Construction and validation of a rat model of acute necrotizing pancreatitis-associated intestinal injury.

Acute pancreatitis (AP) is an acute inflammatory reaction of the pancreatic tissue, which involves auto-digestion, edema, hemorrhage, and necrosis. AP can be categorized into mild, moderately severe, and severe AP, with severe pancreatitis also referred to as acute necrotizing pancreatitis (ANP). ANP is characterized by the accumulation of necrotic material in the peritoneal cavity. This can result in intestinal injury. However, the mechanism of ANP-associated intestinal injury remains unclear. We established an ANP-associated intestinal injury rat model (ANP-IR model) by injecting pancreatitis-associated ascites fluid (PAAF) and necrotic pancreatic tissue at various proportions into the triangular area formed by the left renal artery and ureter. The feasibility of the ANP-IR model was verified by comparing the similar changes in indicators of intestinal inflammation and barrier function between the two rat models. In addition, we detected changes in apoptosis levels and YAP protein expression in the ileal tissues of rats in each group and validated them in vitro in rat epithelial crypt cells (IEC-6) to further explore the potential injury mechanisms of ANP-associated intestinal injury. We also collected clinical data from patients with ANP to validate the effects of PAAF and pancreatic necrosis on intestinal injury. Our findings offer a theoretical basis for restricting the buildup of peritoneal necrosis in individuals with ANP, thus promoting the restoration of intestinal function and enhancing treatment efficacy. The use of the ANP-IR model in further studies can help us better understand the mechanism and treatment of ANP-associated intestinal injury.NEW & NOTEWORTHY We constructed a rat model of acute necrotizing pancreatitis-associated intestinal injury and verified its feasibility. In addition, we identified the mechanism by which necrotic pancreatic tissue and pancreatitis-associated ascites fluid (PAAF) cause intestinal injury through the HIPPO signaling pathway.

Colonic mucin-2 attenuates acute necrotizing pancreatitis in rats by modulating intestinal homeostasis.

Mucin-2 (MUC2) secreted by goblet cells participates in the intestinal barrier, but its mechanism in acute necrotizing pancreatitis (ANP) remains unclear. In acute pancreatitis (AP) patients, the functions of goblet cells (MUC2, FCGBP, CLCA1, and TFF3) decreased, and MUC2 was negatively correlated with AP severity. ANP rats treated with pilocarpine (PILO) (PILO+ANP rats) to deplete MUC2 showed more serious pancreatic and colonic injuries, goblet cell dysfunction, gut dysbiosis, and bacterial translocation than those of ANP rats. GC-MS analysis of feces showed that PILO+ANP rats had lower levels of butyric acid, isobutyric acid, isovaleric acid, and hexanoic acid than those of ANP rats. The expression of MUC2 was associated with colonic injury and gut dysbiosis. All these phenomena could be relieved, and goblet cell functions were also partially reversed by MUC2 supplementation in ANP rats. TNF-α-treated colonoids had exacerbated goblet cell dysfunction. MUC2 expression was negatively correlated with the levels of pro-inflammatory cytokines (IL-1ß and IL-6) (p < .05) and positively related to the expression of tight junction proteins (Claudin 1, Occludin, and ZO1) (p < .05). Downregulating MUC2 by siRNA increased the levels of the pro-inflammatory cytokines in colonoids. MUC2 might maintain intestinal homeostasis to alleviate ANP.

Factors predictive of hospital length of stay in patients with an index episode of acute necrotizing pancreatitis.

