Step-up approach for the treatment of infected necrotising pancreatitis: real life data from a single-centre experience with long-term follow-up.

BACKGROUND: About 20% of patients with acute pancreatitis develop a necrotising form with a worse prognosis due to frequent appearance of organ failure(s) and/or infection of necrosis. Aims of the present study was to evaluate the "step up" approach treatment of infected necrosis in terms of: feasibility, success in resolving infection, morbidity of procedures, risk factors associated with death and long-term sequels. METHODS: In this observational retrospective monocentric study in the real life, necrotizing acute pancreatitis at the stage of infected walled-off necrosis were treated as follow: first step with drainage (radiologic and/or endoscopic-ultrasound-guided with lumen apposing metal stent); in case of failure, minimally invasive necrosectomy sessions(s) by endoscopy through the stent and/or via retroperitoneal surgery (step 2); If necessary open surgery as a third step. Efficacy was assessed upon to a composite clinical-biological criterion: resolution of organ failure(s), decrease of at least two of clinico-biological criteria among fever, CRP serum level, and leucocytes count). RESULTS: Forty-one consecutive patients were treated. The step-up strategy: (i) was feasible in 100% of cases; (ii) allowed the infection to be resolved in 33 patients (80.5%); (iii) Morbidity was mild and rapidly resolutive; (iv) the mortality rate at 6 months was of 19.5% (significant factors: SIRS and one or more organ failure(s) at admission, fungal infection, size of the largest collection ≥ 16 cm). During the follow-up (median 72 months): 27% of patients developed an exocrine pancreatic insufficiency, 45% developed or worsened a previous diabetes, 24% had pancreatic fistula and one parietal hernia. CONCLUSIONS: Beside a very good feasibility, the step-up approach for treatment of infected necrotizing pancreatitis in the real life displays a clinico-biological efficacy in 80% of cases with acceptable morbidity, mortality and long-term sequels regarding the severity of the disease.

SARS-CoV-2 and the pancreas: What do we know about acute pancreatitis in COVID-19 positive patients?

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) can cause pancreatic damage, both directly to the pancreas via angiotensin-converting enzyme 2 receptors (the transmembrane proteins required for SARS-CoV-2 entry, which are highly expressed by pancreatic cells) and indirectly through locoregional vasculitis and thrombosis. Despite that, there is no clear evidence that SARS-CoV-2 is an etiological agent of acute pancreatitis. Acute pancreatitis in coronavirus disease 2019 (COVID-19) positive patients often recognizes biliary or alcoholic etiology. The prevalence of acute pancreatitis in COVID-19 positive patients is not exactly known. However, COVID-19 positive patients with acute pancreatitis have a higher mortality and an increased risk of intensive care unit admission and necrosis compared to COVID-19 negative patients. Acute respiratory distress syndrome is the most frequent cause of death in COVID-19 positive patients and concomitant acute pancreatitis. In this article, we reported recent evidence on the correlation between COVID-19 infection and acute pancreatitis.

Identification of early predictors for infected necrosis in acute pancreatitis.

BACKGROUND: In acute pancreatitis, secondary infection of pancreatic necrosis is a complication that mostly necessitates interventional therapy. A reliable prediction of infected necrotizing pancreatitis would enable an early identification of patients at risk, which however, is not possible yet. METHODS: This study aims to identify parameters that are useful for the prediction of infected necrosis and to develop a prediction model for early detection. We conducted a retrospective analysis from the hospital information and reimbursement data system and screened 705 patients hospitalized with diagnosis of acute pancreatitis who underwent contrast-enhanced computed tomography and additional diagnostic puncture or drainage of necrotic collections. Both clinical and laboratory parameters were analyzed for an association with a microbiologically confirmed infected pancreatic necrosis. A prediction model was developed using a logistic regression analysis with stepwise inclusion of significant variables. The model quality was tested by receiver operating characteristics analysis and compared to single parameters and APACHE II score. RESULTS: We identified a total of 89 patients with necrotizing pancreatitis, diagnosed by computed tomography, who additionally received biopsy or drainage. Out of these, 59 individuals had an infected necrosis. Eleven parameters showed a significant association with an infection including C-reactive protein, albumin, creatinine, and alcoholic etiology, which were independent variables in a predictive model. This model showed an area under the curve of 0.819, a sensitivity of 0.692 (95%-CI [0.547-0.809]), and a specificity of 0.840 (95%-CI [0.631-0.947]), outperforming single laboratory markers and APACHE II score. Even in cases of missing values predictability was reliable. CONCLUSION: A model consisting of a few single blood parameters and etiology of pancreatitis might help for differentiation between infected and non-infected pancreatic necrosis and assist medical therapy in acute necrotizing pancreatitis.

