Clinical characteristics and outcomes of pancreatic fungal infection in patients with necrotizing pancreatitis.

Pancreatic fungal infection (PFI) in patients with necrotizing pancreatitis can lead to significant morbidity and mortality. The incidence of PFI has increased during the past decade. Our study aimed to provide contemporary observations on the clinical characteristics and outcomes of PFI in comparison to pancreatic bacterial infection and necrotizing pancreatitis without infection. We conducted a retrospective study of patients with necrotizing pancreatitis (acute necrotic collection or walled-off necrosis), who underwent pancreatic intervention (necrosectomy and/or drainage) and had tissue/fluid culture between 2005 and 2021. We excluded patients with pancreatic procedures prior to hospitalization. Multivariable logistic and Cox regression models were fitted for in-hospital and 1-year survival outcomes. A total of 225 patients with necrotizing pancreatitis were included. Pancreatic fluid and/or tissue was obtained from endoscopic necrosectomy and/or drainage (76.0%), CT-guided percutaneous aspiration (20.9%), or surgical necrosectomy (3.1%). Nearly half of the patients had PFI with or without concomitant bacterial infection (48.0%), while the remaining patients had either bacterial infection alone (31.1%) or no infection (20.9%). In multivariable analysis to assess the risk of PFI or bacterial infection alone, only previous pancreatitis was associated with an increased odds of PFI vs. no infection (OR 4.07, 95% CI 1.13-14.69, p = .032). Multivariable regression analyses revealed no significant differences in in-hospital outcomes or one-year survival between the 3 groups. Pancreatic fungal infection occurred in nearly half of necrotizing pancreatitis. Contrary to many of the previous reports, there was no significant difference in important clinical outcomes between the PFI group and each of the other two groups.

We examined 225 patients with necrotizing pancreatitis who had tissue/fluid culture available and found that nearly half of the patients had pancreatic fungal infection. Interestingly, there was no difference in clinical outcomes between the fungal infection group and non-fungal infection groups.

Early infection is an independent risk factor for increased mortality in patients with culture-confirmed infected pancreatic necrosis.

BACKGROUND: Mortality in infected pancreatic necrosis (IPN) is dynamic over the course of the disease, with type and timing of interventions as well as persistent organ failure being key determinants. The timing of infection onset and how it pertains to mortality is not well defined. OBJECTIVES: To determine the association between mortality and the development of early IPN. METHODS: International multicenter retrospective cohort study of patients with IPN, confirmed by a positive microbial culture from (peri) pancreatic collections. The association between timing of infection onset, timing of interventions and mortality were assessed using Cox regression analyses. RESULTS: A total of 743 patients from 19 centers across 3 continents with culture-confirmed IPN from 2000 to 2016 were evaluated, mortality rate was 20.9% (155/734). Early infection was associated with a higher mortality, when early infection occurred within the first 4 weeks from presentation with acute pancreatitis. After adjusting for comorbidity, advanced age, organ failure, enteral nutrition and parenteral nutrition, early infection (≤4 weeks) and early open surgery (≤4 weeks) were associated with increased mortality [HR: 2.45 (95% CI: 1.63-3.67), p < 0.001 and HR: 4.88 (95% CI: 1.70-13.98), p = 0.003, respectively]. There was no association between late open surgery, early or late minimally invasive surgery, early or late percutaneous drainage with mortality (p > 0.05). CONCLUSION: Early infection was associated with increased mortality, independent of interventions. Early surgery remains a strong predictor of excess mortality.

Primary Pancreatic Candidiasis Mimicking Pancreatic Cancer in an Immunocompetent Patient.

