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Introduction: Fine-needle aspiration (FNA) is no longer recommended for diagnosing infected pancreatic necrosis (IPN) due to a high false-negative rate. Metagenomic next-generation sequencing (mNGS) is a valuable tool for identifying potential pathogens. We hypothesized that adding mNGS to the standard FNA procedure may increase diagnostic accuracy., Methods: This is a prospective, single-arm feasibility study enrolling patients with acute necrotizing pancreatitis complicated by suspected IPN. Computed tomography-guided FNA was performed immediately after enrollment, and the drainage samples were subjected to culture and mNGS assays simultaneously. Confirmatory IPN within the following week of the index FNA procedure was the reference standard. The diagnostic performance of FNA-mNGS and the impact of mNGS results on treatment were evaluated. Historical controls were used for comparison of clinical outcomes., Results: There was no significant difference between mNGS and culture in the positive rate (75% vs 70%, P = 0.723). The accuracy of FNA-mNGS was 80.0%, with a sensitivity of 82.35%, specificity of 66.67%, positive predictive value of 93.3%, and negative predictive value of 40.0%. The results of the mNGS led to treatment change in 16 of 20 patients (80%), including implementing percutaneous catheter drainage (n = 7), expanding antibiotic coverage (n = 2), percutaneous catheter drainage and expanding coverage (n = 4), narrowing antibiotic coverage (n = 1), and discontinuation of antibiotics (n = 2). The FNA-mNGS approach was not associated with improved clinical outcomes compared with the historical control group., Discussion: The addition of mNGS to standard FNA has comparable diagnostic accuracy with culture-based FNA and may not be associated with improved clinical outcomes., (Copyright © 2024 The Author(s). Published by Wolters Kluwer Health, Inc. on behalf of The American College of Gastroenterology.)

Background: Hypertriglyceridemia is a common cause of acute pancreatitis. Pregnant women are at risk of developing hypertriglyceridemia-induced acute pancreatitis (HTG-AP); however, whether pregnancy increases the risk of infected pancreatic necrosis (IPN) is unknown., Aim: We aimed to assess the association between pregnancy and IPN., Methods: This 10-year retrospective cohort study was conducted at Jinling Hospital. Adult female patients of childbearing age with HTG-AP between January 2013 and September 2022 were screened. Logistic regression analyses were performed to assess the risk factors for IPN. Patients admitted within 7 days were assigned to the training and validation sets to develop a dynamic nomogram for IPN prediction., Results: 489 patients were included, and 144 developed IPN. Logistic regression analyses revealed pregnancy (OR: 2.578 95% CI: 1.474-4.510) as an independent risk factor for IPN. Gestation weeks, ARDS, albumin level, and serum creatinine level were selected as the predictors of the dynamic nomogram for IPN prediction, with good discrimination in the training set (AUC 0.867 95% CI: 0.794-0.940) and validation set (AUC 0.957 95% CI: 0.885-1.000)., Conclusion: Pregnancy increases the risk of IPN in adult patients of childbearing age with HTG-AP, and the dynamic nomogram may help risk stratification for IPN., Competing Interests: Conflict of Interest The authors declare that they have no conflict of interest., (Copyright © 2023 Editrice Gastroenterologica Italiana S.r.l. Published by Elsevier Ltd. All rights reserved.)

Bile acids are altered and associated with prognosis in patients with acute pancreatitis (AP). Here, we conduct targeted metabolomic analyses to detect bile acids changes in patients during the acute (n = 326) and the recovery (n = 133) phases of AP, as well as in healthy controls (n = 60). Chenodeoxycholic acid (CDCA) decreases in the acute phase, increases in the recovery phase, and is associated with pancreatic necrosis. CDCA and its derivative obeticholic acid exhibit a protective effect against acinar cell injury in vitro and pancreatic necrosis in murine models, and RNA sequencing reveals that the oxidative phosphorylation pathway is mainly involved. Moreover, we find that overexpression of farnesoid X receptor (FXR, CDCA receptor) inhibits pancreatic necrosis, and interfering expression of FXR exhibits an opposite phenotype in mice. Our results possibly suggest that targeting CDCA is a potential strategy for the treatment of acinar cell necrosis in AP, but further verification is needed., Competing Interests: Declaration of interests The authors declare no competing interests., (Copyright © 2023 The Authors. Published by Elsevier Inc. All rights reserved.)

Background and Purpose: Recent clinical studies have shown that serum high-density lipoprotein (HDL) levels are correlated with acute pancreatitis (AP) severity. We aimed to investigate the role of HDL in pancreatic necrosis in AP., Experimental Approach: ApoA-I is the main constitution and function component of HDL. The roles of healthy human-derived HDL and apoA-I mimic peptide D4F were demonstrated in AP models in vivo and in vitro. Constitutive Apoa1 genetic inhibition on AP severity, especially pancreatic necrosis was assessed in both caerulein and sodium taurocholate induced mouse AP models. In addition, constitutive (Casp1 -/- ) and acinar cell conditional (Pdx1 Cre Nlrp3 Δ/Δ and Pdx1 Cre Gsdmd Δ/Δ ) mice were used to explore the effects of HDL on acinar cell pyroptosis in AP., Key Results: Apoa1 knockout dramatically aggravated pancreatic necrosis. Human-derived HDL protected against acinar cell death in vivo and in vitro. We found that mimic peptide D4F also protected against AP very well. Constitutive Casp1 or acinar cell-conditional Nlrp3 and Gsdmd genetic inhibition could counteract the protective effects of HDL, implying HDL may exert beneficial effects on AP through inhibiting acinar cell pyroptosis., Conclusion and Implications: This work demonstrates the protective role of HDL and apoA-I in AP pathology, potentially driven by the inhibition of NLRP3 inflammasome signaling and acinar cell pyroptosis. Mimic peptides have promise as specific therapies for AP., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 The Authors. Published by Elsevier B.V. All rights reserved.)