Infected pancreatic necrosis complicating severe acute pancreatitis in critically ill patients: predicting catheter drainage failure and need for necrosectomy.

BACKGROUND: Recent guidelines advocate a step-up approach for managing suspected infected pancreatic necrosis (IPN) during acute pancreatitis. Nearly half the patients require secondary necrosectomy after catheter drainage. Our primary objective was to assess the external validity of a previously reported nomogram for catheter drainage, based on four predictors of failure. Our secondary objectives were to identify other potential predictors of catheter-drainage failure. We retrospectively studied consecutive patients admitted to the intensive care units (ICUs) of three university hospitals in France between 2012 and 2016, for severe acute pancreatitis with suspected IPN requiring catheter drainage. We assessed drainage success and failure rates in 72 patients, with success defined as survival without subsequent necrosectomy and failure as death and/or subsequent necrosectomy required by inadequate improvement. We plotted the receiver operating characteristics (ROC) curve for the nomogram and computed the area under the curve (AUROC). RESULTS: Catheter drainage alone was successful in 32 (44.4%) patients. The nomogram predicted catheter-drainage failure with an AUROC of 0.71. By multivariate analysis, catheter-drainage failure was independently associated with a higher body mass index [odds ratio (OR), 1.12; 95% confidence interval (95% CI), 1.00-1.24; P = 0.048], heterogeneous collection (OR, 16.7; 95% CI, 1.83-152.46; P = 0.01), and respiratory failure onset within 24 h before catheter drainage (OR, 18.34; 95% CI, 2.18-154.3; P = 0.007). CONCLUSION: Over half the patients required necrosectomy after failed catheter drainage. Newly identified predictors of catheter-drainage failure were heterogeneous collection and respiratory failure. Adding these predictors to the nomogram might help to identify patients at high risk of catheter-drainage failure. CLINICALTRIALS: gov number: NCT03234166.

Papel de los estudios microbiológicos en la necrosis pancreática / Role of the microbiological studies in pancreatic necrosis / Papel dos estudos microbiológicos na necrose pancreática

RESUMEN Introducción: la infección de la necrosis pancreática es la complicación local más grave de la pancreatitis aguda. Ocurre aproximadamente en un 35% de los pacientes y presenta una mortalidad cercana al 80%. Objetivo: identificar el espectro microbiológico de la necrosis pancreática infectada Métodos: realizamos un estudio longitudinal, descriptivo, prospectivo en la Unidad de cuidados intensivos del Hospital Universitario Carlos Manuel de Céspedes de la ciudad de Bayamo, Cuba, en el periodo comprendido desde enero de 2012 hasta diciembre de 2018.Fueron incluidos 71 pacientes con el diagnostico o sospecha de pancreatitis aguda necrotizante infectada que requirieron necrosectomía con toma de cultivo intraoperatorio. Resultados: del total de pacientes de la serie la mayoría fueron masculinos representando el 56,3 % de la muestra. la etiología más frecuentemente encontrada fue la litiasica con 38 pacientes (53,5%). Mientras que 52 pacientes (73,2%) presentaban más del 50% de la glándula pancreática con necrosis. En 63 pacientes se confirmó la presencia de infección de la necrosis. Con predominio de la infección monomicrobiana en 48 casos (76,2%).El germen más frecuentemente encontrado fue E. coli (47,9%).La mortalidad post-operatoria fue de 15 pacientes (21, 1%).De ellos 14 pacientes (93,3%) con infección luego de la necrosectomía. Conclusiones: predominó la infección monomicrobiana por E. coli. Los pacientes con confirmación de crecimiento bacteriano post necrosectomía presentaron mayor mortalidad.

