Tissue factor in predicted severe acute pancreatitis

AIM: To study tissue factor (TF) in acute pancreatitis and evaluate the role of TF as a predictive marker of severity. METHODS: Forty-nine consecutive patients admitted to Lund University Hospital, fulfilling the criteria of predicted severe acute pancreatitis (AP), were recruited prospectively between 2002 and 2004. Blood samples for TF analyses were drawn at inclusion in the study and 12 h, 1 d and 3 d later. RESULTS: Twenty-seven patients developed mild AP, and 22 patients severe AP. At inclusion in the study, the groups were comparable with respect to gender, aetiology, Acute Physiology and Chronic Health Evaluation Ⅱ score, and duration of pain. At inclusion in the study and at 12 h, TF was higher in the severe AP group (P = 0.035 and P = 0.049, respectively). After 1 and 3 d, no differences in TF levels were noted. Interleukin (IL)-6 was significantly higher in the severe AP group at all of the studied time points. C-reactive protein (CRP) was significantly higher in the AP group at 1 and 3 d. In receiver operating characteristic-curves, the area under the curve (AUC) for TF was 0.679 (P = 0.035) at inclusion in the study, and a cut off level for TF of 40 pg/mL showed a sensitivity of 71% and a specificity of 67%, whereas corresponding AUC for IL-6 was 0.775, P = 0.001, and for CRP was 0.653. IL-6 showed better AUC-values than TF at all time points studied. CONCLUSION: TF-levels are raised early in severe AP. TF as an early predictive marker of severe AP is superior to CRP, but inferior to IL-6.     

Elevated level of interleukin-6 predicts organ failure and severe disease in patients with acute pancreatitis

BACKGROUND AND AIM: Cytokines play an important role in the pathogenesis of acute pancreatitis (AP). The aim of the present paper was to study the profile of anti- and proinflammatory cytokines in AP and to determine their predictive value for severity of AP, organ failure and mortality. METHODS: Consecutive patients with AP were included in the study. Cytokines were measured in those patients who presented within the first 72 h of the onset of AP. Plasma levels of proinflammatory cytokines tumor necrosis factor (TNF)-alpha, interleukin (IL)-Ibeta, IL-6 and anti-inflammatory cytokine IL-10 were measured on days 1, 3, 7 and 14 of AP. RESULTS: Of 108 patients, 30 presented within 72 h of the onset (mean age 40.27 +/- 13.89 years; 22 males). Of the 30 patients, 13 (43.3%) had severe and 17 (56.7%) had mild pancreatitis. Eleven (36.7%) patients developed organ failure and three died. The level of IL-6 on day 3 was significantly higher in severe pancreatitis than in mild pancreatitis (146.29 +/- 57.53 pg/mL vs 91.42 +/- 71.65 pg/mL; P = 0.04) and was significantly higher in patients who developed organ failure compared with those who did not (161.59 +/- 53.46 pg/mL vs 88.16 +/- 65.50 pg/mL; P = 0.004). At a cut-off value of 122 pg/mL on day 3, IL-6 predicted organ failure and severe pancreatitis with a sensitivity and specificity of 81.8% and 77.7%, respectively. TNF-alpha and IL-10 were detectable only in one-third of patients and were not related to the severity of pancreatitis, while Il-1beta was not detectable. CONCLUSION: Elevated levels of IL-6 predicted organ failure and severe pancreatitis and suggested its pathophysiological significance in AP.     

