Factors affecting the time interval of endoscopic ultrasound-guided endoscopic necrosectomy of walled-off pancreatic necrosis: A retrospective single-center study in China.

BACKGROUND AND AIM: Endoscopic ultrasound (EUS)-guided endoscopic necrosectomy is an effective and minimally invasive treatment for walled-off pancreatic necrosis (WON). This study investigated the factors affecting the time interval of EUS-guided WON necrosectomy. METHODS: Patients who received EUS-guided necrosectomy in the Endoscopy Center of the First Affiliated Hospital of Chongqing Medical University in the past 5 years were retrospectively analyzed. Data including general information, etiology, blood biochemical indexes, physical signs, CT severity grade, location, size, solid necrotic ratio, type and number of stents, and immediate necrosectomy were collected to explore the relationships between these factors and the interval of endoscopic necrosectomy. RESULTS: A total of 51 WON patients were included. No significant correlation has been noted between the endoscopic debridement interval and the following indexes, including the patients' general information, the etiology of pancreatitis, blood biochemical indexes (leukocyte count, neutrophil percentage, C-reactive protein), preoperative fever, and WON's location and size, type and number of stents, and whether immediate necrosectomy. However, there were significant differences between the debridement interval and the modified CT Severity Index (MCTSI) (p < 0.001), the solid necrotic ratio of WON (p < 0.001) before the intervention, postoperative fever (p = 0.038), C-reactive protein increasing (p = 0.012) and fever before reintervention (p = 0.024). CONCLUSIONS: The EUS-measured solid necrotic ratio, the MCTSI, postoperative fever, C-reactive protein increase, and fever before reintervention in patients affect the time interval of EUS-guided endoscopic necrosectomy in WON patients. These five indicators may be promisingly effective in predicting and managing endoscopic necrosectomy intervals.

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

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

Efficacy and Safety of Anhydrous Ethanol-Assisted Endoscopic Ultrasound-Guided Transluminal Necrosectomy in Infected Necrotizing Pancreatitis.

AIM: Endoscopic necrosectomy has become the first-line treatment option for infectious necrotizing pancreatitis (INP), especially walled-off necrosis. However, the problems, including operation-related adverse events (AEs) and the need for multiple endoscopic procedures, have not been effectively addressed. We sought to evaluate the clinical safety and efficacy of anhydrous ethanol-assisted endoscopic ultrasound (EUS)-guided transluminal necrosectomy in INP. METHODS: A single-center observational cohort study of INP patients was conducted in a tertiary endoscopic center. Anhydrous ethanol-assisted EUS-guided transluminal necrosectomy (modified group) and conventional endoscopic necrosectomy (conventional group) were retrospectively compared in INP patients. The technical and clinical success rates, operation time, perioperative AEs, postoperative hospital stay, and recurrent INP rates were analyzed, respectively. RESULTS: A total of 55 patients were enrolled. No statistically significant differences were observed between the two groups regarding baseline characteristics. Compared to patients in the conventional group, patients in the modified group demonstrated significantly reduced times of endoscopic transluminal necrosectomies (1.96 ± 0.89 vs. 2.73 ± 0.98; P = 0.004) and comparable perioperative AEs (P = 0.35). Meanwhile, no statistically significant differences were observed in the technical and clinical success rates (P = 0.92), operation time (P = 0.59), postoperative hospital stay (P = 0.36), and recurrent INP rates (P = 1.00) between the two groups. CONCLUSION: Anhydrous ethanol-assisted EUS-guided transluminal necrosectomy seemed safe and effective in treating INP. Compared with conventional endoscopic transluminal necrosectomy, its advantage was mainly in reducing the number of endoscopic necrosectomies without increasing perioperative AEs.

Early Endoscopic Interventions for Pancreatic Necrosis: Indications, Technique, and Outcomes.

Endoscopic transmural drainage is usually performed for symptomatic well-encapsulated walled-off necrosis (WON) that usually develops in the delayed phase (> 4 weeks after disease onset) of acute necrotising pancreatitis (ANP). Endoscopic drainage is usually not advocated in the early (< 4 weeks after disease onset) stage of illness because of the risk of complications due to an incompletely formed encapsulating wall and poor demarcation of viable from necrotic tissue. However, emerging data from expert tertiary care centres over the last few years shows that the early endoscopic transluminal drainage approach is effective and safe. The development of lumen-apposing metal stents and better accessories for endoscopic necrosectomy has fuelled the expansion of indications of endoscopic drainage of pancreatic necrosis. However, early endoscopic drainage is associated with higher rates of adverse events; therefore, careful patient selection is paramount. This article will review the current indications, techniques and outcomes of early endoscopic transluminal drainage in pancreatic necrotic collections.