ABSTRACT Introduction: infection of pancreatic necrosis is the most serious local complication of acute pancreatitis. It occurs in approximately 35% of patients and has a mortality rate close to 80%. Objective: to identify the microbiological spectrum of infected pancreatic necrosis Methods: we carried out a longitudinal, descriptive, prospective study in the intensive care unit of the Carlos Manuel de Céspedes University Hospital in the city of Bayamo, Cuba, in the period from January 2012 to December 2018. 71 patients with the diagnosis or suspicion of infected acute necrotizing pancreatitis that required necrosectomy with intraoperative culture taking. Results: of the total number of patients in the series, the majority were male, representing 56.3% of the sample. the most frequently found etiology was lithiasis with 38 patients (53.5%). While 52 patients (73.2%) had more than 50% of the pancreatic gland with necrosis. In 63 patients, the presence of necrosis infection was confirmed. With a predominance of monomicrobial infection in 48 cases (76.2%). The most frequent germ found was E. coli (47.9%). Post-operative mortality was 15 patients (21.1%). Of them 14 patients (93.3%) with infection after necrosectomy. Conclusions: monomicrobial infection by E. coli predominated. Patients with confirmed bacterial growth post necrosectomy had higher mortality.

RESUMO Introdução: a infecção da necrose pancreática é a complicação local mais grave da pancreatite aguda. Ocorre em aproximadamente 35% dos pacientes e tem mortalidade próxima a 80%. Objetivo: identificar o espectro microbiológico da necrose pancreática infectada Métodos: foi realizado um estudo longitudinal, descritivo e prospectivo na unidade de terapia intensiva do Hospital Universitário Carlos Manuel de Céspedes, nacidade de Bayamo, Cuba, no período de janeiro de 2012 a dezembro de 2018. 71 pacientes portadores de diagnóstico ou suspeita de pancreatite necrosante aguda infectada que exigiu necrosectomia com coleta de cultura intraoperatória. Resultados: do total de pacientes da série, a maioria era do sexo masculino, representando 56,3% da amostra. a etiologia mais encontrada foi a litíase com 38 pacientes (53,5%). En quanto 52 pacientes (73,2%) apresentavam mais de 50% da glândula pancreática com necrose. Em 63 pacientes, foi confirmada a presença de infecção de necrose. Com predomínio de infecção monomicrobiana em 48 casos (76,2%). O germe mais encontrado foi E. coli (47,9%). A mortalidade pós-operatória foi de 15 pacientes (21,1%). Destes 14 pacientes (93,3%) com infecção após necrosectomia. Conclusões: a infecção monomicrobiana por E. coli predominou. Pacientes com crescimento bacteriano confirmado após necrosectomia apresentaram maior mortalidade.

Long-term Outcomes of Direct Endoscopic Necrosectomy for Complicated or Symptomatic Walled-Off Necrosis: A Korean Multicenter Study.

Background/Aims: The endoscopic step-up approach is accepted as the preferred treatment for complicated or symptomatic walled-off necrosis (WON). Direct endoscopic necrosectomy (DEN) is an effective therapeutic option, but few reports describe long-term follow-up in this patient population. Thus, we aim to assess the long-term outcomes of DEN following severe necrotizing pancreatitis. Methods: The data of all acute pancreatitis patients who underwent DEN following endoscopic transmural drainage from six referral centers between 2007 and 2017 were retrospectively collected. Results: Sixty patients (76.7% male, mean age 48.3 years) underwent a median of 4 sessions of DEN starting at a median of 45.5 days after the onset of acute pancreatitis. Clinical success was achieved in 51 patients (85%), with a 35% complication rate and a 5% mortality rate. Using multivariate analysis, the risk factor associated with DEN failure or major DEN complications requiring intervention or surgery was an identified bacterial/fungal WON infection (odds ratio, 19.3; 95% confidence interval, 1.5 to 261.7). During the median follow-up period of 27 months, complicated WON recurrence was observed in 5.3% of patients, and long-term complications occurred in 24.6% of patients (four exocrine insufficiency, nine newly developed diabetes mellitus, one recurrent small bowel obstruction, one chylous ascites). Conclusions: Considering that long-term complications are similar to those observed after pancreatectomy, DEN should be performed meticulously while minimizing damage to the viable pancreatic parenchyma with adequate antibiotic escalation.