Elevated levels of the complement regulator protein CD59 in severe acute pancreatitis

Objective. Complement activation occurs in patients with acute pancreatitis (AP) and may contribute to the development of organ failure. Because a number of enzymes are released during AP that could influence the complement inhibitor CD59, the purpose of this study was to examine serum levels of CD59 in relation to severity of AP. Material and methods. Twelve patients with severe AP had organ failure (referred to as the grade 2 group). For each of them, we found 2–3 age-matched AP patients who served as controls (n=27). Of these, a total of 13 had mild AP (grade 0 group) and 14 severe AP without organ failure (grade 1 group). Blood samples were collected at admission and on days 1 and 3–7 post-admission. Grade 2 patients were compared with grade 0 and grade 1 patients. CD59 levels were measured by a sandwich enzyme immunoassay. Results. At admission, median CD59 levels were significantly higher (p=0.002) in grade 2 patients (median 104.2 ng/ml, range 26.1–186.3) than in grade 0 patients (37.3, range 30.3–75.9) and grade 1 patients (38.6, range 19.9–96.1). CD59 levels remained higher in grade 2 patients than in grade 0 and 1 patients on day 1 (p=0.001) and days 3–7 (p=0.002). The CD59 levels correlated significantly (p<0.05) with C-reactive protein (CRP) levels (R=0.40) and APACHE II scores (R=0.32) on admission. Conclusions. Organ failure and severity of AP are associated with elevated serum levels of CD59.     

Predictors of severe and critical acute pancreatitis: A systematic review

BackgroundPersistent 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.MethodsWe 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.ResultsThe 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 48 h of admission, and blood urea nitrogen and Japanese Severity Score after 48 h of admission. Systemic Inflammation Response Syndrome was a poor predictor of persistent organ failure. The best predictor of infected pancreatic necrosis was procalcitonin.ConclusionsBased on the best available data, it is justifiable to use blood urea nitrogen for prediction of persistent organ failure after 48 h 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 48 h of admission.     

Detailed fluid resuscitation profiles in patients with severe acute pancreatitis

Background and aim

Appropriate and timely initial fluid resuscitation in acute pancreatitis (AP) is critical. The aim of this retrospective study was to evaluate fluid therapy on an hour-by-hour basis in relation to standard indices of adequate resuscitation during AP.

Methods

Emergency room shock charts, fluid balance sheets and intensive care (ICU) charts for all patients with AP admitted to ICU in a large acute hospital were examined. Vital signs, clinical course and fluid administered during the first 72 h after admission were tabulated against urine output, central venous pressure (CVP) and inotrope/vasopressor therapy.

Results

Sixty-three consecutive patients with AP were initially evaluated. Inter-hospital transfers with established organ dysfunction (n = 11) or where records had insufficient detail (n = 22) were excluded. In the remaining 30 patients, in-hospital death occurred in 7. The cumulative volume of crystalloid given was significantly less at 48 h in patients who died in hospital (3331 ± 800 ml vs. survivors, 7287 ± 544 ml; P < 0.001). Non-survivors had a higher CVP, and received more inotropes/vasopressors.

Conclusion

In severe AP-associated organ failure, fluid resuscitation profiles differ between survivors and non-survivors. CVP alone as a crude indicator of adequate resuscitation may be unreliable, potentially leading to the use of inotropes/vasopressors in the inadequately filled patient.     

Nasogastric feeding in severe acute pancreatitis may be practical and safe

Summary Background. Severe acute pancreatitis may be protracted and some form of nutritional support is frequently required to maintain the patient’s nutritional status. Recent work has suggested that enteral feeding via a jejunal route of delivery may reduce the magnitude of the inflammatory response. Insertion of nasojejunal (NJ) tubes in the patient with severe acute pancreatitis involves both delay and inconvenience. We undertook a prospective, feasibility study to assess the safety and practicability of nasogastric (NG) feeding in patients with severe acute pancreatitis. Patients and Methods. Twenty-six patients with objective evidence of severe acute pancreatitis received nasogastric feeding within 48 h of admission to our unit. Results. Etiology was identified as cholelithiasis (18 patients), ethanol (5), and miscellaneous (3). The median Glasgow score was 4 (range 2–7), APACHE II score 10 (4–28), and C-reactive protein concentration 286 mg/L (79–469). Fifteen patients had pancreatic and/or peripancreatic necrosis. Eleven patients developed severe organ failure, necessitating ventilatory support. Six developed multiple organ system failure, requiring inotropic support and/or renal dialysis. There were four deaths (15.3%). Nine patients underwent early, and nine late, ERCP, respectively; six necrosectomy (5 proven infected necrosis, 1 continued deterioration despite maximal support) and 4 patients internal drainage of a pseudocyst. The feed was well-tolerated in 22 patients. In 3 patients gastric stasis proved troublesome. There was no evidence of clinical or biochemical deterioration on commencing nasogastric feeding. Conclusion. It would appear that early NG feeding is usually possible in severe acute pancreatitis. In most patients it appears safe, well-tolerated, and worthy of further study.     