Pancreatic candidiasis can develop in patients with acute pancreatitis, compromised immune responses, or iatrogenic intervention. This paper reports a case of pancreatic candidiasis presenting as a solid pancreatic mass in a patient without the risk factors. A previously healthy 37-year-old man visited the emergency department with left flank pain. Abdominal CT revealed a 5 cm, irregular heterogeneous enhancing mass accompanied by a left adrenal mass. Positron emission tomography-computed tomography and endoscopic ultrasound-guided fine-needle aspiration (EUS-FNA) could not discriminate pancreatic cancer from infectious disease. A laparoscopic exploration was performed for an accurate diagnosis. After distal pancreatectomy with splenectomy and left adrenalectomy, pancreatic candidiasis and adrenal cortical adenoma were diagnosed based on the pathology findings. His condition improved after the treatment with fluconazole. This paper reports a case of primary pancreatic candidiasis mimicking pancreatic cancer in an immunocompetent patient with a review of the relevant literature.

Western-type diet influences mortality from necrotising pancreatitis and demonstrates a central role for butyrate.

OBJECTIVE: The gut microbiota are the main source of infections in necrotising pancreatitis. We investigated the effect of disruption of the intestinal microbiota by a Western-type diet on mortality and bacterial dissemination in necrotising pancreatitis and its reversal by butyrate supplementation. DESIGN: C57BL/6 mice were fed either standard chow or a Western-type diet for 4 weeks and were then subjected to taurocholate-induced necrotising pancreatitis. Blood and pancreas were collected for bacteriology and immune analysis. The cecum microbiota composition of mice was analysed using 16S rRNA gene amplicon sequencing and cecal content metabolites were analysed by targeted (ie, butyrate) and untargeted metabolomics. Prevention of necrotising pancreatitis in this model was compared between faecal microbiota transplantation (FMT) from healthy mice, antibiotic decontamination against Gram-negative bacteria and oral or systemic butyrate administration. Additionally, the faecal microbiota of patients with pancreatitis and healthy subjects were analysed. RESULTS: Mortality, systemic inflammation and bacterial dissemination were increased in mice fed Western diet and their gut microbiota were characterised by a loss of diversity, a bloom of Escherichia coli and an altered metabolic profile with butyrate depletion. While antibiotic decontamination decreased mortality, Gram-positive dissemination was increased. Both oral and systemic butyrate supplementation decreased mortality, bacterial dissemination, and reversed the microbiota alterations. Paradoxically, mortality and bacterial dissemination were increased with FMT administration. Finally, patients with acute pancreatitis demonstrated an increase in Proteobacteria and a decrease of butyrate producers compared with healthy subjects. CONCLUSION: Butyrate depletion and its repletion appear to play a central role in disease progression towards necrotising pancreatitis.

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

Introducción: la infección de la necrosis pancreática es la complicación local más grave de la pancreatitis aguda. Ocurre aproximadamente en un 35 por ciento de los pacientes y presenta una mortalidad cercana al 80 por ciento. 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 diagnóstico 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 por ciento de la muestra, la etiología más frecuentemente encontrada fue la litiasica con 38 pacientes (53,5 por ciento). Mientras que 52 pacientes (73,2 por ciento) presentaban más del 50 por ciento 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 por ciento). El germen más frecuentemente encontrado fue E. coli (47,9 por ciento). La mortalidad post-operatoria fue de 15 pacientes (21,1 por ciento). De ellos 14 pacientes (93,3 por ciento) 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(AU)

Introduction: infection of pancreatic necrosis is the most serious local complication of acute pancreatitis. It occurs in approximately 35 percent of patients and has a mortality rate close to 80 percent. 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 percent of the sample, the most frequently found etiology was lithiasis with 38 patients (53.5 percent). While 52 patients (73.2 percent) had more than 50 percent 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 percent). The most frequent germ found was E. coli (47.9 percent). Post-operative mortality was 15 patients (21.1 percent). Of them 14 patients (93.3 percent) with infection after necrosectomy. Conclusions: monomicrobial infection by E. coli predominated. Patients with confirmed bacterial growth post necrosectomy had higher mortality(EU)

The microbiology of necrotizing pancreatitis and its impact on in-hospital and 1-year all-cause mortality.