INTRODUCTION: Acute necrotizing pancreatitis (ANP) complicates 15 % of acute pancreatitis cases and is associated with prolonged length of stay (LOS). There are limited studies exploring potential predictors. METHODS: We carried out a retrospective study of all consecutive patients presenting to a large referral healthcare system with ANP. Patients younger than 18 years of age, without confirmed glandular necrosis and with in-hospital mortality were excluded. Poisson regression was carried out to identify potential predictors of prolonged hospital stay. RESULTS: One hundred and sixty-two patients hospitalized between December 2016 and June 2020 were included. The median LOS was 12 days (range: 1-155 days). On multivariate analysis, organ dysfunction at presentation (Incidence rate ratio (IRR) 1.21, p = 0.01) or during admission (IRR 1.32, p = 0.001), Charlson Comorbidity Index scores (IRR 1.1 per CCI point, p < 0.001), known chronic pancreatitis (IRR 1.19, p = 0.03), concurrent (non-pancreas related) infections (IRR 1.13, p = 0.04), need for enteral tube placement (IRR 3.42, p < 0.001) and in-hospital interventions (IRR 1.48-2.85 depending on intervention, p < 0.001) were associated with increased LOS. For patients in the cohort to whom this applied, delayed hospital transfers (IRR 1.02, p < 0.001) and delayed start of enteral feeds (IRR 1.01, p = 0.017) contributed to increased overall LOS. CONCLUSION: We demonstrate that multiple factors including delayed transfers to hospitals with pancreaticobiliary expertise lead to increased length of hospitalization. We suggest various strategies that can be considered to target those gaps and may have a favorable effect on LOS.

Incidence and risk factors for deep vein thrombosis (DVT) and pulmonary embolism (PE) in acute necrotizing pancreatitis (ANP) - A single center experience.

INTRODUCTION: Inflammation-induced dysregulation of the coagulation cascade and vascular stasis in hospitalized patients with acute necrotizing pancreatitis (ANP) serve as a milieu for venous thromboembolism (VTE). Deep vein thrombosis (DVT) and pulmonary embolism (PE) are often underrecognized. We evaluated the incidence and risk factors for VTE in a cohort of patients with ANP. METHODS: All adult patients with ANP at our center between 2009 and 2022 were followed for three months after index hospitalization and categorized into cases and controls based on development of VTE. Demographic, clinical, and radiologic characteristics during admission were compared. A multivariable analysis was done to identify independent predictors for VTE. A p value of <0.05 was taken as significant. RESULTS: Among 643 ANP patients, 512 [males-350, median age-52 years] were eligible for inclusion. VTE developed in 64 (12.5 %) patients - 28 DVT (5 %), 22 PE (4 %) and both in 14 (3 %) after a median 16 days from the diagnosis of ANP. Significant independent predictors for VTE on multivariable analysis were age ≥60 years (OR 1.91; 95 % CI 1.04-3.53), peri-pancreatic extent of necrosis (OR 7.61; 95 % CI 3.94-14.70), infected necrosis (OR 2.26; 95 % CI 1.13-4.50) and total length of stay ≥14 days (OR 4.08; 95 % CI 1.75-9.50). CONCLUSIONS: The overall incidence of VTE in our cohort of patients with ANP was 12.5 %, which was usually diagnosed within one month of hospitalization. High-risk patients can be stratified based on clinical and imaging characteristics and may benefit from intensive DVT screening and prophylaxis during hospitalization and following discharge.

Risks of Post-Endoscopic Retrograde Cholangiopancreatography Pancreatitis After Liver Transplantation.

Biliary complications are common after liver transplantation (LT). Endoscopic retrograde cholangiopancreatography (ERCP) is the preferred method to treat biliary complications. Nevertheless, ERCP is not without complications and may have a greater complication rate in the LT population. Knowledge of the prevalence, severity, and possible risk factors for post-ERCP pancreatitis (PEP) in LT recipients is limited. Therefore, this study aims to determine the incidence and severity of PEP and identify potential risk factors in LT recipients. This retrospective cohort included patients ≥18 years who underwent ≥1 ERCP procedures after LT between January 2010 and October 2021. Two hundred thirty-two patients were included, who underwent 260 LTs and 1125 ERCPs. PEP occurred after 23 ERCP procedures (2%) with subsequent mortality in three (13%). Multivariate logistic regression identified wire cannulation of the pancreatic duct as a significant risk factor for PEP (OR, 3.21). The complication rate of PEP after LT in this study was shown to be low and is lower compared to patients without a history of LT. Nevertheless, the mortality rate of this group of patients was notably higher.

Plastic pigtail vs lumen-apposing metal stents for drainage of walled-off necrosis (PROMETHEUS study): an open-label, multicenter randomized trial.