Endoscopic and surgical treatment of necrotizing pancreatitis-a comparison of short- and long-term outcome.

BACKGROUND: Acute necrotizing pancreatitis is still related to high morbidity and mortality rates. Minimal-invasive treatment options, such as endoscopic necrosectomy, may decrease peri-interventional morbidity and mortality. This study aims to compare the initial operative with endoscopic treatment on long-term parameters, such as endocrine and exocrine functionality, as well as mortality and recurrence rates. METHODS: We included 114 patients, of whom 69 were treated with initial endoscopy and 45 by initial surgery. Both groups were further assessed for peri-interventional and long-term parameters. RESULTS: In the post-interventional phase, patients in the group of initial surgical treatment (IST) showed significantly higher rates of renal insufficiency (p < 0.001) and dependency on invasive ventilation (p < 0.001). The in-house mortality was higher in the surgical group, with 22% vs. 10.1% in the group of patients following initial endoscopic treatment (IET; p = 0.077). In long-term follow-up, the overall mortality was 45% for IST and 31.3% for IET (p = 0.156). The overall in-hospital stay and intensive care unit (ICU) stay were significantly shorter after IET (p < 0.001). In long-term follow-up, the prevalence of endocrine insufficiency was 50% after IST and 61.7% after IET (p = 0.281). 57.1% of the patients following IST and 16.4% of the patients following IET had persistent exocrine insufficiency at that point (p = < 0.001). 8.9% of the IET and 27.6% of the IST patients showed recurrence of acute pancreatitis (p = 0.023) in the long-term phase. CONCLUSION: In our cohort, an endoscopic step-up approach led to a reduced in-hospital stay and peri-interventional morbidity. The endocrine function appeared comparable in both groups, whereas the exocrine insufficiency seemed to recover in the endoscopic group in the long-term phase. These findings advocate for a preference for endoscopic treatment of acute necrotizing pancreatitis whenever feasible.

Controversies in endoscopic ultrasonography-guided management of walled-off necrosis.

Walled-off necrosis (WON) develops as local complications after acute necrotizing pancreatitis. Although less invasive interventions such as endoscopic ultrasonography (EUS)-guided drainage and endoscopic necrosectomy are selected over surgical interventions, delayed and step-up interventions are still preferred to avoid procedure-related adverse events. However, there is a controversy about the appropriate timing of drainage and subsequent necrosectomy. The advent of large-caliber lumen-apposing metal stents has also brought about potential advantages of proactive interventions, which still needs investigation in future trials. When step-up interventions of necrosectomy and additional drainage are necessary, a structured or protocoled approach for WON has been reported to improve safety and effectiveness of endoscopic and/or percutaneous treatment, but has not been standardized yet. Finally, long-term outcomes such as recurrence of WON, pancreatic endocrine, and exocrine function are increasingly investigated in association with disconnected pancreatic duct syndrome. In this review we discuss current evidence and controversy on EUS-guided management of WON.

Endoscopic Ultrasound-Guided Drainage of Pancreatic Fluid Collections: Not All Queries Are Already Solved.

Pancreatic fluid collections (PFCs) are well-known complications of acute pancreatitis. The overinfection of these collections leads to a worsening of the prognosis with an increase in the morbidity and mortality rate. The primary strategy for managing infected pancreatic necrosis (IPN) or symptomatic PFCs is a minimally invasive step-up approach, with endosonography-guided (EUS-guided) transmural drainage and debridement as the preferred and less invasive method. Different stents are available to drain PFCs: self-expandable metal stents (SEMSs), double pigtail stents (DPPSs), or lumen-apposing metal stents (LAMSs). In particular, LAMSs are useful when direct endoscopic necrosectomy is needed, as they allow easy access to the necrotic cavity; however, the rate of adverse events is not negligible, and to date, the superiority over DPPSs is still debated. Moreover, the timing for necrosectomy, the drainage technique, and the concurrent medical management are still debated. In this review, we focus attention on indications, timing, techniques, complications, and particularly on aspects that remain under debate concerning the EUS-guided drainage of PFCs.