Background: Previous studies have shown that minimally invasive treatment for infected necrotizing pancreatitis (INP) may be safer and more effective than open necrosectomy (ON), but ON is still irreplaceable in a portion of INP patients. Furthermore, there is a lack of tools to identify INP patients at risk of minimally invasive step-up approach failure (eventually received ON or died), which may enable appropriate treatment for them. Our study aims to identify risk factors that can predict minimally invasive step-up approach failure in INP patients and to develop a nomogram for early prediction., Methods: Multivariate logistic regression was performed to evaluate the association between minimally invasive step-up approach failure and factors regarding demographics, disease severity, laboratory index, and the location of extrapancreatic necrotic collections. A novel nomogram was developed, and its performance was validated both internally and externally by its discrimination, calibration, and clinical usefulness., Results: There were 267, 89, and 107 patients in the training, internal, and external validation cohorts, respectively. Multivariate logistic regression demonstrated that the computed tomography severity index (CTSI) greater than 8 points, Acute Physiology and Chronic Health Evaluation II (APACHE II) score of 16 points or more, early spontaneous bleeding, fungi infection, granulocyte and platelet decrease within 30 days of acute pancreatitis onset, and extrapancreatic necrosis collection located in small bowel mesentery were independent risk factors for minimally invasive step-up approach failure. The area under the curve and coefficient of determination ( R2 ) of the nomogram constructed from the above factors were 0.920 and 0.644, respectively. The Hosmer-Lemeshow test showed that the model had good fitness ( P =0.206). In addition, the nomogram performed well in both the internal and external validation cohorts., Conclusions: The nomogram had a good performance in predicting minimally invasive step-up approach failure, which may help clinicians distinguish INP patients at risk of minimally invasive step-up approach failure early., (Copyright © 2023 The Author(s). Published by Wolters Kluwer Health, Inc.)

Background: Timely and accurate microbial diagnosis is important in managing patients with infected pancreatic necrosis (IPN)., Aims: To evaluate the diagnostic performance of Metagenomic next-generation sequencing (mNGS) in patients with suspected IPN., Methods: The clinical data of 40 patients with suspected IPN who underwent CT-guided pancreatic fluid aspiration were retrospectively analyzed. Microbial culture and mNGS were simultaneously applied to identify the potential pathogens. The diagnostic performance of the mNGS was assessed by sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV)., Results: The mNGS report can be obtained significantly earlier than culture methods (42 (36-62 h) vs. 60 (42-124 h), P = 0.032). Across all the study samples, seven species of bacteria and two species of fungi were reported accordingly to the culture results, while 22 species of bacteria and two species of fungi were detected by mNGS. The sensitivity, specificity, NPV, and PPV of mNGS were 88.0%, 100%, 83.33%, and 100%, respectively., Conclusions: The diagnostic accuracy of mNGS in patients with suspected IPN is satisfactory. Moreover, mNGS may broaden the range of identifiable infectious pathogens and provide a more timely diagnosis., Competing Interests: Conflicts of Interest None declared., (Copyright © 2022. Published by Elsevier Ltd.)

Objectives: Infected pancreatic necrosis (IPN) is a significant complication of acute necrotizing pancreatitis (ANP). Early identification of patients at high risk of IPN would enable appropriate treatment, but there is a lack of valid tools. This study aimed to assess the performance of the Pancreatitis Activity Scoring System (PASS) and its modifications (by removing or reducing the weight of opioid usage) in predicting IPN in a cohort of predicted severe ANP patients., Methods: Data was prospectively collected in the TRACE trial (2017-2020) involving 16 sites across China. The predictive performance of PASS, modified PASS (mPASS), and conventional indices were assessed by the area under the receiver operating characteristic curve (AUC), Hosmer-Lemeshow Ĉ-test, Brier score, and Fagan's nomogram. Multivariate logistic regression analysis (MLRA) was used to define the relationship between the best-performing PASS/mPASS model and IPN., Results: A total of 508 subjects were enrolled (median age, 43 years; 62.8% males) in the original trial, and 122 developed IPN (24%) within 90 days after randomization. Compared with non-IPN patients, the scores of PASS and its modified models were significantly higher in the IPN patients (all p < 0.001). Among the PASS and its modifications, mPASS-4 had the largest AUC, the lowest Brier score, and good calibration. The mPASS-4 model demonstrated an AUC of 0.752 in predicting IPN (the optimal cut-off for the mPASS-4 was 292.5) and outperformed the conventional indices. The MLRA results showed that mPASS-4 >292.5 was an independent risk factor of IPN (OR: 3.6, 95% CI: 2.1-6.3)., Conclusion: The PASS and its modifications during the first week of ANP onset predict the development of IPN, with mPASS-4 performing best. The mPASS-4 model simplifies the original PASS, increasing the likelihood of clinical implementation., (© 2022 The Authors. United European Gastroenterology Journal published by Wiley Periodicals LLC. on behalf of United European Gastroenterology.)

Background: Infected pancreatic necrosis (IPN) is a life-threatening complication of acute pancreatitis (AP). Timely diagnosis of IPN could facilitate appropriate treatment, but there is a lack of reliable non-invasive screening tests. In this study, we aimed to evaluate the diagnostic value of plasma metagenomic next-generation sequencing (mNGS) based on circulating microbial cell-free DNA in patients with suspected IPN., Methods: From October 2020 to October 2021, 44 suspected IPN patients who underwent plasma mNGS were reviewed. Confirmatory diagnosis of IPN within two weeks after the index blood sampling was considered the reference standard. The confirmation of IPN relied on the microbiological results of drains obtained from the necrotic collections. The distribution of the pathogens identified by plasma mNGS was analyzed. Positive percent agreement (PPA) and negative percent agreement (NPA) were evaluated based on the conformity between the overall mNGS results and culture results of IPN drains. In addition, the clinical outcomes were compared between mNGS positive and negative patients., Results: Across all the study samples, thirteen species of bacteria and five species of fungi were detected by mNGS. The positivity rate of plasma mNGS was 54.55% (24/44). Of the 24 mNGS positive cases, twenty (83.33%, 95% CI, 68.42-98.24%) were consistent with the culture results of IPN drains. The PPA and NPA of plasma mNGS for IPN were 80.0% (20/25; 95% CI, 64.32-95.68%) and 89.47% (17/19; 95% CI, 75.67-100%), respectively. Compared with the mNGS negative group, patients in the positive group had more new-onset septic shock [12 (50.0%) vs. 4 (20.0%), p = 0.039]., Conclusion: IPN relevant pathogens can be identified by plasma mNGS, potentially facilitating appropriate treatment. The clinical application of mNGS in this cohort appears feasible., (© 2022. The Author(s).)

