The Atlanta classification of acute pancreatitis enabled standardised reporting of research and aided communication between clinicians. Deficiencies identified and improved understanding of the disease make a revision necessary.A web-based consultation was undertaken in 2007 to ensure wide participation of pancreatologists. After an initial meeting, the Working Group sent a draft document to 11 national and international pancreatic associations. This working draft was forwarded to all members. Revisions were made in response to comments, and the web-based consultation was repeated three times. The final consensus was reviewed, and only statements based on published evidence were retained.The revised classification of acute pancreatitis identified two phases of the disease: early and late. Severity is classified as mild, moderate or severe. Mild acute pancreatitis, the most common form, has no organ failure, local or systemic complications and usually resolves in the first week. Moderately severe acute pancreatitis is defined by the presence of transient organ failure, local complications or exacerbation of co-morbid disease. Severe acute pancreatitis is defined by persistent organ failure, that is, organ failure >48 h. Local complications are peripancreatic fluid collections, pancreatic and peripancreatic necrosis (sterile or infected), pseudocyst and walled-off necrosis (sterile or infected). We present a standardised template for reporting CT images.This international, web-based consensus provides clear definitions to classify acute pancreatitis using easily identified clinical and radiologic criteria. The wide consultation among pancreatologists to reach this consensus should encourage widespread adoption.

The incidence of acute pancreatitis continues to rise, inducing substantial medical and social burden, with annual costs exceeding $2 billion in the United States alone. Although most patients develop mild pancreatitis, 20% develop severe and/or necrotizing pancreatitis, requiring advanced medical and interventional care. Morbidity resulting from local and systemic complications as well as invasive interventions result in mortality rates historically as high as 30%. There has been substantial evolution of strategies for interventions in recent years, from open surgery to minimally invasive surgical and endoscopic step-up approaches. In contrast to the advances in invasive procedures for complications, early management still lacks curative options and consists of adequate fluid resuscitation, analgesics, and monitoring. Many challenges remain, including comprehensive management of the entire spectrum of the disease, which requires close involvement of multiple disciplines at specialized centers.Copyright © 2019 AGA Institute. Published by Elsevier Inc. All rights reserved.

The purpose of this American Gastroenterological Association (AGA) Institute Clinical Practice Update is to review the available evidence and expert recommendations regarding the clinical care of patients with pancreatic necrosis and to offer concise best practice advice for the optimal management of patients with this highly morbid condition.This expert review was commissioned and approved by the AGA Institute Clinical Practice Updates Committee and the AGA Governing Board to provide timely guidance on a topic of high clinical importance to the AGA membership, and underwent internal peer review by the Clinical Practice Updates Committee and external peer review through standard procedures of Gastroenterology. This review is framed around the 15 best practice advice points agreed upon by the authors, which reflect landmark and recent published articles in this field. This expert review also reflects the experiences of the authors, who are advanced endoscopists or hepatopancreatobiliary surgeons with extensive experience in managing and teaching others to care for patients with pancreatic necrosis. BEST PRACTICE ADVICE 1: Pancreatic necrosis is associated with substantial morbidity and mortality and optimal management requires a multidisciplinary approach, including gastroenterologists, surgeons, interventional radiologists, and specialists in critical care medicine, infectious disease, and nutrition. In situations where clinical expertise may be limited, consideration should be given to transferring patients with significant pancreatic necrosis to an appropriate tertiary-care center. BEST PRACTICE ADVICE 2: Antimicrobial therapy is best indicated for culture-proven infection in pancreatic necrosis or when infection is strongly suspected (ie, gas in the collection, bacteremia, sepsis, or clinical deterioration). Routine use of prophylactic antibiotics to prevent infection of sterile necrosis is not recommended. BEST PRACTICE ADVICE 3: When infected necrosis is suspected, broad-spectrum intravenous antibiotics with ability to penetrate pancreatic necrosis should be favored (eg, carbapenems, quinolones, and metronidazole). Routine use of antifungal agents is not recommended. Computed tomography-guided fine-needle aspiration for Gram stain and cultures is unnecessary in the majority of cases. BEST PRACTICE ADVICE 4: In patients with pancreatic necrosis, enteral feeding should be initiated early to decrease the risk of infected necrosis. A trial of oral nutrition is recommended immediately in patients in whom there is absence of nausea and vomiting and no signs of severe ileus or gastrointestinal luminal obstruction. When oral nutrition is not feasible, enteral nutrition by either nasogastric/duodenal or nasojejunal tube should be initiated as soon as possible. Total parenteral nutrition should be considered only in cases where oral or enteral feeds are not feasible or tolerated. BEST PRACTICE ADVICE 5: Drainage and/or debridement of pancreatic necrosis is indicated in patients with infected necrosis. Drainage and/or debridement may be required in patients with sterile pancreatic necrosis and persistent unwellness marked by abdominal pain, nausea, vomiting, and nutritional failure or with associated complications, including gastrointestinal luminal obstruction; biliary obstruction; recurrent acute pancreatitis; fistulas; or persistent systemic inflammatory response syndrome. BEST PRACTICE ADVICE 6: Pancreatic debridement should be avoided in the early, acute period (first 2 weeks), as it has been associated with increased morbidity and mortality. Debridement should be optimally delayed for 4 weeks and performed earlier only when there is an organized collection and a strong indication. BEST PRACTICE ADVICE 7: Percutaneous drainage and transmural endoscopic drainage are both appropriate first-line, nonsurgical approaches in managing patients with walled-off pancreatic necrosis (WON). Endoscopic therapy through transmural drainage of WON may be preferred, as it avoids the risk of forming a pancreatocutaneous fistula. BEST PRACTICE ADVICE 8: Percutaneous drainage of pancreatic necrosis should be considered in patients with infected or symptomatic necrotic collections in the early, acute period (<2 weeks), and in those with WON who are too ill to undergo endoscopic or surgical intervention. Percutaneous drainage should be strongly considered as an adjunct to endoscopic drainage for WON with deep extension into the paracolic gutters and pelvis or for salvage therapy after endoscopic or surgical debridement with residual necrosis burden. BEST PRACTICE ADVICE 9: Self-expanding metal stents in the form of lumen-apposing metal stents appear to be superior to plastic stents for endoscopic transmural drainage of necrosis. BEST PRACTICE ADVICE 10: The use of direct endoscopic necrosectomy should be reserved for those patients with limited necrosis who do not adequately respond to endoscopic transmural drainage using large-bore, self-expanding metal stents/lumen-apposing metal stents alone or plastic stents combined with irrigation. Direct endoscopic necrosectomy is a therapeutic option in patients with large amounts of infected necrosis, but should be performed at referral centers with the necessary endoscopic expertise and interventional radiology and surgical backup. BEST PRACTICE ADVICE 11: Minimally invasive operative approaches to the debridement of acute necrotizing pancreatitis are preferred to open surgical necrosectomy when possible, given lower morbidity. BEST PRACTICE ADVICE 12: Multiple minimally invasive surgical techniques are feasible and effective, including videoscopic-assisted retroperitoneal debridement, laparoscopic transgastric debridement, and open transgastric debridement. Selection of approach is best determined by pattern of disease, physiology of the patient, experience and expertise of the multidisciplinary team, and available resources. BEST PRACTICE ADVICE 13: Open operative debridement maintains a role in the modern management of acute necrotizing pancreatitis in cases not amenable to less invasive endoscopic and/or surgical procedures. BEST PRACTICE ADVICE 14: For patients with disconnected left pancreatic remnant after acute necrotizing mid-body necrosis, definitive surgical management with distal pancreatectomy should be undertaken in patients with reasonable operative candidacy. Insufficient evidence exists to support the management of the disconnected left pancreatic remnant with long-term transenteric endoscopic stenting. BEST PRACTICE ADVICE 15: A step-up approach consisting of percutaneous drainage or endoscopic transmural drainage using either plastic stents and irrigation or self-expanding metal stents/lumen-apposing metal stents alone, followed by direct endoscopic necrosectomy, and then surgical debridement is reasonable, although approaches may vary based on the available clinical expertise.Copyright © 2020. Published by Elsevier Inc.

