Early prediction and prevention of infected pancreatic necrosis

Approximately 20%-30%of patients with acute necrotizing pancreatitis develop infected pancreatic necrosis(IPN),a highly morbid and potentially lethal complication.Early identification of patients at high risk of IPN may facilitate appropriate preventive measures to improve clinical outcomes.In the past two decades,several markers and predictive tools have been proposed and evaluated for this purpose.Conventional biomarkers like C-reactive protein,procalcitonin,lymphocyte count,interleukin-6,and interleukin-8,and newly developed biomarkers like angiopoietin-2 all showed significant association with IPN.On the other hand,scoring systems like the Acute Physiology and Chronic Health Evaluation II and Pancreatitis Activity Scoring System have also been tested,and the results showed that they may provide better accuracy.For early prevention of IPN,several new therapies were tested,including early enteral nutrition,anti-biotics,probiotics,immune enhancement,etc.,but the results varied.Taken together,several evidence-supported predictive markers and scoring systems are readily available for predicting IPN.However,effective treatments to reduce the incidence of IPN are still lacking apart from early enteral nutrition.In this editorial,we summarize evidence concerning early prediction and prevention of IPN,providing insights into future practice and study design.A more homo-geneous patient population with reliable risk-stratification tools may help find effective treatments to reduce the risk of IPN,thereby achieving individualized treatment.

Analysis of the delayed approach to the management of infected pancreatic necrosis

AIM: To analyze outcomes of delayed single-stage necrosectomy after early conservative management of patients with infected pancreatic necrosis (IPN) associated with severe acute pancreatitis (SAP). METHODS: Between January 1998 and December 2009, data from patients with SAP who developed IPN and were managed by pancreatic necrosectomy were analyzed. RESULTS: Fifty-nine of 61 pancreatic necrosectomies were performed by open surgery and 2 laparoscopically. In 55 patients, single-stage necrosectomy could be performed (90.2%). Patients underwent surgery at a median of 29 d (range 13-46 d) after diagnosis of acute pancreatitis. Sepsis and multiple organ failure accounted for the 9.8% mortality rate. Pancreatic fistulae (50.8%) predominantly accounted for the morbidity. The median hospital stay was 23 d, and the median interval for return to regular activities was 110 d.CONCLUSION: This series supports the concept of delayed single-stage open pancreatic necrosectomy for IPN. Advances in critical care, antibiotics and interventional radiology have played complementary role in improving the outcomes.

Infected pancreatic necrosis: Not necessarily a late event in acute pancreatitis

It is widely believed that infection of pancreatic necrosis is a late event in the natural course of acute pancreatitis. This paper discusses the available data on the timing of pancreatic infection. It appears that infected pancreatic necrosis occurs early in almost a quarter of patients. This has practical implications for the type, timing and duration of preventive strategies used in these patients. There are also implications for the classification of severity in patients with acute pancreatitis. Given that the main determinants of severity are both local and systemic complications and that they can occur both early and late in the course of acute pancreatitis, the classification of severity should be based on their presence or absence rather than on when they occur. To do otherwise, and in particular overlook early infected pancreatic necrosis, may lead to a misclassification error and fallacies of clinical studies in patients with acute pancreatitis.

One-step laparoscopic pancreatic necrosectomy verse surgical step-up approach for infected pancreatic necrosis:a case-control study

BACKGROUND:The surgical step-up approach often requires multiple debridements and might not be suitable for infected pancreatic necrosis(IPN)patients with various abscesses or no safe route for percutaneous catheter drainage(PCD).This case-control study aimed to investigate the safety and effectiveness of one-step laparoscopic pancreatic necrosectomy(LPN)in treating IPN.METHODS:This case-control study included IPN patients undergoing one-step LPN or surgical step-up in our center from January 2015 to December 2020.The short-term and long-term complications after surgery,length of hospital stay,and postoperative ICU stays in both groups were analyzed.Univariate and multivariate logistic regression analyses were performed to explore the risk factors of major complications or death.RESULTS:A total of 53 IPN patients underwent one-step LPN and 37 IPN patients underwent surgical step-up approach in this study.There was no significant difference in the incidence of death,major complications,new-onset diabetes,or new-onset pancreatic exocrine insufficiency between the two groups.However,the length of hospital stay in the one-step LPN group was significantly shorter than that in the surgical step-up group.Univariate regression analysis showed that the surgical approach(one-step/step-up)was not the risk factor for major complications or death.Multivariate logistic regression analysis indicated that computed tomography(CT)severity index,American Society of Anesthesiologists(ASA)class IV,and white blood cell(WBC)were the significant risk factors for major complications or death.CONCLUSION:One-step LPN is as safe and effective as the surgical step-up approach for treating IPN patients,and reduces total hospital stay.