A Protocolized Management of Walled-Off Necrosis (WON) Reduces Time to WON Resolution and Improves Outcomes.

BACKGROUND AND AIMS: Patients with infected or symptomatic walled-off necrosis (WON) have high morbidity and health care utilization. Despite the recent adoption of nonsurgical treatment approaches, WON management remains nonalgorithmic. We investigated the impact of a protocolized early necrosectomy approach compared with a nonprotocolized, clinician-driven approach on important clinical outcomes. METHODS: Records were reviewed for consecutive patients with WON who underwent a protocolized endoscopic drainage with a lumen-apposing metal stent (cases), and for patients with WON treated with a lumen-apposing metal stent at the same tertiary referral center who were not managed according to the protocol (control subjects). The protocol required repeat cross-sectional imaging within 14 days after lumen-apposing metal stent placement, with regularly scheduled endoscopic necrosectomy if WON diameter reduction was <50%. Control patients were treated according to their clinician's preference without an a priori strategy. Inverse probability of treatment weighting-adjusted analysis was used to evaluate the influence of being in the protocolized group on time to resolution. RESULTS: A total of 24 cases and 47 control subjects were included. There were no significant differences in baseline characteristics. Although numbers of endoscopies and necrosectomies were similar, cases had lower adverse event rates, shorter intensive care unit stay, and required nutritional support for fewer days. On matched multivariate Cox regression, cases had earlier WON resolution (hazard ratio, 5.73; 95% confidence interval, 2.62-12.5). This was confirmed in the inverse probability of treatment weighting-adjusted analysis (hazard ratio, 3.4; 95% confidence interval, 1.92-6.01). CONCLUSIONS: A protocolized strategy resulted in faster WON resolution compared with a discretionary approach without the need for additional therapeutic interventions, and with a better safety profile and decreased health care utilization.

Endoscopic treatment of pancreatic necrosis: Still searching for perfection!

Over last few years, there has been a paradigm shift in the management of infected pancreatic necrosis with endoscopic and minimally invasive "step-up" management approach replacing open surgical necrosectomy. Because of being associated with reduced occurrence of new onset multi-organ failure, external pancreatic fistulae, shorter hospital stay, lower costs, and better quality of life compared with minimally invasive surgical approach, endoscopic "step-up" management approach is the preferred intervention for endoscopically accessible pancreatic necrotic collections at expert centers with endoscopic expertise. Development of lumen apposing metal stents and improvised accessories for interventional endoscopic ultrasound has revolutionized the endoscopic management of pancreatic necrosis making it more effective and safer. Despite these promising developments, endoscopic transluminal necrosectomy (ETN) remains the Achilles heel. Lack of dedicated endoscopic accessories, poor endoscopic visualization within the necrotic cavity, limited diameter of the instrument channel of the endoscope that is a significant impediment to remove large amount of necrotic material, and uncertain ability to avoid vessels and vital structures in the necrotic cavity are important limitations during endoscopic necrosectomy. Recent devices and solutions including use of cap assisted necrosectomy, over the scope grasper and powered endoscopic debridement device are welcome steps in our pursuit for an ideal, safer, and efficacious ETN device. This review will discuss recent advances as well as challenges in the endoscopic management of pancreatic necrosis.

Time to think prime times for treatment of necrotizing pancreatitis: Pendulum conundrum.

Pancreatic fluid collections (PFCs) typically develop as local complications of acute pancreatitis and complicate the clinical course of patients with acute pancreatitis and potentially fatal clinical outcomes. Interventions are required in cases of symptomatic walled-off necrosis (WON) (matured PFCs with necrosis) and pancreatic pseudocysts (matured PFCs without necrosis). In the management of necrotizing pancreatitis and WON, endoscopic ultrasound-guided transluminal drainage combined with on-demand endoscopic necrosectomy (i.e. the step-up approach) is increasingly used as a less invasive treatment modality compared with a surgical or percutaneous approach. Through the substantial research efforts and development of specific devices and stents (e.g. lumen-apposing metal stents), endoscopic techniques of PFC management have been standardized to some extent. However, there has been no consensus about timing of carrying out each treatment step; for instance, it is uncertain when direct endoscopic necrosectomy should be initiated and finished and when a plastic or metal stent should be removed following clinical treatment success. Despite emerging evidence for the effectiveness of noninterventional supportive treatment (e.g. antibiotics, nutritional support, irrigation of the cavity), there has been only limited data on the timing of starting and stopping the treatment. Large studies are required to optimize the timing of those treatment options and improve clinical outcomes of patients with PFCs. In this review, we summarize the current available evidence on the indications and timing of interventional and supportive treatment modalities for this patient population and discussed clinical unmet needs that should be addressed in future research.