BACKGROUND/OBJECTIVES: The data regarding the microbial spectrum in necrotizing pancreatitis and its impact on mortality is limited. Therefore, in this study, we aimed to investigate the agents identified in cultures and their impact on in-hospital and 1-year all-cause mortality. METHODS: Patients with necrotizing pancreatitis were retrospectively included in the study. Based on culture results, patients were classified as either negative culture or positive culture necrotizing acute pancreatitis. The main outcomes of the study were the identification of agents isolated in patients with pancreatic necrosis and to assess in-hospital, 30-day and 1-year all-cause mortality according to culture results. RESULTS: In total, 109 patients of whom 33 had positive cultures were included in the study. Most positive cultures were polymicrobial (66%) with a marked gram-negative bacterial dominance (63%). Klebsiella spp. were the most common identified pathogens. The patients a with positive culture had worse outcomes in terms of in-hospital, 30-day and 1-year all-cause mortality compared to patients with sterile culture results (n = 9, 27.3% vs. n = 4, 5.3%, P < 0.01 for in-hospital mortality; n = 11, 33.3% vs. n = 5, 6.6%, P < 0.01 for 30-day mortality; and n = 14, 42.4% vs. n = 10, 13.2%, P < 0.01 for 1-year mortality). CONCLUSION: When a microorganism was identified in patients with necrotizing acute pancreatitis, it was mostly polymicrobial in etiology with a gram-negative bacterial dominance. In our cohort, Klebsiella spp. were the most common isolated organisms. Especially the patients with polymicrobial etiology showed a very poor outcome both in-hospital and in the long-term. Local hospital flora may have an impact on culture results.

The morbidity of C. difficile in necrotizing pancreatitis.

INTRODUCTION: Necrotizing pancreatitis (NP) patients commonly require antibiotic treatment during the several month-long disease course. We hypothesized that Clostridium difficile infection (CDI) is common in NP and significantly impacts outcomes. MATERIALS AND METHODS: Retrospective review of 704 NP patients treated at a single-institution (2005-2018). RESULTS: 10% (67/704) of patients developed CDI a mean 78 days after NP onset. Patients developing CDI experienced increased total hospital days (CDI, 104; No CDI, 42; P < 0.001), readmission rates (CDI, 85%; No CDI, 64%; P = 0.006), and duration of NP (CDI, 248 days; No CDI, 183; P = 0.001). Risk factors for CDI included antibiotic use (OR, 96.2; 95% CI, 5.9-1556.2; P = 0.001) and any organ failure (OR, 2.0; 95% CI, 1.2-3.3, P = 0.008). Mortality was not affected by CDI (CDI, 10%; No CDI, 9%; P = 0.7). CONCLUSION: Clostridium difficile infection is common in necrotizing pancreatitis and negatively impacts morbidity and disease recovery.

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.

Adverse clinical outcomes associated with multidrug-resistant organisms in patients with infected pancreatic necrosis.

BACKGROUND: Multidrug-resistant organisms (MDROs) is becoming a serious worldwide threat to public health. However, the impact of MDROs on the outcomes of the patients with infected pancreatic necrosis (IPN) remains unclear. This study aims to evaluate the roles of MDROs in IPN. METHODS: A prospectively maintained database of 188 patients with IPN between January 2010 and May 2019 was analyzed. The microbiology profile of organisms isolated from wall-off necrosis (WON) was specifically investigated to correlate with the outcomes of the patients. RESULTS: Of the 188 patients with IPN, 108 patients (57.4%) had MDROs detected in aspirates from WON. Carbapenem-resistant Klebsiella pneumoniae (CRKP) accounted for 43.5% of the MDROs isolated (60/138), followed by Carbapenem-resistant Acinetobacter baumanii (CRAB) (34.8%, 48/138) and Escherichia coli producing an extended-spectrum beta-lactamase (ESBLp) (6.5%, 9/138). MDROs infection was associated with higher mortality (35.2% vs 11.3%, P < 0.001), higher rate of hemorrhage (36.1% vs 11.3%, P < 0.001), longer intensive care unit (ICU) stay (23 vs 12 days, P < 0.001), longer hospital stay (68 vs 51 days, P = 0.001) and more hospitalization expenses (45,190 ±â€¯31,680 vs 26,965 ±â€¯17,167 $, P < 0.001). Multivariate analysis of predictors of mortality indicated that MDROs infection (OR = 2.6; 95% confidence interval [CI], 1.0-6.5; P = 0.042), age ≥ 50 years (OR = 2.6; 95% CI, 1.2-5.8; P = 0.016), severe category (OR = 2.9; 95% CI, 1.1-8.0; P = 0.035), bloodstream infection (OR = 3.4; 95% CI, 1.5-7.6; P = 0.049), step-down surgical approach (OR = 2.7; 95% CI, 1.1-6.2; P = 0.023) were significant factors. CONCLUSIONS: MDROs infection was prevalent among patients with IPN and associated with adverse clinical outcomes and increased mortality.

