on Hospital Outcomes in Severe Acute Pancreatitis

Background/Aims: The role of age as an important independent risk factor in severe acute pancreatitis is debated. We evaluated clinical outcomes, including in-hospital mortality and long-term disease stigmata, in elderly patients admitted with severe acute pancreatitis. Methods: We performed a retrospective case-control study in which cases were 56 elderly patients ≥70 years old and controls were 56 younger patients <70 years old. All patients were admitted to the Mayo Medical Center between 1992 and 2007 with severe acute pancreatitis, as defined by the Atlanta classification. The groups were matched for body mass index, medical comorbidities and etiology of pancreatitis. Both hospitalization and subsequent follow-up data were collected. Results: With the exception of age, the baseline characteristics of the two groups were similar. In-hospital mortality in the elderly was 3-fold greater than in controls (21.4 vs. 7.1%, p = 0.028), although length of stay was similar between the groups (26.9 vs. 31.0 days, p = 0.460). The development of organ failure, but not necrosis, was more frequent in the elderly group (64.3 vs. 48.2%, p = 0.043). There was no in-hospital mortality among patients without organ failure. The subsequent development of diabetes, recurrence of acute pancreatitis and incidence of post-hospitalization mortality was similar between groups. Conclusion: Age ≥70 years is an independent riskfactorfor mortality in patients admitted with severe acute pancreatitis.

The Impact of Obesity on the Course and Outcome of Acute Pancreatitis

Obesity has reached epidemic proportions in many countries and is an established risk factor in many chronic illnesses, but its role in acute illness is less clear. Pancreatologists have long recognized obesity as a risk factor for a poor outcome in severe acute pancreatitis. There are now several studies that have identified obesity as a primary risk factor for developing local complications (abscess, pseudocyst, necrosis), organ failure, and death. Indeed, meta-analysis of these studies gives a relative risk of 4.3 for local complications, 2.0 for systemic complications, and 2.1 for death. This has led to proposed modifications of acute pancreatitis scoring systems to include obesity as an independent primary predictive factor of severe disease. Obesity is associated with a low-grade inflammatory state, which may predispose obese patients to such complications. Furthermore, visceral obesity and visceral adipose tissue may be particularly important in underlying the pathophysiology of these observations.

OPTIMIZED CONCEPT FOR THE TREATMENT OF ACUTE PANCREATITIS IN PATIENTS

Background: Current guidelines recommend fine needle aspiration (FNA) in patients with severe acute pancreatitis (SAP) and signs of sepsis. Infected necrosis is an indication for surgery. We found high mortality in patients operated early in the course of the disease. Currently we treat patients with SAP conservatively without FNA. We evaluated the impact of this concept on outcome in SAP. Methods: Prospective analysis of patients with SAP since 09/2003 (group 1) and comparison with retrospectively analyzed patients from 03/2000 until 08/2003 (group 2). Results: Group 1: 20 consecutive patients with SAP were treated according to the new concept. All patients required ICU treatment. One patient had early surgery and died. Six pts. needed late surgery due to secondary complications and survived. One out of 13 conservatively treated patient died. CT-guided drainage was performed in one patient with abdominal compartment due to pseudocyst formation. All patients in group 2 were operated following positive FNA. 9 patients died in this group. Degree of pancreatic damage was the same in both groups as well as percentage of endocrine insufficiency. All pts of both groups received antibiotic prophylaxis. Prognostic scores indicated a severe course of the disease in both groups (no statistical difference): APACHE II was 16 ± 2.2 (group 1) vs. 19.8 ± 1.7 (group 2) and SOFA score 6.5 ± 1.1 and 8.7 ± 1.4, respectively. CRP on day 3 was 283 ± 25 (group 1) and 243 ± 21 in group 2, CTSI score was 7.9 ± 0.5 (group 1) and 7.8 ± 0.5 (group 2). Only mortality differed significantly with 10% in group 1 vs. 45 % in group 2. Conclusion: Patients with SAP treated conservatively without FNA had a significant lower mortality compared with patients treated in accordance to current guidelines. Difference in treatment included avoidance of FNA and surgery within the first 3-4 weeks. We suggest that FNA should be avoided within the first 3 weeks of SAP in a stable patient regardless of secondary organ complications since surgery increases mortality during this early phase independent from the infection of pancreatic necrosis.

