Acute Necrotizing Pancreatitis Research Articles

The effect of procalcitonin and immature granulocyte ratio in predicting the development of acute necrotizing pancreatitis: evidence from 582 cases.

Acute pancreatitis (AP) is one of the diseases that surgical clinics deal with the most. While mortality rates are approximately 1% in all cases, this rate may increase to 15% in pancreatic necrosis cases. Therefore, early diagnosis and treatment are very important in necrotizing pancreatitis. Our aim in this study is to present the guiding effectiveness of procalcitonin and immature granulocyte ratios (IG%) in planning the early diagnosis and treatment of acute necrotizing pancreatitis. 582 patients hospitalized in our clinic with the diagnosis of acute pancreatitis were included in this study. All patients were divided into two groups as acute edematous pancreatitis (AEP) and acute necrotizing pancreatitis (ANP) according to tomography results. White blood cell (WBC) count, procalcitonin, IG%, C-reactive protein (CRP), amylase and lipase, albumin, CRP/albumin levels were recorded. The differences between the two groups were analyzed statistically. According to the results of contrast-enhanced abdominal tomography (CECT), 525 patients were diagnosed with AEP and 57 with ANP. WBC, CRP, procalcitonin, IG and CRP/albumin were found to be significantly higher in ANP patients when compared to AEP (p<0.0001). According to the ROC analysis result, procalcitonin (AUROC: 0.999), IG% (AUROC: 0.995), WBC count (AUROC: 0.841), CRP (AUROC: 0.947), albumin (AUROC: 0.862), and CRP/albumin (AUROC: 0.946) ratio were markers that could be used for early prediction of ANP. Early diagnosis of ANP can reduce morbidity and mortality. Procalcitonin and IG% levels can be easily accessible and effective markers in the early diagnosis of ANP and in the planning of treatment.

S100 Predictors of Need of Surgery in Patients With Acute Necrotic Collections Treated With Percutaneous Drainage

Introduction: Percutaneous drainage (PCD) is an important initial component of the “step-up” treatment strategy for the management of infected acute necrotic collections consequent to acute necrotizing pancreatitis (ANP). However, PCD alone has a high failure rate and these patients require additional necrosectomy. Delaying necrosectomy can increase morbidity and mortality and therefore, timely intervention is important. Identifying predictors of failure of percutaneous therapy can help in making timely management decisions. In this prospective single-center study, we attempted to identify predictors of failure of PCD in patients with infected ANC. Methods: Twenty-one patients (males:13, mean age:36.05years) (etiology: ethanol-related 47.6% (10/21), GSD related 28.6% (6/21) unknown19% (4/21) PEP 4.8% (1/21)) admitted with infected ANC who were treated with step-up strategy of initial PCD followed by endoscopic or surgical necrosectomy in non-responders were enrolled and studied prospectively. We studied the association between the success of PCD (survival without necrosectomy) & baseline clinical and investigational parameters including etiology, severity scores, C-reactive protein (CRP), computed tomography severity indices (CTSI), and PCD parameters (size of catheter & timing). Results: Nine (42.8%) patients with infected ANC were successfully treated with PCD alone whereas 12 (57.2%) patients either underwent necrosectomy or succumbed to the illness. The frequency of males was significantly higher (83.3% vs 33.33%) in the PCD failure group(p=0.03). The PCD was inserted later in the failure group as compared to the successful group (mean day of insertion of PCD being 20.5 days vs 15.1 days respectively; p=0.023). The mean SIRS score at admission (2.92 vs 2.33; p=0.102) & at 48 hours (3.5 vs 2.89; p=0.12), mean APACHE-II score (7.8 vs 7.0; p=0.508), mean ferritin levels (2916.9 vs 1033.4ng/mL; p= 0.394), and mean CRP levels (249.5 vs 209.6ng/mL; p=0.508.) were higher in the PCD failure group but did not reach statistical significance. The corrected calcium levels were lower(8.3 vs 9.0gm/dL p=0.069) in the PCD failure group. Also, the mean diameter of PCD catheters was more in the success group but the difference was not statistically significant (16.2 vs 14.7F; p=0.277). (Table) Conclusion: Male gender & delayed insertion of PCD seem to be associated with failure of PCD alone in patients with infected necrotic collections. Table 1. - Comparison of parameters between PCD Success and PCD Failure Group Parameter PCD Success group n=9 PCD failure group n=12 P Value Age 37.3±7.5yrs 36.8±13.4yrs 0.65 Males 3(33.33%) 10(83.33%) 0.03 BMI 24.5±4.3Kg/m2 22.4±3.8kg/m2 0.22 TLC 13871±6616.1/mm3 15014.2±7818.6/mm3 0.862 Platelet Count 321666.7±187813.7/mm3 304350.0±155671.1/mm 0.972 Ferritin Level 1033.4±628.2ng/mL 2916.9±2961.8ng/mL 0.394 Corrected Calcium 9.0±0.3gm/dL 8.3±1.2gm/dL 0.069 qCRP Levels 209.6±95.9mg/L 249±107.1mg/L 0.508 SIRS At admission 2.33±0.5 2.92±1.0 0.10 At 48hrs 2.89±0.93 3.50±0.52 0.12 APACHE-II 7.0±3.0 7.8±8.0 0.51 MMS 1.4±0.9 1.7±1.8 0.70 BISAP 2.1±0.3 2.3±0.8 0.55 Size of largest collection on CT 10.3±4.34cm 11.15±3.42cm 0.81 CTSI Score 7.3±2.5 7.8±2.5 0.65 mCTSI Score 8.7±1.7 9.2±1.3 0.60 Day of PCD placement 15.1±4.9 20.5±3.9 0.02 Size of largest PCD in the French scale 16.2±3.1 14.7±4.2 0.28