Experimental acute pancreatitis induces mitochondrial dysfunction in rat pancreas,kidney and lungs but not in liver

Background/aimsExcessive systemic inflammatory response syndrome during severe acute pancreatitis (AP) leads to multiple organ dysfunction syndrome, which is the main cause of death and may be associated with primary mitochondrial disturbances. The aim of our study was to evaluate the role of mitochondria during experimental AP in pancreas and vital organs like kidney, lungs and liver within the first 48 h.MethodsAP was induced in 39 male Wistar rats by intraductal application of sodium taurocholate (5%, 1.75 ml/kg). Animals were divided into groups reflecting the time from induction of the AP till collection of tissues (control and 1, 3, 6, 12, 24, 48 h). Mitochondria were isolated by differential centrifugation and mitochondrial respiration rates were measured oxygraphically.Results(1) Mitochondria in pancreas are affected within the first 6 h after onset of AP, (2) kidney mitochondria are affected 24 h after onset of AP, (3) lungs mitochondria are affected within 48 h after onset of AP whereas (4) liver mitochondria remain well preserved within the first 48 h. Severe AP–induced decrease in the oxidative phosphorylation of pancreas, kidney and lungs mitochondria was more pronounced with Complex I-linked (glutamate/malate) than with Complex II-linked (succinate) substrates and was associated with inhibition of Complex I.ConclusionOur data show that the disturbances of mitochondrial energy metabolism in pancreas, kidney and lungs may play an important role in the development and progression of AP as a systemic disease.     

Timing of mortality in severe acute pancreatitis： Experience from 643 patients

AIM： 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. METHODS： 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. RESULTS： 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. Intraabdominal bleeding significantly caused higher mortality in late death. CONCLUSION： 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.     

自噬、炎症反应及免疫功能异常在急性胰腺炎中的研究进展

急性胰腺炎(acute pancreatitis,AP)是临床较常见的由不同原因引起的一种急危重病,其发病机制复杂多样,易并发多脏器损伤,导致死亡率升高,故充分了解AP的发病机制可为临床早期干预、准确治疗及判断预后提供重要的参考价值。虽然启动该病发生和影响其进展的机制复杂多样,并且目前对AP的病理生理方面的认识已取得很大进步,但关键问题是其机制中精确而关键的分子机制尚不清楚,目前尚无特效的治疗方法。由于胰腺的解剖位置和担心获取人胰腺组织的操作会加重胰腺炎的严重程度而无法取样,因此,实验动物模型的研究证明,自噬、炎症反应和免疫功能异常在AP发病机制中的作用尤为重要。为此,本文探讨上述机制在AP中的作用,可能为AP的缓解及治疗提供新的靶点。     

重症急性胰腺炎患者器官功能衰竭的临床特点与治疗

器官功能衰竭是导致重症急性胰腺炎(SAP)患者死亡的重要因素。近年得益于对SAP病理生理研究的进一步深入和经验技术的不断积累,在SAP患者器官功能衰竭诊断治疗方面取得了长足的进步。介绍了SAP并发器官功能衰竭的临床特点和SAP应注意重点加强的治疗措施。目前认为SAP一旦发生容易造成器官功能衰竭,及时规范的治疗能缩短病程,显著降低病死率。     