Treatment outcome of selective digestive decontamination and enteral nutrition in patients with severe acute pancreatitis

Sepsis due to infected pancreatic necrosis is the most serious complication in the late phase of severe acute pancreatitis (SAP). Bacterial translocation from the gut is thought to be the main cause of pancreatic infection. The possibility has recently been reported that selective digestive decontamination (SDD) and enteral nutrition (EN) may alleviate the complications and reduce the mortality rate in patients with SAP. We analyzed the treatment outcome of SDD and EN in patients with SAP. We divided 90 patients with SAP into three groups: SDD(-)EN(-),group A; SDD(+)EN(-), group B; and SDD(+)EN(+), group C. Clinical outcome was analyzed retrospectively. The effect of SDD was compared in groups A and B, and the effect of EN was compared in groups B and C. The background of patients was not significantly different between the groups. SDD reduced the incidence of organ dysfunction (from 70% to 59%) and the mortality rate (from 40% to 28%), but the differences were not significant. EN reduced the incidence of infected pancreatic necrosis (from 31% to 24%) and the frequency of surgery for pancreas (from 28% to 18%), and further reduced the mortality rate (from 28% for SDD to 16%), but the differences were not significant. The peripheral lymphocyte count was significantly increased in patients with EN. SDD and EN did not significantly affect the treatment outcome in SAP. However, the results in this study raise the possibility that SDD and EN may decrease the complications and reduce the mortality rate in SAP. The efficacy of SDD and EN for SAP should be evaluated in a randomized controlled trial.

New advances in pancreatic surgery

New understanding of the dynamic of acute pancreatitis, the clinical impact of local pathology in chronic pancreatitis and cystic neoplastic lesions bearing high potential for malignant transformation has changed the management of pancreatic diseases. In acute pancreatitis, risk factors independently determining outcome in severe acute pancreatitis are early and persistent multiorgan failure, infected necrosis and extended sterile necrosis. The management of severe acute pancreatitis is based on early intensive-care treatment and late surgical debridement. In chronic pancreatitis, recent data from randomized controlled clinical trials have demonstrated duodenum-preserving pancreatic head resection with an inflammatory mass of the head as superior to pylorus-preserving Whipple resection. Cystic neoplasms are local lesions of the pancreas with high malignant potential. Local organ-preserving resection techniques have been applied with low morbidity and mortality, replacing a Whipple-type resection. Resection of pancreatic cancer is ineffective to cure patients. After an R0-resection, a significant survival benefit has been achieved when adjuvant chemotherapy has additionally been applied. New knowledge about the nature of inflammatory diseases, cystic neoplastic lesions and malignant pancreatic tumours has changed the indication for surgical treatment and the application of organ-preserving surgical techniques.

Treatment strategy against infection: clinical outcome of continuous regional arterial infusion, enteral nutrition, and surgery in severe acute pancreatitis

In severe acute pancreatitis (SAP), infectious complications are the main contributors to high mortality. Since 1995, we have performed continuous regional arterial infusion of protease inhibitor and antibiotics (CRAI) and enteral nutrition (EN) as prevention therapies against infection. When infected pancreatic necrosis was proven, surgical intervention was adapted. The aim of this study was to investigate the clinical outcome of these treatments. We examined the relationship between the historical change of treatment strategy and clinical outcome. We divided 84 patients with acute necrotizing pancreatitis into two groups, CRAI (-) and CRAI (+), and compared the outcome. We divided 145 patients with SAP into two groups, EN (-) and EN (+), and compared the outcome. We also analyzed the outcome of surgical treatment. In the CRAI (+) group, the incidence of infection, the frequency of surgery, and the mortality rate were lower than those in CRAI (-) group: 34% versus 51%, 27% versus 63% (P < 0.05), and 37% versus 54%, respectively. In the EN (+) group, the frequency of surgery and the mortality rate were lower than those in the EN (-) group: 23% versus 32% and 19% versus 35% (P < 0.05), respectively. These improvement effects were manifest in stage 3 (9 < or = Japanese Severity Score < or = 14). Treatment outcome of necrosectomy for infected pancreatic necrosis was still poor. Bleeding and abscess-gut fistula were postoperative life-threatening complications. CRAI and EN may improve the clinical outcome of SAP, reducing infection and averting pancreatic surgery.

Polymorphism in the IL-8 Gene, but Not in the TLR4 Gene, Increases the Severity of Acute Pancreatitis