Wall maturation in necrotic collections in acute pancreatitis: a computed tomography based evaluation.

To systematically investigate the timing of encapsulation of necrotic collections in acute necrotizing pancreatitis (ANP) using contrast-enhanced computed tomography (CECT). This retrospective study comprised consecutive patients of ANP who underwent CECT of the abdomen between the second and fourth weeks of illness. Number and site of collections and presence and completeness of the wall (defined as a thin smooth enhancing rim more than 1 mm in thickness) were documented. A total of 195 patients of ANP were included. Seven hundred seventy-three collections were evaluated in 284 CECT scans. The most common site of the collection was anterior pararenal space (n=290, 37.5%). The mean maximum dimension of the collection was 8.1 cm (range, 3.1-16 cm). Two hundred twentytwo (28.7%) collections had a complete wall. The mean interval to complete wall maturation was 18 days (range, 8-28). Overall, 13.3%, 37.1%, and 56.2% of the collections showed complete encapsulation in the second, third, and fourth weeks, respectively. Our study suggests that a significant proportion of necrotic collections show complete encapsulation within 4 weeks of the onset of ANP.

CHANGES IN THE OPTICAL DENSITY OF VENOUS BLOOD PLASMA IN PATIENTS WITH PATHOLOGY OF DIFFERENT TISSUES OF THE ABDOMINAL CAVITY