BACKGROUND: Lumen-apposing metal stents (LAMS) have displaced double-pigtail plastic stents (DPS) as the standard treatment for walled-off necrosis (WON),ß but evidence for exclusively using LAMS is limited. We aimed to assess whether the theoretical benefit of LAMS was superior to DPS. METHODS: This multicenter, open-label, randomized trial was carried out in 9 tertiary hospitals. Between June 2017, and Oct 2020, we screened 99 patients with symptomatic WON, of whom 64 were enrolled and randomly assigned to the DPS group (n = 31) or the LAMS group (n = 33). The primary outcome was short-term (4-weeks) clinical success determined by the reduction of collection. Secondary endpoints included long-term clinical success, hospitalization, procedure duration, recurrence, safety, and costs. Analyses were by intention-to-treat. CLINICALTRIALS: gov, NCT03100578. RESULTS: A similar clinical success rate in the short term (RR, 1.41; 95% CI 0.88-2.25; p = 0.218) and in the long term (RR, 1.2; 95% CI 0.92-1.58; p = 0.291) was observed between both groups. Procedure duration was significantly shorter in the LAMS group (35 vs. 45-min, p = 0.003). The hospital admission after the index procedure (median difference, - 10 [95% CI - 17.5, - 1]; p = 0.077) and global hospitalization (median difference - 4 [95% CI - 33, 25.51]; p = 0.82) were similar between both groups. Reported stent-related adverse events were similar for the two groups (36 vs.45% in LAMS vs. DPS), except for de novo fever, which was significantly 26% lower in LAMS (RR, 0.26 [0.08-0.83], p = 0.015). CONCLUSIONS: The clinical superiority of LAMS over DPS for WON therapy was not proved, with similar clinical success, hospital stay and similar safety profile between both groups, yet a significant reduction in procedure time was observed. TRIAL REGISTRATION NUMBER: ClinicalTrials.gov, NCT03100578.

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.

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.

Early systemic anticoagulation reduces hospital readmission in acute necrotizing pancreatitis patients: A retrospective cohort study.

BACKGROUND: Early systemic anticoagulation (SAC) is a common practice in acute necrotizing pancreatitis (ANP), and its impact on in-hospital clinical outcomes had been assessed. However, whether it affects long-term outcomes is unknown. This study aimed to evaluate the effect of SAC on 90-day readmission and other long-term outcomes in ANP patients. METHODS: During January 2013 and December 2018, ANP patients admitted within 7 days from the onset of abdominal pain were screened. The primary outcome was 90-day readmission after discharge. Cox proportional-hazards regression model and mediation analysis were used to define the relationship between early SAC and 90-day readmission. RESULTS: A total of 241 ANP patients were enrolled, of whom 143 received early SAC during their hospitalization and 98 did not. Patients who received early SAC experienced a lower incidence of splanchnic venous thrombosis (SVT) [risk ratio (RR) = 0.40, 95% CI: 0.26-0.60, P < 0.01] and lower 90-day readmission with an RR of 0.61 (95% CI: 0.41-0.91, P = 0.02) than those who did not. For the quality of life, patients who received early SAC had a significantly higher score in the subscale of vitality (P = 0.03) while the other subscales were all comparable between the two groups. Multivariable Cox regression model showed that early SAC was an independent protective factor for 90-day readmission after adjusting for potential confounders with a hazard ratio of 0.57 (95% CI: 0.34-0.96, P = 0.04). Mediation analysis showed that SVT mediated 37.0% of the early SAC-90-day readmission causality. CONCLUSIONS: The application of early SAC may reduce the risk of 90-day readmission in the survivors of ANP patients, and reduced SVT incidence might be the primary contributor.

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.

Does the site, size, and number of necrotic collections affect the outcome of necrotizing pancreatitis? - a prospective analysis.

