Pancreas Splanchnic and Pancreatic Tissue Perfusion in Experimental Acute Pancreatitis

Background: Gut hypoperfusion has a major role in the pathogenesis of multiple organ failure, which is the main cause of death in severe acute pancreatitis. The effects of experimental acute pancreatitis on splanchnic and pancreatic perfusion and oxygenation were studied to find out whether gut hypoperfusion occurs already at the same time as changes in pancreatic perfusion. Methods: Twenty-four domestic pigs weighing 21-27 kg were randomized to severe or mild acute pancreatitis or control groups. Eight anaesthetized and mechanically ventilated pigs were intraductally infused with taurocholic acid to induce severe acute pancreatitis and eight received intraductal saline to induce mild acute pancreatitis. Eight pigs served as controls. Results: Intraductally infused taurocholic acid rapidly induced severe necrotizing acute pancreatitis as assessed macroscopically and histologically. Histological changes of mild acute pancreatitis were seen in animals after intraductal saline infusion. After the induction, pancreatic tissue oxygen tension decreased promptly in severe acute pancreatitis and increased in mild acute pancreatitis. Laser-Doppler red cell flux decreased in severe acute pancreatitis. Gut pH gap and pCO 2 gap decreased in 2 h after the induction of severe acute pancreatitis. Central haemodynamics were fairly stable throughout the study period in all groups. Conclusion: In experimental severe acute pancreatitis, splanchnic malperfusion seems to begin with pancreatic hypoperfusion before disturbances in gut microcirculation.     

Splanchnic and pancreatic tissue perfusion in experimental acute pancreatitis

BACKGROUND: Gut hypoperfusion has a major role in the pathogenesis of multiple organ failure, which is the main cause of death in severe acute pancreatitis. The effects of experimental acute pancreatitis on splanchnic and pancreatic perfusion and oxygenation were studied to find out whether gut hypoperfusion occurs already at the same time as changes in pancreatic perfusion. METHODS: Twenty-four domestic pigs weighing 21-27 kg were randomized to severe or mild acute pancreatitis or control groups. Eight anaesthetized and mechanically ventilated pigs were intraductally infused with taurocholic acid to induce severe acute pancreatitis and eight received intraductal saline to induce mild acute pancreatitis. Eight pigs served as controls. RESULTS: Intraductally infused taurocholic acid rapidly induced severe necrotizing acute pancreatitis as assessed macroscopically and histologically. Histological changes of mild acute pancreatitis were seen in animals after intraductal saline infusion. After the induction, pancreatic tissue oxygen tension decreased promptly in severe acute pancreatitis and increased in mild acute pancreatitis. Laser-Doppler red cell flux decreased in severe acute pancreatitis. Gut pH gap and pCO2 gap decreased in 2 h after the induction of severe acute pancreatitis. Central haemodynamics were fairly stable throughout the study period in all groups. CONCLUSION: In experimental severe acute pancreatitis, splanchnic malperfusion seems to begin with pancreatic hypoperfusion before disturbances in gut microcirculation.     

Therapeutic anticoagulation for splanchnic vein thrombosis in acute pancreatitis: A systematic review and meta-analysis

ObjectivesThe optimal management of patients with acute pancreatitis (AP) and splanchnic vein thrombosis (SVT) remains unknown. This systematic review and meta-analysis aimed to see if therapeutic anticoagulation (AC) improves outcomes in patients with AP and SVT.MethodsA systematic review was performed according to PRISMA guidelines. Main outcomes were recanalization, recurrent venous thromboembolism, development of varices, collaterals or cavernoma, haemorrhage and mortality. Meta-analysis were performed with the Mantel-Haenszel random effect models.ResultsSeven retrospective cohort studies (3495 patients) were included. SVT occurred in 233 (7%) patients and involved most frequently the splenic vein (44%). Therapeutic AC was administered to 109 (47%) patients, most frequently to those with triple vessel thrombosis (72%) and least to those with isolated splenic vein (22%) or superior mesenteric vein thrombosis (0%). Most studies administered (low molecular weight) heparin followed by warfarin (duration ranged between 1.5 and 12 months). This meta-analysis showed an absolute risk difference of 9% (95% confidence interval [CI] = -11-28%) for recanalization, ?3% (95% CI = ?19-12%) for the development of varices, collaterals or cavernoma, 3% (95% CI = ?6-12%) for haemorrhage and 2% (95% CI = ?8-12%) for mortality.ConclusionsBased on the currently available data, it remains unclear if therapeutic anticoagulation provides benefit to acute pancreatitis patients with splanchnic vein thrombosis. These results are based on low quality data underlining the need for further higher quality studies.     