Rapid and adequate diagnosis of infl ammatory and destructive injuries of the abdominalorgans is an urgent problem of emergency abdominal surgery. The basis of laboratorydiagnosis in emergency abdominal surgery is to determine the number of leukocytes andtheir forms, the content of C-reactive protein. But the results of such studies are nonspecific. With unclear clinical symptoms, this creates the preconditions for diagnostic errors.To avoid such errors, the determination of the optical characteristics of venous bloodplasma is used. In particular, we studied the optical density of venous blood plasma in theultraviolet spectrum. However, the informativeness of the method was about 86%. Thisneeds improvement. Previous studies of the optical density of venous blood plasma in theinfrared range have shown prospects. Therefore, we conducted new research.The aim of the study – to evaluate the possibility of using the determination of theoptical density of venous blood plasma in the infrared range for diagnosis in emergencyabdominal surgery. The aim of the work is to evaluate the possibilities of using thedetermination of the optical density of venous blood plasma for the diagnosis of acuteinfl ammatory- destructive intra- abdominal pathology.Materials and methods. 42 patients were examined. Among them were: liver abscess –3 cases, acute necrotic pancreatitis – 7, acute intestinal obstruction with intestinalnecrosis – 4, acute edematous pancreatitis – 3, acute phlegmonous appendicitis – 4, acutephlegmonous cholecystitis – 11, unclamped hernia, uncomplicated care – 6.Results. We found in the infrared spectrum a number of maxima of the values of theoptical density of blood plasma, which are localized at wavelengths λ = 365, 555, 620,715, and 770 nm (table). Indicators of optical density at these wavelengths diff ered indiff erent diseases and complications. The obtained results indicate that the optical densityof venous blood plasma in the infrared range varies, depending on the characteristics ofintra- abdominal pathology. At each of the wavelengths, the indicators for diff erent diseasesdiff ered signifi cantly. The most pronounced changes were at wavelengths λ = 365, 555.In all patients with destructive changes in organs (phlegmonous appendicitis, phlegmonouscholecystitis, necrotic pancreatitis, acute intestinal obstruction with intestinal necrosis,liver abscess) in this range were signifi cantly lower in this range. (0.05) than in patientsfrom the control group and in patients with acute edematous pancreatitis. Exceptions werepatients with pinched hernias without intestinal necrosis. The optical density of venousblood plasma in these patients did not diff er statistically signifi cantly from other patients.Conclusions. 1. Patients with diseases of the abdominal cavity at wavelengths = 365-770 nm have characteristic maxima of the optical density of venous bloodplasma, the values of which diff er depending on the type of disease. 2. At wavelengths  =365, 555 nm in patients with destructive changes in organs, the optical density of venousblood plasma is statistically signifi cantly lower (p &lt;0.05) than in most patients withoutdestructive changes in organs. 3. Determination of optical density is a promising area forimproving the diagnosis of acute surgical pathology of the abdominal cavity.

Immune enhancement in patients with predicted severe acute necrotising pancreatitis: a multicentre double-blind randomised controlled trial.

PurposeInfected 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.MethodsWe 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.ResultsA 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%).ConclusionThe immune-enhancing Tα1 treatment of patients with predicted severe ANP did not reduce the incidence of IPN during the index admission.Supplementary InformationThe online version contains supplementary material available at 10.1007/s00134-022-06745-7.

Abbreviated non-enhanced magnetic resonance imaging in patients with acute necrotizing pancreatitis.

To investigate the performance of T2-weighted abbreviated magnetic resonance imaging (T2W-AMRI) protocol in evaluating patients with acute necrotizing pancreatitis (ANP). A retrospective analysis of consecutive hospitalized patients with ANP who underwent MRI (contrast-enhanced, CE or non-contrast, NC) between January 2017 and November 2020was performed. The T2W-AMRI and complete MRI (cMRI) sequences were anonymized, and subsequently, two separate sets of data (AMRI and cMRI) were created for presentation to the radiologists involved in reading the data. The T2W-AMRI was based on a single-axial T2 half-Fourier acquisition single-shot turbo spin-echo (HASTE) sequence. The pancreatic and extrapancreatic findings were recorded and tabulated independently by two radiologists on T2W-AMRI and cMRI. In addition, the interobserver agreement and association of findings between T2W-AMRI and cMRI were analyzed. Twenty-eight patients (mean age 31.7 ± 12.2years, 17 females) were included. Thirteen patients had CE-cMRI, while the rest underwent NC-cMRI. There was no significant difference in the identification of pancreatic necrosis on T2W-AMRI vs. cMRI (p = 1.00). However, T2W-AMRI underestimated necrosis in one patient. Collections were accurately detected in all patients on T2W-AMRI. The mean size of the collection was larger on cMRI (6.5 ± 3.7cm) than T2W-AMRI (6 ± 3.7cm) with p = 0.006. cMRI detected more patients with disrupted pancreatic duct (n = 9) than T2W-AMRI (n = 6). However, the difference was not statistically significant (p = 0.375). There was a good to an excellent interobserver agreement between the readers for T2W-AMRI (k = 0.62-1). T2W-AMRI may offer a suitable alternative to cMRI in ANP, especially severe disease, as it can be acquired rapidly without the need for contrast injection.