Timing, distribution, and microbiology of infectious complications after necrotizing pancreatitis.

BACKGROUND: Acute pancreatitis (AP) is a common acute abdominal disease worldwide, and its incidence rate has increased annually. Approximately 20% of AP patients develop into necrotizing pancreatitis (NP), and 40% to 70% of NP patients have infectious complications, which usually indicate a worse prognosis. Infection is an important sign of complications in NP patients. AIM: To investigate the difference in infection time, infection site, and infectious strain in NP patients with infectious complications. METHODS: The clinical data of AP patients visiting the Department of General Surgery of Xuanwu Hospital of Capital Medical University from January 1, 2014 to December 31, 2018 were collected retrospectively. Enhanced computerized tomography or magnetic resonance imaging findings in patients with NP were included in the study. Statistical analysis of infectious bacteria, infection site, and infection time in NP patients with infectious complications was performed, because knowledge about pathogens and their antibiotic susceptibility patterns is essential for selecting an appropriate antibiotic. In addition, the factors that might influence the prognosis of patients were analyzed. RESULTS: In this study, 539 strains of pathogenic bacteria were isolated from 162 patients with NP infection, including 212 strains from pancreatic infections and 327 strains from extrapancreatic infections. Gram-negative bacteria were the main infectious species, the most common of which were Escherichia coli and Pseudomonas aeruginosa. The extrapancreatic infection time (9.1 ± 8.8 d) was earlier than the pancreatic infection time (13.9 ± 12.3 d). Among NP patients with early extrapancreatic infection (< 14 d), bacteremia (25.12%) and respiratory tract infection (21.26%) were predominant. Among NP patients with late extrapancreatic infection (> 14 d), bacteremia (15.94%), respiratory tract infection (7.74%), and urinary tract infection (7.71%) were predominant. Drug sensitivity analysis showed that P. aeruginosa was sensitive to enzymatic penicillins, third- and fourth-generation cephalosporins, and carbapenems. Acinetobacter baumannii and Klebsiella pneumoniae were sensitive only to tigecycline; Staphylococcus epidermidis and Enterococcus faecium were highly sensitive to linezolid, tigecycline, and vancomycin. CONCLUSION: In this study, we identified the timing, the common species, and site of infection in patients with NP.

[Prognostic factors of multi-drug resistant organism infection in infected pancreatic necrosis patients].