Restoration of energy level in the early phase of acute pediatric pancreatitis

Acute pancreatitis (AP) is a serious inflammatory disease with rising incidence both in the adult and pediatric populations. It has been shown that mitochondrial injury and energy depletion are the earliest intracellular events in the early phase of AP. Moreover, it has been revealed that restoration of intracellular ATP level restores cellular functions and defends the cells from death. We have recently shown in a systematic review and meta-analysis that early enteral feeding is beneficial in adults; however, no reviews are available concerning the effect of early enteral feeding in pediatric AP. In this minireview, our aim was to systematically analyse the literature on the treatmentof acute pediatric pancreatitis. The preferred reporting items for systematic review(PRISMA-P) were followed, and the question was drafted based on participants, intervention, comparison and outcomes: P: patients under the age of twenty-one suffering from acute pancreatitis; I: early enteral nutrition (per os and nasogastric- or nasojejunal tube started within 48 h); C: nil per os therapy; O: length of hospitalization, need for treatment at an intensive care unit, development of severe AP, lung injury (including lung oedema and pleural effusion), white blood cell count and pain score on admission. Altogether, 632 articles (Pub Med: 131; EMBASE: 501) were found. After detailed screening of eligible papers, five of them met inclusion criteria. Only retrospective clinical trials were available. Due to insufficient information from the authors, it was only possible to address length of hospitalization as an outcome of the study. Our mini-meta-analysis showed that early enteral nutrition significantly(SD = 0.806, P = 0.034) decreases length of hospitalization compared with nil per os diet in acute pediatric pancreatitis. In this minireview, we clearly show that early enteral nutrition, started within 24-48 h, is beneficial in acute pediatric pancreatitis. Prospective studies and better presentation of research are crucially needed to achieve a higher level of evidence.     

Splanchnic vein thrombosis in severe acute pancreatitis: a 2-year, single-institution experience

ObjectivesThis study aimed to determine current practice in the management and outcome of splanchnic vein thrombosis complicating acute pancreatitis (AP).MethodsAn audit of prospectively collected data for all patients presenting with AP was conducted. Patients with splanchnic vein thrombosis were grouped according to vessel involvement and whether or not systemic anticoagulation was administered.ResultsOf 127 consecutive patients admitted with AP, 20 had splanchnic venous thrombosis; in all cases the thrombosis was associated with a severe attack of AP. Involvement of the splenic vein (SV), portal vein (PV) and superior mesenteric vein (SMV) was observed in 14, 10 and three patients, respectively. Involvement of more than one vessel was observed in six patients (SV and PV in four patients; SMV and SV in one patient; all three veins in one patient). Thromboses were colocalized with collections in 19 patients. Only four patients received systemic anticoagulation. Resolution of thrombosis was observed in six patients over a median of 77 days. No significant differences were observed in recanalization rates following anticoagulation (P= 0.076). No complications associated with systemic anticoagulation occurred. One patient developed liver failure associated with progressive PV thrombosis and one patient died.ConclusionsSplanchnic vein thrombosis is a relatively common observation in severe AP and is associated with pancreatic necrosis and peripancreatic collections. Recanalization is observed in almost a third of patients, irrespective of whether or not they receive systemic anticoagulation.     

Practice guidance for diagnosis and treatment of pancreatitis‐related splanchnic vein thrombosis (Shenyang, 2020)

Splanchnic vein thrombosis is a severe complication of pancreatitis. To date, no consensus over the management of pancreatitis‐related splanchnic vein thrombosis has been established. Based on the consensus of multidisciplinary experts, this practice guidance systematically reviewed the epidemiology, anatomy, pathophysiology, risk assessment and clinical presentations of splanchnic vein thrombosis, and formulated a diagnosis and treatment strategy for providing guidance in clinical practice for this disease.     