How to Identify the Indications for Early Intervention in Acute Necrotizing Pancreatitis Patients: A Long-Term Follow-Up Study.

AimTo explore the indications for early intervention in patients with acute necrotizing pancreatitis (ANP) and evaluate the effect of early intervention on the prognosis of ANP patients.MethodsThe clinical data of patients with ANP who underwent general surgery at Xuanwu Hospital of Capital Medical University from January 1, 2014, to December 31, 2020, were collected retrospectively. The patients were followed-up every 6 months after discharge, and the last follow-up date was June 30, 2021.ResultsA total of 98 patients with ANP were included in the study. They were divided into an early group (n= 43) and a delayed group (n = 55) according to the first percutaneous drainage (PCD) intervention time (≤ 4 weeks or > 4 weeks). Body temperature, inflammatory factor levels, and the number of patients with persistent organ failure (POF) were higher in the early group than in the delayed group. After the minimally invasive intervention, the body temperature and inflammatory factors of the two groups decreased significantly, most patients with POF improved, and the number of patients with reversal of POF in the early group was higher than that in the delayed group. Although the patients in the early group required more surgical intervention than those in the delayed group, there was no significant difference in mortality, incidence of postoperative complications, total length of hospital stay, or operation cost between the two groups. During long-term follow-up, there was no significant difference in the incidence of short-term and long-term complications and overall survival between the two groups.ConclusionsCompared to patients in the delayed group, early intervention did not affect the prognosis of patients with ANP. It may be more suitable for patients with ANP with deterioration [such as POF or infected pancreatic necrosis (IPN)].

Effect of TRAF6 in acute pancreatitis-induced intestinal barrier injury via TLR4/NF-κB signal pathway

BackgroundThe aim of this study was to investigate the effect of tumor necrosis factor receptor-related factor 6 (TRAF6) in acute pancreatitis (AP)-induced intestinal barrier injury via the Toll-like receptor 4/nuclear factor kappa-B (TLR4/NF-κB) signal pathway. MethodsRat models of acute edematous pancreatitis (AEP) and acute necrotizing pancreatitis (ANP) were established by intraperitoneal injection of caerulein and retrograde infusion of sodium taurocholate solution into the biliopancreatic duct, respectively. Separate groups of model rats were pretreated with the TRAF6 inhibitor, MG-132. Rats were sacrificed at 12 h after the last injection for inducing AP. Histopathological changes, inflammatory response, intestinal barrier function, and protein expression levels were assessed by pathological score, ELISA, TUNEL, qRT-PCR, immunohistochemistry and western blotting. ResultsRat models of AEP and ANP were successfully established as evidenced by the pathological changes in the pancreas and intestine. Pre-treatment with MG-132 significantly alleviated pancreatic and intestinal pathological scores, reduced serum levels of amylase, IL-1β, and IL-6, and ameliorated apoptosis of mucosal cells. MG-132 reduced intestinal barrier injury, including serum levels of diamine oxidase and lipopolysaccharide, and intestinal expressions of ZO-1 and occludin. Moreover, it significantly suppressed the activation of the intestinal TLR4/NF-κB signaling pathway. ConclusionsTRAF6 inhibitor alleviated pancreatic and intestinal injury in AEP and ANP. This effect may be mediated through inhibition of the TLR4/NF-κB signaling pathway, which in turn regulates the inflammatory response and intestinal barrier injury.

The Complement and Coagulation Cascades Pathway is Associated with Acute Necrotizing Pancreatitis by Genomics and Proteomics Analysis.