The microbiology of infected pancreatic necrosis

Background: Acute pancreatitis(AP) continues to cause significant morbidity and mortality, especially when it leads to infected pancreatic necrosis(IPN). Modern treatment of IPN frequently involves prolonged courses of antibiotics in combination with minimally invasive therapies. This study aimed to update the existing evidence base by identifying the pathogens causing IPN and therefore aid future selection of empirical antibiotics. Methods: Clinical data, including microbiology results, of consecutive patients with IPN undergoing minimally invasive necrosectomy at our institution between January 2009 and July 2016 were retrospectively reviewed. Results: The results of 40 patients(22 males and 18 females, median age 60 years) with IPN were reviewed. The etiology of AP was gallstones, alcohol, dyslipidemia and unknown in 31, 2, 2 and 5 patients, respectively. The most frequently identified microbes in microbiology cultures were Enterococcus faecalis and faecium(22.5% and 20.0%) and Escherichia coli(20.0%). In 19 cases the cultures grew multiple organisms. The antibiotics with the least resistance amongst the microbiota were teicoplanin(5.0%), linezolid(5.6%), ertapenem(6.5%), and meropenem(7.4%). Conclusion: The carbapenem antibiotics, ertapenem and meropenem provide good antimicrobial cover against the common, mainly enteral, microorganisms causing IPN. Culture and sensitivity results of acquired samples should be regularly reviewed to adjust prescribing and monitor for emergence of resistance.

Risk factors of infected pancreatic necrosis secondary to severe acute pancreatitis

BACKGROUND： Severe acute pancreatitis（SAP） remains a clinical challenge with considerable morbidity and mortality.An early identification of infected pancreatic necrosis（IPN）, a life-threatening evolution secondary to SAP, is obliged for a more preferable prognosis. Thus, the present study was conducted to identify the risk factors of IPN secondary to SAP. METHODS： The clinical data of patients with SAP were retrospectively analyzed. Univariate and multivariate logistic regression analyses were sequentially performed to assess the associations between the variables and the development of IPN secondary to SAP. A receiver operating characteristic（ROC） curve was created for each of the qualified independent risk factors. RESULTS： Of the 115 eligible patients, 39（33.9%） progressed to IPN, and the overall in-hospital mortality was 11.3%（13/115）.The early enteral nutrition（EEN）（P=0.0092, OR=0.264）, maximum intra-abdominal pressure（IAP）（P=0.0398, OR=1.131）and maximum D-dimer level（P=0.0001, OR=1.006） in the first three consecutive days were independent risk factors associated with IPN secondary to SAP. The area under ROC curve（AUC） was 0.774 for the maximum D-dimer level in the first three consecutive days and the sensitivity was 90% and the specificity was 58% at a cut-off value of 933.5 μg/L; the AUC was 0.831 for the maximum IAP in the first three consecutive days and the sensitivity was 95% and specificity was 58%at a cut-off value of 13.5 mm Hg. CONCLUSIONS： The present study suggested that the maximum D-dimer level and/or maximum IAP in the first three consecutive days after admission were risk factors of IPN secondary to SAP; an EEN might be helpful to prevent the progression of IPN secondary to SAP.

Modified single transluminal gateway transcystic multiple drainage technique for a huge infected walled-off pancreatic necrosis: A case report

We report a successful endoscopic ultrasonographyguided drainage of a huge infected multilocular walledoff necrosis(WON) that was treated by a modified single transluminal gateway transcystic multiple drainage(SGTMD) technique. After placing a widecaliber fully covered metal stent, follow-up computed tomography revealed an undrained subcavity of WON. A large fistula that was created by the wide-caliber metal stent enabled the insertion of a forward-viewing upper endoscope directly into the main cavity, and the narrow connection route within the main cavity to the subcavity was identified with a direct view, leading to the successful drainage of the subcavity. This modified SGTMD technique appears to be useful for seeking connection routes between subcavities of WON in some cases.

