In patients with pancreatitis, early persisting organ failure is believed to be the most important cause of mortality. This study investigates the relation between the timing (onset and duration) of ...organ failure and mortality and its association with infected pancreatic necrosis in patients with necrotising pancreatitis.
We performed a post hoc analysis of a prospective database of 639 patients with necrotising pancreatitis from 21 hospitals. We evaluated the onset, duration and type of organ failure (ie, respiratory, cardiovascular and renal failure) and its association with mortality and infected pancreatic necrosis.
In total, 240 of 639 (38%) patients with necrotising pancreatitis developed organ failure. Persistent organ failure (ie, any type or combination) started in the first week in 51% of patients with 42% mortality, in 13% during the second week with 46% mortality and in 36% after the second week with 29% mortality. Mortality in patients with persistent multiple organ failure lasting <1 week, 1-2 weeks, 2-3 weeks or longer than 3 weeks was 43%, 38%, 46% and 52%, respectively (p=0.68). Mortality was higher in patients with organ failure alone than in patients with organ failure and infected pancreatic necrosis (44% vs 29%, p=0.04). However, when excluding patients with very early mortality (within 10 days of admission), patients with organ failure with or without infected pancreatic necrosis had similar mortality rates (28% vs 34%, p=0.33).
In patients with necrotising pancreatitis, early persistent organ failure is not associated with increased mortality when compared with persistent organ failure which develops further on during the disease course. Furthermore, no association was found between the duration of organ failure and mortality.
To assess the safety of Auxora in patients with acute pancreatitis (AP), systemic inflammatory response syndrome (SIRS), and hypoxemia, and identify efficacy endpoints to prospectively test in future ...studies.
This phase 2, open-label, dose-response study randomized patients with AP, accompanying SIRS, and hypoxemia (n = 21) to receive low-dose or high-dose Auxora plus standard of care (SOC) or SOC alone. All patients received pancreatic contrast-enhanced computed tomography scans at screenings, day 5/discharge, and as clinically required 90 days postrandomization; scans were blinded and centrally read to determine AP severity using computed tomography severity index. Solid food tolerance was assessed at every meal and SIRS every 12 hours.
The number of patients experiencing serious adverse events was not increased with Auxora versus SOC alone. Three (36.5%) patients with moderate AP receiving low-dose Auxora improved to mild AP; no computed tomography severity index improvements were observed with SOC. By study end, patients receiving Auxora better tolerated solid foods, had less persistent SIRS, and had reduced hospitalization versus SOC.
The favorable safety profile and patient outcomes suggest Auxora may be an appropriate early treatment for patients with AP and SIRS. Clinical development will continue in a randomized, controlled, blinded, dose-ranging study.
To assess the safety of Auxora in patients with acute pancreatitis (AP), systemic inflammatory response syndrome (SIRS), and hypoxemia, and identify efficacy endpoints to prospectively test in future ...studies.
This phase 2, open-label, dose-response study randomized patients with AP, accompanying SIRS, and hypoxemia (n = 21) to receive low-dose or high-dose Auxora plus standard of care (SOC) or SOC alone. All patients received pancreatic contrast-enhanced computed tomography scans at screenings, day 5/discharge, and as clinically required 90 days postrandomization; scans were blinded and centrally read to determine AP severity using computed tomography severity index. Solid food tolerance was assessed at every meal and SIRS every 12 hours.
The number of patients experiencing serious adverse events was not increased with Auxora versus SOC alone. Three (36.5%) patients with moderate AP receiving low-dose Auxora improved to mild AP; no computed tomography severity index improvements were observed with SOC. By study end, patients receiving Auxora better tolerated solid foods, had less persistent SIRS, and had reduced hospitalization versus SOC.
The favorable safety profile and patient outcomes suggest Auxora may be an appropriate early treatment for patients with AP and SIRS. Clinical development will continue in a randomized, controlled, blinded, dose-ranging study.
AbstractObjectiveTo assess whether laparoscopic cholecystectomy is superior to percutaneous catheter drainage in high risk patients with acute calculous cholecystitis.DesignMulticentre, randomised ...controlled, superiority trial.Setting11 hospitals in the Netherlands, February 2011 to January 2016.Participants142 high risk patients with acute calculous cholecystitis were randomly allocated to laparoscopic cholecystectomy (n=66) or to percutaneous catheter drainage (n=68). High risk was defined as an acute physiological assessment and chronic health evaluation II (APACHE II) score of 7 or more.Main outcome measuresThe primary endpoints were death within one year and the occurrence of major complications, defined as infectious and cardiopulmonary complications within one month, need for reintervention (surgical, radiological, or endoscopic that had to be related to acute cholecystitis) within one year, or recurrent biliary disease within one year.ResultsThe trial was concluded early after a planned interim analysis. The rate of death did not differ between the laparoscopic cholecystectomy and percutaneous catheter drainage group (3% v 9%, P=0.27), but major complications occurred in eight of 66 patients (12%) assigned to cholecystectomy and in 44 of 68 patients (65%) assigned to percutaneous drainage (risk ratio 0.19, 95% confidence interval 0.10 to 0.37; P<0.001). In the drainage group 45 patients (66%) required a reintervention compared with eight patients (12%) in the cholecystectomy group (P<0.001). Recurrent biliary disease occurred more often in the percutaneous drainage group (53% v 5%, P<0.001), and the median length of hospital stay was longer (9 days v 5 days, P<0.001).ConclusionLaparoscopic cholecystectomy compared with percutaneous catheter drainage reduced the rate of major complications in high risk patients with acute cholecystitis.Trial registrationDutch Trial Register NTR2666.