PurposeAcute pancreatitis can be classified histologically as interstitial edema pancreatitis (IEP) or as acute necrotizing pancreatitis (ANP). ANP has a higher mortality and long-term or short-term sequelae than IEP. Therefore, this work aims to explore the differences in pathogenesis between ANP and IEP and it has great clinical importance for the treatment and prevention of ANP.MethodsIn this work, whole blood samples from IEP and ANP patients were analyzed by whole gene sequencing (WGS). Serum samples from IEP and ANP patients were evaluated via enzyme-linked immunosorbent assay (ELISA). Meanwhile, pancreatic tissues of IEP and ANP rat models were subjected to data independent acquisition (DIA) proteomics assays. Then, the WGS analysis and DIA proteomics assay data were analyzed comprehensively.ResultsSix pathways were found to be significantly different in the ANP/IEP groups through WGS analysis. DIA proteomics found eleven different pathways. In both assays, the complement and coagulation cascades pathway was the most significantly different (p < 0.01) pathway between the two groups. WGS analysis showed base mutations in ten genes in the complement and coagulation cascades pathway. These results were consistent with the ten proteins detected by DIA proteomics analysis, which were significantly upregulated in the ANP/IEP groups. In addition, five of these proteins, complement C3, complement Factor I, alpha-2-macroglobulin, complement C9, and serpin family C member 1, were successfully verified by parallel reaction monitoring analysis and ELISA.ConclusionC3, CFI, A2m, C9, and Serpinc1, which belong to complement and coagulation cascades pathway, may promote pancreatic necrosis and aggravate the severity of ANP.

Routine laboratory parameters in patients with necrotizing pancreatitis by the time of operative pancreatic debridement: Food for thought.

BACKGROUNDTiming of invasive intervention such as operative pancreatic debridement (OPD) in patients with acute necrotizing pancreatitis (ANP) is linked to the degree of encapsulation in necrotic collections and controlled inflammation. Additional markers of these processes might assist decision-making on the timing of surgical intervention. In our opinion, it is logical to search for such markers among routine laboratory parameters traditionally used in ANP patients, considering simplicity and cost-efficacy of routine laboratory methodologies.AIMTo evaluate laboratory variables in ANP patients in the preoperative period for the purpose of their use in the timing of surgery.METHODSA retrospective analysis of routine laboratory parameters in 53 ANP patients undergoing OPD between 2017 and 2020 was performed. Dynamic changes of routine hematological and biochemical indices were examined in the preoperative period. Patients were divided into survivors and non-survivors. Survivors were divided into subgroups with short and long post-surgery length of stay (LOS) in hospital. Correlation analysis was used to evaluate association of laboratory variables with LOS. Logistic regression was used to assess risk factors for patient mortality.RESULTSSeven patients (15%) with severe acute pancreatitis (SAP) and 46 patients (85%) with moderately SAP (MSAP) were included in the study. Median age of participants was 43.2 years; 33 (62.3%) were male. Pancreatitis etiology included biliary (15%), alcohol (80%), and idiopathic/other (5%). Median time from diagnosis to OPD was ≥ 4 wk. Median postoperative LOS was at the average of 53 d. Mortality was 19%. Progressive increase of platelet count in preoperative period was associated with shortened LOS. Increased aspartate aminotransferase and direct bilirubin (DB) levels the day before the OPD along with weak progressive decrease of DB in preoperative period were reliable predictors for ANP patient mortality.CONCLUSIONMultifactorial analysis of dynamic changes of routine laboratory variables can be useful for a person-tailored timing of surgical intervention in ANP patients.

Simple scoring for acute necrotizing pancreatitis: mortality in acute necrotizing pancreatitis during admission (MANP-A).

BackgroundAcute necrotizing pancreatitis (ANP) can result in a significant healthcare burden. The present study aimed to develop a new scoring system to accurately and promptly identify patients with a high likelihood of mortality to determine the need for aggressive measures.MethodsWe retrospectively analyzed patients diagnosed with ANP using the National Inpatient Sample (NIS). The mortality in ANP during admission (MANP-A) scoring system was derived using multivariate Cox regression analysis and validated using receiver operating characteristic (ROC) curves in a validation cohort.ResultsA total of 22,980 hospitalizations were identified in the derivation cohort. There was a predominance of males (65%) and white race (73%). Five variables showed significant association with mortality and were selected for developing the MANP-A scoring system: age ≥60 years; acute renal failure/kidney injury; sepsis with shock; vasopressor use; and disseminated intravascular coagulation. The MANP-A score has a maximum of 5 points and the cutoff for predicting mortality was set at 2 points. The area under the curve (AUC) using the ROC curve of the derivation cohort was 0.9195, 95% confidence interval [CI] 0.8838-0.9551 (P<0.001) for 7- and 0.8954, 95%CI 0.8723-0.9185 (P<0.001) for 30-day periods. The AUC of the Validation Cohort was 0.9204, 95%CI 0.8937-0.9469 (P<0.001) for 7- and 0.9059, 95%CI 0.8893-0.9223 (P<0.001) for 30-day periods.ConclusionWe propose a simple and objective score for predicting ANP inpatient mortality at 7- and 30-day intervals with high validity.