PURPOSE: In patients with acute necrotizing pancreatitis (ANP), the site, size, and the number of acute necrotic collections (ANC) may determine the outcome of patients. The current study aimed to correlate the nature of ANC with the adverse outcomes in ANP patients. METHODS: This was a single-center, prospective study (August 2019-August 2022) recruiting patients with ANP, correlating the site, size, and number of ANC with the length of hospital stay, intensive care unit (ICU) stays, development of organ failure and infection, need for intervention, and mortality. RESULTS: A total of 114 patients (mean age: 37.3 ± 13.4 years, 85.1% males) with ANP were included in the study. The number and maximum diameter of collections significantly correlated with the length of the hospital and ICU stay and the need for intervention. Taking a cut-off size of 8 cm, the sensitivity and specificity for predicting the need for intervention were 82.7% and 74.2%, respectively. ANCs located in the perinephric, paracolic, subhepatic, and epigastric regions had a significant correlation with two or more adverse outcomes. Additional points were added to the modified CT severity index (mCTSI) based on the present study's findings. The new score had significantly higher AUROC than mCTSI for predicting infection, need for intervention, ICU stay > 1 week, and mortality. CONCLUSION: The site, size, and number of EPNs have a significant correlation with adverse clinical outcomes in patients with ANP. The inclusion of these parameters, along with present scoring systems, will help further improve the prognostication of patients.

Emphysematous Pancreatitis as a Life-Threatening Condition: A Case Report and Review of the Literature.

Emphysematous pancreatitis represents the presence of gas within or around the pancreas on the ground of necrotizing pancreatitis due to superinfection with gas-forming bacteria. This entity is diagnosed on clinical grounds and on the basis of radiologic findings. Computed tomography is the preferred imaging modality used to detect this life-threating condition. The management of emphysematous pancreatitis consists of conservative measures, image-guided percutaneous catheter drainage or endoscopic therapy, and surgical intervention, which is delayed as long as possible and undertaken only in patients who continue to deteriorate despite conservative management. Due to its high mortality rate, early and prompt recognition and treatment of emphysematous pancreatitis are crucial and require individualized treatment with the involvement of a multidisciplinary team. Here, we present a case of emphysematous pancreatitis as an unusual occurrence and discuss disease features and treatment options in order to facilitate diagnostics and therapy.

Endoscopic Versus Surgical Step-Up Approach for Infected Necrotizing Pancreatitis (ExTENSION): Long-term Follow-up of a Randomized Trial.

BACKGROUND & AIMS: Previous randomized trials, including the Transluminal Endoscopic Step-Up Approach Versus Minimally Invasive Surgical Step-Up Approach in Patients With Infected Pancreatic Necrosis (TENSION) trial, demonstrated that the endoscopic step-up approach might be preferred over the surgical step-up approach in patients with infected necrotizing pancreatitis based on favorable short-term outcomes. We compared long-term clinical outcomes of both step-up approaches after a period of at least 5 years. METHODS: In this long-term follow-up study, we reevaluated all clinical data on 83 patients (of the originally 98 included patients) from the TENSION trial who were still alive after the initial 6-month follow-up. The primary end point, similar to the TENSION trial, was a composite of death and major complications. Secondary end points included individual major complications, pancreaticocutaneous fistula, reinterventions, pancreatic insufficiency, and quality of life. RESULTS: After a mean follow-up period of 7 years, the primary end point occurred in 27 patients (53%) in the endoscopy group and in 27 patients (57%) in the surgery group (risk ratio [RR], 0.93; 95% confidence interval [CI], 0.65-1.32; P = .688). Fewer pancreaticocutaneous fistulas were identified in the endoscopy group (8% vs 34%; RR, 0.23; 95% CI, 0.08-0.83). After the initial 6-month follow-up, the endoscopy group needed fewer reinterventions than the surgery group (7% vs 24%; RR, 0.29; 95% CI, 0.09-0.99). Pancreatic insufficiency and quality of life did not differ between groups. CONCLUSIONS: At long-term follow-up, the endoscopic step-up approach was not superior to the surgical step-up approach in reducing death or major complications in patients with infected necrotizing pancreatitis. However, patients assigned to the endoscopic approach developed overall fewer pancreaticocutaneous fistulas and needed fewer reinterventions after the initial 6-month follow-up. Netherlands Trial Register no: NL8571.