Purpose: Infected pancreatic necrosis (IPN) is a highly morbid complication of acute necrotising pancreatitis (ANP). Since there is evidence of early-onset immunosuppression in acute pancreatitis, immune enhancement may be a therapeutic option. This trial aimed to evaluate whether early immune-enhancing Thymosin alpha 1 (Tα1) treatment reduces the incidence of IPN in patients with predicted severe ANP., Methods: We conducted a multicentre, double-blind, randomised, placebo-controlled trial involving ANP patients with an Acute Physiology and Chronic Health Evaluation II (APACHE II) score ≥ 8 and a computed tomography (CT) severity score ≥ 5 admitted within 7 days of the advent of symptoms. Enrolled patients were assigned to receive a subcutaneous injection of Tα1 1.6 mg every 12 h for the first 7 days and 1.6 mg once a day for the subsequent 7 days or matching placebos (normal saline). The primary outcome was the development of IPN during the index admission., Results: A total of 508 patients were randomised, of whom 254 were assigned to receive Tα1 and 254 placebo. The vast majority of the participants required admission to the intensive care unit (ICU) (479/508, 94.3%). During the index admission, 40/254(15.7%) patients in the Tα1 group developed IPN compared with 46/254 patients (18.1%) in the placebo group (difference -2.4% [95% CI - 7.4 to 5.1%]; p = 0.48). The results were similar across four predefined subgroups. There was no difference in other major complications, including new-onset organ failure (10.6% vs. 15%), bleeding (6.3% vs. 3.5%), and gastrointestinal fistula (2% vs. 2.4%)., Conclusion: The immune-enhancing Tα1 treatment of patients with predicted severe ANP did not reduce the incidence of IPN during the index admission., (© 2022. Springer-Verlag GmbH Germany, part of Springer Nature.)

Background: While the management of infected pancreatic necrosis (IPN) has evolved in the last two decades with the adoption of minimally invasive interventions (drainage ± debridement), it is unknown whether the principle of delaying intervention inherited from the open surgery era still applies. The aim of the current study was to investigate the impact of the timing of minimally invasive intervention on the outcomes of patients with IPN requiring intervention., Methods: PubMed, Embase, MEDLINE and Web of Science databases were searched for appropriate studies. The primary outcome of interest was hospital mortality, the secondary outcomes were the incidence of complications during the hospitalization, including new-onset organ failure, gastrointestinal fistula or perforation, bleeding and length of hospital or intensive care unit (ICU) stay., Results: Seven clinical studies were included with a total of 742 patients with IPN requiring intervention, of whom 321 received early intervention and 421 delayed intervention. Results from the meta-analysis showed that early minimally invasive intervention did not increase hospital mortality (odds ratio 1.65, 95% confidence interval 0.97-2.81; p = 0.06) but was associated with a remarkably prolonged hospital stay and an increased incidence of gastrointestinal fistula or perforation when compared with delayed intervention., Conclusions: Although no firm conclusion can be drawn because of the quality of available studies, it does appear that timing of intervention is a risk factor for adverse outcomes and ought to be investigated more rigorously in prospective studies., (© 2022. Japanese Society of Gastroenterology.)

Objectives: Minimally invasive interventions have become standard treatment for infected pancreatic necrosis (IPN). Despite the marginal clinical advantage of endoscopic approaches over the surgical approach shown in recent studies, percutaneous techniques still have a role when endoscopic treatment is not indicated. Stent-assisted percutaneous endoscopic necrosectomy (SAPEN) is an alternative option for surgical necrosectomy, but the theoretical advantages to this procedure remain unproven. This study aimed to report the efficacy and efficiency of SAPEN in patients with IPN., Methods: This is a retrospective, historically-controlled, cohort study. All IPN patients admitted to our center from January 2015 to December 2018 were screened for eligibility. Patients admitted between January 2015 and October 2017 were historical controls, and patients admitted thereafter were treated with additional self-expandable metal stent (SEMS). The primary endpoint was a composite of major complications and/or death. Other outcomes, including individual components of the primary endpoint, new-onset sepsis, length of ICU and hospital stay, and pancreatic fistula, were also compared., Results: There were 73 historical-control patients and 37 patients who had SAPEN included for analysis. The introduction of the SAPEN procedure failed to reduce the incidence of the primary endpoint (35 versus 52%, P = 0.095). However, significantly shorter hospital stay (38 versus 48 days, P = 0.035) and lower incidence of new-onset sepsis were observed in the SAPEN group (35 versus 56%, P = 0.037)., Conclusion: The application of SEMS in percutaneous endoscopic necrosectomy procedures shortened hospital stay, decreased new-onset sepsis, and allowed earlier necrosectomy., (Copyright © 2021 Wolters Kluwer Health, Inc. All rights reserved.)

Acute pancreatitis (AP) is one of the most widespread clinical emergencies. Macrophages are the most common immune cells in AP pancreatic tissue and are closely associated with pancreatic necrosis and recovery. The level of heparin-binding protein (HBP) is closely linked to inflammation. In this study, we assessed the effect of HBP on AP tissue necrosis severity and whether HBP is associated with M1 macrophages in pancreatic necrosis. We observed the dynamic changes of HBP levels in the pancreas during acute inflammation in the caerulein-induced AP mice model. We used hematoxylin-eosin staining to evaluate pancreatic edema and necrosis, and to detect infiltration of macrophages by immunohistochemistry. Moreover, expressions of the maker and cytokines of macrophages, including inducible nitric oxide synthase (iNOS), and arginase 1 (Arg-1), interleukin-1β (IL-1β), tumor necrosis factor-α (TNF-α), and interleukin-6 (IL-6) mRNA, were detected by real-time polymerase-chain reaction (RT-PCR). High levels of HBP in the pancreas were detected at 48 h, and heparin inhibited HBP expression in AP pancreatic tissue. Inhibiting HBP expression by injecting heparin before AP can alleviate pancreatic necrosis and inhibit F4/80 labeled M1 macrophage infiltration and IL-6, TNF-α, and iNOS mRNA expression. Clodronate liposome (CLDL) intraperitoneally treated mice showed no change in pancreatic HBP levels, but pancreatic macrophage-specific antigen F4/80 and TNF-α, IL-1β, and IL-6 mRNA levels decreased after CLDL treatment. HBP is critical for pancreatic necrosis response in acute pancreatitis by increasing the infiltration of M1 macrophages and promoting the secretion of inflammatory factors, such as TNF-α, IL-6, IL-1β, which can be reduced by heparin.