To examine the surgical indications and clinical outcomes of a large cohort of patients with necrotizing pancreatitis.Mortality after debridement for necrotizing pancreatitis continues to be inordinately high. The clinical experience with patients who underwent uniform surgical treatment for necrotizing pancreatitis at the Massachusetts General Hospital over a 15-year period is described.Retrospective review of 167 patients with necrotizing pancreatitis who required intervention and were treated with single stage debridement and a closed packing technique. Particular emphasis was placed on the indication for surgery and the presence of infected necrosis. Multiple logistic regression models were used to identify predictors of mortality.The primary preoperative indication for operation was infected necrosis (51%), but intraoperative cultures proved that 72% of the entire cohort was infected. The rate of reoperation was 12.6%, and 29.9% of patients required percutaneous interventional radiology drainage after initial debridement. Overall operative mortality was 11.4% (19/167), but higher in patients who were operated upon before 28 days (20.3% vs. 5.1%, P = 0.002). Other important predictors of mortality included organ failure > or =3 (OR = 2.4, P = 0.001), postoperative intensive care unit stay > or =6 days (OR = 15.9, P = 0.001), and female gender (OR = 5.41, P = 0.02).Open, transperitoneal debridement followed by closed packing and drainage results in the lowest reported mortality and reoperation rates, and provides a standard for comparing other methods of treatment. A negative FNA does not reliably rule out infection. The clinical status of the patients and not proof of infection should determine the need for debridement.

This guideline presents recommendations for the management of patients with acute pancreatitis (AP). During the past decade, there have been new understandings and developments in the diagnosis, etiology, and early and late management of the disease. As the diagnosis of AP is most often established by clinical symptoms and laboratory testing, contrast-enhanced computed tomography (CECT) and/or magnetic resonance imaging (MRI) of the pancreas should be reserved for patients in whom the diagnosis is unclear or who fail to improve clinically. Hemodynamic status should be assessed immediately upon presentation and resuscitative measures begun as needed. Patients with organ failure and/or the systemic inflammatory response syndrome (SIRS) should be admitted to an intensive care unit or intermediary care setting whenever possible. Aggressive hydration should be provided to all patients, unless cardiovascular and/or renal comorbidites preclude it. Early aggressive intravenous hydration is most beneficial within the first 12-24 h, and may have little benefit beyond. Patients with AP and concurrent acute cholangitis should undergo endoscopic retrograde cholangiopancreatography (ERCP) within 24 h of admission. Pancreatic duct stents and/or postprocedure rectal nonsteroidal anti-inflammatory drug (NSAID) suppositories should be utilized to lower the risk of severe post-ERCP pancreatitis in high-risk patients. Routine use of prophylactic antibiotics in patients with severe AP and/or sterile necrosis is not recommended. In patients with infected necrosis, antibiotics known to penetrate pancreatic necrosis may be useful in delaying intervention, thus decreasing morbidity and mortality. In mild AP, oral feedings can be started immediately if there is no nausea and vomiting. In severe AP, enteral nutrition is recommended to prevent infectious complications, whereas parenteral nutrition should be avoided. Asymptomatic pancreatic and/or extrapancreatic necrosis and/or pseudocysts do not warrant intervention regardless of size, location, and/or extension. In stable patients with infected necrosis, surgical, radiologic, and/or endoscopic drainage should be delayed, preferably for 4 weeks, to allow the development of a wall around the necrosis.

A 66-year-old man was admitted for severe acute alcoholic pancreatitis with infected pancreatic necrosis (IPN). Abdominal computed tomography revealed an inflamed pancreatic head, a dilated main pancreatic duct (MPD), and a large cavity with heterogeneous fluid containing gas adjacent to the pancreatic head, and extending to the pelvis. The cavity was drained percutaneously near the pancreatic head on admission; another tube was inserted into the pelvic cavity on hospital day 3. The drained fluid contained pus with high amylase concentration. Nasopancreatic drainage tube placement was unsuccessfully attempted on hospital day 9. On hospital day 23, percutaneous puncture of the MPD and placement of a pancreatic duct drainage tube was performed. Pancreatography revealed major extravasation from the pancreatic head. The IPN cavity receded; the percutaneous IPN drainage tube was removed on hospital day 58. On hospital day 83, the pancreatic drainage was changed to a transpapillary pancreatic stent, and the patient was discharged. Measuring the amylase concentration of peripancreatic fluid collections can aid in the diagnosis of pancreatic duct disruption; moreover, dual percutaneous necrotic cavity drainage plus pancreatic duct drainage may be essential for treating IPN. If transpapillary drainage tube placement is difficult, percutaneous pancreatic duct drainage may be feasible.

Low-dose ionizing radiation from medical imaging has been indirectly linked with subsequent cancer. Computed tomography (CT) is the gold standard for defining pancreatic necrosis. The primary goal was to identify the frequency and effective radiation dose of CT imaging for patients with necrotizing pancreatitis.All patients with necrotizing pancreatitis (2003-2007) were retrospectively analyzed for CT-related radiation exposure.Necrosis was identified in 18% (238/1290) of patients with acute pancreatitis (mean age = 53 years; hospital/ICU length of stay = 23/7 days; mortality = 9%). A median of five CTs/patient [interquartile range (IQR) = 4] were performed during a median 2.6-month interval. The average effective dose was 40 mSv per patient (equivalent to 2,000 chest X-rays; 13.2 years of background radiation; one out of 250 increased risk of fatal cancer). The actual effective dose was 63 mSv considering various scanner technologies. CTs were infrequently (20%) followed by direct intervention (199 interventional radiology, 118 operative, 12 endoscopic) (median = 1; IQR = 2). Magnetic resonance imaging did not have a CT-sparing effect. Mean direct hospital costs increased linearly with CT number (R = 0.7).The effective radiation dose received by patients with necrotizing pancreatitis is significant. Management changes infrequently follow CT imaging. The ubiquitous use of CT in necrotizing pancreatitis raises substantial public health concerns and mandates a careful reassessment of its utility.

Antibiotic prophylaxis in necrotizing pancreatitis remains controversial. Until now, there have been no double-blind studies dealing with this topic.A total sample size of 200 patients was calculated to demonstrate with a power of 90% that antibiotic prophylaxis reduces the proportion of patients with infected pancreatic necrosis from 40% placebo (PLA) to 20% ciprofloxacin/metronidazole (CIP/MET). One hundred fourteen patients with acute pancreatitis in combination with a serum C-reactive protein exceeding 150 mg/L and/or necrosis on contrast-enhanced CT scan were enrolled and received either intravenous CIP (2 x 400 mg/day) + MET (2 x 500 mg/day) or PLA. Study medication was discontinued and switched to open antibiotic treatment when infectious complications, multiple organ failure sepsis, or systemic inflammatory response syndrome (SIRS) occurred. After half of the planned sample size was recruited, an adaptive interim analysis was performed, and recruitment was stopped.Fifty-eight patients received CIP/MET and 56 patients PLA. Twenty-eight percent in the CIP/MET group required open antibiotic treatment vs. 46% with PLA. Twelve percent of the CIP/MET group developed infected pancreatic necrosis compared with 9% of the PLA group (P = 0.585). Mortality was 5% in the CIP/MET and 7% in the PLA group. In 76 patients with pancreatic necrosis on contrast-enhanced CT scan, no differences in the rate of infected pancreatic necrosis, systemic complications, or mortality were observed.This study detected no benefit of antibiotic prophylaxis with respect to the risk of developing infected pancreatic necrosis.