Peritoneal lavage with aprotinin in patients with severe acute pancreatitis

Summary Conclusion Although high-dose aprotinin given intraperitoneally to patients with severe acute pancreatitis seems to inhibit activated trypsin in the peritoneal cavity, the treatment has little effect on the balance between proteases and antiproteases. Plasma levels of leukocyte proteases were high in all the patients, indicating leukocyte activation to be an important feature of the pathophysiology of severe acute pancreatitis. A surprise finding was that the patients had higher peritoneal levels of pancreatic secretory trypsin inhibitor (PSTI) after the lavage procedure. Background Although most studies have shown protease inhibitor therapy to have little or no effect on acute pancreatitis, in an earlier study we found that very high doses of the protease inhibitor aprotinin given intraperitoneally to patients with severe acute pancreatitis seemed to reduce the need of surgical treatment for pancreatic necrosis. In the present study we have further analyzed plasma and peritoneal samples from the same patients to ascertain whether the aprotinin treatment affects the balance between proteases and endogenous antiproteases. Methods In a prospective double-blind randomized multicenter trial, 48 patients with severe acute pancreatitis were treated with intraperitoneal lavage. One group (aprotinin group,n=22) was also treated with high doses (20 million KIU given over 30 h) of aprotinin intraperitoneally. The remaining 26 patients made up the control group. The protease-antiprotease balance was studied by measuring immunoreactive anionic trypsin (irAT), cationic trypsin (irCT), complexes between cationic trypsin and alpha 1-protease inhibitor (irCT-α1PI), leukocyte elastase and neutrophil proteinase 4 (NP4), as well as the endogenous protease inhibitors, pancreatic secretory trypsin inhibitor (PSTI), alpha 2-macroglobulin (α 2M), alpha 1-protease inhibitor (α 1PI), antichymotrypsin (ACHY), and secretory leukocyte protease inhibitor (SLPI). Intraperitoneal levels were studied before and after the lavage procedure, and plasma levels were followed for 21 d. Results The control group had lower plasma levels of SLPI and analysis of peritoneal fluid showed the reduction of irCT-α 1PI to be more pronounced in the aprotinin group. None of the other variables measured differed significantly between the two groups. All patients had very high levels of leukocyte elastase and NP4 both in peritoneal exudate and in plasma. Peritoneal levels of PSTI were higher after the lavage procedure in contrast to the other measured variables that all showed lower peritoneal levels after the lavage.     

Evaluation of Chinese updated guideline for acute pancreatitis on management of moderately severe and severe acute pancreatitis

Background/Objectives: The management of acute pancreatitis (AP) in China has undergone major changes since the launch of the updated guideline in 2013. This study aimed to evaluate the impact of this guideline on clinical practice and patient outcome.MethodsModerately severe and severe adult AP patients, who were admitted to Peking Union Medical College Hospital from January 1, 2001 to December 31, 2016, were retrospectively included in the study. All enrolled patients were divided into two groups based on the publication date of the updated guideline, as the pre-guideline (Pre) group and post-guideline (Post) group. In-hospital case-fatality rates were compared between two groups after adjusting baseline features, including gender, age, etiology and disease severity. In addition, the associations between specific therapeutic approaches recommended in the updated guideline and in-hospital case-fatality rates were explored.ResultsA total of 475 patients were enrolled in this study, including 273 (57%) in the Pre group and 202 (43%) in the Post group. The adjusted in-hospital case-fatality rate significantly decreased in the Post group (14.3% vs. 5.9%, OR 0.39, 95%CI 0.19–0.82). In the post-hoc analysis, the use of enteral nutrition was a protective factor against in-hospital death (OR: 0.08, 95%CI: 0.03–0.18), while open surgery showed an opposite effect (OR: 3.81, 95%CI: 1.06–13.74). Prophylactic antibiotics was not significantly associated with in-hospital death (OR: 1.00, 95%CI: 0.39–2.60).ConclusionsThere was a prominent transition in the management of moderately severe and severe AP after the release of the guideline in China in 2013, which made the prognosis better.     