Introduction: Infected pancreatic necrosis (IPN) is an important complication of acute pancreatitis (AP). Absolute lymphocyte count (ALC) was reported to be associated with immunosuppression and the development of IPN. The aim of this study was to describe the trajectory of ALC during the early phase of AP and assess its association with IPN., Methods: We retrospectively screened patients with AP admitted to our center between January 2016 and July 2019. The ALC levels for the first 7 days after admission were collected. Group-based trajectory modeling was performed to detect the trajectories. Cox proportional hazards regression model was adopted to identify potential risk factors of IPN., Results: Overall, 292 patients were enrolled for analysis. A triple-group trajectory model was developed, assigning 116 patients to the low-level ALC group, 133 to the medium-level ALC group, and 43 to the high-level ALC group. There was no overall significant difference regarding the incidence of IPN among the 3 groups (P = 0.066). In pairwise comparison, patients in the low-level ALC group had significantly higher incidence of IPN than those in the high-level ALC group (hazard ratio: 3.50; 95% confidence interval: 1.22-10.00, P = 0.020). Length of hospital stay and intensive care unit stay differed significantly among patients with different trajectories (P = 0.042 and 0.033, respectively)., Discussion: Despite the fact that the trajectories of ALC is overall insignificant for the development of IPN, patients with persistent low ALC trajectories during the early phase of AP are more likely to develop IPN when compared with patients with high ALC trajectories., (Copyright © 2021 The Author(s). Published by Wolters Kluwer Health, Inc. on behalf of The American College of Gastroenterology.)

Background/purpose: The current standard care for acute pancreatitis with acute necrotic collections (ANC) is to postpone invasive intervention for 4 weeks when indicated. However, in patients with persistent organ failure (POF), this delayed approach may prolong organ failure. In this study, we aimed to assess the feasibility and safety of earlier drainage for acute pancreatitis patients with ANC and POF., Methods: A single-center, randomized controlled trial was conducted. Eligible patients were randomly assigned to either the early on-demand (EOD) group or the standard management (SM) group. Within 21 days of randomization, early drainage was triggered by unremitted or worsening organ failure in the EOD group. The primary endpoint was a composite of major complications/death during 90-days follow-up., Results: Thirty patients were randomized. Within 21 days of randomization, eight of the 15 patients (53%) in the EOD group underwent percutaneous drainage compared to four of the 15 patients (27%) in the SM group (P = 0.26). The primary outcome occurred in three of the 15 (20%) patients in the EOD group and seven of the 15(46.7%) in the controls (P = 0.25, relative risk 0.43, 95%CI 0.14 to 1.35)., Conclusions: Although the EOD approach did not result in significant differences between groups, the primary outcome assessed in this trial demonstrated the potential for clinical benefits favoring early drainage., (© 2021 Japanese Society of Hepato-Biliary-Pancreatic Surgery.)

Objectives: Splanchnic venous thrombosis (SVT) is a relevant complication in patients with acute necrotizing pancreatitis. So far, no specific treatment for preventing development of SVT exists, and the effect of systemic anticoagulation (SAC) is unclear., Methods: Patients with acute necrotizing pancreatitis admitted to our center within 7 days from onset of abdominal pain were screened. In the historic group, during which period, most patients received no SAC. Patients in the study group received SAC therapy considering the risk of deep vein thrombosis and SVT. The primary outcome measure was the incidence of SVT., Results: Splenic vein was involved in 71% of all 84 SVT patients. Compared with the historic cohort, patients who received SAC experienced lower incidence of SVT (P < 0.001), especially for splenic venous thrombosis (P = 0.002). Patients in the study group also showed lower mortality (P = 0.04) and incidence of new-onset organ failure (P = 0.03). The incidence of bleeding shows no statistical significance between 2 groups., Conclusions: Application of SAC seems to reduce the incidence of SVT and improve clinical outcomes without increasing the risk of bleeding. Randomized clinical trials are needed to confirm our findings.

Introduction/aim: Pancreatic necrosis occurs in a quarter of patients with acute pancreatitis, many of whom form an acute necrotic collection (ANC). The current standard treatment is to defer percutaneous catheter drainage (PCD) until the latter becomes "walled off," which takes approximately four weeks. The majority of patients that develop persistent organ failure (POF), the primary determinant of mortality, do so within four weeks. To defer PCD until after four weeks may result in a worse outcome because of a missed opportunity to treat early infection and thereby reduce the severity and/or duration of POF. This study is aimed to compare the clinical outcome of the current standard approach with early on-demand PCD in acute necrotizing pancreatitis (ANP) patients with ANC and POF., Methods/design: This is an open-label, multi-center, parallel, randomized, controlled trial. All patients with ANP who develop POF during the first week of onset will be screened for eligibility. In total, 120 study subjects will be randomized to either early on-demand PCD or standard care. Patients assigned to the former will receive PCD when they show signs of decompensation like new-onset OF, aggravation of pre-existent OF, and persistent OF for more than a week. The primary composite endpoint is major complication and/or death. Patients will be followed until discharge or death with an additional follow-up 90 days after randomization., Discussion: This study challenges the standard 4-week delay before PCD and will answer the question whether early on-demand PCD is associated with a lower incidence of major complications and/or death., (Copyright © 2020 IAP and EPC. Published by Elsevier B.V. All rights reserved.)