In patients with severe, necrotizing pancreatitis, it is common to administer early, broad-spectrum antibiotics, often a carbapenem, in the hope of reducing the incidence of pancreatic and peripancreatic infections, although the benefits of doing so have not been proved.A multicenter, prospective, double-blind, placebo-controlled randomized study set in 32 centers within North America and Europe.One hundred patients with clinically severe, confirmed necrotizing pancreatitis: 50 received meropenem and 50 received placebo.Meropenem (1 g intravenously every 8 hours) or placebo within 5 days of the onset of symptoms for 7 to 21 days.Primary endpoint: development of pancreatic or peripancreatic infection within 42 days following randomization. Other endpoints: time between onset of pancreatitis and the development of pancreatic or peripancreatic infection; all-cause mortality; requirement for surgical intervention; development of nonpancreatic infections within 42 days following randomization.Pancreatic or peripancreatic infections developed in 18% (9 of 50) of patients in the meropenem group compared with 12% (6 of 50) in the placebo group (P = 0.401). Overall mortality rate was 20% (10 of 50) in the meropenem group and 18% (9 of 50) in the placebo group (P = 0.799). Surgical intervention was required in 26% (13 of 50) and 20% (10 of 50) of the meropenem and placebo groups, respectively (P = 0.476).This study demonstrated no statistically significant difference between the treatment groups for pancreatic or peripancreatic infection, mortality, or requirement for surgical intervention, and did not support early prophylactic antimicrobial use in patients with severe acute necrotizing pancreatitis.

Intra-abdominal infections of pancreatic or peripancreatic necrotic tissue complicate the clinical course of severe acute pancreatitis (SAP) and are associated with significant morbidity. Fungal infection of necrotic pancreatic tissue is increasingly being reported. The incidence of intra-abdominal pancreatic fungal infection (PFI) varies from 5% to 68.5%. Candida albicans is the most frequently isolated fungus in patients with necrotizing pancreatitis. Prolonged use of prophylactic antibiotics, prolonged placement of chronic indwelling devices, and minimally invasive or surgical interventions for pancreatic fluid collections further increase the risk of PFI. Computed tomography- or ultrasound-guided fine-needle aspiration of pancreatic necrosis is a safe, reliable method for establishing pancreatic infection. Amphotericin B appears to be the most effective antifungal treatment. Drainage and debridement of infected necrosis are also critical for eradication of fungi from the poorly perfused pancreatic or peripancreatic tissues where the antifungal agents may not reach to achieve therapeutic levels. Fungal infection adversely affects the outcome of patients with SAP and is associated with increased morbidity, although the mortality rate is not increased specifically because of PFI. Although antifungal prophylaxis has been suggested for patients on broad-spectrum antibiotics, no randomized controlled trials have yet studied its efficacy in preventing PFI.

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.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.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 ± 31,680 vs 26,965 ± 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.MDROs infection was prevalent among patients with IPN and associated with adverse clinical outcomes and increased mortality.Copyright © 2019 IAP and EPC. Published by Elsevier B.V. All rights reserved.

The International Association of Pancreatology, alongside the American Pancreatic Association, the European Pancreatic Club, the Indian Pancreas Club, and the Japan Pancreas Society, decided to update its earlier guidelines for the management of acute pancreatitis (AP) given the remarkable advances in our understanding of AP and its management over the last decade.These organizations put together a group of international experts to address important issues related to the management of AP. Guideline Development Groups comprising international domain experts framed clinically relevant questions and conducted thorough literature searches and systematic reviews to address the questions. Questions were framed in the PICO (Participant, Intervention, Comparator, and Outcome) format where appropriate. The evidence from the literature was synthesized to develop evidence-based recommendations for each question. The quality of evidence and the strength of the recommendations were graded according to the Grading of Recommendations Assessment, Development and Evaluation (GRADE). For some questions, we have provided Good Practice Statements if enough direct evidence was unavailable.The guidelines pertain to 18 domains comprising 96 questions. The recommendations cover almost all aspects of managing AP, including pain control, fluid therapy, patient stabilization, nutritional support, conservative and interventional treatment for infected necrotizing pancreatitis, management of complications, discharge criteria, guidance on follow-up, and strategies for prevention of recurrence. Specific types of AP, such as those associated with pregnancy, trauma, and metabolic factors have been given special attention.The recommendations presented here should serve as an evidence-based resource for practicing physicians and caregivers to treat patients with AP more effectively. In addition, the guidelines identify areas for future research, mainly targeted therapies for controlling systemic inflammation and mitigating organ dysfunction.Copyright © 2025 IAP and EPC. Published by Elsevier B.V. All rights reserved.

Unwarranted administration of antibiotics in acute pancreatitis presents a global challenge. The clinical reasoning behind the misuse is poorly understood. Our aim was to investigate current clinical practices and develop recommendations that guide clinicians in prescribing antibiotic treatment in acute pancreatitis.Four methods were used. 1) Systematic data collection was performed to summarize current evidence; 2) a retrospective questionnaire was developed to understand the current global clinical practice; 3) five years of prospectively collected data were analysed to identify the clinical parameters used by medical teams in the decision making process, and finally; 4) the UpToDate Grading of Recommendations, Assessment, Development and Evaluation (GRADE) system was applied to provide evidence based recommendations for healthcare professionals.The systematic literature search revealed no consensus on the start of AB therapy in patients with no bacterial culture test. Retrospective data collection on 9728 patients from 22 countries indicated a wide range (31-82%) of antibiotic use frequency in AP. Analysis of 56 variables from 962 patients showed that clinicians initiate antibiotic therapy based on increased WBC and/or elevated CRP, lipase and amylase levels. The above mentioned four laboratory parameters showed no association with infection in the early phase of acute pancreatitis. Instead, procalcitonin levels proved to be a better biomarker of early infection. Patients with suspected infection because of fever had no benefit from antibiotic therapy.The authors formulated four consensus statements to urge reduction of unjustified antibiotic treatment in acute pancreatitis and to use procalcitonin rather than WBC or CRP as biomarkers to guide decision-making.Copyright © 2019 IAP and EPC. Published by Elsevier B.V. All rights reserved.

Acute pancreatitis is the acute inflammation of the pancreas; 30% of cases may progress to pancreatic necrosis. The aim of this study was to assess the diagnostic accuracy of inflammatory biomarkers (C-reactive protein (CRP), procalcitonin (PCT), and lactate dehydrogenase (LDH)) in detecting pancreatic necrosis in adults with confirmed acute pancreatitis within 14 days of symptom onset and without organ failure. A systematic search was conducted across the Cumulative Index of Nursing and Allied Health (CINAHL), Cochrane, Embase, PubMed, and Web of Science until May 30, 2022, with the following keywords: acute disease, biomarkers, C-reactive protein, calcitonin, differential, diagnosis, lactate dehydrogenase, pancreatitis, acute necrotizing, necrosis, sensitivity, specificity. Statistical analysis was conducted in RevMan 5.4.1 (Cochrane). Five studies pooling 645 participants were included of which 59.8% were males, with a mean age of 49 years. CRP was the best cutoff at 279 mg/L (χ2 = 47.43, p &lt; 0.001), followed by 200 mg/L (χ2 = 36.54, p &lt; 0.001). LDH was cut off at 290 units/L (χ2 = 51.6, p &lt; 0.001), whereas PCT did not display the most reliable results at 0.05 ng/mL. Inflammatory biomarkers are scalable diagnostic tools that may confer clinical value by decreasing the mortality of acute pancreatitis sequelae.

The aim of the study was to verify whether antibiotics excreted by the normal pancreas are also excreted in human necrotizing pancreatitis, reaching the tissue sites of the infection. Twelve patients suffering from acute necrotizing pancreatitis were treated with imipenem-cilastatin (0.5 g), mezlocillin (2 g), gentamicin (0.08 g), amikacin (0.5 g), pefloxacin (0.4 g), and metronidazole (0.5 g). Serum and necrotic samples were collected simultaneously at different time intervals after parenteral drug administration by computed tomography-guided needle aspiration, intraoperatively, and from surgical drainages placed during surgery. Drug concentrations were determined by microbiological and high-performance liquid chromatography assays. All antibiotics reached the necrotic tissues, but with varying degrees of penetration, this being low for aminoglycosides (13%) and high in the case of pefloxacin (89%) and metronidazole (99%). The concentrations of pefloxacin (13.0 to 23 micrograms/g) and metronidazole (8.4 micrograms/g) in the necrotic samples were distinctly higher than the MICs for the organisms most commonly isolated in this disease; the concentrations in tissue of imipenem (3.35 micrograms/g) and mezlocillin (8.0 and 15.0 micrograms/g) did not always exceed the MICs for 90% of strains tested, whereas the aminoglycoside concentrations in necrotic tissue (0.5 microgram/g) were inadequate. Repeated administration of drugs (for 3, 7, 17, and 20 days) seems to enhance penetration of pefloxacin, imipenem, and metronidazole into necrotic pancreatic tissue. The choice of antibiotics in preventing infected necrosis during necrotizing pancreatitis should be based on their antimicrobial activity, penetration rate, persistence, and therapeutic concentrations in the necrotic pancreatic area. These requisites are provided by pefloxacin and metronidazole and to a variable extent by imipenem and mezlocillin.