Incidence,management and recurrence rate of acute pancreatitis

Background: Acute pancreatitis is a common condition that is still associated with substantial morbidity and mortality rates. Management, outcome and recurrence rate in acute pancreatitis in a clinical setting using a conservative management approach are described. Methods: A total of 1376 consecutive cases representing 2211 hospitalizations due to acute pancreatitis treated at the Dept. of Surgery, Lund University Hospital, Lund, were reviewed retrospectively. Management, outcome and recurrence rate were recorded. Results: Incidence, including recurrences, was 300 per million per year; 21% of patients had recurrent (≥2) attacks. In relapsing disease, two‐thirds of patients had the first attack within 3 months. Mortality decreased over the period studied, but overall it was 4.2%; mortality in relapsing attacks was 2.5%, related to multiple organ dysfunction (MODS) in 67% and occurring within the first week in 36%. Conclusions: Despite a conservative approach in the management of acute pancreatitis, mortality is still substantial, frequently occurs early after admission, is associated with MODS and is also seen in relapsing disease. Early cholecystectomy and bile duct clearance could decrease recurrent attacks of biliary pancreatitis.     

Mechanisms of interleukin-22's beneficial effects in acute pancreatitis

Acute pancreatitis(AP) is a disorder characterized by parenchymal injury of the pancreas controlled by immune cell-mediated inflammation. AP remains a significant challenge in the clinic due to a lack of specific and effective treatment. Knowledge of the complex mechanisms that regulate the inflammatory response in AP is needed for the development of new approaches to treatment, since immune cell-derived inflammatory cytokines have been recognized to play critical roles in the pathogenesis of the disease. Recent studies have shown that interleukin(IL)-22, a cytokine secreted by leukocytes, when applied in the severe animal models of AP, protects against the inflammation-mediated acinar injury. In contrast, in a mild AP model, endogenous IL-22 has been found to be a predominantly antiinflammatory mediator that inhibits inflammatory cell infiltration via the induction of Reg3 proteins in acinar cells, but does not protect against acinar injury in the early stage of AP. However, constitutively over-expressed IL-22 can prevent the initial acinar injury caused by excessive autophagy through the induction of the antiautophagic proteins Bcl-2 and Bcl-XL. Thus IL-22 plays different roles in AP depending on the severity of the AP model. This review focuses on these recently reported findings for the purpose of better understanding IL-22's regulatory roles in AP which could help to develop a novel therapeutic strategy.     

重症急性胰腺炎治疗研究进展

重症急性胰腺炎是一种累及多种脏器的全身性疾病,并发症多,病死率高.由于病情的复杂性,其治疗方法涉及内科、外科、中医和内镜治疗等方面,在选择治疗方法时需要判断患者的病情,给予全面综合及个体化治疗.本文就重症急性胰腺炎各类治疗措施的研究进展及治疗的新观念作一综述.     

Esmolol attenuates lung injury and inflammation in severe acute pancreatitis rats