Omental infarction with liquefied necrosis after Roux Y gastric bypass: case report and literature review.

Omental infarction is a rare phenomenon that can be idiopathic or secondary to a surgical intervention. Greater omentum division has been advocated to decrease tension at the gastro-jejunal anastomosis during laparoscopic Roux-en-Y gastric bypass (RYGB). We report a case of omental infraction complicated by liquefied infected necrosis presenting 3 weeks after antecolic antegastric RYGB. The patient underwent laparotomy and subtotal omentectomy with a protracted hospital course due to intra-abdominal abscesses, acute kidney injury and small bowel obstruction that were successfully managed non-operatively. We reviewed the available literature on omental infarction after RYGB, focusing on associated symptoms, possible etiology, timing of presentation, management and propose an alternative technique without omental division.

Management of infected pancreatic necrosis in the intensive care unit: a narrative review.

BACKGROUND: Severe acute pancreatitis is marked by organ failure and (peri)pancreatic necrosis with local complications such as infected necrosis. Infection of these necrotic collections together with organ failure remain the major causes of admission to an intensive care unit (ICU) in acute pancreatitis. Appropriate treatment of infected necrosis is essential to reduce morbidity and mortality. Overall knowledge of the treatment options within a multidisciplinary team-with special attention to the appropriate use of antimicrobial therapy and invasive treatment techniques for source control-is essential in the treatment of this complex disease. OBJECTIVES: To address the current state of microbiological diagnosis, antimicrobial treatment, and source control for infected pancreatic necrosis in the ICU. SOURCES: A literature search was performed using the Medline and Cochrane libraries for articles subsequent to 2003 using the keywords: infected necrosis, pancreatitis, intensive care medicine, treatment, diagnosis and antibiotic(s). CONTENT: This narrative review provides an overview of key elements of diagnosis and treatment of infected pancreatic necrosis in the ICU. IMPLICATIONS: In pancreatic necrosis it is essential to continuously (re)evaluate the indication for antimicrobial treatment and invasive source control. Invasive diagnostics (e.g. through fine-needle aspiration, FNA), preferably prior to the start of broad-spectrum antimicrobial therapy, is advocated. Antimicrobial stewardship principles apply: paying attention to altered pharmacokinetics in the critically ill, de-escalation of broad-spectrum therapy once cultures become available, and early withdrawal of antibiotics once source control has been established. This is important to prevent the development of antimicrobial resistance, especially in a group of patients who may require repeated courses of antibiotics during the prolonged course of their illness.

2019 WSES guidelines for the management of severe acute pancreatitis.

Although most patients with acute pancreatitis have the mild form of the disease, about 20-30% develops a severe form, often associated with single or multiple organ dysfunction requiring intensive care. Identifying the severe form early is one of the major challenges in managing severe acute pancreatitis. Infection of the pancreatic and peripancreatic necrosis occurs in about 20-40% of patients with severe acute pancreatitis, and is associated with worsening organ dysfunctions. While most patients with sterile necrosis can be managed nonoperatively, patients with infected necrosis usually require an intervention that can be percutaneous, endoscopic, or open surgical. These guidelines present evidence-based international consensus statements on the management of severe acute pancreatitis from collaboration of a panel of experts meeting during the World Congress of Emergency Surgery in June 27-30, 2018 in Bertinoro, Italy. The main topics of these guidelines fall under the following topics: Diagnosis, Antibiotic treatment, Management in the Intensive Care Unit, Surgical and operative management, and Open abdomen.

Validation of Modified Determinant-Based Classification of severity for acute pancreatitis in a tertiary teaching hospital.