The goal of this study was to study the incidence of fungal infection in necrotizing pancreatitis (NP) and its impact on mortality.Infected pancreatic necrosis is a major contributor to morbidity and mortality in patients with NP. While pancreatic fungal infection (PFI) has frequently been identified in patients with NP, its effect on the clinical outcomes is unclear.A literature search was performed in Medline (Ovid), Embase (Ovid), and the Cochrane library. All prospective and retrospective studies that examined the incidence of fungal infection in NP with subgroup mortality data were included. For fungal infection of NP, studies with fungal isolation from pancreatic necrotic tissue were included. Newcastle Ottawa Scale and Joanna Briggs Institute's critical appraisal tool were used for bias assessment.Twenty-two studies comprising 2151 subjects with NP were included for the quantitative analysis. The mean incidence of fungal infection was 26.6% (572/2151). In-hospital mortality in the pooled sample of NP patients with PFI (N=572) was significantly higher [odds ratio (OR)=3.95, 95% confidence interval (CI): 2.6-5.8] than those without PFI. In a separate analysis of 7 studies, the mean difference in the length of stay between those with and without fungal infection was 22.99 days (95% CI: 14.67-31.3). The rate of intensive care unit admission (OR=3.95; 95% CI: 2.6-5.8), use of prophylactic antibacterials (OR=2.76; 95% CI: 1.31-5.81) and duration of antibacterial therapy (mean difference=8.71 d; 95% CI: 1.33-16.09) were all significantly higher in patients with PFI. Moderate heterogeneity was identified among the studies on estimating OR for mortality (I2=43%) between the 2 groups.PFI is common in patients with NP and is associated with increased mortality, intensive care unit admission rate, and length of stay. Further prospective studies are needed to better understand the pathophysiology of PFIs and to determine the role for preemptive therapeutic strategies, such as prophylactic antifungal therapy.Copyright © 2020 Wolters Kluwer Health, Inc. All rights reserved.

Evidence-based guidelines for implementation and measurement of antibiotic stewardship interventions in inpatient populations including long-term care were prepared by a multidisciplinary expert panel of the Infectious Diseases Society of America and the Society for Healthcare Epidemiology of America. The panel included clinicians and investigators representing internal medicine, emergency medicine, microbiology, critical care, surgery, epidemiology, pharmacy, and adult and pediatric infectious diseases specialties. These recommendations address the best approaches for antibiotic stewardship programs to influence the optimal use of antibiotics.

Reduced duration of antibiotic treatment might contain the emergence of multidrug-resistant bacteria in intensive care units. We aimed to establish the effectiveness of an algorithm based on the biomarker procalcitonin to reduce antibiotic exposure in this setting.In this multicentre, prospective, parallel-group, open-label trial, we used an independent, computer-generated randomisation sequence to randomly assign patients in a 1:1 ratio to procalcitonin (n=311 patients) or control (n=319) groups; investigators were masked to assignment before, but not after, randomisation. For the procalcitonin group, antibiotics were started or stopped based on predefined cut-off ranges of procalcitonin concentrations; the control group received antibiotics according to present guidelines. Drug selection and the final decision to start or stop antibiotics were at the discretion of the physician. Patients were expected to stay in the intensive care unit for more than 3 days, had suspected bacterial infections, and were aged 18 years or older. Primary endpoints were mortality at days 28 and 60 (non-inferiority analysis), and number of days without antibiotics by day 28 (superiority analysis). Analyses were by intention to treat. The margin of non-inferiority was 10%. This trial is registered with ClinicalTrials.gov, number NCT00472667.Nine patients were excluded from the study; 307 patients in the procalcitonin group and 314 in the control group were included in analyses. Mortality of patients in the procalcitonin group seemed to be non-inferior to those in the control group at day 28 (21.2% [65/307] vs 20.4% [64/314]; absolute difference 0.8%, 90% CI -4.6 to 6.2) and day 60 (30.0% [92/307] vs 26.1% [82/314]; 3.8%, -2.1 to 9.7). Patients in the procalcitonin group had significantly more days without antibiotics than did those in the control group (14.3 days [SD 9.1] vs 11.6 days [SD 8.2]; absolute difference 2.7 days, 95% CI 1.4 to 4.1, p<0.0001).A procalcitonin-guided strategy to treat suspected bacterial infections in non-surgical patients in intensive care units could reduce antibiotic exposure and selective pressure with no apparent adverse outcomes.Assistance Publique-Hôpitaux de Paris, France, and Brahms, Germany.Copyright 2010 Elsevier Ltd. All rights reserved.

<i>Background:</i> Infectious complications are the main cause of late death in patients with acute pancreatitis. Routine prophylactic antibiotic use following a severe attack has been proposed but remains controversial. On the other hand, nutritional support has recently yielded promising clinical results. The aim of study was to compare enteral vs. parenteral feeding for prevention of infectious complications in patients with predicted severe acute pancreatitis. <i>Methods:</i> We screened 466 consecutive patients with acute pancreatitis. A total of 70 patients with objectively graded severe acute pancreatitis were randomly allocated to receive either total enteral nutrition (TEN) or total parenteral nutrition (TPN), within 72 h of onset of symptoms. Baseline characteristics were well matched in the two groups. <i>Results:</i> The incidence of pancreatic infectious complications (infected pancreatic necrosis, pancreatic abscess) was significantly lower in the enterally fed group (7 vs. 16, p = 0.02). In the TEN group, 7 patients developed multiple organ failure whereas 17 parenterally fed patients developed multiple organ failure (p = 0.02). Overall mortality was 20% with two deaths in the TEN group and twelve in the TPN group (p &lt; 0.01). <i>Conclusion:</i> Early TEN could be used as prophylactic therapy for infected pancreatic necrosis since it significantly decreased the incidence of pancreatic infectious complications as well as the frequency of multiple organ failure and mortality.

The importance of enteral nutrition (EN) in acute pancreatitis (AP) has been emphasised. Nasogastric (NG) feeding has been the preferred route for EN delivery in most AP patients intolerant to oral intake. However, gastric feeding intolerance (GFI) was frequently reported, especially in patients with more severe diseases. This study aimed to investigate the incidence and risk factors for GFI in moderately-severe to severe AP.This is a single-centre, retrospective study. All the data were extracted from an electronic database from April 2020 to May 2021. Data were prospectively collected during hospitalisation. Patients diagnosed with moderately-severe to severe AP and admitted within seven days from the onset of abdominal pain were assessed for eligibility. Patients who showed signs of intolerance to gastric feeding and required switching to nasojejunal (NJ) feeding were deemed GFI. Multivariable logistic regression was performed to assess potential risk factors of GFI.A total of 93 patients were analysed, of whom 24 were deemed GFI (25.8%), and the rest tolerated NG feeding well (n = 69). In patients with GFI, the median time of switching to NJ feeding was five days (interquartile range: 4-7 days) after admission. The multivariable analysis showed that respiratory failure (odds ratio = 3.135, 95% CI: 1.111-8.848, P = 0.031) was an independent risk factor for GFI.The mean daily energy delivery in the following three days after switching to NJ feeding was significantly higher than the first three days after initiation of NG feeding in patients with GFI [920.83 (493.33-1326) vs. 465 (252.25-556.67) kcal, P < 0.001].GFI is common in moderately-severe to severe AP patients with an incidence of 25.8%, and the presence of respiratory failure may increase the risk of GFI.© 2022. The Author(s).