Objective: To investigate the prognostic factors of multi-drug resistant organism (MDRO) infection in patients with infected pancreatic necrosis(IPN). Methods: A retrospective study was performed to assess the MDRO in IPN patients. The clinical data of 104 IPN patients admitted to the Department of Pancreatic and Biliary Surgery, the First Affiliated Hospital of Harbin Medical University from June 2013 to January 2019 were analyzed. Fifty-six patients were allocated in the MDRO group and 48 patients in the non-MDRO group depended on drug sensitivity test. There were 37 males and 19 females in the MDRO group with age of 40 (23) years. The duration time was 3(5) days between onset and admission. In the non-MDRO group,34 males and 14 females were included with age of (42±14)years. The duration time was 3(4) days between onset and admission. Normally distributed quantitative variables was represented by x±s, non-normally distributed quantitative variables was represented by M(Q(R)). Wilcoxon rank-sum test and χ(2) test were used to analyze the data. Univariate and multivariable Logistic regression analytic model were used to figure out the risk factors associated with MDRO infection. Results: The mean duration of hospital stay was 29.5(31.8) days and hospitalization expenses were CNY 166 991(270 692), which were much higher than those in non-MDRO group (16.5(15.7) days, 56 789(62 354) yuan) (W=1 889, 2 019, both P<0.01). Gram-negative isolates(67.2%, 80 /119) were commonly detected in IPN patients. Acinetobacter baumannii was the most common MDRO(27.0%,20/74). Initial use of carbapenem(OR=2.22, 95%CI: 1.02-4.96, P=0.047) and open necrosectomy(OR=10.00, 95%CI: 3.14-44.77, P<0.01) were the potential risk factors for MDRO-induced infections in IPN. Furthermore, the Logistic regression analysis revealed that open necrosectomy is the independent variable for MDRO infections (OR=9.42, 95%CI: 2.92-42.42, P<0.01). Conclusion: Open necrosectomy was the independent risk factor for the infection of MDRO.

High-mobility group box-1 inhibition stabilizes intestinal permeability through tight junctions in experimental acute necrotizing pancreatitis.

BACKGROUND: In acute necrotizing pancreatitis (ANP), bacterial translocation (BT) from the gastrointestinal tract is the essential pathogenesis in the development of septic complications. Although high-mobility group box-1 (HMGB1) is associated with BT and organ dysfunction in ANP, the mechanism of HMGB1 in the intestinal barrier dysfunction and BT has not been well addressed. In this study, we intend to address the role of HMGB1 in ANP involving BT and intestinal barrier dysfunction. METHODS: Experimental ANP was achieved in male Sprague-Dawley rats through a retrograde injection of taurocholate into the common biliopancreatic duct following a laparotomy operation. HMGB1 blockade intervention was conducted with a subcutaneous injection of anti-HMGB1 antibody immediately before the laparotomy procedure. Twenty-four hours after ANP induction, pancreatic and intestinal tissues and blood samples were collected for a histopathological assessment and lipid peroxidation or glutathione (GSH) evaluation. AP-induced barrier dysfunction was determined by an intestinal permeability assessment. Tight junction proteins and autophagy regulators were investigated by western blotting, immunohistological analysis and confocal immunofluorescence imaging. RESULTS: ANP developed as indicated by microscopic parenchymal necrosis and fat necrosis, which were associated with intestinal mucosal barrier dysfunction. HMGB1 inhibition played a protective role in intestinal mucosal barrier dysfunction, protected against microbiome changes in ANP, and relieved intestinal oxidative stress. Additionally, HMGB1 inhibition attenuated intestinal permeability; preserved the expression of TJs, such as claudin-2 and occludin; and decreased autophagy. Furthermore, the autophagy regulator LC3 and TJ protein claudin-2 were both upregulated in ANP according to dual immunofluorescence analysis. CONCLUSION: HMGB1 inhibition ameliorated the severity of experimental ANP though beneficial effects on BT, mainly involving in TJ function.

Commensal Escherichia coli Aggravates Acute Necrotizing Pancreatitis through Targeting of Intestinal Epithelial Cells.