Utility of Presepsin for Prognosis of Infected Complications of Acute Necrotizing Pancreatitis

Introduction: Early determination of the patients with high risk for infected complications of acute necrotizing pancreatitis (ANP) is crucial for their effective treatment. So purpose of our research was to study utility of presepsin determination for prognosis of subsequent development of infected complications of ANP.

Relationship of Arterial Changes in Acute Pancreatitis on CT Angiography with Modified CT Severity Index

Abstract Purpose To evaluate the prevalence of arterial changes in patients with acute pancreatitis (AP) on computed tomography angiography (CTA) and determine their association with etiology of AP, presence of necrosis, collections and severity of AP. Materials and Methods A total of 50 patients (20 women, 30 men; mean age: 43.04 ± 13.98; age range: 18–77 years) with AP underwent contrast-enhanced computed tomography (CECT) scan and CTA of abdomen, which was evaluated for necrosis and fluid collection (s). On CTA, splanchnic arterial structures were assessed for vascular complications. Association between vascular changes and presence of necrosis, fluid collections, etiology of AP and severity of AP (as assessed by modified computed tomography severity index CTSI) was determined. Results Arterial complications were seen in 28 percent (14/50). The most frequently involved artery was superior pancreaticoduodenal artery (12 percent), followed by splenic artery (8 percent) and right gastric artery (8 percent; Fig. 1). No significant association was seen between arterial changes and gallstone or alcohol-induced AP. Arterial changes showed a significant association with presence of acute necrotizing pancreatitis (ANP), presence of collections and severe AP (CTSI 8–10) (p &lt; 0.05 for each). Conclusion Arterial changes on CTA are frequently seen in patients of AP having ANP. There is a significant association between arterial changes and presence of necrosis, collections and severe AP.

СИНДРОМ ПОЛИОРГАННОЙ ДИСФУНКЦИИ ПРИ ОСТРОМ НЕКРОТИЗИРУЮЩЕМ ПАНКРЕАТИТЕ

Acute necrotizing pancreatitis (ANP) is associated with significantlyhighermorbidity and mortality. It is still difficult for the surgeon to choose and schedule the most appropriate treatment.In the early phase of the disease, surgical activity is considered to be ineffective and is associated with high risks. The only chance to save the patient is to conduct the intensive therapy in the intensive care unit, based on current pathogenetic approaches. The present review analyzed the current understanding of the pathogenesis of multiple organ dysfunction syndrome (MODS) in acute necrotizing pancreatitis. The role of inflammatory mediators, cytokines, biogenic amines, bradykinins, and lipid peroxidation products in the development of organ hypoperfusion is reflected. It is shown that the violation of the intestinal barrier function with the translocation of microorganisms exacerbates endogenous intoxication and contributes to the development of MODS. The endothelial dysfunction that develops in acute necrotizing pancreatitis has a significant effect on hemostasis. The literature analysis revealed the contradictory data on the functional activity of the coagulation and anticoagulation systems at different stages of the disease. The mechanisms of development of intra-abdominal hypertension and its multisystem negative impact are reflected. There are still controversialquestionof appropriatetiming and indications for surgical decompression. The analysis of the available literature data showed the need for further study of the mechanisms of multiple organ dysfunction development in acute necrotizing pancreatitis to work out new pathogenetically justified methods of its intensive therapy with an assessment of their effectiveness.