Severe acute pancreatitis may be complicated by intra-abdominal hypertension (IAH), abdominal compartment syndrome (ACS), and intestinal ischemia. The aim of this retrospective study is to describe the incidence, treatment, and outcome of patients with severe acute pancreatitis and ACS, in particular the occurrence of intestinal ischemia.The medical records of all patients admitted with severe acute pancreatitis admitted to the ICU of a tertiary referral center were reviewed. The criteria proposed by the World Society of the Abdominal Compartment Syndrome (WSACS) were used to determine whether patients had IAH or ACS.Fifty-nine patients with severe acute pancreatitis were identified. Intra-abdominal pressure (IAP) measurements were performed in 29 patients (49.2 %). IAH was present in all patients (29/29). ACS developed in 13/29 (44.8 %) patients. Ten patients with ACS underwent decompressive laparotomy. A large proportion of patients with ACS had intra-abdominal ischemia upon laparotomy: 8/13 (61.5 %). Mortality was high in both the ACS group and the IAH group.This study confirms that ACS is common in severe acute pancreatitis. Intra-abdominal ischemia occurs in a large proportion of patients with ACS. Swift surgical intervention may be indicated when conservative measures fail in patients with ACS. National and international guidelines need to be updated so that routine IAP measurements become standard of care for patients with severe acute pancreatitis in the ICU.

Infectious complications and associated mortality are a major concern in acute pancreatitis. Enteral administration of probiotics could prevent infectious complications, but convincing evidence is scarce. Our aim was to assess the effects of probiotic prophylaxis in patients with predicted severe acute pancreatitis.In this multicentre randomised, double-blind, placebo-controlled trial, 298 patients with predicted severe acute pancreatitis (Acute Physiology and Chronic Health Evaluation [APACHE II] score > or =8, Imrie score > or =3, or C-reactive protein >150 mg/L) were randomly assigned within 72 h of onset of symptoms to receive a multispecies probiotic preparation (n=153) or placebo (n=145), administered enterally twice daily for 28 days. The primary endpoint was the composite of infectious complications--ie, infected pancreatic necrosis, bacteraemia, pneumonia, urosepsis, or infected ascites--during admission and 90-day follow-up. Analyses were by intention to treat. This study is registered, number ISRCTN38327949.One person in each group was excluded from analyses because of incorrect diagnoses of pancreatitis; thus, 152 individuals in the probiotics group and 144 in the placebo group were analysed. Groups were much the same at baseline in terms of patients' characteristics and disease severity. Infectious complications occurred in 46 (30%) patients in the probiotics group and 41 (28%) of those in the placebo group (relative risk 1.06, 95% CI 0.75-1.51). 24 (16%) patients in the probiotics group died, compared with nine (6%) in the placebo group (relative risk 2.53, 95% CI 1.22-5.25). Nine patients in the probiotics group developed bowel ischaemia (eight with fatal outcome), compared with none in the placebo group (p=0.004).In patients with predicted severe acute pancreatitis, probiotic prophylaxis with this combination of probiotic strains did not reduce the risk of infectious complications and was associated with an increased risk of mortality. Probiotic prophylaxis should therefore not be administered in this category of patients.

The PROPATRIA (Probiotics in Pancreatitis Trial) study was a multicenter, double-blind, placebo-controlled clinical trial that aimed to reduce infectious complications in patients with predicted severe acute pancreatitis by the enteral use of a multispecies probiotic preparation. An unprecedented 24 of 152 patients (16%) in the group receiving probiotics died versus 9 of 144 (6%) in the placebo group. This high mortality rate in the probiotic-treated group contrasts strongly with observations from a previous smaller study and from our observations regarding the effects of abundant intestinal lactobacilli in patients with short small bowel (SSB) syndrome. We argue here that a lethal combination of mainly proteolytic pancreas enzymes and probiotic therapy resulted in the high mortality rate of the PROPATRIA trial and that elevated levels of lactic acid produced by bacterial fermentation of carbohydrates were a key contributing factor. We suggest that probiotic therapy may not be counter-indicated for the prevention of secondary infections associated with acute pancreatitis, provided that future clinical studies (i) start probiotic therapy immediately after first onset of disease symptoms, (ii) limit the supply of fermentable carbohydrates, (iii) prevent bacterial (over)growth of patient's own intestinal flora and (iv) massively increase the dose of probiotic bacteria.

Introduction : The role of pre-, pro-, and synbiotics supplemented to standard enteral nutrition in severe acute pancreatitis (SAP) remains unclear. We performed this updated meta-analysis to determine the value of pre-, pro- and synbiotics supplemented to standard enteral nutrition in predicted SAP.Methods : A systematic search in PubMed, EMBASE and Cochrane Central Register of Controlled Trials (CENTRAL) databases was performed. Eligible studies were randomized controlled trials (RCTs) that compared the effects of pre-, pro-, and synbiotics supplemented to standard enteral nutrition with control regime in predicted SAP patients. Risk ratio (RR) and mean difference (MD) with 95% confidence interval (95% CI) were used to express the estimates of dichotomous and continuous data respectively.Results : 13 RCTs comprising an aggregate total of 950 patients were eventually enrolled. Pooled results suggested that supplemented use of pre-, pro- and synbiotics effectively shorten the length of hospital stay in Chinese SAP cohorts (6 RCTs, MD = - 5.57, 95% CI = - 8.21 to - 2.93, P < 0.001); however significant differences with regard to remaining clinical outcomes were not detected for all patients. Further analysis based on category of interventions including pre-, pro- and synbiotics also confirmed the findings to be reliable.Conclusions : Supplemented use of pre-, pro and synbiotics reduced the length of hospital stay in Chinese SAP cohorts. And thus, we concluded that pre-, pro- and synbiotics supplemented to standard enteral nutrition may be a potential option for the treatment of SAP patients. However, we also suggest designing further studies with large-scale and rigorous methods of addressing data to establish the effects and safety of supplemented use of pre-, pro- and synbiotics for SAP patients due to the presence of limitations.

This meta-analysis aimed to assess the efficacy and safety of probiotics in conjunction with early enteral nutrition for the treatment of severe acute pancreatitis (SAP). This study focused on multiple clinical endpoints, including mortality rate, risk of organ failure, and duration of hospital stay.

A randomized, controlled, multicenter trial was undertaken in 102 patients with objective evidence of severe acute pancreatitis to evaluate whether selective decontamination reduces mortality.Secondary pancreatic infection is the major cause of death in patients with acute necrotizing pancreatitis. Controlled clinical trials to study the effect of selective decontamination in such patients are not available.Between April 22, 1990 and April 19, 1993, 102 patients with severe acute pancreatitis were admitted to 16 participating hospitals. Patients were entered into the study if severe acute pancreatitis was indicated, on admission, by multiple laboratory criteria (Imrie score > or = 3) and/or computed tomography criteria (Balthazar grade D or E). Patients were randomly assigned to receive standard treatment (control group) or standard treatment plus selective decontamination (norfloxacin, colistin, amphotericin; selective decontamination group). All patients received full supportive treatment, and surveillance cultures were taken in both groups.Fifty patients were assigned to the selective decontamination group and 52 were assigned to the control group. There were 18 deaths in the control group (35%), compared with 11 deaths (22%) in the selective decontamination group (adjusted for Imrie score and Balthazar grade: p = 0.048). This difference was mainly caused by a reduction of late mortality (> 2 weeks) due to significant reduction of gram-negative pancreatic infection (p = 0.003). The average number of laparotomies per patient was reduced in patients treated with selective decontamination (p < 0.05). Failure of selective decontamination to prevent secondary gram-negative pancreatic infection with subsequent death was seen in only three patients (6%) and transient gram-negative pancreatic infection was seen in one (2%). In both groups of patients, all gram-negative aerobic pancreatic infection was preceded by colonization of the digestive tract by the same bacteria.Reduction of gram-negative colonization of the digestive tract, preventing subsequent pancreatic infection by means of selective decontamination, significantly reduces morbidity and mortality in patients with severe acute necrotizing pancreatitis.