Introduction: Infected pancreatic necrosis (IPN) and its related septic complications are the major causes of death in patients with acute necrotising pancreatitis (ANP). Therefore, the prevention of IPN is of great clinical value, and immunomodulatory therapy with thymosin alpha 1 may be beneficial. This study was designed to test the hypothesis that the administration of thymosin alpha 1 during the acute phase of ANP will result in a reduced incidence of IPN., Methods and Analysis: This is a randomised, multicentre, double-blind, placebo-controlled study. 520 eligible patients with ANP will be randomised in a 1:1 ratio to receive either the thymosin alpha 1 or the placebo using the same mode of administration. The primary endpoint is the incidence of IPN during the index admission. Most of the secondary endpoints will be registered within the index admission including in-hospital mortality, the incidence of new-onset organ failure and new-onset persistent organ failure (respiration, cardiovascular and renal), receipt of new organ support therapy, requirement for drainage or necrosectomy, bleeding requiring intervention, human leucocyte antigens-DR(HLA-DR) on day 0, day 7, day 14, and so on and adverse events. Considering the possibility of readmission, an additional follow-up will be arranged 90 days after enrolment, and IPN and death at day 90 will also be served as secondary outcomes., Ethics and Dissemination: This study was approved by the ethics committee of Jinling Hospital, Nanjing University (Number 2015NZKY-004-02). The thymosin alpha 1 in the prevention of infected pancreatic necrosis following acute necrotising pancreatitis(TRACE) trial was designed to test the effect of a new therapy focusing on the immune system in preventing secondary infection following ANP. The results of this trial will be disseminated in peer-reviewed journals and at scientific conferences., Trial Registration Number: ClinicalTrials.gov Registry (NCT02473406)., Competing Interests: Competing interests: This study is supported by SBE2016750187 of Science and technology project, Jiangsu Province, China. SciClone Pharmaceuticals provides the study drug for this investigator-initiated study., (© Author(s) (or their employer(s)) 2020. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Background and Aims: A variety of minimally invasive techniques have been proposed to replace open surgery for the treatment of infected pancreatic necrosis (IPN). In this study, we evaluate the feasibility and safety of the stent-assisted percutaneous endoscopic necrosectomy (SAPEN) procedure., Methods: Data were collected on all patients who underwent the SAPEN procedure between October 2017 and March 2018. The demographic and clinical characteristics of the study patients were analyzed. A composite primary endpoint of major complications and/or death was used. Three different cases were selected to illustrate different technical aspects of the SAPEN procedure., Results: The placement of a percutaneous stent was successful in all of the 23 patients (17 males, six females). IPN was successfully managed in 16/23 (70%) patients, with the need for open surgery in seven patients (30%), with a median of two (range 1-5) SAPEN procedures. No significant procedure-related complications occurred. Overall 11/23 (48%) patients had a major complication and/or death., Conclusions: In conclusion, the SAPEN procedure was effective in treating IPN without adding extra procedural risk. The role and benefits of the SAPEN procedure now need to be demonstrated in larger controlled study.

Endocrine pancreatic insufficiency secondary to acute pancreatitis (AP) drew increasing attention in the recent years. The aim of the present study was to assess the impact of pancreatic necrosis and organ failure on the risk of developing new-onset diabetes after AP.The follow-up study was conducted for patients recovered from AP in the treatment center of Jinling Hospital. Endocrine function was evaluated by simplified oral glucose tolerance test (OGTT). Pancreatic necrosis was examined by abdominal contrast-enhanced CT (CECT) scan during hospitalization. The data including APACHE II score, Balthazar's score, organ failure (AKI and ARDS) was also collected from the medical record database. All patients were divided into group diabetes mellitus (DM) and group non-DM according to the endocrine function and group pancreatic necrosis (PN) and persistent organ failure (OF), group PN and non-OF, group non-PN and OF, and group non-PN and non-OF according to the occurrence of pancreatic necrosis and persistent organ failure.Around 256 patients were included for the final analysis. 154 patients (60.2%) were diagnosed with DM (include impaired glucose tolerance, IGT), while 102 patients (39.8%) were deemed as normal endocrine function. APACHE II score and Balthazar score of the patients in the group DM were significant higher than those in the non-DM group (F = 6.09, P = .01; F = 10.74, P = .001). The incidence of pancreatic necrosis in group DM and group non-DM was, respectively, 64.7% and 53.0% (χ = 3.506, P = .06). The patients underwent necrosis debridement by percutaneous catheter drainage (PCD) and/or the operative necrosectomy (ON) were more likely to developed new onset DM than the patients without PCD or ON (χ = 2.385, P = .02). The morbidity of new-onset DM after AP gradually increased from group non-PN and non-OF, group non-PN and OF, group PN and non-OF to group PN and OF in order (χ = 4.587, P = .03). The value of HOMA-IR of patients at follow-up time was significant higher in group DM than group non-DM (F = 13.414, P = .000).Patients with both PN and persistent OF may were at increased risk of developing new-onset diabetes after AP. Insulin resistance could be the pivotal mechanism of the development of diabetes.

Background: Step-up approach consisting of multiple minimally invasive techniques has gradually become the mainstream for managing infected pancreatic necrosis (IPN). In the present study, we aimed to compare the safety and efficacy of a novel four-step approach and the conventional approach in managing IPN., Methods: According to the treatment strategy, consecutive patients fulfilling the inclusion criteria were put into two time intervals to conduct a before-and-after comparison: the conventional group (2010-2011) and the novel four-step group (2012-2013). The conventional group was essentially open necrosectomy for any patient who failed percutaneous drainage of infected necrosis. And the novel drainage approach consisted of four different steps including percutaneous drainage, negative pressure irrigation, endoscopic necrosectomy and open necrosectomy in sequence. The primary endpoint was major complications (new-onset organ failure, sepsis or local complications, etc.). Secondary endpoints included mortality during hospitalization, need of emergency surgery, duration of organ failure and sepsis, etc., Results: Of the 229 recruited patients, 92 were treated with the conventional approach and the remaining 137 were managed with the novel four-step approach. New-onset major complications occurred in 72 patients (78.3%) in the two-step group and 75 patients (54.7%) in the four-step group (p < 0.001). For other important endpoints, although there was no statistical difference in mortality between the two groups (p = 0.403), significantly fewer patients in the four-step group required emergency surgery when compared with the conventional group [14.6% (20/137) vs. 45.6% (42/92), p < 0.001]. In addition, stratified analysis revealed that the four-step approach group presented significantly lower incidence of new-onset organ failure and other major complications in patients with the most severe type of AP., Conclusion: Comparing with the conventional approach, the novel four-step approach significantly reduced the rate of new-onset major complications and requirement of emergency operations in treating IPN, especially in those with the most severe type of acute pancreatitis.