Full text
Available for:
BFBNIB, CMK, NMLJ, NUK, PNG, SAZU, UL, UM, UPUK
Background Diagnosing infected necrotizing pancreatitis (INP) may be challenging. The aim of this study was to determine the added value of routine fine-needle aspiration (FNA) in addition to ...clinical and imaging signs of infection in patients who underwent intervention for suspected INP. Methods We conducted a post hoc analysis of 208 consecutive patients from a prospective, multicenter database who underwent intervention because of suspected INP. In retrospect, 3 groups were constructed based on the patients preoperative characteristics: Clinical, imaging, and FNA. Patients in the clinical group had clinical signs of infection but no gas on preoperative computed tomography (CT) and no FNA performed before intervention. Patients in the imaging group had gas bubbles on the preoperative CT but no was FNA performed, whereas patients in the FNA group had a positive FNA before intervention. The reference standard for infection was the culture taken during the first intervention (either catheter drainage or necrosectomy). Results The initial intervention for INP was performed a median of 27 days (interquartile range, 20–39) after admission without difference between the 3 groups ( P = .15). Infection was confirmed in 80% of 92 patients of the clinical group, in 94% of 88 patients of the imaging group, and in 86% of 28 patients of the FNA group ( P = .07). Mortality was 19% and was not different between groups ( P = .39). Conclusion INP can generally be diagnosed based on clinical or imaging signs of infection. FNA may be useful in patients with unclear clinical signs and no imaging signs of INP.
Full text
Available for:
GEOZS, IJS, IMTLJ, KILJ, KISLJ, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UL, UM, UPCLJ, UPUK
Background & Aims There is limited information on the incidence of and factors associated with severe disease among patients with interstitial pancreatitis (IP). We evaluated a large cohort of ...patients with IP and compared data with those from patients with extrapancreatic necrosis (EXPN). Methods We evaluated 149 consecutive patients with IP admitted over a 2.5-year period. Transferred patients were excluded. We collected data on age, Charlson comorbidity score (CCI), measures of severity on admission or within 24 hours (Acute Physiology and Chronic Health Evaluation II, bedside index for severity of acute pancreatitis scores), persistent (>48 h) systemic inflammatory response syndrome, persistent organ failure, need for intensive care unit, length of hospital stay (in days), and mortality. We also analyzed levels of severity among those with IP and EXPN. Statistical analysis was performed using SAS version 9.1 (Cary, NC). Results Among the patients with IP, the median CCI score was 1, the median Acute Physiology and Chronic Health Evaluation II score was 7, and the median bedside index for severity of acute pancreatitis score was 1. In addition, the median length of hospital stay was only 4 days; only 1% had persistent organ failure and only 1% to 2% required intervention. The mortality rate of IP was 3%; it was associated significantly with comorbidity (the median CCI scores of nonsurvivors and survivors was 4 and 1, respectively, P = .003). Patients with EXPN had greater levels of disease severity, compared with patients with IP. Conclusions IP is severe in only 1% to 3% of patients; mortality of IP is associated strongly with comorbidity. EXPN is more frequently severe than IP; EXPN must be distinguished from IP in clinical studies.