To update the World Society of the Abdominal Compartment Syndrome (WSACS) consensus definitions and management statements relating to intra-abdominal hypertension (IAH) and the abdominal compartment syndrome (ACS).We conducted systematic or structured reviews to identify relevant studies relating to IAH or ACS. Updated consensus definitions and management statements were then derived using a modified Delphi method and the Grading of Recommendations, Assessment, Development, and Evaluation (GRADE) guidelines, respectively. Quality of evidence was graded from high (A) to very low (D) and management statements from strong RECOMMENDATIONS (desirable effects clearly outweigh potential undesirable ones) to weaker SUGGESTIONS (potential risks and benefits of the intervention are less clear).In addition to reviewing the consensus definitions proposed in 2006, the WSACS defined the open abdomen, lateralization of the abdominal musculature, polycompartment syndrome, and abdominal compliance, and proposed an open abdomen classification system. RECOMMENDATIONS included intra-abdominal pressure (IAP) measurement, avoidance of sustained IAH, protocolized IAP monitoring and management, decompressive laparotomy for overt ACS, and negative pressure wound therapy and efforts to achieve same-hospital-stay fascial closure among patients with an open abdomen. SUGGESTIONS included use of medical therapies and percutaneous catheter drainage for treatment of IAH/ACS, considering the association between body position and IAP, attempts to avoid a positive fluid balance after initial patient resuscitation, use of enhanced ratios of plasma to red blood cells and prophylactic open abdominal strategies, and avoidance of routine early biologic mesh use among patients with open abdominal wounds. NO RECOMMENDATIONS were possible regarding monitoring of abdominal perfusion pressure or the use of diuretics, renal replacement therapies, albumin, or acute component-parts separation.Although IAH and ACS are common and frequently associated with poor outcomes, the overall quality of evidence available to guide development of RECOMMENDATIONS was generally low. Appropriately designed intervention trials are urgently needed for patients with IAH and ACS.

Intra-abdominal hypertension (IAH) in acute pancreatitis (AP) is associated with deterioration in organ function. This trial aimed to assess the efficacy of neostigmine for IAH in patients with AP.

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.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.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.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.Copyright © 2019 AGA Institute. Published by Elsevier Inc. All rights reserved.

Acute pancreatitis (AP) is defined as an acute inflammatory attack of the pancreas of sudden onset. Around 25% of patients have either moderately severe or severe disease with a mortality rate of 15–20%.

Initial management of severe acute pancreatitis (SAP) is conservative. As a step-up approach, percutaneous catheter drainage (PCD) with saline irrigation is reported to be effective. Factors leading to surgery are unclear.In this ongoing prospective study, 70 consecutive patients with SAP were recruited. As a step-up approach, all patients initially received medical management and later underwent PCD and surgery as per the indication.Of the 70 consecutive patients with SAP, 14 were managed medically, 29 managed with PCD alone, whereas 27 required surgery after initial PCD. Sepsis reversal was achieved with PCD alone in 62.5%. The curative efficacy of PCD alone was in 27 patients (48%). Overall mortality in the whole group was 24%. On univariate analysis, factors significantly affecting surgical intervention included initial acute physiology and chronic health evaluation (APACHE) II score, APACHE II score at first intervention, sepsis reversal by PCD within a week, number of organs failed, organ failure within a week of the onset of disease, number of bacteria isolated per patient, renal failure, respiratory failure, Escherichia coli, computerized tomography severity index score at admission, parenteral nutrition requirement before or after radiological intervention, maximum extent of necrosis of more than 50% of the pancreas, and extrapancreatic necrosis. On multivariate analysis, renal failure (P = -0.03), APACHE II score at first intervention (P = -0.006), and the number of bacteria isolated per patient (P = -0.01) remained independent predictors of surgery. An APACHE II score of more than 7.5 at first intervention (PCD) had the ability to predict surgery with a sensitivity of 88.9% and a specificity of 69%.PCD reversed sepsis in 62% and avoided surgery in 48% of the patients. Reversal of sepsis within a week of PCD, APACHE II score at first intervention (PCD), and organ failure within a week of the onset of disease could predict the need for surgery in the early course of disease.

Current guidelines for necrotizing pancreatitis (NP) recommend delay in drainage ± necrosectomy until 4 or more weeks after initial presentation to allow collections to wall off. However, evidence of infection with clinical deterioration despite maximum support may mandate earlier (<4 weeks) intervention. There are concerns, but scant data regarding risk of complications and outcomes with early endoscopic intervention. Our aim was to compare the results of an endoscopic centered step-up approach to NP when initiated before versus 4 or more weeks.All patients undergoing intervention for NP were managed using an endoscopically centered step-up approach, with transluminal drainage whenever feasible, ±necrosectomy, and/or percutaneous catheter drainage as needed, with surgery only for failures. Interventions were categorized as early or standard based on timing of intervention (<4 weeks or ≥ 4 weeks from onset of pancreatitis). Demographic data, indications and timing for interventions, number and type of intervention, mortality and morbidity (length of stay in hospital and ICU) and complications were compared.Of 305 patients with collections associated with NP, 193 (63%) (median age-52 years) required intervention, performed by a step-up approach. Of the 193 patients, 76 patients underwent early and 117 patients standard intervention. 144 (75%) interventions included endoscopic drainage ± necrosectomy. As compared with standard intervention, early intervention was more often performed for infection (91% vs. 39%, p < 0.05), more associated with acute kidney injury (43% vs. 32%, p = 0.09), respiratory failure (41% vs. 22%, p = 0.005), and shock (13% vs. 4%, p < 0.05). Organ failure improved significantly after intervention in both groups. There was a significant difference in mortality (13% vs. 4%, p = 0.02) and need for rescue open necrosectomy (7% vs. 1%, p = 0.03) between groups. Patients undergoing early intervention had increased median hospital (37 days vs. 26 days, p = 0.01) and ICU stay (median 2.5 days vs. 0 days, p = 0.001). There was no difference in complications.When using an endoscopically centered step-up strategy in necrotizing pancreatitis, early (<4 weeks) interventions were more often performed for infection and organ failure, with no increase in complications, similar improvement in organ failure, slightly increased need for surgery, and relatively low mortality. Early endoscopic drainage ± necrosectomy should be considered when there is a strong indication for intervention.

Evidence regarding the optimal timing of intervention for symptomatic acute necrotic collections (ANCs) in necrotizing pancreatitis remains inconsistent, particularly in the era of minimally invasive step-up approaches. This systematic review and meta-analysis (SR&amp;MA) aimed to compare patient-centered clinical outcomes between early and delayed interventions.

A series of randomized controlled trials have investigated the efficacy and safety of different timings of interventions and methods of intervention. However, the optimal treatment strategy is not yet clear.We searched PubMed, EMBASE, ClinicalTrials.gov and the Cochrane Library until November 30, 2022. A systematic review and Bayesian network meta-analysis were performed following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. Trials comparing different treatment strategies for necrotizing pancreatitis were included. This study was registered in the Prospective Register of Systematic Reviews (CRD42022364409) to ensure transparency.We analyzed a total of 10 studies involving 570 patients and 8 treatment strategies. Although no statistically significant differences were identified comparing odds ratios, trends were confirmed by the surface under the cumulative ranking (SUCRA) scores. The interventions with a low rate of mortality were delayed surgery (DS), delayed surgical step-up approach (DSU) and delayed endoscopic step-up approach (DEU), while the interventions with a low rate of major complications were DSU, DEU and DS. According to the clustered ranking plot, DSU performed the best overall in reducing mortality and major complications, while DD performed the worst. Analysis of the secondary endpoints confirmed the superiority of DEU and DSU in terms of individual components of major complications (organ failure, pancreatic fistula, bleeding, and visceral organ or enterocutaneous fistula), exocrine insufficiency, endocrine insufficiency and length of stay. Overall, DSU was superior to other interventions.DSU was the optimal treatment strategy for necrotizing pancreatitis. Drainage alone should be avoided in clinical practice. Any interventions should be postponed for at least 4 weeks if possible. The step-up approach was preferred.© 2023. The Author(s).