Background: In recent years, a step-up approach based on minimally invasive techniques was recommended by latest guidelines as initial invasive treatment for infected pancreatic necrosis (IPN). In this study, we aimed to describe a novel step-up approach for treating IPN consisting of four steps including negative pressure irrigation (NPI) and endoscopic necrosectomy (ED) as a bridge between percutaneous catheter drainage (PCD) and open necrosectomy METHODS: A retrospective review of a prospectively collected internal database of patients with a diagnosis of IPN between Jan, 2012 to Dec, 2012 at a single institution was performed. All patients underwent the same drainage strategy including four steps: PCD, NPI, ED and open necrosectomy. The demographic characteristics and clinical outcomes of study patients were analyzed., Results: A total of 71 consecutive patients (48 males and 23 females) were included in the analysis. No significant procedure-related complication was observed and the overall mortality was +21.1 % (15 of 71 patients). Seven different strategies like PCD+ NPI, PCD+NPI+ED, PCD+open necrosectomy, etcetera, were applied in study patients and a half of them received PCD alone. In general, each patient underwent a median of 2 drainage procedures and the median total drainage duration was 11 days (interquartile range, 6-21days)., Conclusions: This four-step approach is effective in treating IPN and adds no extra risk to patients when compared with other latest step-up strategies. The two novel techniques (NPI and ED) could offer distinct clinical benefits without posing unanticipated risks inherent to the procedures.

Background: Splanchnic venous thrombosis (SVT) is a relatively rare but important complication of necrotizing acute pancreatitis (NAP). Clinical manifestations and severity of this complication in different patients vary greatly, ranging from mild abdominal discomfort even asymptomatic to lethal gastrorrhagia or hepatic failure. The aim of the present study was to develop a model to predict the clinical manifestations of SVT in NAP patients., Methods: This retrospective cohort study was conducted in the surgical intensive care unit (SICU) of Jinling Hospital. Patients with the presence of both pancreatic necrosis and SVT were selected for possible inclusion. Both univariate and multivariate logistic regression analyses were applied using 12 indices including age, gender, Acute Physiology and Chronic Health Evaluation II scores (APACHE II), CRP(C - reactive protein) levels, etc to assess potential predictors for symptomatic pancreatic splanchnic venous thrombosis (PSVT) in this cohort. A prognostic nomogram was also applied to develop an easy-to-use prediction model., Results: A total of 104 patients with necrotizing acute pancreatitis (NAP) and splanchnic vein thrombosis (SVT) from January 2012 to December 2013 were enrolled for analysis. A quarter of study subjects (26 of 104, 25%) developed variable symptomatic manifestations including variceal bleeding, persistent ascites and enteral nutrition (EN) intolerance during the disease course. In the multivariable regression model, the following factors were found to be associated with the occurrence of symptomatic SVT: Balthazar's computed tomography (CT) score (OR = 1.818; 95% CI: 1.251-2.641; P = 0.002), intra-abdominal pressure (IAP) (OR = 1.172; 95% CI: 1.001-1.251; P = 0.043 and presence of SMVT (OR = 6.946; 95% CI: 2.290-21.074; P = 0.001). A prediction model incorporating these factors demonstrated an area under the receiver operating characteristic curve of 0.842., Conclusions: Balthazar's CT score, IAP and SMVT are predictors of symptomatic SVT in NAP patients. The nomogram we conducted can be used as an easy-to-use risk stratification tool in either clinical practice or future studies., (Copyright © 2016 IAP and EPC. Published by Elsevier B.V. All rights reserved.)

Background: Early occurrence of immunosuppression is a risk factor for infected pancreatic necrosis (IPN) in the patients with acute pancreatitis (AP). However, current measures for the immune systems are too cumbersome and not widely available. Significantly decreased lymphocyte count has been shown in patients with severe but not mild type of AP. Whereas, the correlation between the absolute lymphocyte count and IPN is still unknown. We conduct this study to reveal the exact relationship between early lymphocyte count and the development of IPN in the population of AP patients., Methods: One hundred and fifty-three patients with acute pancreatitis admitted to Jinling Hospital during the period of January 2012 to July 2014 were included in this retrospective study. The absolute lymphocyte count and other relevant parameters were measured on admission. The diagnosis of IPN was based on the definition of the revised Atlanta classification., Results: Patients were divided into two groups according to the presence of IPN. Thirty patients developed infected necrotizing pancreatitis during the disease course. The absolute lymphocyte count in patients with IPN was significantly lower on admission (0.62 × 10(9)/L, interquartile range [IQR]: 0.46-0.87 × 10(9)/L vs. 0.91 × 10(9)/L, IQR: 0.72-1.27 × 10(9)/L, p < 0.001) and throughout the whole clinical course than those without IPN. Logistic regression indicated that reduced lymphocyte count was an independent risk factor for IPN. The optimal cut-offs from ROC curve was 0.66 × 10(9)/L giving sensitivity of 83.7 % and specificity of 66.7 %., Conclusions: Reduced lymphocyte count within 48 h of AP onset is significantly and independently associated with the development of IPN.