Background/Aim: Activated granulocytes and inflammatory mediators of the innate immune response play fundamental roles in the pathogenesis of acute pancreatitis. We studied whether polymorphisms of interleukin-8 (IL-8) and Toll-like receptor 4 (TLR4) genes correlate with the severity of acute pancreatitis. Methods: Patients with acute pancreatitis (n = 92) were grouped according to the severity of the disease on the basis of the Ranson scores. Healthy blood donors (n = 200) served as controls. The IL-8 –251 gene polymorphism was analyzed by amplification-refractory mutation system; the single-nucleotide polymorphisms (Asp299Gly and Thr399Ile) of TLR4 were investigated by using a real-time polymerase chain reaction method with melting point analysis. Results: The IL-8 A/T heterozygote mutant variants were detected with a significantly higher frequency among the patients with severe pancreatitis than among the healthy blood donors (60 vs. 42%; p = 0.0264, odds ratio = 2.071, 95% confidence interval = 1.101–3.896), while the frequency of the normal allelic genotype (TT) was higher among the patients with mild pancreatitis than in the group with severe pancreatitis (35 vs. 16%; p = 0.051, odds ratio = 2.917, 95% confidence interval = 1.089–7.811). There was no significant correlation between TLR4 polymorphisms and the acute pancreatitis itself, but nonsignificantly increased frequencies of Asp299Gly and Thr399Ile heterozygotes among patients with severe infected pancreatic necrosis could be observed relative to the patients with mild pancreatitis. Conclusions: Determination of the frequency of IL-8 polymorphism in acute pancreatitis may be informative and may provide further evidence concerning the role of IL-8 in the severe form of this disease. The possible role of TLR4 polymorphism in the outcome of severe acute pancreatitis requires further investigations in a larger series of patients.

Severe Acute Pancreatitis – Outcome following a Primarily Non-Surgical Regime

Background/Aims: 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. Methods: 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. Results: 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. Conclusion: 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.

Treatment Outcome of Severe Acute Pancreatitis in Our Department

Treatment Outcome of Severe Acute Pancreatitis in Our Department

Captopril, an Angiotensin-Converting Enzyme Inhibitor, Attenuates the Severity of Acute Pancreatitis in Rats by Reducing Expression of Matrix Metalloproteinase 9

It has been reported that matrix metalloproteinase 9 (MMP-9) disrupts basement membrane and increases vascular permeability. MMP-9 therefore might participate in the pathogenesis of severe acute pancreatitis (SAP). Captopril, an angiotensin-converting enzyme inhibitor, could reduce MMP-9 expression. However, the effect of captopril on the outcome of SAP is not ascertained. The aim of this study was to determine whether captopril attenuates the severity of SAP by reducing MMP-9 expression. Thirty Sprague-Dawley rats were randomly divided into 3 groups (n = 10 for each). Rats were given intraperitoneal injection of saline (SAP group) or captopril (4 mg/kg) (treated group), and then given retrograde infusion of 5% sodium taurocholate (1.5 ml/kg) into the pancreatic duct under laparotomy to induce SAP. One group of rats, injected with saline, underwent only sham operation (Control). Experimental samples were collected at 24 hrs after the induction of SAP or sham operation. Various markers of severity of SAP, such as serum levels of amylase and trypsinogen activation peptide and the vascular permeability, were increased in rats with SAP, but were significantly decreased in captopril-treated rats (p < 0.01). Likewise, the serum MMP-9 levels and expression levels of pancreatic tissue MMP-9 were significantly higher in rats with SAP than those in captopril-treated rats and control rats (p < 0.01 for both parameters), but showed no difference between captopril-treated and control rats. These results suggest that captopril may attenuate vascular permeability by reducing MMP-9 expression in SAP, thereby ameliorating severity of the disease. The use of captopril might become a new therapeutic agent for SAP.

Pancreatitis-associated pulmonary injury: Effects of lexipafant, a platelet-activating factor antagonist

Objective. Pulmonary injury is an important determinant of outcome in severe acute pancreatitis. The aim of this experimental study was to investigate the potential effect of lexipafant, a platelet-activating factor (PAF) antagonist, on pancreatitis-associated pulmonary injury in experimental acute pancreatitis. Material and methods. Acute pancreatitis was induced by intraductal infusion of 5% sodium taurodeoxycholate in rats that were given the PAF antagonist lexipafant either before (pretreatment) or after (treatment) induction of pancreatitis. Pulmonary endothelial barrier permeability, oedema, protease inhibitor levels, pulmonary ultrastructure and membrane system integrity and levels of interleukin-1 and -6 were evaluated. Results. Pulmonary injury was characterized by increased pulmonary endothelial barrier permeability, alveolar oedema and hypoxaemia, which were noted 12 h after the induction of pancreatitis. Pretreatment with lexipafant counteracted the increase in endothelial permeability and par...

Early localization of necrosis by contrast-enhanced computed tomography can predict outcome in severe acute pancreatitis.

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.