BACKGROUND: The relative merits of two recent classifications of acute pancreatitis severity, the Determinant-Based Classification (DBC) and the Revised Atlanta Classification (RAC), have been debated. A Modified DBC (MDBC) was recently proposed in intensive care unit (ICU) patients. By dividing the DBC 'severe' category into two groups, the MDBC classified non-mild acute pancreatitis into 4 groups rather than 2 in RAC and 3 in DBC. In this study we aim to validate MDBC in both ICU and non-ICU patients and evaluate infected necrosis as a determinant of severity. METHODS: Prospective data collected on consecutive patients admitted to a tertiary teaching hospital were retrospectively analyzed. Patients were assigned to the categories of severity defined by the DBC, RAC and MDBC. Clinical interventions and outcomes were compared between categories. RESULTS: A total of 1102 patients were enrolled and the overall mortality was 5.7%. When MDBC was applied, the four Groups were significantly different in regard to ICU admission rates (30%, 40%, 69% and 87%) and mortality (2%, 15%, 40% and 57%). Groups 2 and 3 were different in intervention rates and morbidity, providing evidence that IN is an important determinant of severity. CONCLUSIONS: This study validates the MDBC proposal to subdivide the DBC 'severe' category into two groups for ICU and non-ICU patients in a tertiary hospital.

Superiority of Step-up Approach vs Open Necrosectomy in Long-term Follow-up of Patients With Necrotizing Pancreatitis.

BACKGROUND & AIMS: In a 2010 randomized trial (the PANTER trial), a surgical step-up approach for infected necrotizing pancreatitis was found to reduce the composite endpoint of death or major complications compared with open necrosectomy; 35% of patients were successfully treated with simple catheter drainage only. There is concern, however, that minimally invasive treatment increases the need for reinterventions for residual peripancreatic necrotic collections and other complications during the long term. We therefore performed a long-term follow-up study. METHODS: We reevaluated all the 73 patients (of the 88 patients randomly assigned to groups) who were still alive after the index admission, at a mean 86 months (±11 months) of follow-up. We collected data on all clinical and health care resource utilization endpoints through this follow-up period. The primary endpoint was death or major complications (the same as for the PANTER trial). We also measured exocrine insufficiency, quality of life (using the Short Form-36 and EuroQol 5 dimensions forms), and Izbicki pain scores. RESULTS: From index admission to long-term follow-up, 19 patients (44%) died or had major complications in the step-up group compared with 33 patients (73%) in the open-necrosectomy group (P = .005). Significantly lower proportions of patients in the step-up group had incisional hernias (23% vs 53%; P = .004), pancreatic exocrine insufficiency (29% vs 56%; P = .03), or endocrine insufficiency (40% vs 64%; P = .05). There were no significant differences between groups in proportions of patients requiring additional drainage procedures (11% vs 13%; P = .99) or pancreatic surgery (11% vs 5%; P = .43), or in recurrent acute pancreatitis, chronic pancreatitis, Izbicki pain scores, or medical costs. Quality of life increased during follow-up without a significant difference between groups. CONCLUSIONS: In an analysis of long-term outcomes of trial participants, we found the step-up approach for necrotizing pancreatitis to be superior to open necrosectomy, without increased risk of reinterventions.

Mis-use of antibiotics in acute pancreatitis: Insights from the United Kingdom's National Confidential Enquiry into patient outcome and death (NCEPOD) survey of acute pancreatitis.

BACKGROUND: International guidelines for the management of acute pancreatitis state that antibiotics should only be used to treat infectious complications. Antibiotic prophylaxis is not recommended. The aim of this study was to analyse antibiotic use, and its appropriateness, from a national review of acute pancreatitis. METHODS: Data were collected from The National Confidential Enquiry into Patient Outcome and Death (NCEPOD) study into the management of acute pancreatitis. Adult patients admitted to hospitals in England and Wales between January and June 2014 with a coded diagnosis of acute pancreatitis were included. Clinical and organisational questionnaires were used to collect data and these submissions subjected to peer review. Antibiotic use, including indication and duration were analysed. RESULTS: 439/712 (62%) patients received antibiotics, with 891 separate prescriptions and 23 clinical indications. A maximum of three courses of antibiotics were prescribed, with 41% (290/712) of patients receiving a second course and 24% (174/712) a third course. For the first antibiotic prescription, the most common indication was "unspecified" (85/439). The most common indication for the second course was sepsis (54/290), "unspecified" was the most common indication for the third course (50/174). In 72/374 (19.38%) the indication was deemed inappropriate by the clinicians and in 72/393 (18.3%) by case reviewers. CONCLUSIONS: Inappropriate use of antibiotics in acute pancreatitis is common. Healthcare providers should ensure that antimicrobial policies are in place as part of an antimicrobial stewardship process. This should include specific guidance on their use and these policies must be accessible, adherence audited and frequently reviewed.