The Usefulness and Reliability of Coagrasper for Artery Bleeding during Endoscopic Necrosectomy.

Although endoscopic necrosectomy (EN) is a less invasive therapy for walled-off necrosis (WON), arterial bleeding can occur during EN. A 60-year-old man with infected WON underwent the EN procedure. During EN, the artery in the WON cavity was injured. As the artery was directly visible, we grasped it using a Coagrasper and coagulated the bleeding point. However, the bleeding was aggravated after coagulation owing to an extension of the vessel damage. The entire vessel was grasped, and complete hemostasis was achieved. The Coagrasper is useful for managing arterial bleeding; however, it should be employed only on the basis of its characteristics and in suitable scenarios.

Clinical Outcomes of the Endoscopic Step-Up Approach with or without Radiology-Guided Percutaneous Drainage for Symptomatic Walled-Off Pancreatic Necrosis.

Background and objectives: Symptomatic walled-off pancreatic necrosis is a serious local complication of acute necrotising pancreatitis. The endoscopic step-up approach is the standard treatment for symptomatic walled-off pancreatic necrosis; however, adjunctive radiologic percutaneous drainage for this condition is controversial. This study compared the clinical and radiologic resolution of walled-off pancreatic necrosis achieved with the endoscopic step-up approach with or without radiology-guided percutaneous drainage. Material and Methods: This retrospective, single-centre cohort study enrolled patients with symptomatic walled-off pancreatic necrosis who underwent endoscopic transmural drainage (ETD) followed by directed endoscopic necrosectomy (DEN) with or without radiology-guided drainage. A total of 34 patients (endoscopic approach, n = 22; combined modality approach, n = 12) underwent the endoscopic step-up approach (ETD followed by DEN). Baseline characteristics, clinical success, and resolution of necrosis were compared between groups. Results: All patients achieved symptom resolution from walled-off pancreatic necrosis. The mean patient age was 58.4 years, and 21 (61.8%) were men. Following treatment with the endoscopic approach and combined modality approach, clinical success was achieved in 90.9% of patients within 11.5 days, and 66.7% of patients within 16.5 days, respectively. Both length of hospital stay (55 days vs. 71 days; p = 0.071) and time to complete radiologic resolution were shorter (93 days vs. 124 days; p = 0.23) in the endoscopic approach group. Conclusion: Both the endoscopic step-up approach and the CMD approach resulted in a favourably high clinical resolution rates in patients with symptomatic WON. However, clinical success rates seemed to be higher, and the length of hospital stay tended to be shorter in the endoscopic approach than in the CMD approach, as well as the significantly shorter necrosectomy time in each procedure was observed. Of note, these findings might be from some inherited differences in baseline characteristics of the patients between the two groups, and a randomized controlled trial with a larger sample size to verify these results is warranted.

Cost-effectiveness analysis of infected necrotizing pancreatitis management in an academic setting.

BACKGROUND AND AIMS: Traditional management for infected necrotizing pancreatitis (INP) often utilizes open necrosectomy, which carries high morbidity and complication rates. Thus, minimally invasive strategies have gained favor, specifically step-up approaches utilizing endoscopic or minimally-invasive surgery (MIS); however, the ideal management modality for INP has not been identified. METHODS: A decision tree model was designed to analyze costs and survival associated with open necrosectomy, endoscopic step-up, and MIS step-up protocols for management of INP after 4 weeks of necrosis development with adequate retroperitoneal access. Costs were based on a third-party payer perspective using Medicare reimbursement rates. The model's effectiveness was represented by quality-adjusted life-years (QALYs). Sensitivity analyses were performed to validate results. RESULTS: Endoscopic step-up was the dominant economic strategy with 7.92 QALYs for $90,864.09. Surgical step-up resulted in a decrease of 0.09 QALYs and a cost increase of $10,067.89 while open necrosectomy resulted in a decrease of 0.4 QALYs and an increased cost of $18,407.52 over endoscopic step-up. In 100,000 random-sampling simulations, 65.5% of simulations favored endoscopic step-up. MIS step-up was favored when MIS acute mortality rates fell and when MIS drainage success rates rose. CONCLUSIONS: In our simulated patients with INP, the most cost-effective management strategy is endoscopic step-up. Cost-effectiveness varies with changes in acute mortality and drainage success, which will depend on local expertise.