Risk factors for concomitant infectious pancreatic necrosis in patients with severe acute pancreatitis: A systematic review and meta-analysis

ObjectiveAcute pancreatitis (AP) is a self-limiting disease. However, 20–30% of patients will develop into severe AP (SAP), and infectious pancreatic necrosis in the late course of SAP is the leading cause of death for such patients. This review aims to provide a comprehensive and systematic report of the currently published risk factors for complicated infectious pancreatic necrosis in patients with severe acute pancreatitis by meta-analysis of published retrospective case-control studies.MethodsFive electronic database systems were selected to search for articles on risk factors of infectious pancreatic necrosis in patients with severe acute pancreatitis. According to the heterogeneity among studies, the standardized mean difference (SMD), odds ratio and 95% confidence interval (95%CI) were calculated by applying a random-effects model or fixed-effects model, respectively.ResultsAs of 2nd Jun, 2021, a total of 1408 articles were searched, but only 21 articles were finally included in this meta-analysis. The results found that patients with severe acute pancreatitis complicated by infected pancreatic necrosis had higher APACHE II scores and higher levels of lipase (LPS), C-reactive protein (CRP) and procalcitonin (PCT) compared to patients with severe acute pancreatitis alone. The differences were statistically significant (APACHE II: SMD = 0.86, 95%CI: 0.55, 1.18; LPS: SMD = 1.52, 95%CI: 1.13, 1.92; CRP: SMD = 1.42, 95%CI: 1.05, 1.79; PCT: SMD = 1.82, 95%CI: 1.36, 2.28).ConclusionsCompared with patients with severe acute pancreatitis alone, high levels of LPS, CRP, PCT and high APACHE II score were risk factors for infectious pancreatic necrosis in patients with severe acute pancreatitis.     

Treatment of acute pancreatitis with protease inhibitors: a meta-analysis

OBJECTIVES: Protease inhibitors are used to treat acute pancreatitis, but their effectiveness remains unclear. We performed a meta-analysis to determine whether treatment with protease inhibitors reduces overall mortality or morbidity from acute pancreatitis. METHODS: Articles of randomized controlled trials evaluating effects of protease inhibitors for acute pancreatitis were retrieved by systematically searching Medline, the Cochrane Library and Journal@ovid databases published from January 1966 through December 2003. References of review articles were also searched manually. The main outcome in interest was the overall mortality rate from acute pancreatitis. RESULTS: Ten studies met the inclusion criteria. Treatment with protease inhibitors did not significantly reduce the mortality rate from acute pancreatitis (pooled risk difference, -0.03; 95% confidence interval, -0.07 to 0.01). Subgroup analyses showed that treatment with protease inhibitors significantly reduced the mortality rate in patients with moderate to severe pancreatitis (pooled risk difference, -0.07; 95% confidence interval, -0.13 to -0.01) as defined by mortality rate in the control group (control mortality rate > 0.10). The decrease in mortality rate was not significant in mild pancreatitis (pooled risk difference, 0.00; 95% confidence interval, -0.04 to 0.05). CONCLUSIONS: Treatment with protease inhibitors does not significantly reduce the mortality in patients with acute or mild pancreatitis, but may reduce the mortality in patients with moderate to severe pancreatitis.     

The association between portal system vein diameters and outcomes in acute pancreatitis

Background/objectives

Acute pancreatitis (AP) progresses to necrotizing pancreatitis in 15% of cases. An important pathophysiological mechanism in AP is third spacing of fluids, which leads to intravascular volume depletion. This results in a reduced splanchnic circulation and reduced venous return. Non-visualisation of the portal and splenic vein on early computed tomography (CT) scan, which might be the result of smaller vein diameter due to decreased venous flow, is associated with infected necrosis and mortality in AP. This observation led us to hypothesize that smaller diameters of portal system veins (portal, splenic and superior mesenteric) are associated with increased severity of AP.

Understanding the Colonic Complications of Pancreatitis

Background: Colonic necrosis, fistula and stricture are infrequent but potentially lethal complications of pancreatitis. As any individual unit will have only limited experience, this study aims to provide a structured, systematic appraisal of published experience to identify any consistent trends and disease patterns that may help in practical management. Methods: A computerized search of the MEDLINE databases for the period January 1950 through January 2006 yielded 43 articles. Pooled extracted data were examined for type of pancreatitis and colonie complications, method and time of diagnosis, treatment and outcome. Results: 43 reports provided pooled data on 97 patients. Colonie complications were more frequent in severe disease, occurring in 15%. The principal presentations were necrosis, fistula and stricture. All episodes of colonie necrosis complicated severe acute pancreatitis, were diagnosed operatively, presented at a median of 25 (1–55) days into the episode and were associated with a mortality of 54%. In contrast, stricture presented at a median of 50 (10–270) days. Surgical resection without anastomosis is the mainstay of management of necrosis. Trial of conservative management in a stable patient with a fistula may facilitate spontaneous closure. Conclusions: This study highlights several consistent trends: preoperative diagnosis is difficult, colonie necrosis and fistula are rare complications principally of severe acute pancreatitis and they present either as ongoing abdominal sepsis or rectal bleeding. Surgical resection remains the mainstay of management. A high index of suspicion should be maintained in patients with severe acute pancreatitis, with ongoing sepsis and evidence of gastrointestinal blood loss.     