The Open Packing of the Lesser Sac Technique in Infected Severe Acute Pancreatitis

Aim: The goal of this study is to evaluate the open packing of the lesser sac (OPLS) in treatment of infected severe acute pancreatitis Methodology: The study was based on 98 cases in which this technique was applied during the period between 19942007, in two departments of surgery (Clinical Hospital CF 2 and Clinical Hospital ?Sf. Maria” Bucharest). The technique was applied based on the therapeutically protocol previously established beginning with 2000. The OPLS technique was analyzed relatively to: timing of surgery, the localization of the infected necrosis or abscesses, growing germs on the cultures, antibiotics received, executed primarily or at reintervention, the number of debridement, hospitalization, morbidity and mortality. The information was statistically processed using SPSS test version 17 for Windows. Results: The OPLS technique improved the control of the local sepsis, in the retrospective/prospective study in 83.7%. Mortality was 16.3% (16/98), with a global mortality of 26.3% (75/285) and a postoperative mortality of 29.5% (66/224). Conclusions: Considering the fact that the intensive care techniques are approximately the same in the last 15 years, we thought that this improvement in the survival rate may be due to the application of OPLS in cases with indication and optimal timing for surgery.

Severe acute pancreatitis: Clinical course and management

Severe acute pancreatitis (SAP) develops in about 25% of patients with acute pancreatitis (AP). Severity of AP is linked to the presence of systemic organ dysfunctions and/or necrotizing pancreatitis pathomorphologically. Risk factors determining independently the outcome of SAP are early multi-organ failure, infection of necrosis and extended necrosis (> 50%). Up to one third of patients with necrotizing pancreatitis develop in the late course infection of necroses. Morbidity of SAP is biphasic, in the first week strongly related to early and persistence of organ or multi-organ dysfunction. Clinical sepsis caused by infected necrosis leading to multi-organ failure syndrome (MOFS) occurs in the later course after the first week. To predict sepsis, MOFS or deaths in the first 48-72 h, the highest predictive accuracy has been objectified for procalcitonin and IL-8; the Sepsis- Related Organ Failure Assessment (SOFA)-score predicts the outcome in the first 48 h, and provides a daily assessment of treatment response with a high positive predictive value. Contrast-enhanced CT provides the highest diagnostic accuracy for necrotizing pancreatitis when performed after the first week of disease. Patients who suffer early organ dysfunctions or at risk of developing a severe disease require early intensive care treatment. Early vigorous intravenous fluid replacement is of foremost importance. The goal is to decrease the hematocrit or restore normal cardiocirculatory functions. Antibiotic prophylaxis has not been shown as an effective preventive treatment. Early enteral feeding is based on a high level of evidence, resulting in a reduction of local and systemic infection. Patients suffering infected necrosis causing clinical sepsis, pancreatic abscess or surgical acute abdomen are candidates for early intervention. Hospital mortality of SAP after interventional or surgical debridement has decreased in high volume centers to below 20%.

Severe acute pancreatitis: Pathogenetic aspects and prognostic factors

Approximately 20% of patients with acute pancreatitis develop a severe disease associated with complications and high risk of mortality. The purpose of this study is to review pathogenesis and prognostic factors of severe acute pancreatitis （SAP）. An extensive medline search was undertaken with focusing on pathogenesis, complications and prognostic evaluation of SAP. Cytokines and other inflammatory markers play a major role in the pathogenesis and course of SAP and can be used as prognostic markers in its early phase. Other markers such as simple prognostic scores have been found to be as e^ective as multifactorial scoring systems （MFSS） at 48 h with the advantage of simplicity, efficacy, low cost, accuracy and early prediction of SAP. Recently, several laboratory markers including hematocrit, blood urea nitrogen （BUN）, creatinine, matrix metalloproteinase-9 （MMP-9） and serum amyloid A （SAA） have been used as early predictors of severity within the first 24 h. The last few years have witnessed a tremendous progress in understanding the pathogenesis and predicting the outcome of SAP. In this review we classified the prognostic markers into predictors of severity, pancreatic necrosis （PN）, infected PN （IPN） and mortality.

Advances in prognostic factors in acute pancreatitis:a mini-review

BACKGROUND:Early assessment of the severity of acute pancreatitis is essential to the proper management of the disease.It is dependent on the criteria of the Atlanta classification system.DATA SOURCES:PubMed search of recent relevant articles was performed to identify information about the severity and prognosis of acute pancreatitis.RESULTS:The scoring systems included the Ranson’s or Glasgow’s criteria ≥3,the APACHE II classification system ≥8,and the Balthazar’s criteria ≥4 according to the computed tomography enhanced scanning findings.The single factors on admission included age >65 years,obesity,hemoconcentration(>44%),abnormal chest X-ray,creatinine >2 mg/dl,C-reactive protein>150 mg/dl,procalcitonin >1.8 ng/ml,albumin <2.5 mg/dl,calcium <8.5 mg/dl,early hyperglycemia,increased intra-abdominal pressure,macrophage migration inhibitory factor,or a combination of IL-10 >50 pg/ml with calcium <6.6 mg/dl.CONCLUSION:The prediction of the severity of acute pancreatitis is largely based on well defined multiple factor scoring systems as well as several single risk factors.