Predicting need for intervention in acute necrotizing pancreatitis following discharge- A single center experience in 525 patients.

BACKGROUND AND AIMS: The clinical course of necrotizing pancreatitis (NP) is variable and unpredictable, with some patients managed conservatively, but a significant proportion become symptomatic and needing intervention for drainage and/or necrosectomy. The aim of this study was to identify patients based on baseline clinical and imaging metrics who will likely need intervention and therefore closer follow-up. METHODS: All NP patients managed in our institution between 2010 and 2019 were identified from a prospective database and those who did not undergo intervention during initial hospitalization were followed longitudinally post discharge until clinical and imaging resolution of necrosis. Patients were categorized into a conservative arm or intervention arm (endoscopic/percutaneous/surgical drainage and/or necrosectomy) for criteria defined according to IAP/APA guidelines. Clinical and imaging characteristics during initial presentation were analyzed between the two groups to identify independent predictors for eventual intervention using multivariable logistic regression. A nomogram was designed based on factors that were significant as defined by P value < 0.05. RESULTS: Among 525 patients, 340 who did not meet criteria for intervention during initial admission were included for study and followed for an average 7.4 ± 11.3 months. 140 were managed conservatively and 200 needed intervention (168 within 6 months and 32 after 6 months). Independent predictors of need for eventual intervention were white race [OR 3.43 (1.11-10.62)], transferred status [OR 3.37 (1.81-6.27)], and need for TPN [OR 6.86 (1.63-28.9)], necrotic collection greater than 6 cm [OR 8.66 (4.10-18.32)] and necrotic collection with greater than 75% encapsulation [OR 41.3 (8.29-205.5)]. A prediction model incorporating these factors demonstrated an area under the curve of 0.88. CONCLUSIONS: Majority of NP patients do not need intervention during initial admission but may require drainage/necrosectomy mostly in the first 6 months following discharge. Need for subsequent intervention can be accurately predicted by a combination of clinical and imaging features on index admission.

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

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

Predictors of the need for necrosectomy in patients with walled-off pancreatic necrosis treated with lumen apposition metal stents.

BACKGROUND AND AIMS: Endoscopic necrosectomy through lumen apposition metal stents (LAMS) is increasingly being used for complicated walled-off pancreatic necrosis (WOPN), but the need for necrosectomy after stent placement is not well understood. The aim of this study was to evaluate clinical, endoscopic, and radiologic predictors of the need for necrosectomy in patients treated with LAMS. METHODS: We retrospectively reviewed patients with WOPN treated with LAMS from 2014 to 2017. Necrosectomy was performed only in patients who had recurrent fever or hemodynamic instability during follow-up. Univariate and multivariate analyses were performed. RESULTS: We included 15 patients, 67% men and median age was 75 (54-76) years. Two (13%) presented adverse events, one immediate and one delayed. In the first case, the stent migrated to the gastric cavity during deployment but was relocated in the same procedure. In the second case, the patient presented bleeding on day 36 due to a pseudoaneurysm that was successfully treated with embolization. Clinical success was 100%, but five patients (33%) required endoscopic necrosectomy (4 mechanical and 1 irrigation) and one (7%) required surgical necrosectomy of distant collections. The percentage of necrosis in the collection detected in a previous CT scan (45 [35-66]% vs 10 [5-17]%) was the only factor to predict the need for necrosectomy in the multivariate analysis (OR 1.18 [1.01-1.39]). CONCLUSION: LAMS is efficient to treat WOPN but more than a third will need necrosectomy. The percentage of necrosis in the collection detected in the CT scan seems to predict the need for necrosectomy.

American Gastroenterological Association Clinical Practice Update: Management of Pancreatic Necrosis.

DESCRIPTION: 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. METHODS: 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.

Hydrogen peroxide assisted endoscopic necrosectomy for walled-off pancreatic necrosis: A systematic review and meta-analysis.