Severe acute pancreatitis: pathogenesis,diagnosis and surgical management

BACKGROUND: Severe acute pancreatitis is a subtype of acute pancreatitis, associated with multiple organ failure and systemic inflammatory response syndrome. In this qualitative review we looked at the principles of pathogenesis, classification and surgical management of severe acute pancreatitis. We also looked at the current shift in paradigm in the management of severe acute pancreatitis since the guideline developed by the British Society of Gastroenterology.DATA SOURCES: Studies published between 1st January 1991 and 31st December 2015 were identified with Pub Med, MEDLINE, EMBASE and Google Scholar online search engines using the following Medical Subject Headings: "acute pancreatitis, necrosis, mortality, pathogenesis, incidence" and the terms "open necrosectomy and minimally invasive necrosectomy".The National Institute of Clinical Excellence(NICE) Guidelines were also included in our study. Inclusion criteria for our clinical review included established guidelines, randomized controlled trials and non-randomized controlled trials with a follow-up duration of more than 6 weeks.RESULTS: The incidence of severe acute pancreatitis within the UK is significantly rising and pathogenetic theories are still controversial. In developed countries, the most common cause is biliary calculi. The British Society of Gastroenterology,acknowledges the Revised Atlanta criteria for prediction of severity. A newer Determinant-based system has been developed.The principle of surgical management of acute necrotizing pancreatitis requires intensive care management, identifying infection and if indicated, debridement of any infected necrotic area. The current procedures opted for include standard surgical open necrosectomy, endoscopic necrosectomy and minimally invasive necrosectomy. The current paradigm is shifting towards a step-up approach.CONCLUSIONS: Severe acute pancreatitis is still a subject of grey areas in its surgical management even though new studies have been recorded since the origin of the latest UK guidelines for management of severe acute pancreatitis.     

Splanchnic vein thrombosis in candidates for liver transplantation: usefulness of screening and anticoagulation

BACKGROUND AND AIMS: Splanchnic vein thrombosis is a significant source of complications in candidates for liver transplantation. The aims of this study were: (a) to determine the prevalence of and risk factors for splanchnic vein thrombosis in cirrhotic patients awaiting transplantation and (b) to assess the usefulness of anticoagulation. METHODS: A total of 251 cirrhotic patients listed for transplantation were analysed. All underwent systematic screening for thrombosis with Doppler ultrasonography. During the second period of the study, all patients with thrombosis received anticoagulation up to transplantation while during the first period none had received anticoagulation. RESULTS: The incidence of splanchnic vein thrombosis at evaluation was 8.4%. Seventeen additional patients (7.4%) developed de novo thrombosis after evaluation. Independent risk factors for thrombosis were low platelet count (77.4 (36.3) v 111.6 (69.2) 10(9)/l; p = 0.001), a past history of variceal bleeding (47.4% v 29.1%; p = 0.003), and a prolonged interval from listing to transplantation (8.5 (6.8) v 4.8 (4.4) months; p = 0.002). The proportion of partial or complete recanalisation was significantly higher in those who received (8/19) than in those who did not receive (0/10, p = 0.002) anticoagulation. Survival was significantly lower in those who had complete portal vein thrombosis at the time of surgery (p = 0.04). CONCLUSION: These results support a systematic screening for splanchnic vein thrombosis in patients awaiting transplantation. They suggest that in these patients, anticoagulation is safe and has a significant impact on recanalisation as well as prevention of extension of thrombosis.     

Should anticoagulants be administered for portal vein thrombosis associated with acute pancreatitis?