Severe acute pancreatitis (SAP) is a critical illness in clinical practice, which is characterized by intensive inflammatory response in the early phase and infected pancreatic necrosis in the later phase. Despite the knowledge of SAP and critical care support technology got significant progress in recent years, SAP still carries approximately 30%mortality rate. Some SAP patients also have many other kinds of underlying disease such as hyperlipidemia, hypertension, coronary atherosclerotic heart disease, and heart rhythm abnormalities, which are related to cardiopulmonary arrest to some extent. Thus, the incidence of unpredictive cardiopulmonary arrest is high. Recently, a SAP patient in our intensive care unit had sudden cardiac arrest. After 52 minutes of cardiopulmonary resuscitation, she had return of spontaneous circulation and regained consciousness within 2 hours. To our knowledge, there is no successful report after such long resuscitation in SAP patients. She was receiving continuous renal replacement therapy (CRRT) and continuous veno-venous hemofiltration, in the event of cardiopulmonary arrest. No study reported what kind of role CRRT can play when cardiac arrest occurs. Usually, we would stop existing CRRT when cardiac arrest occurred.We would not start CRRT for the complexity of operation and additional loss of blood. This time, we used CRRT to regulate electrolyte and acid-base imbalance and implement hypothermia brain protection, which played an important role in the patient that we report here.We strongly recommended a prolonged cardiopulmonary cerebral resuscitation in some not quite old SAP patients and continue to use existing CRRT but not remove it.

The incidence of acute bleeding is reported to be 13.5% in patients with acute necrotizing pancreatitis. However, of all the bleeding events, intra-abdominal bleeding was less studied in the literature and its risk factors have not been well defined yet. The purpose of the present study was to investigate the risk factors for massive intra-abdominal bleeding among the patients with infected necrotizing pancreatitis and assessed the outcome of these patients. Both univariate and multivariate logistic regression models were applied for evaluating risk factors for intra-abdominal bleeding using 33 indices, including age, sex, etiology of acute pancreatitis (AP), APACHE II score, etc. Outcome assessments such as mortality, hospital and intensive care unit (ICU) durations, and cost were also compared between patients with or without intra-abdominal bleeding. Acute kidney injury (AKI) (odds ratio [OR]: 7.54, 95% confidence interval [CI]: 2.53-22.52, P < 0.001) and number of operation (OR: 8.84, 95% CI: 2.01-38.86, P = 0.004) were 2 predictors for massive intra-abdominal bleeding in the patients with infected necrotizing pancreatitis. In addition, AP patients with intra-abdominal bleeding also showed significantly higher mortality rate, prolonged hospital and ICU durations, more complications and invasive treatments, as well as increased cost. Our study revealed that AKI and multiple operations were 2 critical factors increasing the risk of intra-abdominal bleeding among patients with infected necrotizing pancreatitis. Additionally, massive intra-abdominal bleeding was also associated with poor prognosis.

Objectives: Retroperitoneal necrosis in the pelvic cavity is a rare complication of severe acute pancreatitis (SAP), mainly developing in critically ill patients. Because of its particular anatomy, it is difficult to perform drainage or surgery. We hypothesized that computed tomography (CT)-guided drainage is an effective approach for the infected retroperitoneal necrosis. The aim of this study is to evaluate the safety and effectiveness of CT-guided transgluteal drainage in SAP patients with infected retroperitoneal pelvic necrosis., Materials and Methods: Twelve SAP patients with infected retroperitoneal pelvic necrosis underwent CT-guided transgluteal drainage with a 12-month follow-up. The safety and effectiveness of drainage were measured by the complication rate and the rate of clinical success., Results: All the 12 patients underwent a successful drainage under the guidance of CT and their clinical symptoms disappeared within 48 h. One patient died of another serious complication of SAP and in the remaining 11 patients, complete resolution was achieved without major complications. The mean catheter indwelling time was 21.5 days. Repeated CT during the follow-up period showed no recurrence in the remaining 11 patients., Conclusion: Transgluteal drainage under the guidance of CT was found to be an effective and appropriate approach for infected pelvic necrosis in SAP patients.

Background: Splanchnic venous thrombosis (SVT) is considered a rare but important complication in patients with acute pancreatitis (AP) and literatures regarding this topic were sparse. The aim of the present study was to investigate the risk factors of SVT in necrotizing acute pancreatitis (NAP) and assess the prognosis of these patients., Methods: Both univariate and multivariate logistic regression analyses were applied using 15 indices including age, gender, Acute Physiology and Chronic Health Evaluation II scores (APACHE II), CRP (C - reactive protein) levels, etc to explore potential risk factors for the development of SVT in NAP patients. Moreover, clinical outcome measures such as mortality, organ failure and length of hospital and ICU stay were also compared between NAP patients with or without SVT., Results: According to the statistical results, only intra-abdominal pressure (IAP) was proved to be an independent risk factor for SVT (OR, 1.283; 95% CI, 1.091-1.509,P=0.003). In addition, Balthazar's CT score and occurrence of IPN (infected pancreatic necrosis) also reached statistical significance (P=0.040 and 0.047, respectively), but the 95% confidence interval shown in the multivariate logistic regression suggested that the observed ORs are not significant (1.326;95% CI 0.984-1.787 and 2.61;95 CI 0.972-7.352, respectively), which indicates weaker association between the two parameters and SVT. Regarding the clinical outcomes, patients with SVT showed higher mortality, longer hospital and intensive care unit duration, higher rates of a variety of complications and more utilization of invasive interventions., Conclusions: IAP is an independent risk factor for the development of SVT in patients with NAP, while Balthazar's CT score and occurrence of IPN are also associated with SVT, although not as strong as IAP. Moreover, occurrence of SVT relates with extremely poor prognosis in NAP patients, evidenced by increased mortality, morbidity and need for invasive interventions., (Copyright © 2014 Elsevier Ltd. All rights reserved.)

Objective: To learn the clinical outcome of percutaneous catheter drainage (PCD) for patients with infective pancreatic necrosis and the possible influencing factors., Methods: A retrospective review of medical records of patients with infective pancreatic necrosis who received PCD as the first choice for treatment in the recent 2 years. The patients were divided into 2 groups: (1) PCD success group and (2) PCD alteration group. Characteristics, complications, and PCD process were compared., Results: In this study, 19 of 34 patients were cured by PCD alone (55.9%), whereas open necrosectomy were needed for 15 patients (44.1%). Between these 2 groups, most baseline and clinical characteristics did not show any statistical difference, including the number and size of catheter used and the bacterial culture result. The PCD alteration group had higher mean computed tomographic density (P = 0.012) and larger distribution range of infected pancreatic necrosis (4.53 ± 1.35 vs 5.93 ± 1.62; P = 0.009) than the PCD success group (P < 0.01). The logistic regression analysis revealed the same facts., Conclusion: The mean computed tomographic density and distribution range of infective pancreatic necrosis could significantly influence the success rate of PCD; higher values of them indicate less appropriate for PCD; thus, it should be considered seriously before the treatment decision.