BACKGROUND AND AIMS: Endoscopic necrosectomy (EN) is the preferred approach for management of symptomatic or infected walled-off pancreatic necrosis (WOPN). Hydrogen peroxide (H2O2) has been reported to be a good adjunctive therapy for EN. We performed a systematic review and meta-analysis to evaluate effectiveness and safety of H2O2 assisted EN for WOPN. METHODS: A comprehensive search of multiple databases (through December 2020) was performed to identify studies that reported outcomes of H2O2 assisted EN for WOPN. Outcomes assessed included clinical success, technical success, and adverse events. RESULTS: A total of 454 patients with mean age (47.3 ± 7.9 years) and WOPN size (12.4 ± 3.1 cm) were included from 15 studies. The median H2O2 concentration was 3% (range 0.1-3%), with dilution and volume ranging from 1:1 to 10:1 and 20 ml to 1 L, respectively. The rates of technical success, clinical success and adverse events was 97.3% (95% confidence interval [CI]: 94.8-98.6, I2 = 0), 89.8% (95% CI: 86.3-92.5, I2 = 0) and 17.9% (95% CI: 12.6-24.7, I2 = 38), respectively. The most common adverse event was bleeding (7.1%) followed by stent migration (5.3%). On meta-regression, WOPN size, patient age, use of metal stent, number of necrosectomies and transgastric access were not significant predictor for technical success, clinical success or adverse events. CONCLUSION: H2O2 assisted EN is effective and safe for management of WOPN. Its use may be encouraged, and future randomized controlled studies are needed to study the optimal technique, concentration and best predictors of success.

Endoscopic drainage with local infusion of antibiotics to avoid necrosectomy of infected walled-off necrosis.

BACKGROUND: Current treatment of infected pancreatic necrosis (IPN) follows a step-up approach. Our group designed a step-up protocol that associates endoscopic drainage with local infusion of antibiotics through transmural nasocystic catheter. Aim of our study was to evaluate our step-up protocol for IPN in terms of proportion of patients avoiding necrosectomy. METHODS: Retrospective analysis of patients admitted with acute pancreatitis (AP) between January 2015 and December 2018. The number of patients who responded to each therapeutic step were analysed: step 1, systemic antibiotics; step 2, endoscopic transmural drainage and local infusion of antibiotics; step 3, endoscopic necrosectomy. RESULTS: 1158 patients with AP were included. 110 patients (8.4%) suffered from necrotising pancreatitis; 48 of them had IPN (42.6% of necrotising pancreatitis) and were treated with systemic antibiotics. Nineteen patients (39.6% of IPN) responded and did not required any invasive therapy. Six patients with IPN on systemic antibiotics died within the first 4 weeks of disease before step 2 could be applied. Urgent surgical necrosectomy in the first 4 weeks was performed in three additional patients. Endoscopic drainage and local antibiotic therapy was performed in the remaining 20 patients; 9 (45% of them) did well and 9 patients underwent necrosectomy (18.7% of IPN). Two patients died on drainage. Overall mortality of the total cohort of AP was 2.53% CONCLUSIONS: Addition of local infusion of antibiotics to endoscopic drainage avoids the need of necrosectomy in half of patients with IPN not responding to systemic antibiotics.

Severe acute pancreatitis: surgical indications and treatment.

BACKGROUND: 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%. PURPOSE: The aim of this article was to summarize the advances being made in the understanding of this disease and the important role of surgery. RESULTS AND CONCLUSIONS: An accurate diagnosis should be made a soon as possible, initiating resuscitation with large volume intravenous fluids and oxygen by mask. Predicted severe disease will require intensive monitoring. Most deaths within the first week are due to multi-organ failure; thus, these patients will require intensive therapy unit management. During the second phase of the disease, death is due to local complications arising from the pancreatic inflammation, requiring accurate identification to determine the correct form of treatment. Acute peripancreatic fluid collections arise < 4 weeks after onset of interstitial edematous pancreatitis, not requiring any treatment. Most pancreatic pseudocysts arise > 4 weeks and largely resolve on conservative management. Necrotizing pancreatitis causing acute necrotic collections and later walled-off necrosis will require treatment if symptomatic or infected. Initial endoscopic transgastric or percutaneous drainage will resolve less serious collections but necrosectomy using minimally invasive approaches will be needed for more serious collections. To prevent recurrent attacks of AP, causative factors need to be removed where possible such as cholecystectomy and cessation of alcohol. Future progress requires improved management of multi-organ failure and more effective minimally invasive techniques for the removal of necrosis.