Profile of and risk factors for early unplanned readmissions in patients with acute necrotizing pancreatitis.

INTRODUCTION: Acute necrotizing pancreatitis (ANP) complicates up to 15% of acute pancreatitis cases. ANP has historically been associated with a significant risk for readmission, but there are currently no studies exploring factors that associate with risk for unplanned, early (<30-day) readmissions in this patient population. METHODS: We performed a retrospective review of all consecutive patients presenting to hospitals in the Indiana University (IU) Health system with pancreatic necrosis between December 2016 and June 2020. Patients younger than 18 years of age, without confirmed pancreatic necrosis and those that suffered in-hospital mortality were excluded. Logistic regression was performed to identify potential predictors of early readmission in this group of patients. RESULTS: One hundred and sixty-two patients met study criteria. 27.7% of the cohort was readmitted within 30-days of index discharge. The median time to readmission was 10 days (IQR 5-17 days). The most frequent reason for readmission was abdominal pain (75.6%), followed by nausea and vomiting in (35.6%). Discharge to home was associated with 93% lower odds of readmission. We found no additional clinical factors that predicted early readmission. CONCLUSION: Patients with ANP have a significant risk for early (<30 days) readmission. Direct discharge to home, rather than short or long-term rehabilitation facilities, is associated with lower odds of early readmission. Analysis was otherwise negative for independent, clinical predictors of early unplanned readmissions in ANP.

Involvement of transverse mesocolon is associated with development of colonic fistula in patients with acute necrotizing pancreatitis.

BACKGROUND: Involvement of transverse mesocolon (TM) during acute necrotizing pancreatitis(ANP) indicates that inflammation has spread from retroperitoneal space to peritoneum. Nevertheless, the impact of TM involvement, as confirmed by contrast-enhanced computed tomography (CECT), on local complications and clinical outcomes was poorly investigated. PURPOSE: This study aimed to explore the association between CECT-diagnosed TM involvement and the development of colonic fistula in a cohort of ANP patients. METHODS: This is a single-center, retrospective cohort study involving ANP patients admitted from January 2020 to December 2020. TM involvement was diagnosed by two experienced radiologists. The study subjects were enrolled consecutively and divided into two groups: TM involvement and non-TM involvement. The primary outcome was colonic fistula during the index admission. Clinical outcomes were compared between the two groups, and the association between the TM involvement and the development of colonic fistula was assessed using multivariable analysis to adjust for baseline unbalances. RESULTS: A total of 180 patients with ANP were enrolled, and 86 (47.8%) patients had TM involvement. The incidence of the colonic fistula is significantly higher in patients with TM involvement (16.3% vs. 5.3%;p = 0.017). Moreover, the length of hospital stay was 24(13,68) days in patients with TM involvement and 15(7,31) days in those not (p = 0.001). Analysis of multivariable logistic regression revealed that TM involvement is an independent risk factor for the development of colonic fistula (odds ratio: 10.253, 95% CI: 2.206-47.650, p = 0.003). CONCLUSION: TM involvement in ANP patients is associated with development of colonic fistula in ANP patients.

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

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

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

Clinical characteristics and risk factors of organ failure and death in necrotizing pancreatitis.

BACKGROUND: Organ failure (OF) and death are considered the most significant adverse outcomes in necrotizing pancreatitis (NP). However, there are few NP-related studies describing the clinical traits of OF and aggravated outcomes. PURPOSE: An improved insight into the details of OF and death will be helpful to the management of NP. Thus, in our research, we addressed the risk factors of OF and death in NP patients. METHODS: We performed a study of 432 NP patients from May 2017 to December 2021. All patients with NP were followed up for 36 months. The primary end-points were risk factors of OF and death in NP patients. The risk factors were evaluated by logistic regression analysis. RESULTS: NP patients with OF or death patients were generally older, had a higher APACHE II score, longer hospital stay, longer ICU stay, as well as a higher incidence of severe acute pancreatitis (SAP), shock and pancreatic necrosis. Independent risk factors related to OF included BMI, APACHE II score and SAP (P < 0.05). Age, shock and APACHE II score (P < 0.05) were the most significant factors correlated with the risk of death in NP patients. Notably, increased mortality was linked to the number of failed organs. CONCLUSIONS: NP is a potentially fatal disease with a long hospital or ICU stay. Our study indicated that the incidence of OF and death in NP patients was 69.9% and 10.2%, respectively. BMI, SAP, APACHE II score, age and shock are potential risk factors of OF and death in NP patients. Clinicians should focus on these factors for early diagnosis and appropriate therapy.