BackgroundRecent studies suggest that beta-adrenergic blockers attenuate systemic inflammation and improve survival in sepsis. We investigated whether esmolol can reduce lung injury and modulate inflammatory response in a rat model of severe acute pancreatitis (SAP).MethodsA taurocholate-induced SAP was used, with or without continuously intravenous pumping of esmolol (15 mg/kg/h). Heart rate and arterial pressure were monitored. Nine hrs after esmolol administration, blood was drawn for blood gas analyses and cytokine (interleukin(IL)-6, tumor necrosis factor (TNF)-α) detections, lungs and pancreata were isolated for measurements of myeloperoxidase (MPO) activity and histological damage. In an additional 20 animals, rats were randomized into SAP or SAP + esmolol groups to assess effects of esmolol on survival time.ResultsTreatment with esmolol was associated with improved survival time (11.1 ± 1.6 h vs. 9.2 ± 2.0 h, p = 0.044) and less severe disease, as assessed by lung and pancreas histology. Blood gas analyses were ameliorated in esmolol group. Arterial PO₂ increased (109.7 ± 12.4 mmHg vs 93.9 ± 4.1 mmHg, p = 0.008) while lactate levels (2.1 ± 0.5 vs 3.1 ± 0.7 mmol/L, p = 0.001) decreased in SAP + esmolol group as compared with SAP group. Esmolol treatment also abated the increase in bronchoalveolar lavage fluid protein and proinflammatory cytokines. Furthermore, esmolol reduced SAP-induced plasma amylase activity (p = 0.02), blunted the expression of TNF-α (p = 0.003) and IL-6 (p < 0.001), and decreased pancreas/lung MPO activities.ConclusionsContinuous infusion of esmolol, a selective beta-1 adrenergic blocker, improves outcome, reduces inflammatory responses and also offers lung and pancreas protective effects in SAP rats. This may offer novel therapeutic strategies in treating patients suffering from SAP.     

连续性静脉-静脉血液滤过在重症胰腺炎治疗中的价值

目的 观察在传统治疗重症急性胰腺炎(SAP)的同时行连续性静脉-静脉血液滤过(CVVH)的疗效。方法 53例SAP患者在接受传统治疗的同时行CVVH,每次至少持续24h。监测CVVH前后病情及血清淀粉酶、脂肪酶的变化,行动脉血气分析和APACHlE Ⅱ评分,测血中内毒素水平。结果 CVVH治疗后患者心动过速、呼吸窘迫、腹痛、腹胀等症状明显缓解,APACHEⅡ评分明显降低,淀粉酶、脂肪酶、尿素氮、肌酐明显降低,酸中毒、低氧血症纠正。CVVH治疗6h后,血中内毒素水平下降,24h后又恢复至治疗前的水平。53例患者中38例痊愈出院,存活率为71．7％。结论 在传统治疗SAP的同时行CVVH,能提高抢救的成功率,降低病死率。     

Indications for surgery in severe acute pancreatitis

The decision to operate on a patient with severe acute pancreatitis is often difficult and requires mature clinical judgment. Those indications that are widely accepted include:

连续性血液净化治疗重症急性胰腺炎合并多器官功能障碍综合征的效果观察

目的观察连续性血液净化(CBP)对重症急性胰腺炎(SAP)合并多器官功能障碍综合征(MODS)患者血清炎症介质的影响。方法选取2008年4月-2013年12月成都军区总医院收治的SAP合并MODS患者65例,采用非随机同期对照试验方法按治疗方式不同分为两组,其中对照组(n=33)接受内科综合治疗,治疗组(n=32)在内科综合治疗基础上给予CBP治疗。监测患者CBP治疗前后APACHEⅡ评分、MODS评分以及血清肿瘤坏死因子(TNF)α、C-反应蛋白(CRP)、血小板衍化生长因子(PAF)、白细胞介素(IL)6、IL-18、一氧化氮(NO)水平变化。计量资料组间比较采用成组t检验,同组治疗前后比较采用配对t检验;计数资料组间比较采用χ2检验。结果两组患者治疗后,APACHEⅡ、MODS评分及血清TNFα、CRP、IL-6、IL-18、PAF、NO水平均较治疗前明显降低,差异均有统计学意义(P值均0.05),且治疗组较对照组降低更为明显(P值均0.001);治疗组患者存活率为90.6%(29/32),对照组患者存活率为78.8%(26/33),两组存活率比较差异无统计学意义(χ2=1.749,P=0.186)。结论 CBP能够有效清除SAP合并MODS患者血清中的炎症介质,从而阻断炎症反应,改善脏器功能,是治疗SAP的有效方法之一。     

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.