[A comparison between the revision of Atlanta classification and determinant-based classification in acute pancreatitis].

Objective: To compare the performance of the revision of Atlanta classification (RAC) and determinant-based classification (DBC) in acute pancreatitis. Methods: Consecutive patients with acute pancreatitis admitted to a single center from January 2001 to January 2015 were retrospectively analyzed. Patients were classified into mild, moderately severe and severe categories based on RAC and were simultaneously classified into mild, moderate, severe and critical grades according to DBC. Disease severity and clinical outcomes were compared between subgroups. The receiver operating curve (ROC) was used to compare the utility of RAC and DBC by calculating the area under curve (AUC). Results: Among 1 120 patients enrolled, organ failure occurred in 343 patients (30.6%) and infected necrosis in 74 patients(6.6%). A total of 63 patients (5.6%) died. Statistically significant difference of disease severity and outcomes was observed between all the subgroups in RAC and DBC (P<0.001). The category of critical acute pancreatitis (with both persistent organ failure and infected necrosis) had the most severe clinical course and the highest mortality (19/31, 61.3%). DBC had a larger AUC (0.73, 95%CI 0.69-0.78) than RAC (0.68, 95%CI 0.65-0.73) in classifying ICU admissions (P=0.031), but both were similar in predicting mortality(P=0.372) and prolonged ICU stay (P=0.266). Conclusions: DBC and RAC perform comparably well in categorizing patients with acute pancreatitis regarding disease severity and clinical outcome. DBC is slightly better than RAC in predicting prolonged hospital stay. Persistent organ failure and infected necrosis are risk factors for poor prognosis and presence of both is associated with the most dismal outcome.

Unrecognized necrosis at same admission cholecystectomy for pancreatitis increases organ failure and infected necrosis.

BACKGROUND AND AIMS: Guidelines recommend same admission cholecystectomy (SAC) in the management of mild acute gallstone pancreatitis (AGP) with a recent randomized trial supporting this recommendation. However, the push for early cholecystectomy will lead a subset of patients with evolving, unrecognized necrotizing pancreatitis (NP) to undergo laparoscopic cholecystectomy (LC) with unknown consequences. With concerns about potentially serious outcomes, we studied the outcomes in patients with unrecognized NP who underwent SAC and identified predictors of unrecognized NP at the time of SAC. METHODS: Retrospective study of patients who appeared to have mild AGP but subsequently discovered to have unrecognized NP after SAC (study group). Outcomes were compared to a similar cohort with necrotizing AGP who did not undergo SAC (control group 1). Predictors for unrecognized NP at the time of SAC were identified through logistic regression using a second control group with truly mild AGP undergoing SAC. RESULTS: Patients in the study group (N = 46) undergoing SAC demonstrated higher rates of persistent organ failure (p = 0.0003), infected necrosis (p = 0.02), and length of hospital stay (p = 0.049) compared to a similar group (N = 48) with necrotizing AGP who did not undergo SAC. Persistent SIRS (p < 0.0001) and WBC >12 × 109/L (p < 0.0001) on the day of cholecystectomy were associated with evolving/unrecognized NP. CONCLUSIONS: Unrecognized NP at the time of SAC is associated with increased rates of subsequent persistent organ failure, infected necrosis, and length of hospital stay. Persistent leukocytosis and SIRS at the time of proposed cholecystectomy are predictive of unrecognized NP and should prompt contrast enhanced CT prior to proceeding with LC.

Infection increases mortality in necrotizing pancreatitis: A systematic review and meta-analysis.