Inhibition of Notch activity promotes pancreatic cytokeratin 5-positive cell differentiation to beta cells and improves glucose homeostasis following acute pancreatitis

Some individuals develop prediabetes and/or diabetes following acute pancreatitis (AP). AP-induced beta-cell injury and the limited regenerative capacity of beta cells might account for pancreatic endocrine insufficiency. Previously, we found that only a few pancreatic cytokeratin 5 positive (Krt5+) cells differentiated into beta cells in the murine AP model, which was insufficient to maintain glucose homeostasis. Notch signaling determines pancreatic progenitor differentiation in pancreas development. This study aimed to examine whether Notch signaling inhibition could promote pancreatic Krt5+ cell differentiation into beta cells and improve glucose homeostasis following AP. Pancreatic tissues from patients with acute necrotizing pancreatitis (ANP) were used to evaluate beta-cell injury, Krt5+ cell activation and differentiation, and Notch activity. The murine AP model was induced by cerulein, and the effect of Notch inhibition on Krt5+ cell differentiation was evaluated both in vivo and in vitro. The results demonstrated beta-cell loss in ANP patients and AP mice. Krt5+ cells were activated in ANP pancreases along with persistently elevated Notch activity, which resulted in the formation of massive duct-like structures. AP mice that received Notch inhibitor showed that impaired glucose tolerance was reversed 7 and 15 days following AP, and increased numbers of newborn small islets due to increased differentiation of Krt5+ cells to beta cells to some extent. In addition, Krt5+ cells isolated from AP mice showed increased differentiation to beta cells by Notch inhibition. Collectively, these findings suggest that beta-cell loss contributes to pancreatic endocrine insufficiency following AP, and inhibition of Notch activity promotes pancreatic Krt5+ cell differentiation to beta cells and improves glucose homeostasis. The findings from this study may shed light on the potential treatment of prediabetes/diabetes following AP.

The Diagnosis and Treatment of Local Complications of Acute Necrotizing Pancreatitis in China: A National Survey.

Background The optimal management strategy in acute necrotizing pancreatitis (ANP) is debated, and compliance with current guidelines in China is not known. In this study, we performed a national survey on this topic in China. Methods An online questionnaire about the diagnosis and treatment of local complications of ANP was distributed through a national collaborative network. The local and systemic complications were defined according to the Revised Atlanta Classification. Results There were 321 survey respondents from the 394 who opened the link (response rate 81%) from 208 hospitals located in 30/34 provinces across China. There was a lack of consensus in terms of early diagnosis of infected pancreatic necrosis (IPN) as the respondents chose to depend on clinical symptoms (70/321, 22%), organ failure (82/321, 26%), imaging changes (84/321, 26%), and fine needle aspiration (51/321, 16%), respectively. A “step-up” approach has been widely adopted in patients with IPN (294/321, 92%). The decision for initial intervention (without confirmed/suspected infection) was based on clinical condition, CT imaging, or laboratory indicators for most respondents (229/321, 71%). Conclusion While the “step-up” approach has been widely adopted, there is still significant variation in regard to the diagnosis of infection, the best timing for drainage, and the indications for early intervention.

New Paradigm for Determining Necrosis, Stage and Prognosis of Severe Acute Necrotizing Pancreatitis

Objective: To determine the clinical features and diagnostic parameters of acute alcohol-induced pancreatic necrosis to develop a new system to assess the severity of acute pancreatitis, diagnose necrotic inflammation, and understand prognosis. Methods: We performed a retrospective chart review of patients admitted to the General Surgery Department and Gastroenterology Department of The Third Central Hospital, and The First Central Hospital in Ulaanbaatar from November 1, 2008, to January 1, 2020, admitted with acute pancreatitis, gathering clinical data using a structured form. From these data, we developed a new scoring system. Results: The median age of patients with acute necrotic pancreatitis was 43 (range 25-71) years, with the majority (87.4%) ages 26 to 60. Of the 31 deaths reported in the study, 24 (77.4%) were hospitalized more than 72 hours after the onset of the disease. Using the new evaluation system, 12 out of 122 patients were classified as class A (score 0-3), 69 (56.5%) were class B (score 4-6), and 41 (33.6%) of the patients were class C (score ≥7) points. Conclusion: The evaluation system we developed aids with early diagnosis, progression and prognosis of severe forms of acute pancreatitis. It is easy to score, and it is possible to score using information available in Mongolia’s secondary and tertiary hospitals.