Venous complications in patients with acute pancreatitis typically occur as a form of splenic, portal, or superior mesenteric vein thrombosis and have been detected more frequently in recent reports. Although a well-organized protocol for the treatment of venous thrombosis has not been established, anticoagulation therapy is commonly recommended. A 73-year-old man was diagnosed with acute progressive portal vein thrombosis associated with acute pancreatitis. After one month of anticoagulation therapy, the patient developed severe hematemesis. With endoscopy and an abdominal computed tomography scan, hemorrhages in the pancreatic pseudocyst, which was ruptured into the duodenal bulb, were confirmed. After conservative treatment, the patient was stabilized. While the rupture of a pseudocyst into the surrounding viscera is a well-known phenomenon, spontaneous rupture into the duodenum is rare. Moreover, no reports of upper gastrointestinal bleeding caused by pseudocyst rupture in patients under anticoagulation therapy for venous thrombosis associated with acute pancreatitis have been published. Herein, we report a unique case of massive upper gastrointestinal bleeding due to pancreatic pseudocyst rupture into the duodenum, which developed during anticoagulation therapy for portal vein thrombosis associated with acute pancreatitis.     

Ultrasonographic splanchnic arterial flow measurement in severe acute pancreatitis

INTRODUCTION: Duplex ultrasonographic technology is now capable of detecting flow signals in the various splanchnic vessels and calculating the concomitant flow velocities using fast-Fourier transformation. AIM: To use Doppler sonography to investigate how splanchnic hemodynamics vary during the early stage of severe acute pancreatitis. METHODOLOGY: Six patients with severe acute pancreatitis (age, 59.0 +/- 6.57 years; four men, two women) and seven with mild to moderate acute pancreatitis (age, 60.1 +/- 7.41 years; five men, two women) were examined with Doppler sonography immediately after disease onset. The maximum velocity, minimum velocity, mean velocity, pulsatility index, and resistive index were determined from the Doppler spectra from the proper hepatic artery, celiac artery, and superior mesenteric artery. We also examined 15 healthy subjects (age, 59.3 +/- 4.60 years; 10 men, five women) as controls. RESULTS: The maximum velocity of the proper hepatic artery in patients with severe acute pancreatitis was significantly higher than that in patients with mild to moderate acute pancreatitis (p = 0.011) and in control subjects (p = 0.0047). Similarly, significant increases in both the minimum velocity and the mean velocity of the proper hepatic artery were observed in patients with severe acute pancreatitis. Neither pulsatility index nor resistive index of the proper hepatic artery showed a significant difference among the three groups. There were no significant differences among the three groups with respect to the flow velocity of the superior mesenteric artery. In contrast, the pulsatility index of the superior mesenteric artery in patients with severe acute pancreatitis was significantly lower than that in patients with mild to moderate acute pancreatitis (p = 0.0058) or in control subjects (p = 0.0024). For patients with acute pancreatitis, a significant inverse correlation was obtained between the maximum velocity of the proper hepatic artery and the pulsatility index of the superior mesenteric artery (r = -0.658, p = 0.0145). CONCLUSION: The increase in the hepatic arterial flow velocity and the decrease in the superior mesenteric arterial pulsatility index may represent early events of the severe type of acute pancreatitis.     

Biliary pancreatitis.

Gallstone-induced acute pancreatitis is a prevalent condition that is associated with an unacceptably high mortality rate. Early endoscopic intervention, including endoscopic retrograde cholangiopancreatography and endoscopic sphincterotomy within 24 to 72 h of hospital admission, can be used to remove stones in the common bile duct (CBD) and establish biliary drainage. Anecdotal evidence of its effectiveness led to formal testing in randomized clinical trials. Although the design and results of the four published studies have varied, the overall conclusion is that early endoscopic therapy reduces morbidity and mortality in patients with acute biliary pancreatitis. Benefits are especially apparent in patients who satisfy generally accepted criteria for severe pancreatitis. The author's practice is to undertake endoscopic retrograde cholangiopancreatography in patients with severe or worsening pancreatitis, or in patients with jaundice, cholangitis or dilation of the CBD. Endoscopic sphincterotomy is performed in patients with CBD stones or in patients with biliary pancreatitis and cholelithiasis who are not candidates for cholecystectomy. The roles of newer diagnostic modalities, including magnetic resonance cholangiopancreatography and endoscopic ultrasonography, are not yet clear.     