Surgical management of necrotizing pancreatitis:An overview

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

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

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

Percutaneous direct endoscopic pancreatic necrosectomy

Approximately 10%-20% of the cases of acute pancreatitis have acute necrotizing pancreatitis. The infection of pancreatic necrosis is typically associated with a prolonged course and poor prognosis. The multidisciplinary, minimally invasive “step-up” approach is the cornerstone of the management of infected pancreatic necrosis(IPN). Endosonography-guided transmural drainage and debridement is the preferred and minimally invasive technique for those with IPN. However, it is technically not feasible in patients with early pancreatic/peripancreatic fluid collections(PFC)(< 2-4 wk) where the wall has not formed;in PFC in paracolic gutters/pelvis;or in walled off pancreatic necrosis(WOPN) distant from the stomach/duodenum. Percutaneous drainage of these infected PFC or WOPN provides rapid infection control and patient stabilization. In a subset of patients where sepsis persists and necrosectomy is needed, the sinus drain tract between WOPN and skin-established after percutaneous drainage or surgical necrosectomy drain, can be used for percutaneous direct endoscopic necrosectomy(PDEN). There have been technical advances in PDEN over the last two decades.An esophageal fully covered self-expandable metal stent, like the lumen-apposing metal stent used in transmural direct endoscopic necrosectomy, keeps the drainage tract patent and allows easy and multiple passes of the flexible endoscope while performing PDEN. There are several advantages to the PDEN procedure. In expert hands, PDEN appears to be an effective, safe, and minimally invasive adjunct to the management of IPN and may particularly be considered when a conventional drain is in situ by virtue of previous percutaneous or surgical intervention. In this current review, we summarize the indications, techniques, advantages, and disadvantages of PDEN. In addition, we describe two cases of PDEN in distinct clinical situations, followed by a review of the most recent literature.

Antibiotic prophylaxis in patients with severe acute pancreatitis

BACKGROUND: The prophylactic use of antibiotics in pa- tients with severe acute pancreatitis remains contentious. This study was undertaken to review the current studies on antibiotic prophylaxis in patients with severe acute pancrea- titis. DATA RESOURCES: All papers found by a Medline search were relevant to human trials of antibiotic prophylaxis in patients with severe acute pancreatitis. RESULTS: In the 1970s, three small randomized studies of prophylactic ampicillin in the treatment of acute pancreati- tis showed no effect on mortality or morbidity, but the in- clusion of patients at low risk for infection and the use of an ineffective antibiotic were insufficient to detect any diffe- rences. From 1993 to 2001, eight prospective clinical trials of antibiotic prophylaxis were conducted in patients with severe acute pancreatitis ( SAP ). Seven of the 8 trials showed significant effect of the prophylaxis in prevention of pancreatic infections, and one showed significant improve- ment of clinical course documented by the Acute Physiolo- gy and Chronic Health Evaluation (APACHE ) scores. Only two trials did demonstrate the significance of the prophylaxis in lowering the mortality rate. Despite varia- tions in drug agents, study size and patient selection, dura- tion of treatment, and methodology ( None of the studies was double-blinded), a meta-analysis showed the positive effect of antibiotics in reducing the mortality. We suggested that antibiotic prophylaxis with proven efficacy in necrotic pancreatic tissues should be given to all patients with acute necrotizing pancreatitis. In recent years, however, the first double-blind, placebo-controlled multicenter study from Germany detected no benefit of antibiotic prophylaxis with respect to the risk of developing infected pancreatic necrosis. CONCLUSION: Prophylactic antibiotics for severe acute pancreatitis is still a matter of discussion and further studies are required to provide adequate data to answer many ques-tions and to define the role of antibiotic prophylaxis in pa- tients with severe acute pancreatitis.