CONTEXT Most patients with infected necrotizing pancreatitis require necrosectomy. Surgical necrosectomy induces a proinflammatory response and is associated with a high complication rate. Endoscopic ...transgastric necrosectomy, a form of natural orifice transluminal endoscopic surgery, may reduce the proinflammatory response and reduce complications. OBJECTIVE To compare the proinflammatory response and clinical outcome of endoscopic transgastric and surgical necrosectomy. DESIGN, SETTING, AND PATIENTS Randomized controlled assessor-blinded clinical trial in 3 academic hospitals and 1 regional teaching hospital in the Netherlands between August 20, 2008, and March 3, 2010. Patients had signs of infected necrotizing pancreatitis and an indication for intervention. INTERVENTIONS Random allocation to endoscopic transgastric or surgical necrosectomy. Endoscopic necrosectomy consisted of transgastric puncture, balloon dilatation, retroperitoneal drainage, and necrosectomy. Surgical necrosectomy consisted of video-assisted retroperitoneal debridement or, if not feasible, laparotomy. MAIN OUTCOME MEASURES The primary end point was the postprocedural proinflammatory response as measured by serum interleukin 6 (IL-6) levels. Secondary clinical end points included a predefined composite end point of major complications (new-onset multiple organ failure, intra-abdominal bleeding, enterocutaneous fistula, or pancreatic fistula) or death. RESULTS We randomized 22 patients, 2 of whom did not undergo necrosectomy following percutaneous catheter drainage and could not be analyzed for the primary end point. Endoscopic transgastric necrosectomy reduced the postprocedural IL-6 levels compared with surgical necrosectomy (P = .004). The composite clinical end point occurred less often after endoscopic necrosectomy (20% vs 80%; risk difference RD, 0.60; 95% CI, 0.16-0.80; P = .03). Endoscopic necrosectomy did not cause new-onset multiple organ failure (0% vs 50%, RD, 0.50; 95% CI, 0.12-0.76; P = .03) and reduced the number of pancreatic fistulas (10% vs 70%; RD, 0.60; 95% CI, 0.17-0.81; P = .02). CONCLUSION In patients with infected necrotizing pancreatitis, endoscopic necrosectomy reduced the proinflammatory response as well as the composite clinical end point compared with surgical necrosectomy. TRIAL REGISTRATION isrctn.org Identifier: ISRCTN07091918
Patients with a first episode of acute pancreatitis can develop recurrent or chronic pancreatitis (CP). However, little is known about the incidence or risk factors for these events.
We performed a ...cross-sectional study of 669 patients with a first episode of acute pancreatitis admitted to 15 Dutch hospitals from December 2003 through March 2007. We collected information on disease course, outpatient visits, and hospital readmissions, as well as results from imaging, laboratory, and histology studies. Standardized follow-up questionnaires were sent to all available patients to collect information on hospitalizations and interventions for pancreatic disease, abdominal pain, steatorrhea, diabetes mellitus, medications, and alcohol and tobacco use. Patients were followed up for a median time period of 57 months. Primary end points were recurrent pancreatitis and CP. Risk factors were evaluated using regression analysis. The cumulative risk was assessed using Kaplan-Meier analysis.
Recurrent pancreatitis developed in 117 patients (17%), and CP occurred in 51 patients (7.6%). Recurrent pancreatitis developed in 12% of patients with biliary disease, 24% of patients with alcoholic etiology, and 25% of patients with disease of idiopathic or other etiologies; CP occurred in 3%, 16%, and 10% of these patients, respectively. Etiology, smoking, and necrotizing pancreatitis were independent risk factors for recurrent pancreatitis and CP. Acute Physiology and Chronic Health Evaluation II scores at admission also were associated independently with recurrent pancreatitis. The cumulative risk for recurrent pancreatitis over 5 years was highest among smokers at 40% (compared with 13% for nonsmokers). For alcohol abusers and current smokers, the cumulative risks for CP were similar-approximately 18%. In contrast, the cumulative risk of CP increased to 30% in patients who smoked and abused alcohol.
Based on a retrospective analysis of patients admitted to Dutch hospitals, a first episode of acute pancreatitis leads to recurrent pancreatitis in 17% of patients, and almost 8% of patients progress to CP within 5 years. Progression was associated independently with alcoholic etiology, smoking, and a history of pancreatic necrosis. Smoking is the predominant risk factor for recurrent disease, whereas the combination of alcohol abuse and smoking produces the highest cumulative risk for chronic pancreatitis.
Pancreatic and peripancreatic necrosis may result in significant morbidity and mortality in patients with acute pancreatitis. Many recommendations have been made for management of necrotizing ...pancreatitis, but no published guidelines have incorporated the many recent developments in minimally invasive techniques for necrosectomy. Hence, a multidisciplinary conference was convened to develop a consensus on interventions for necrotizing pancreatitis. Participants included most international experts from multiple disciplines. The evidence for efficacy of interventions was reviewed, presentations were given by experts, and a consensus was reached on each topic. In summary, intervention is primarily indicated for infected necrosis, less often for symptomatic sterile necrosis, and should ideally be delayed as long as possible, preferably 4 weeks or longer after the onset of disease, for better demarcation and liquefaction of the necrosis. Both the step-up approach using percutaneous drainage followed by minimally invasive video-assisted retroperitoneal debridement and per-oral endoscopic necrosectomy have been shown to have superior outcomes to traditional open necrosectomy with respect to short-term and long-term morbidity and are emerging as treatments of choice. Applicability of these techniques depends on the availability of specialized expertise and a multidisciplinary team dedicated to the management of severe acute pancreatitis and its complications.
Acute pancreatitis is an acute inflammatory process of the pancreatic gland with increasing incidence worldwide. Usually the clinical presentation and course are mild, with an uneventful recovery. In ...10% to 20% of patients, however, local and systemic complications develop, resulting in significant morbidity and mortality. In 1992, the Atlanta symposium provided definitions for acute pancreatitis and its severity. Insights into the pathophysiology of the disease, improved diagnostic imaging, and implementation of minimally invasive techniques have led to classification updates. This article reviews the cross-sectional imaging features of acute pancreatitis and presents proposed definitions of the revised Atlanta classification.
PDF