The effects of the step-jump approach on the survival and prognosis of infected pancreatic necrosis (IPN) patients have not yet been determined.Between November 2018 and June 2023, 188 patients were included in this study. There were 144 patients in the step-up group (the SU group) and 44 in the step-jump group (the SJ group). In the SU group, patients successfully treated with percutaneous catheter drainage (PCD) alone were classified into the SU-1 group (n=101), while those requiring additional surgery after PCD were categorized into the SU-2 group (n=43). In the SJ group, patients who underwent minimally invasive necrosectomy (MIN) without PCD were assigned to the SJ-1 group (n=34), whereas those who initially underwent PCD followed by immediate open surgery were placed in the SJ-2 group (n=10). Propensity score matching (PSM) was used to mitigate bias.After PSM, a total of 34 pairs were successfully matched. A comparison of the SU group with the SJ-1 group (upfront MIN without PCD) revealed similar mortality rates (=0.239); however, the incidences of multiple drug-resistant organisms (MDROs) (=0.029) and surgical complications (<0.001) were significantly lower in the SJ-1 group. After comparing the SU-2 and SJ-2 groups (patients who underwent direct open necrosectomy without MIN after PCD failure), the incidences of surgical complications and MDRO in the SJ-2 group were significantly lower (<0.05).Compared with the step-up approach, the step-jump approach is safer and more effective and can significantly reduce the incidence of MDRO and surgical complications.© 2024 Bai et al.

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.

Interventions for necrotizing pancreatitis are generally postponed until 4 weeks after the onset of acute pancreatitis, but there remains controversy about whether we should always wait &gt;4 weeks or can intervene early when necessary. This meta‐analysis was conducted to evaluate treatment outcomes of necrotizing pancreatitis according to the cut‐off defined in the revised Atlanta classification (≤4 vs. &gt;4 weeks).

The minimally invasive step-up approach for treatment of walled off necrosis (WON) involves drainage followed by later necrosectomy as needed, and is superior to primary surgical necrosectomy. Reported series of endoscopic transluminal necrosectomy include highly selected patients. We report outcomes of a large series of patients with WON managed by an algorithm based on an endoscopically centered step-up approach.Consecutive patients with necrotizing pancreatitis from 2009 to 2014, with intervention only for infected or persistently symptomatic WON. The primary approach involved endoscopic transluminal drainage plus minus necrosectomy whenever feasible, with percutaneous catheter drainage (PCD) plus minus sinus tract endoscopy if not feasible or sufficient. Surgery was reserved for failures of the step up approach.Of 109 consecutive patients with necrotizing pancreatitis, intervention was required in 83, including endoscopic transluminal drainage in 73 (88%) (alone in 49 and combined with PCD in 24), and PCD alone in 10 (12%). 64 (77%) of the 83 patients required endoscopic transluminal and/or sinus tract necrosectomy. Adverse events occurred in 11 (13%). Three patients (4%) failed step up approach and required open surgical necrosectomy. All-cause mortality occurred in 6 (7%) of 83 patients after intervention, including 2 of 3 requiring surgery.An algorithm based step-up approach for interventions in necrotizing pancreatitis using primarily endoscopic techniques with adjunctive percutaneous approaches as needed resulted in favorable outcomes with small numbers proceeding to open surgery, and with acceptable rates of major complications and mortality. A purely endoscopic transluminal approach was feasible in approximately 60% of patients requiring intervention in this series.Copyright © 2017 IAP and EPC. Published by Elsevier B.V. All rights reserved.

Infected necrotising pancreatitis is a potentially lethal disease and an indication for invasive intervention. The surgical step-up approach is the standard treatment. A promising alternative is the endoscopic step-up approach. We compared both approaches to see whether the endoscopic step-up approach was superior to the surgical step-up approach in terms of clinical and economic outcomes.In this multicentre, randomised, superiority trial, we recruited adult patients with infected necrotising pancreatitis and an indication for invasive intervention from 19 hospitals in the Netherlands. Patients were randomly assigned to either the endoscopic or the surgical step-up approach. The endoscopic approach consisted of endoscopic ultrasound-guided transluminal drainage followed, if necessary, by endoscopic necrosectomy. The surgical approach consisted of percutaneous catheter drainage followed, if necessary, by video-assisted retroperitoneal debridement. The primary endpoint was a composite of major complications or death during 6-month follow-up. Analyses were by intention to treat. This trial is registered with the ISRCTN registry, number ISRCTN09186711.Between Sept 20, 2011, and Jan 29, 2015, we screened 418 patients with pancreatic or extrapancreatic necrosis, of which 98 patients were enrolled and randomly assigned to the endoscopic step-up approach (n=51) or the surgical step-up approach (n=47). The primary endpoint occurred in 22 (43%) of 51 patients in the endoscopy group and in 21 (45%) of 47 patients in the surgery group (risk ratio [RR] 0·97, 95% CI 0·62-1·51; p=0·88). Mortality did not differ between groups (nine [18%] patients in the endoscopy group vs six [13%] patients in the surgery group; RR 1·38, 95% CI 0·53-3·59, p=0·50), nor did any of the major complications included in the primary endpoint.In patients with infected necrotising pancreatitis, the endoscopic step-up approach was not superior to the surgical step-up approach in reducing major complications or death. The rate of pancreatic fistulas and length of hospital stay were lower in the endoscopy group. The outcome of this trial will probably result in a shift to the endoscopic step-up approach as treatment preference.The Dutch Digestive Disease Foundation, Fonds NutsOhra, and the Netherlands Organization for Health Research and Development.Copyright © 2018 Elsevier Ltd. All rights reserved.

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.To compare the proinflammatory response and clinical outcome of endoscopic transgastric and surgical necrosectomy.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.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.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.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).In patients with infected necrotizing pancreatitis, endoscopic necrosectomy reduced the proinflammatory response as well as the composite clinical end point compared with surgical necrosectomy.isrctn.org Identifier: ISRCTN07091918.

Infected necrotizing pancreatitis is a highly morbid disease with poor outcomes. Intervention strategies have progressed from open necrosectomy to minimally invasive approaches. We compared outcomes of minimally invasive surgery vs endoscopic approaches for patients with infected necrotizing pancreatitis.We performed a single-center, randomized trial of 66 patients with confirmed or suspected infected necrotizing pancreatitis who required intervention from May 12, 2014, through March 24, 2017. Patients were randomly assigned to groups that received minimally invasive surgery (laparoscopic or video-assisted retroperitoneal debridement, depending on location of collection, n = 32) or an endoscopic step-up approach (transluminal drainage with or without necrosectomy, n = 34). The primary endpoint was a composite of major complications (new-onset multiple organ failure, new-onset systemic dysfunction, enteral or pancreatic-cutaneous fistula, bleeding and perforation of a visceral organ) or death during 6 months of follow-up.The primary endpoint occurred in 11.8% of patients who received the endoscopic procedure and 40.6% of patients who received the minimally invasive surgery (risk ratio 0.29; 95% confidence interval 0.11-0.80; P =.007). Although there was no significant difference in mortality (endoscopy 8.8% vs surgery 6.3%; P = .999), none of the patients assigned to the endoscopic approach developed enteral or pancreatic-cutaneous fistulae compared with 28.1% of the patients who underwent surgery (P =.001). The mean number of major complications per patient was significantly higher in the surgery group (0.69 ± 1.03) compared with the endoscopy group (0.15 ± 0.44) (P =.007). The physical health scores for quality of life at 3 months was better with the endoscopic approach (P =.039) and mean total cost was lower ($75,830) compared with $117,492 for surgery (P =.039).In a randomized trial of 66 patients, an endoscopic transluminal approach for infected necrotizing pancreatitis, compared with minimally invasive surgery, significantly reduced major complications, lowered costs, and increased quality of life. Clinicaltrials.gov no: NCT02084537.Copyright © 2019 AGA Institute. Published by Elsevier Inc. All rights reserved.