Objective: Acute pancreatitis during pregnancy is a rare and dangerous disease. This study attempts to present a comprehensive analysis of severe acute pancreatitis (SAP) during pregnancy and to identify the factors associated with poor outcomes., Methods: This study was a retrospective review of the medical records of SAP patients during pregnancy consecutively admitted into the Research Institute of General Surgery from 1999 to 2010., Results: Information was collected on presentation, management, and outcome. Eighteen patients were identified to have been diagnosed with SAP during pregnancy. Eleven patients (61.1%) were nulliparous; most attacks (88.9%) occurred during the third trimester. There were seven cases with preterm labor, six with fetal losses, and no maternal death. The etiology was biliary disease in seven patients (38.9%), hypertriglyceridemia in five patients (27.8%), both biliary and hypertriglyceridemia in four patients (22.2%), and idiopathic in two patients (11.1%). Patients with failure in more than one (≥2) organ were more likely to result in fetal loss (OR = 25, P = 0.016)., Conclusions: SAP during pregnancy is predominantly biliary in etiology, but a significant proportion is caused by hypertriglyceridemia. Patients with failure in at least two organs result in relatively worse fetal outcomes.

Objective: The aim of this study was to investigate the effect of high-volume hemofiltration (HVHF) on ameliorating immune dysfunction in patients with severe acute pancreatitis (SAP)., Methods: Twelve patients diagnosed with SAP admitted to the intensive care unit of general surgery, Jinling Hospital, from January 2004 to December 2006 were included in this study. They were assigned to the standard medical therapy group (SMT group, n=4) or HVHF group (n=8) immediately after enrollment, in a 1:2 ratio. The SMT group were given standard treatment for SAP, while the HVHF group were given standard as well as 72-hour HVHF treatment initiated within 2 hours after enrollment. Patients in the 2 groups were comparable for the baseline clinical parameters. All patients were monitored over a 72-hour observation period for continuous clinical status, blood cell counts including monocytes, CD4+ and CD8+ T cells, and HLA-DR expression on monocytes. Blood samples were collected from those patients at 0, 6, 12, 24, 48, and 72 hour after enrollment for measurement of plasma Th1-type cytokines (interleukin-1 [IL-1], IL-2, interferon-gamma [IFN-gamma], and tumor necrosis factor-alpha [TNF-alpha]) and Th2-type cytokines (IL-4, IL-5, IL-6, IL-IO, and IL-13) using ELISA., Results: Within 72 hours, all measured cytokines except IL-4 were maintained at high levels, accompanied with a low level of peripheral monocytes, CD4+ and CD8+ T cell counts, and HLA-DR expression. Seventy-two hours later, plasma cytokines IFN-gamma, IL-1, IL-2, IL-5, IL-10, and IL-13 (p<0.05), but not TNF-alpha and IL-6, in patients in the HVHF group were significantly reduced, while there was no change for these parameters in the SMT group. Plasma levels of IFN-gamma, TNF-alpha, IL-1, IL-2, IL-5, and IL-13 in the HVHF group were significantly lower than those in the SMT group. Peripheral CD4+ and CD8+ T cells, monocyte count, and HLA-DR expression were increased significantly (p<0.05) only in the HVHF group, not in the SMT group. HLA-DR expression in the HVHF group was significant higher than that in the SMT group (p<0.05)., Conclusions: HVHF significantly reduced plasma inflammatory cytokine concentrations including those of IFN-gamma, TNF-alpha, IL-1, IL-2, IL-5, and IL-13, while it increased monocyte HLA-DR expression in patients with SAP. The association of plasma cytokine reduction and cellular immune function recovery and clinical outcome needs further investigation.

Objective: To investigate the effectiveness of using continuous veno venous hemofiltration (CVVH) in the treatment of acute necrotizing pancreatitis (ANP)., Methods: Thirteen ANP patients were involved in this study, including 4 females and 9 males, averaging 50.6 +/- 10.8 years old. CT scans upon admission revealed 33% necrosis involving the body of the pancreas in 2 patients, 67% necrosis in 3 patients and 100% necrosis in the other 8; the CT severity score was 8.9 +/- 2.1. CVVH was maintained for at least 72 hours and the AN69 hemofilter (1.2 m(2)) was changed every 24 hours. The ultrafiltration rate during CVVH was 2993.9 +/- 983.0 ml/h, the blood flow rate was 250 - 300 ml/min, and the substitute fluid was infused in a pre-diluted manner. Low molecular weight heparin was used as anticoagulant., Results: CVVH was well tolerated in all the patients. Bloody abdominal cavity drainage fluid was observed in 2 patients, but no other side-effects related with CVVH were observed. Two patients died of systemic fungal infections and another died of intracranial fungi infection, resulting in an ICU mortality of 23.1%. Ten of the patients survived in the ICU, but one of them died for other reasons unrelated to the SAP before discharge. The APACHE II score before CVVH was 15.2 +/- 6.5, but decreased significantly to 8.1 +/- 5.3, 7.5 +/- 4.9 and 8.0 +/- 5.2 at the 24th, 48th and 72nd hour after CVVH, respectively (P < 0.01). Serum concentration of IL-1beta and TNFalpha decreased to the trough at the 6th hour after a new hemofilter was used and increased slowly to pre-CVVH levels 12 hours later. After CVVH had ceased, the serum levels of two cytokines increased to their peaks at the 120th hour and decreased eventually at the 144th hour. The sieving coefficient (SC) of IL-1beta and TNFalpha was 0.33 +/- 0.11 and 0.16 +/- 0.08., Conclusion: CVVH offered therapeutic options for ANP and was well tolerated resulting in clearance of IL-1beta and TNFalpha; CVVH at early stages of SAP may contribute to the improvement of outcome.