Management of walled-off necrosis with nasocystic irrigation with hydrogen peroxide versus biflanged metal stent: randomized controlled trial.

Background and study aims Walled-off necrosis (WON) is a known complication of acute necrotizing pancreatitis (ANP). There is no study comparing nasocystic irrigation with hydrogen peroxide (H 2 O 2 ) versus biflanged metal stent (BMS) in the management of WON. The aim of this study was to compare the clinical efficacy of both the treatment strategies. Patients and methods This study was conducted on patients with symptomatic WON who were randomized to nasocystic irrigation with H 2 O 2 (Group A) and BMS placement (Group B). Primary outcomes were clinical and technical success while secondary outcomes were procedure time, adverse events, need for additional procedures, duration of hospitalization, and mortality. Results Fifty patients were randomized into two groups. Group A (n = 25, age 37.8 ± 17.6 years, 16 men) and Group B (n = 25, age 41.8 ± 15.2 years, 17 men). There were no significant differences in baseline characteristics between the two groups. The most common etiology of pancreatitis was alcohol, observed in 27 (54 %) patients. Technical success (100 % vs 96 %, P = 0.98), clinical success (84 % vs 76 %, P = 0.76), requirement of additional procedures (16 % vs 24 %, P = 0.70) and adverse events (4 vs 7, P = 0.06) were comparable in both the groups. The duration to clinical success (34.4 ± 12 vs 14.8 ± 10.8 days, P = 0.001) and procedure time (36 ± 15 vs 18 ± 12 minutes, P = 0.01) were longer in Group A compared to Group B. Conclusions Nasocystic irrigation with H 2 O 2 and BMS are equally effective in the management of WON but time to clinical success and procedure time is longer with nasocystic irrigation.

Continue peritoneal lavage in acute pancreatitis: How do peritoneal cells response?

Continuous peritoneal lavage is part of a set of minimally invasive techniques, called the Step up approach. These techniques have been used in the management of acute necrotizing (severe) pancreatitis (SAP), as they remove toxins and reduce serious metabolic disorders, although their effects on mild acute pancreatitis and on the content of peritoneal cells during mild and SAP are still unknown, since inflammation is an important factor in the progression of the disease. The peritoneum is a tissue with important immunological functions, and the characterization of peritoneal cells during acute pancreatitis can be a relevant strategy to understand the mechanism by which peritoneal lavage has worked during clinical practice, as well as to uncover possible pharmacological targets. This review presents an approach to minimally invasive techniques in the management of AP, emphasizing peritoneal lavage and its nuances.

Inhibition of the p38 MAPK pathway attenuates renal injury in pregnant rats with acute necrotizing pancreatitis.

The p38 mitogen-activated protein kinase (MAPK) pathway is an important intracellular signalling pathway that leads to increased expression of pro-inflammatory mediators. Our previous studies have shown that the p38 MAPK pathway was changed in the acute renal injury (ARI) in acute pancreatitis in late pregnancy (APIP), whereas the role of p38 MAPK in APIP-induced ARI has been poorly understood. The present study was undertaken to investigate the participation of the p38 MAPK signalling pathway and the protective effect of SB203580, an inhibitor of p38 MAPK in ARI in APIP. Twenty-four late-gestation SD rats were randomly assigned to four groups: the normal group (N), sham-operated group (SO), acute necrotizing pancreatitis (ANP) group, and p38 MAPK inhibitor (SB203580) treatment group (T). The results showed that serum amylase, lipase, urea, and creatinine levels of p38 inhibitor of T groups were markedly lower than the ANP groups. Additionally, the expression of phosphorylated p38 and myeloperoxidase (MPO), tumour necrosis factor alpha (TNF-α), interleukin (IL)-1β, IL-6, nuclear factor kappa-B (NF-κB), caspase-3, and terminal deoxynucleotidyl TUNEL-positive cells was markedly lower in the T group than in the ANP group. Our results suggest that SB203580 can inhibit renal injury by inhibiting the P38 MAPK signalling pathway and blocking the inflammatory responses in APIP.