A systematic review of the extra-pancreatic infectious complications in acute pancreatitis

Background and aimExtra-pancreatic infectious complications in acute pancreatitis increase morbidity, but their incidence and association with infected pancreatic necrosis is unknown. Half of bacterial cultures of pancreatic necrosis are of non-enteric origin, raising the possibility of other sources of infection. The aim of this systematic review was to assess the incidence of extra-pancreatic infectious complications in acute pancreatitis, their timing, and relation to severity of pancreatitis and mortality.MethodsA systematic review was performed using Ovid MEDLINE, Embase and Cochrane Libraries, following PRISMA guidelines. Search terms were “Pancreatitis” AND “Infection” AND (“Complication” OR “Outcome”).Results19 studies with 1741 patients were included. Extra-pancreatic infectious complication incidence was 32% (95% CI 23–41%), with the commonest being respiratory infection (9.2%) and bacteraemia (8.4%). Extra-pancreatic infectious complications were not associated with the predicted severity or the mortality of acute pancreatitis. Only 3 studies reported a relation of timing between extra-pancreatic and pancreatic infectious complications.ConclusionsThis is the first systematic review to evaluate the incidence of extra-pancreatic infectious complications in acute pancreatitis, which a third of patients with acute pancreatitis will develop. Implications are vigilance and prompt treatment of extra-pancreatic infection, to reduce possibility of progression to infected pancreatic necrosis.     

Value of adipokines in predicting the severity of acute pancreatitis: Comprehensive review

AIM: To analyze the prognostic value of adipokines in predicting the course, complications and fatal outcome of acute pancreatitis (AP).METHODS: We performed the search of PubMed database and the systemic analysis of the literature for both experimental and human studies on prognostic value of adipokines in AP for period 2002-2012. Only the papers that described the use of adipokines for prediction of severity and/or complications of AP were selected for further analysis. Each article had to contain information about the levels of measured adipokines, diagnosis and verification of AP, to specify presence of pancreatic necrosis, organ dysfunction and/or mortality rates. From the very beginning, study was carried out adhering to the PRISMA checklist and flowchart for systemic reviews. To assess quality of all included human studies, the Quality Assessment of Diagnostic Accuracy Studies tool was used. Because of the high heterogeneity between the studies, it was decided to refrain from the statistical processing or meta-analysis of the available data.RESULTS: Nine human and three experimental studies were included into review. In experimental studies significant differences between leptin concentrations at 24 and 48 h in control, acute edematous and acute necrotizing pancreatitis groups were found (P = 0.027 and P < 0.001). In human studies significant differences between leptin and resitin concentrations in control and acute pancreatitis groups were found. 1-3 d serum adiponectin threshold of 4.5 μg/mL correctly classified the severity of 81% of patients with AP. This threshold yielded a sensitivity of 70%, specificity 85%, positive predictive value 64%, negative predictive value88% (area under curve 0.75). Resistin and visfatin concentrations differ significantly between mild and severe acute pancreatitis groups, they correlate with severity of disease, need for interventions and outcome. Both adipokines are good markers for parapancreatic necrosis and the cut-off values of 11.9 ng/mL and 1.8 ng/mL respectively predict the high ranges of radiological scores. However, the review revealed that all nine human studies with adipokines are very different in terms of methodology and objectives, so it is difficult to generalize their results. It seems that concentrations of the leptin and resistin increases significantly in patients with acute pancreatitis compared with controls. Serum levels of adiponectin, visfatin and especially resitin (positive correlation with Acute Physiology and Chronic Health Evaluation II, Ranson and C-reactive protein) are significantly different in mild acute pancreatitis and severe acute pancreatitis patients, so, they can serve as a markers for the disease severity prediction. Resistin and visfatin can also be used for pancreatic and parapancreatic necrosis prediction, interventions needs and possible, outcome.CONCLUSION: High levels of adipokines could allow for prediction of a severe disease course and outcome even in small pancreatic lesions on computed tomography scans.     

Evaluation of factors that have reduced mortality from acute pancreatitis over the past 20 years