An increase of Escherichia-Shigella was previously reported in acute necrotizing pancreatitis (ANP). We investigated whether Escherichia coli MG1655, an Escherichia commensal organism, increased intestinal injury and aggravated ANP in rats. ANP was induced by retrograde injection of 3.5% sodium taurocholate into the biliopancreatic duct. Using gut microbiota-depleted rats, we demonstrated that gut microbiota was involved in the pancreatic injury and intestinal barrier dysfunction in ANP. Using 16S rRNA gene sequencing and quantitative PCR, we found intestinal dysbiosis and a significant increase of E. coli MG1655 in ANP. Afterward, administration of E. coli MG1655 by gavage to gut microbiota-depleted rats with ANP was performed. We observed that after ANP induction, E. coli MG1655-monocolonized rats presented more severe injury in the pancreas and intestinal barrier function than gut microbiota-depleted rats. Furthermore, Toll-like receptor 4 (TLR4)/MyD88/p38 mitogen-activated protein (MAPK) and endoplasmic reticulum stress (ERS) activation in intestinal epithelial cells were also increased more significantly in the MG1655-monocolonized ANP rats. In vitro, the rat ileal epithelial cell line IEC-18 displayed aggravated tumor necrosis factor alpha-induced inflammation and loss of tight-junction proteins in coculture with E. coli MG1655, as well as TLR4, MyD88, and Bip upregulation. In conclusion, our study shows that commensal E. coli MG1655 increases TLR4/MyD88/p38 MAPK and ERS signaling-induced intestinal epithelial injury and aggravates ANP in rats. Our study also describes the harmful potential of commensal E. coli in ANP.IMPORTANCE This study describes the harmful potential of commensal E. coli in ANP, which has not been demonstrated in previous studies. Our work provides new insights into gut bacterium-ANP cross talk, suggesting that nonpathogenic commensals could also exhibit adverse effects in the context of diseases.

Postponed or immediate drainage of infected necrotizing pancreatitis (POINTER trial): study protocol for a randomized controlled trial.

BACKGROUND: Infected necrosis complicates 10% of all acute pancreatitis episodes and is associated with 15-20% mortality. The current standard treatment for infected necrotizing pancreatitis is the step-up approach (catheter drainage, followed, if necessary, by minimally invasive necrosectomy). Catheter drainage is preferably postponed until the stage of walled-off necrosis, which usually takes 4 weeks. This delay stems from the time when open necrosectomy was the standard. It is unclear whether such delay is needed for catheter drainage or whether earlier intervention could actually be beneficial in the current step-up approach. The POINTER trial investigates if immediate catheter drainage in patients with infected necrotizing pancreatitis is superior to the current practice of postponed intervention. METHODS: POINTER is a randomized controlled multicenter superiority trial. All patients with necrotizing pancreatitis are screened for eligibility. In total, 104 adult patients with (suspected) infected necrotizing pancreatitis will be randomized to immediate (within 24 h) catheter drainage or current standard care involving postponed catheter drainage. Necrosectomy, if necessary, is preferably postponed until the stage of walled-off necrosis, in both treatment arms. The primary outcome is the Comprehensive Complication Index (CCI), which covers all complications between randomization and 6-month follow up. Secondary outcomes include mortality, complications, number of (repeat) interventions, hospital and intensive care unit (ICU) lengths of stay, quality-adjusted life years (QALYs) and direct and indirect costs. Standard follow-up is at 3 and 6 months after randomization. DISCUSSION: The POINTER trial investigates if immediate catheter drainage in infected necrotizing pancreatitis reduces the composite endpoint of complications, as compared with the current standard treatment strategy involving delay of intervention until the stage of walled-off necrosis. TRIAL REGISTRATION: ISRCTN, 33682933 . Registered on 6 August 2015. Retrospectively registered.

Impact of Antimicrobial Prophylaxis for Severe Acute Pancreatitis on the Development of Invasive Candidiasis: A Large Retrospective Multicenter Cohort Study.

OBJECTIVE: Antimicrobial prophylaxis is not generally recommended for patients with severe acute pancreatitis (SAP) owing to the limited clinical benefits. Nonetheless, it is frequently administered in actual practice given the patients' critical condition and the lack of solid evidence showing adverse effects of antimicrobial prophylaxis. We evaluated herein an association between antimicrobial prophylaxis and invasive pancreatic candidiasis as an adverse effect in patients with SAP. METHODS: This is a retrospective cohort study of all consecutive patients with SAP who were admitted to the study institutions (n = 44) between January 1, 2009, and December 31, 2013. We performed multivariable logistic regression analysis adjusting for the extent of pancreatic necrosis and surgical interventions for invasive pancreatic candidiasis. RESULTS: Of the 1097 patients with SAP, 850 (77.5%) received antimicrobial prophylaxis, and 21 (1.9%) had invasive pancreatic candidiasis. In multivariable logistic regression analysis, antimicrobial prophylaxis was significantly associated with the development of invasive pancreatic candidiasis (adjusted odds ratio, 4.23; 95% confidence interval, 1.14-27.6) (P = 0.029). CONCLUSIONS: The results suggest that antimicrobial prophylaxis may contribute to the development of invasive pancreatic candidiasis, and therefore, the routine use of antimicrobial prophylaxis for SAP may be discouraged.