OBJECTIVES: To assess the influence of infection on mortality in necrotizing pancreatitis. METHODS: Eligible prospective and retrospective studies were identified through manual and electronic searches (August 2015). The risk of bias was assessed using the Newcastle-Ottawa Scale (NOS). Meta-analyses were performed with subgroup, sensitivity, and meta-regression analyses to evaluate sources of heterogeneity. RESULTS: We included 71 studies (n = 6970 patients). Thirty-seven (52%) studies used a prospective design and 25 scored ≥5 points on the NOS suggesting a low risk of bias. Forty studies were descriptive and 31 studies evaluated invasive interventions. In total, 801 of 2842 patients (28%) with infected necroses and 537 of 4128 patients (13%) with sterile necroses died with an odds ratio [OR] of 2.57 (95% confidence interval [CI], 2.00-3.31) based on all studies and 2.02 (95%CI, 1.61-2.53) in the studies with the lowest bias risk. The OR for prospective studies was 2.96 (95%CI, 2.51-3.50). In sensitivity analyses excluding studies evaluating invasive interventions, the OR was 3.30 (95%CI, 2.81-3.88). Patients with infected necrosis and organ failure had a mortality of 35.2% while concomitant sterile necrosis and organ failure was associated with a mortality of 19.8%. If the patients had infected necrosis without organ failure the mortality was 1.4%. CONCLUSIONS: Patients with necrotizing pancreatitis are more than twice as likely to die if the necrosis becomes infected. Both organ failure and infected necrosis increase mortality in necrotizing pancreatitis.

The chemokine ligand CXCL16 is an indicator of bacterial infection in necrotizing pancreatitis.

OBJECTIVES: Current guidelines tell us that intervention in severe necrotizing pancreatitis ought to be performed as late as possible. However, when pancreatic necrosis becomes infected, the necrotic tissue needs to be removed. Unfortunately, bacterial infection can only be proven by invasive methods. METHODS: Necrotizing pancreatitis with sterile or infected necrosis was induced in mice. Mice serum samples were examined by antibody-based protein array. After identifying candidate proteins that showed strong regulation, the serum concentration of these proteins was examined by sandwich ELISA. Then, human serum samples were collected from patients with mild pancreatitis, severe pancreatitis with and without pancreatic necrosis and patients with microbiologically proven infection of pancreatic necrosis. These serum samples were then analyzed by sandwich ELISA. RESULTS: In mice 6 proteins were strongly up-regulated and were further investigated by ELISAs. Of these proteins, CXCL16 and TRANCE (RANKL) concentrations were analyzed in human serum samples. CXCL16 and TRANCE were increased in patients with pancreatic necrosis and abdominal infection. Receiver operated characteristics showed that CXCL16 was superior in predicting infected pancreatic necrosis when compared to C-reactive protein and TRANCE. CONCLUSIONS: Serum CXCL16 is increased in severe pancreatitis with infected pancreatic necrosis and identifies patients who benefit from surgical necrosectomy.

Surgery for Acute Pancreatitis.

Surgery for acute pancreatitis has undergone significant changes over the last 3 decades. A better understanding of the pathophysiology has contributed to this, but the greatest driver for change has been the rise of less invasive interventions in the fields of laparoscopy, endoscopy and radiology. Surgery has a very limited role in the diagnosis of acute pancreatitis. The most common indication for intervention in acute pancreatitis is for the treatment of complications and most notably the treatment of infected walled off necrosis. Here, the step-up approach has become established, with prior drainage (either endoscopic or percutaneous) followed by delay for maturing of the wall and then debridement by endoscopic or minimally invasive surgical methods. Open surgery is only indicated when this approach fails. Other indications for surgery in acute pancreatitis are for the treatment of acute compartment syndrome, non-occlusive intestinal ischaemia and necrosis, enterocutaneous fistulae, vascular complications and pseudocyst. Surgery also has a role in the prevention of recurrent acute pancreatitis by cholecystectomy. Despite the more restricted role, surgeons have an important contribution to make in the multidisciplinary care of patients with complicated acute pancreatitis.

Surgical management of necrotizing pancreatitis: an overview.

Necrotizing pancreatitis is an uncommon yet serious complication of acute pancreatitis with mortality rates reported up to 15% that reach 30% in case of infection. Traditionally open surgical debridement was the only tool in our disposal to manage this serious clinical entity. This approach is however associated with poor outcomes. Management has now shifted away from open surgical debridement to a more conservative management and minimally invasive approaches. Contemporary approach to patients with necrotizing pancreatitis and/or infectious pancreatitis is summarized in the 3Ds: Delay, Drain and Debride. Patients can be managed in the intensive care unit and any intervention should be delayed. Percutaneous drainage can be utilized first and early in the course of the disease, followed by endoscopic drainage or video assisted retroperitoneoscopic drainage if necrosectomy is deemed necessary. Open surgery is now less frequently performed and should be reserved for cases refractory to any other approach. The management of necrotizing pancreatitis therefore requires a multidisciplinary dynamic model of approach rather than being a surgical disease.