BACKGROUND: The mortality associated with acute pancreatitis varies markedly in different studies, with most frequently reported mortality rates of 10% to 15% for all cases and 15% to 90% for attacks regarded as "severe." More recently, various centers have recorded lower mortality rates of 4% to 7% for all attacks of acute pancreatitis and 20% to 50% for those regarded as severe. GOALS: To investigate whether there has been a reduction in mortality associated with acute pancreatitis over the past 20 years and the reasons for this reduction. STUDY: Intended as a review, this study included the authors' 20-year prospective assessment of mortality as it relates to the severity of the disease, complications, and current therapy. For the mortality results, the study was divided into four 4-year periods from 1977 to 1998 and the past 3 years (i.e., 1998-2001). For comparison, the mortality figures from some other large studies are presented. RESULTS: This study showed that the initial reduction in mortality related to acute pancreatitis coincided with the recognition and application of the signs of severity, either Ranson's prognostic signs or Bank's clinical criteria. These signs dictated admission to intensive care unit (ICU) therapy, the intensity of ICU monitoring, and the importance of organ-specific emergent therapy. Further mortality reduction in the 1990s could be attributed to either a more select study sample or earlier and more selective endoscopic or surgical debridement of infected tissue, endoscopic cyst drainage, and angiographic control of gastrointestinal bleeding. Improved nutritional support by jejunal feeding, earlier use of antibiotic therapy, gut sterilization, early endoscopic retrograde cholangiopancreatography for common bile duct stones and necrosectomy for noninfected necrosis have reduced the overall mortality associated with acute pancreatitis to a mean of 5% (range, 3.8-7%) for all cases and 20% (range, 15-25%) for severe cases. However, it is clear that the greater the number of signs denoting severity of organ failure, the higher the mortality. CONCLUSIONS: There has been considerable reduction in the mortality associated with acute pancreatitis over the past 20 years. The reasons are multifactorial, but recognition of severity signs, early implementation of organ-specific therapy, and newer endoscopic, surgical, and angiographic therapy for infection cyst and bleeding appear to have been the major factors in reducing mortality.     

Comparing the Usefulness of the 1997 and 2009 WHO Dengue Case Classification: A Systematic Literature Review

The 1997 and 2009 WHO dengue case classifications were compared in a systematic review with 12 eligible studies (4 prospective). Ten expert opinion articles were used for discussion. For the 2009 WHO classification studies show: when determining severe dengue sensitivity ranges between 59–98% (88%/98%: prospective studies), specificity between 41–99% (99%: prospective study) - comparing the 1997 WHO classification: sensitivity 24.8–89.9% (24.8%/74%: prospective studies), specificity: 25%/100% (100%: prospective study). The application of the 2009 WHO classification is easy, however for (non-severe) dengue there may be a risk of monitoring increased case numbers. Warning signs validation studies are needed. For epidemiological/pathogenesis research use of the 2009 WHO classification, opinion papers show that ease of application, increased sensitivity (severe dengue) and international comparability are advantageous; 3 severe dengue criteria (severe plasma leakage, severe bleeding, severe organ manifestation) are useful research endpoints. The 2009 WHO classification has clear advantages for clinical use, use in epidemiology is promising and research use may at least not be a disadvantage.     

New approaches for the treatment of acute pancreatitis

In recent years, a number of articles have been published on the treatment of acute pancreatitis in experimental models and most of them were published about animals with mild disease. However, it is difficult to translate these results into clinical practice. For example, infliximab, a monoclonal TNF antibody, was experimentally tested in rats and it was able to significantly reduce the pathologic score and serum amylase activity, and also alleviate alveolar edema and acute respiratory distress syndrome; no studies are available in clinical human acute pancreatitis. Another substance, such as interleukin 10, was efficacious in decreasing the severity and mortality of lethal pancreatitis in rats, but seems to have no effect on human severe acute pancreatitis. Thus, the main problem in acute pancreatitis, especially in the severe form of the disease, is the difficulty of planning clinical studies capable of giving hard statistically significant answers regarding the benefits of the various proposed therapeutic agents previously tested in experimental settings. According to the pathophysiology of acute pancreatitis, we may re-evaluate the efficacy of the drugs already available, such as gabexate mesilate, lexipafant and somatostatin which should be probably administered in a different manner. Of course, also in this case, we need large studies to test this hypothesis. Another great problem is prevention of the infection of pancreatic necrosis. A randomized study has been published to test the hypothesis that probiotics and specific fibres used as supplements in early enteral nutrition may be effective in reducing pancreatic sepsis and the number of surgical interventions. A study named PROPATRIA (Probiotic Prophylaxis in Patients with Predicted Severe Acute Pancreatitis) has been planned to give a more robust confirmation to the previous study. Furthermore, the open question of the prevention of the fungal infection of necrosis is still being debated. Finally, the prevention of pain relapse after oral feeding in patients with mild or severe acute pancreatitis should be explored. Even if some studies exist on this issue, the question of optimal treatment is still unanswered. As in other diseases, obtaining results when treating patients with acute pancreatitis is difficult and will take continuous small steps.