Mitochondrial DNA Copy Number, a Damage-Associated Molecular Pattern Molecule, Can Predict Pancreatic Necrosis and Is Correlated with the Severity of Acute Pancreatitis.

BACKGROUND: Mitochondrial DNA (mtDNA) is a damage-associated molecular pattern molecule that can trigger an immune-inflammatory response during pancreatic necrosis (PN). AIM: To evaluate the role of mtDNA in the detection of PN and severe acute pancreatitis (SAP). METHODS: The present study included 40 AP patients and 30 controls. AP patients were grouped into mild AP (MAP, n = 15), moderately severe AP (MSAP, n = 17), and SAP (n = 8). Also, the SAP + MSAP group, n = 25, was compared to MAP. AP patients were divided into NAP (n = 7) and non-necrotizing AP (n = 33). The mtDNA copy number, IL-6, and STAT3 expression levels were measured using quantitative real-time PCR. RESULTS: The mtDNA, IL-6, and STAT3 levels were significantly higher in AP patients than in controls and in the SAP + MSAP than in the MAP. However, the SAP had non-significantly higher levels of mtDNA, STAT3, and IL-6 levels than the MSAP and statistically significant mtDNA, STAT3, and IL-6 when compared to the MAP. mtDNA, IL-6, and STAT3 showed significantly higher levels in NAP compared with non-necrotizing AP. mtDNA was positively correlated with STAT3, IL-6, CRP, APACHE, and CT severity index (CTSI) and negatively correlated with albumin. In the receiver operating curve (ROC), mtDNA was the most significant independent predictor of PN and MAP vs. SAP + MSAP. IL-6 and mtDNA + CRP had higher diagnostic abilities for SIRS and high CTSI. CONCLUSIONS: mtDNA could enhance the prediction of NAP; however, its diagnostic ability of SAP needs further study.

Deep Venous Thrombosis in Acute Pancreatitis Is Associated with High Mortality: A Prospective Study.

BACKGROUND: Incidence and risk factors for the development of extremity deep vein thrombosis (eDVT) in admitted patients of acute pancreatitis have been rarely explored. AIMS: To identify the incidence of eDVT and to explore role of clinical scores for predicting eDVT in admitted patients of acute pancreatitis. METHODS: We prospectively enrolled admitted patients of acute pancreatitis and performed a weekly eDVT screen for the duration of their admission. Well's score and Padua's score were also calculated weekly. The incidence of venous thrombosis (eDVT and splanchnic thrombosis based on contrast-enhanced CT scan abdomen) was noted, and the risk factors were determined using multivariate analysis. The correlation between Well's score, Padua's score, and development of DVT was calculated using Pearson's correlation. RESULTS: Of the 102 patients of acute pancreatitis enrolled, 73.5% of patients had necrotizing pancreatitis. Total of 46 patients (45.1%) developed thrombosis: 43 patients had splanchnic vein thrombosis; 5 patients had eDVT; and 1 patient had pulmonary embolism. Patients with eDVT had higher BISAP score (2.6 ± 0.9 vs 1.7 ± 0.8; p = 0.039), requirement of mechanical ventilation (60% vs 8.2%; p = 0.008), and mortality (60% vs 12.4%; p = 0.022). Well's score of ≥ 2 had sensitivity and specificity of 80% and 96.9% for prediction of eDVT and it had better correlation with the development of eDVT compared to Pauda's score. CONCLUSION: Incidence of DVT is 5% in patients with acute pancreatitis requiring admission. It is associated with higher disease severity and mortality. The Well's score is useful to predict the development of eDVT in routine clinical practice.

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.