DOES PROPHYLACTIC ANTIBIOTIC THERAPY IMPROVE OUTCOMES IN SEVERE ACUTE PANCREATITIS: A CLINICAL DECISION MODEL

Background: The prophylactic administration of antibiotics in subjects with severe acute pancreatitis (SAP) is a controversial subject. Although antibiotic administration may prevent infection in SAP it may also worsen outcomes by the creating of fungal superinfection. Prior studies have suffered from small sample size and missclassification bias. Aim: The goal of our study was to simulate a randomized clinical trial of prophylactic antibiotics versus placebo of up to one million patients with SAP. Methods: We modeled a randomized placebo controlled trial (RCT) of antibiotics versus placebo using the technique of decision analysis. We conducted a systematic review of the English published medical literature and obtained all articles on prophylactic antibiotic therapy in the management of acute pancreatitis. All point estimates and ranges of variable inputs for the model were derived from the published medical literature. We designed the model to provide input on three key parameters: 1. The length of administration of antibiotics, 2. The likelihood of developing fungal, bacterial or mixed infection and 3. Whether administration of prophylactic antibiotics was favorable vs. a no antibiotic strategy. Our base case consisted of a subject with SAP with or without necrosis. We tested the robustness of our model by using the technique of MonteCarlo simulation to simulate a series of randomized trials in which 100-1,000,000 patients were enrolled. Clinical endpoints were likelihood of death vs. life. Results: Our model demonstrated that the base case simulated RCT a short course of antibiotics (<14 days) was the preferred strategy. When we varied the model such that giving antibiotics was associated with a higher risk of fungal or bacterial infection no antibiotics was the preferred strategy. Monte-Carlo simulation for simulated trials of 100-1,000,000 patients demonstrated that short course of prophylactic antibiotics and fungal treatment was the preferred strategy 93% of the time. Conclusion: A short course of antibiotics appears to improve outcome in SAP. Consideration should be given to antifungal treatment as well.

Outcome of severe acute pancreatitis

Background The treatment of severe acute pancreatitis has been evolving from routine operative management to nonoperative care for patients without evidence of pancreatic infection. Methods Retrospective chart review of patients with severe acute pancreatitis at a single institution during a 9-year period. Results Sixty consecutive patients had severe pancreatitis. Forty-two had pancreatic necrosis on computed axial tomography (13 infected and 29 sterile). Patients with infected necrosis and 8 with sterile necrosis had operative debridement; the remaining patients were managed without operation (n = 39). The overall mortality was 15%. Mortality was directly related to the Acute Physiology and Chronic Health Examination II and Marshall organ failure scores ( P <0.001). Patients who died had a greater incidence of nosocomial infection. Conclusions Patients with infected pancreatic necrosis require early operative debridement, whereas those with sterile necrosis or severe pancreatitis without necrosis can usually be managed safely without surgery.

Significance of apoptotic cell death in systemic complications with severe acute pancreatitis

In severe acute pancreatitis, multiple organ failure in the early stage after onset, and sepsis in the late stage, due to infection of pancreatic or peripancreatic devitalized tissue, contribute to its high mortality. In analogy with sepsis, evidence has accumulated of the significance of apoptotic cell death in the systemic manifestations associated with acute pancreatitis. Since we identified apoptosis-inducing activity in pancreatitis-associated ascitic fluid in 1995, a number of investigators, including our group, have reported, through animal experiments, that apoptosis occurred in the parenchymal cells constituting organs, such as alveolar epithelial cells in the lung, renal tubular cells in the kidney, and hepatocytes in the liver, and this apoptosis was involved in organ dysfunction with severe acute pancreatitis. Moreover, through clinical and experimental investigations, apoptosis has been revealed to be involved in the mechanism of infectious complications in acute pancreatitis. Namely, apoptosis in lymphatic tissues and peripherally circulating lymphocytes is involved in the impairment of cellular immunity, and apoptosis in gut epithelial cells is implicated in bacterial translocation. These results suggest that apoptotic cell death may play a considerable role in affecting mortality and morbidity in severe acute pancreatitis. Control of apoptosis could be a potent strategy for improvement of the clinical outcome in severe acute pancreatitis.

Influence of PMN leukocyte-mediated pancreatic damage on the systemic immune response in severe acute pancreatitis in rats.

The outcome of severe acute pancreatitis is determined by the development of the systemic inflammatory response and subsequent multiorgan dysfunction. Using the taurocholate-induced model of acute pancreatitis in rats, we investigated the relationship between early polymorphonuclear (PMN)-mediated pancreatic tissue damage and the systemic inflammatory response. The respiratory burst of PMN leukocytes was increased in animals with acute pancreatitis and was reduced by anti-ICAM-1 antibody and oxygen radical scavenger treatment after 24 hr. In acute pancreatitis a reduced number of peripheral helper T cells was evident, most likely due to L-selectin-mediated increased lymphocyte homing. After 24 hr the CD45RC(high)/CD45RC(low) ratio of helper T cells, a critical factor in T cell-mediated disease was increased due to a reduction of regulatory CD45RC(low) cells. Only the treatment with anti-ICAM-1 mAb affected these changes, indicating that immunological changes in necrotizing pancreatitis are only in part affected by early PMN leukocyte-mediated pancreatic damage.