Timing of enteral nutrition in acute pancreatitis: meta-analysis of individuals using a single-arm of randomised trials.

INTRODUCTION: In acute pancreatitis, enteral nutrition (EN) reduces the rate of complications, such as infected pancreatic necrosis, organ failure, and mortality, as compared to parenteral nutrition (PN). Starting EN within 24 h of admission might further reduce complications. METHODS: A literature search for trials of EN in acute pancreatitis was performed. Authors of eligible trials were requested to provide the data of all patients in the EN-arm of their trials. A meta-analysis of individual patient data was performed. The cohort of patients with EN was divided into patients receiving EN within 24 h or after 24 h of admission. Multivariable logistic regression, adjusting for predicted disease severity and trial, was used to study the effect of timing of EN on a composite endpoint of infected pancreatic necrosis, organ failure, or mortality. RESULTS: Observational data from 165 individuals from 8 randomised trials were obtained; 100 patients with EN within 24 h and 65 patients with EN after 24 h of admission. In the multivariable model, EN started within 24 h of admission compared to EN started after 24 h of admission, reduced the composite endpoint from 45% to 19% (adjusted odds ratio [OR] of 0.44; 95% confidence interval [CI] 0.20-0.96). Within the composite endpoint, organ failure was reduced from 42% to 16% (adjusted OR 0.42; 95% CI 0.19-0.94). CONCLUSIONS: In this meta-analysis of observational data from individuals with acute pancreatitis, starting EN within 24 h after hospital admission, compared with after 24 h, was associated with a reduction in complications.

Clinical utility of the revised Atlanta classification of acute pancreatitis in a prospective cohort: have all loose ends been tied?

BACKGROUND AND AIM: Revision of the Atlanta classification for acute pancreatitis (AP) was long awaited. The Revised Atlanta Classification has been recently proposed. In this study, we aim to prospectively evaluate and validate the clinical utility of the new definitions. PATIENT AND METHODS: 163 consecutive patients with AP were followed till death/6 mths after discharge. AP was categorized as mild (MAP) (no local complication[LC] and organ failure[OF]), moderate (MSAP)(transient OF and/or local/systemic complication but no persistent OF) and severe (SAP) AP (persistent OF). LC included acute peripancreatic fluid collections, pseudocyst, acute necrotic collection, walled-off necrosis, gastric outlet dysfunction, splenic/portal vein thrombosis, and colonic necrosis. Baseline characteristics (age/gender/hematocrit/BUN/SIRS/BISAP) and outcomes (total hospital stay/need for ICU care/ICU days/primary infected (peri)pancreatic necrosis[IN]/in-hospital death) were compared. RESULTS: 43 (26.4%) patients had ANP, 87 (53.4%) patients had MAP, 58 (35.6%) MSAP and 18 (11.04%) SAP. Among the baseline characteristics, BISAP score was significantly higher in MSAP compared to MAP [1.6 (1.5-2.01) vs 1.2 (1.9-2.4); p = 0.002]; and BUN was significantly higher in SAP compared to MSAP[64.9 (50.7-79.1) vs 24.9 (20.7-29.1); p < 0.0001]. All outcomes except mortality were significantly higher in MSAP compared to MAP. Need for ICU care (83.3%vs43.1%; p = 0.01), total ICU days[7.9 (4.8-10.9) vs 3.5 (2.7-5.1); p = 0.04] and mortality (38.9%vs1.7%; p = 0.0002) was significantly more in SAP compared to MSAP. 8/18 (44.4%) patients had POF within seven days of disease onset (early OF). This was associated with 37.5% of total in-hospital mortality. Patients with MSAP who had primary IN (n = 10) had similar outcomes as SAP. CONCLUSIONS: This study prospectively validates the clinical utility of the Revised Atlanta definitions of AP. However, MSAP patients with primary infected necrosis may behave as SAP. Furthermore, patients with early severe acute pancreatitis (early OF) could represent a subgroup that needs to be dealt with separately in classification systems.