Endoscopic fibrin glue injection for closure of pancreatocutaneous fistula following transgastric endoscopic necrosectomy

Transgastric endoscopic necrosectomy has been recently introduced as the effective and alternative management of infected pancreatic necrosis and pancreatic abscess. However,up to 40% of patients who undergo endoscopic necrosectomy may need an additional percutaneous approach for subsequent peripancreatic fluid collection or non-resolution of pancreatic necrosis. This percutaneous approach may lead to persistent pancreatocutaneous fistula,which remains a serious problem and usually requires prolonged hospitalization,or even open-abdominal surgery. We describe the first case of pancreatocutaneous fistula and concomitant abdominal wall defect following transgastric endoscopic necrosectomy and percutaneous drainage,which were endoscopically closed with fibrin glue injection via the necrotic cavity.

Correlative factor of death in patients with infected pancreatic necrosis after surgical intervention

Background:Acute pancreatitis(AP)was a potentially fatal disease with a variation in severity.Infected pancreatic necrosis was a common complication in AP which needed surgical intervention.The present study was to study the correlative factors of death in patients with infected pancreatic necrosis after surgical intervention.Methods:From January 2016 to October 2019,a total of 186 patients with infected pancreatic necrosis after surgical intervention in the First Medical Center,Chinese PLA General Hospital were retrospectively enrolled in this study.Of the 186 patients,22 who died in the hospital were defined as a mortality group and the others as a survival group.The clinical characteristic of the 2 groups was compared and the relative risk of mortality in patients with infected pancreatic necrosis after the surgical intervention was studied.Results:Acute fluid collection,acute kidney injury,acute lung injury,acute liver injury,multiple organ dysfunction syndromes,abdominal bleeding,abdominal Acinetobacter baumannii infection,pulmonary infection,pulmonary A baumannii infection,positive blood culture,A baumannii of blood culture,severe acute pancreatitis according to Atlanta 2012,the use of continuous renal replacement therapy,mechanical ventilation and minimally invasive retroperitoneal pancreatic necrosectomy was associated with death in hospital.Older age,longer acute kidney injury lasting time,longer acute lung injury lasting time,longer acute liver injury lasting time,and longer multiple organ dysfunction syndromes lasting time in predicting mortality in patients with infected pancreatic necrosis after surgical intervention were(0.635[95%confidence interval(CI):0.512-0.758],P=.040),(0.877[95%CI:0.788-0.965],P=.000),(0.932[95%CI:0.897-0.968],P=.000),(0.822[95%CI:0.708-0.935],P=.000),and(0.943[95%CI:0.887-0.998],P=.000).Due to the small number of death cases,the results of the multivariate analyses were not available.Conclusion:In this single-center retrospective study of 186 cases of infected pancreas necrosis,the correlative factors of death are identified.The results warranted further strategies are needed especially focusing on elder patients to prevent blood infection and to protect the functions of vital organs.

Timing, treatment strategies and approach for infected pancreatic necrosis:a narrative review

Infected pancreatic necrosis(IPN)is a serious complication resulting in organ failure and death in patients with acute pancreatitis,and surgery is an important way to treat this disease.An increasing number of high-quality studies have provided evidence for mini-invasive necrosectomy and have also changed the traditional treatment model.The advancements of surgical technology provide more choices for IPN treatment.Timing,strategies,and treatment approach are still the most critical issues,even in today’s era of minimally invasive surgery.Should“delayed surgery”or“postponed drainage”still be adhered to?The“step-up”approach has been proven to hold an advantage in the treatment of IPN in terms of reducing postoperative complications.However,there is growing evidence that"step-up"is not the only option for all patients.The one-step approach is also effective for selected patients.Currently,endoscopic surgery is increasingly widely used in the treatment of IPN.On the other hand,open debridement is still an position for patients who do not respond to minimally invasive surgery.How to personalize treatment strategies is still not fully clear.Multidisciplinary consulting treatment is bound to be the main direction of development for future studies.

Acute necrotizing pancreatitis:challenges and interventions—a narrative review

Acute pancreatitis(AP)is a complicated disease with rising incidence over the years.Twenty percent of AP will develop into acute necrotizing pancreatitis(ANP).Interventions for ANP have evolved from traditional open surgery to minimally invasive step-up approaches.Infected pancreatic necrosis(IPN)is the most serious event of ANP and associated with extremely poor prognosis.The contrast-enhanced computed tomography(CECT)-based classification of IPN describes various types of IPN and will help to carry out surgical interventions for each subtype.Nevertheless,many challenges are still remaining during the treatment of ANP.Including the balance between endoscopic and surgical approaches,and the selection of optimal timing of surgical intervention for infected necrosis.In nowadays treatment scenario of ANP,the necessity for open surgery remains to be debated.Despite of the development of advanced interventional techniques,postoperative residual infection(PRI)remains thorny,and effective prevention and treatment of PRI is of significance.