Management options for symptomatic and infected walled-off pancreatic necrosis (WOPN) have evolved over the past decade from open surgical necrosectomy to more minimally invasive approaches. We reported the use of a combined percutaneous and endoscopic approach (dual modality drainage [DMD]) for the treatment of symptomatic and infected WOPN, with good short-term outcomes in a small cohort of patients.To describe the long-term outcomes of 117 patients with symptomatic and infected WOPN treated by DMD.Review of a prospective, internal review board-approved database.Single, North American, tertiary-care center.All patients with symptomatic and infected WOPN treated by DMD at our institution between 2007 and 2012.DMD of symptomatic and infected WOPN.Disease-related mortality, pancreaticocutaneous fistula formation, need for early and late surgical intervention, procedure-related adverse events.A total of 117 patients underwent DMD for symptomatic and infected WOPN. A total of 103 have completed treatment, with all percutaneous drains removed. Ten patients are still undergoing treatment, and 4 patients died with percutaneous drains in place (3.4% disease-related mortality). For the patients completing therapy, the median duration of follow-up was 749.5 days. No patients required surgical necrosectomy or surgical treatment of DMD-related adverse events; 3 patients required late surgery for pain (n = 2) and gastric outlet obstruction (n = 1). There were no procedure-related deaths. In patients who have completed treatment, percutaneous drains have been removed in 100%; no patients have developed pancreaticocutaneous fistulas.Single-center design, lack of a comparison group.DMD for symptomatic and infected WOPN results in favorable clinical outcomes; complete avoidance of pancreaticocutaneous fistulae, surgical necrosectomy, and major procedure-related adverse events, while maintaining single-digit disease-related mortality.Copyright © 2014 American Society for Gastrointestinal Endoscopy. Published by Mosby, Inc. All rights reserved.

To compare outcomes of laparoscopic transgastric necrosectomy (LTN) and direct endoscopic necrosectomy (DEN) in the management of retrogastric walled-off necrosis.

To evaluate the impact of initial catheter size on the clinical outcomes in acute pancreatitis (AP).This retrospective study comprised consecutive patients with AP who underwent percutaneous catheter drainage (PCD) between January 2018 and May 2019. Three hundred fifteen consecutive patients underwent PCD during the study period. Based on the initial catheter size, patients were divided into group I (≤ 12 F) and group II (> 12 F). The differences in the clinical outcomes between the two groups, as well as multiple subgroups (based on the severity, timing of drainage, and presence of organ failure (OF)), were evaluated.One hundred forty-six patients (mean age, 41.2 years, 114 males) fulfilled the inclusion criteria. Ninety-nine (67.8%) patients had severe AP based on revised Atlanta classification. The mean pain to PCD was 22 days (range, 3-267 days). Mean length of hospitalization (LOH) was 27.9 ± 15.8 days. Necrosectomy was performed in 20.5% of patients, and mortality was 16.4%. Group I and II comprised 74 and 72 patients, respectively. There was no significant difference in baseline characteristics, except for a greater number of patients with OF in group II (p = 0.048). The intensive care unit stay was significantly shorter, and multiple readmissions were less frequent in group II (p = 0.037 and 0.013, respectively). Patients with severe AP and moderately severe AP in group II had significantly reduced rates of readmissions (p = 0.035) and significantly shorter LOH (p = 0.041), respectively.Large-sized catheters were associated with better clinical outcomes regardless of disease severity and other baseline disease characteristics.• Larger catheter size for initial PCD was associated with better clinical outcomes in AP. • The benefits were independent of the severity of AP, timing of PCD (ANC vs. WON) and presence of organ failure.

More than 200000 hospital admissions happen per year for acute pancreatitis and more than 50000 for chronic pancreatitis in the United States of America. Necrotizing pancreatitis accounts for 20%-30% of the cases. One-quarter of the patients with pancreatitis develop vascular complications, which carries a high mortality. This mini-review will address these complications that can help primary care physicians and hospitalists in managing their patients effectively.©The Author(s) 2022. Published by Baishideng Publishing Group Inc. All rights reserved.

Sinistral portal hypertension, a localized (left-sided) form of portal hypertension may complicate chronic pancreatitis as a result of splenic vein thrombosis/obstruction.To determine appropriate surgical strategy for patients with splenic vein thrombosis/obstruction secondary to chronic pancreatitis.We reviewed our experience with operative management of 484 consecutive patients with histologically documented chronic pancreatitis treated between 1976 and 1997. The diagnosis of sinistral portal hypertension was based on clinical presentation, preoperative endoscopic and radiographic imaging, and operative findings. "Symptomatic," herein defined, denotes those patients with sinistral hypertension and either gastrointestinal bleeding or hypersplenism. "Asymptomatic" patients were those with sinistral hypertension alone.Sinistral portal hypertension was present in 34 of the 484 patients (7%). Gastric or gastroesophageal varices were confirmed in 12 patients (35%), of whom 6 had variceal bleeding and 4 had hypersplenism (25%). All symptomatic patients were treated by splenectomy alone or in conjunction with distal pancreatectomy. Splenectomy at the time of pancreatectomy for primary pancreatic symptoms was also performed in 15 patients with (asymptomatic) sinistral portal hypertension. None of the 23 patients who had splenectomy rebled in mean follow-up of 4.8 years. In contrast, 1 of the 11 patients with asymptomatic sinistral portal hypertension who underwent pancreatic surgery without splenectomy died of later variceal bleeding 3 years after lateral pancreatojejunostomy.Symptomatic sinistral portal hypertension is best treated by splenectomy. Concomitant splenectomy should be strongly considered in patients undergoing operative treatment of symptomatic chronic pancreatitis if sinistral portal hypertension and gastroesophageal varices are also present.

For decades, infected or symptomatic pancreatic necrosis was managed by open surgical necrosectomy, an approach that has now been largely supplanted by an array of techniques referred to as the step-up approach.

The aim of this study was to explore the incidence, risk factors, clinical course and treatment of perforation and fistula of the gastrointestinal (GI) tract in a large unselected cohort of patients with necrotizing pancreatitis.

The identification of high-risk patients in the early stages of infected pancreatic necrosis (IPN) is critical, because it could help the clinicians to adopt more effective management strategies. We conducted a post hoc analysis of the MANCTRA-1 international study to assess the association between clinical risk factors and mortality among adult patients with IPN. Univariable and multivariable logistic regression models were used to identify prognostic factors of mortality. We identified 247 consecutive patients with IPN hospitalised between January 2019 and December 2020. History of uncontrolled arterial hypertension (p = 0.032; 95% CI 1.135-15.882; aOR 4.245), qSOFA (p = 0.005; 95% CI 1.359-5.879; aOR 2.828), renal failure (p = 0.022; 95% CI 1.138-5.442; aOR 2.489), and haemodynamic failure (p = 0.018; 95% CI 1.184-5.978; aOR 2.661), were identified as independent predictors of mortality in IPN patients. Cholangitis (p = 0.003; 95% CI 1.598-9.930; aOR 3.983), abdominal compartment syndrome (p = 0.032; 95% CI 1.090-6.967; aOR 2.735), and gastrointestinal/intra-abdominal bleeding (p = 0.009; 95% CI 1.286-5.712; aOR 2.710) were independently associated with the risk of mortality. Upfront open surgical necrosectomy was strongly associated with the risk of mortality (p < 0.001; 95% CI 1.912-7.442; aOR 3.772), whereas endoscopic drainage of pancreatic necrosis (p = 0.018; 95% CI 0.138-0.834; aOR 0.339) and enteral nutrition (p = 0.003; 95% CI 0.143-0.716; aOR 0.320) were found as protective factors. Organ failure, acute cholangitis, and upfront open surgical necrosectomy were the most significant predictors of mortality. Our study confirmed that, even in a subgroup of particularly ill patients such as those with IPN, upfront open surgery should be avoided as much as possible. Study protocol registered in ClinicalTrials.Gov (I.D. Number NCT04747990).© 2023. The Author(s).