An endoscopic or minimally invasive surgical approach for infected necrotizing pancreatitis: a systematic review and meta-analysis.

BACKGROUND AND AIM: the incidence of acute pancreatitis is rising across the world, thus further increasing the burden on healthcare services. Approximately 10% of patients with acute pancreatitis will develop infected necrotizing pancreatitis (INP), which is the leading cause of high mortality in the late phase. There is currently no consensus with regard to the use of endoscopic or minimally invasive surgery as the first-line therapy of choice for INP. However, more clinical research with regard to the superiority of an endoscopic approach has been recently published. Therefore, we conducted a systematic review and meta-analysis to determine which of the two treatments leads to a better prognosis. METHODS: four databases (Medline, SINOMED, EMBASE and Cochrane Library) were searched for eligible studies from 1980 to 2018, comparing endoscopic and minimally invasive surgery for INP. RESULTS: two randomized controlled trials (RCTs) and seven clinical cohort studies were included. After the analysis of data amenable to polling, significant advantages were found in favor of the endoscopic approach in terms of pancreatic fistulas (OR = 0.10, 95% CI 0.04-0.30, p < 0.001) and the length of hospital stay (weighted mean difference [WMD] = -24.72, 95% CI = -33.87 to -15.57, p < 0.001). No marked differences were found in terms of mortality, multiple organ failure, intra-abdominal bleeding, enterocutaneous fistula, recurrence of pseudocysts, and length of stay (LOS) in the Intensive Care Unit (ICU), endocrine insufficiency and exocrine insufficiency. CONCLUSION: compared with minimally invasive surgery, an endoscopic approach evidently improved short-term outcomes for infected necrotizing pancreatitis, including pancreatic fistula and the length of hospital stay. Furthermore, relevant multicenter RCTs are eager to validate these findings.

Outcomes of Infected versus Symptomatic Sterile Walled-Off Pancreatic Necrosis Treated with a Minimally Invasive Therapy.

Background/Aims: Acute pancreatitis complicated by walled-off necrosis (WON) is associated with high morbidity and mortality, and if infected, typically necessitates intervention. Clinical outcomes of infected WON have been described as poorer than those of symptomatic sterile WON. With the evolution of minimally invasive therapy, we sought to compare outcomes of infected to symptomatic sterile WON. Methods: We performed a retrospective cohort study examining patients who were undergoing dual-modality drainage as minimally invasive therapy for WON at a high-volume tertiary pancreatic center. The main outcome measures included mortality with a drain in place, length of hospital stay, admission to intensive care unit, and development of pancreatic fistulae. Results: Of the 211 patients in our analysis, 98 had infected WON. The overall mortality rate was 2.4%. Patients with infected WON trended toward higher mortality although not statistically significant (4.1% vs 0.9%, p=0.19). Patients with infected WON had longer length of hospitalization (29.8 days vs 17.3 days, p<0.01), and developed more spontaneous pancreatic fistulae (23.5% vs 7.8%, p<0.01). Multivariate analysis showed that infected WON was associated with higher odds of spontaneous pancreatic fistula formation (odds ratio, 2.65; 95% confidence interval, 1.20 to 5.85). Conclusions: This study confirms that infected WON has worse outcomes than sterile WON but also demonstrates that WON, once considered a significant cause of death, can be treated with good outcomes using minimally invasive therapy.