Treatment Of Acute Necrotizing Pancreatitis Research Articles

Step-Up versus Open Approach in the Treatment of Acute Necrotizing Pancreatitis: A Case-Matched Analysis of Clinical Outcomes and Long-Term Pancreatic Sufficiency.

Background/Objectives: Acute necrotizing pancreatitis (ANP) with secondary infection of necrotic tissue is associated with a high rate of complications and mortality. The optimal approach is still debatable, but the minimally invasive modality has gained great attention in the last decade as it follows the principle of applying minimal surgical trauma to achieve a satisfying therapeutic objective. We compared clinical outcomes between the step-up approach (SUA) and open necrosectomy (ON) in the treatment of acute necrotizing pancreatitis. Methods: A prospective cohort study over the period of 2011-2021 in a university teaching hospital was performed. Results of 99 consecutive patients with ANP who required surgical/radiological intervention were collected. A case match analysis (2:1) was performed, and the final groups comprised 40 patients in the OA group and 20 patients in the SUA group. Demographic, clinicopathologic, and treatment data were reviewed. Results: Baseline characteristics and disease severity were comparable between the two groups. The patients from the SUA group had a significantly lower morbidity rate and rate of pancreatic insufficiency. Death occurred in 4 of 20 patients (20%) in the SUA group and in 11 of 40 patients (27.5%) in the ON group (risk ratio with the step-up approach, 0.72; 95% confidence interval, 0.26 to 1.99; p = 0.53). Conclusions: A minimally invasive step-up approach provides comparable outcomes to open necrosectomy in the treatment of ANP with infected pancreatic necrosis. While mortality and hospital stay were comparable between the groups, morbidity and pancreatic insufficiency were significantly lower in the SUA group. Further studies on a larger number of patients are required to define the place of SUA in the modern treatment of ANP.

Acute necrotizing pancreatitis: challenges and interventions—a narrative review

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

Acute Necrotizing Pancreatitis Treatment: Endoscopic Sfincterotomy and Minimal Invasive Step Up Approach of Liver Hydatid Cysts.

Acute Necrotizing Pancreatitis Treatment: Endoscopic Sfincterotomy and Minimal Invasive Step Up Approach of Liver Hydatid Cysts.

MODERN PRINCIPLES OF MANAGEMENT OF PATIENTS WITH ACUTE PANCREATITIS

New and optimized existing approaches to the diagnosis, prognosis and treatment of acute necrotic pancreatitis have been developed. Implementation of the suggested treatment strategy and therapeutic tactics enabled to improve substantially results of treatment of patients with acute pancreatitis: decrease rate of occurrence of pancreatic fistulas and erosive bleeding by 25.7 % and 31.0 % respectively, number of repeated surgical invasion by 34.0 %, frequency of postoperative complications from 31.6 % to 12.5 %, hospital stay in case of focal pancreatonecrosis by 8 days, mortality rate in patients with generalized pancreatonecrosis from 30.0 % to 14.3 %. All this is indicative of the effectiveness of the suggested therapeutic tactics and reasonability of its wide clinical implementation.

Efficacy of complex treatment of acute necrotic pancreatitis using antibacterial drugs and polyvalent piobacteriophag

Among surgical diseases of the abdominal cavity, acute necrotic pancreatitis is important. The total lethality in this disease is 4.28 - 5.50 %, and with its destructive forms in the postoperative period, it reaches 20 - 40 % [1,2,3]. The number of cases in which the development of the disease involved antibiotic resistant microorganisms significantly increased. In this regard, the treatment of acute necrotic pancreatitis needs improvement.Aim. Improvement of the treatment of patients with acute necrotizing pancreatitis with the complex application of polyvalent pyobacteriofag and antibacterial preparations.Method. A bacteriological study was performed on patients with acute necrotic pancreatitis, in which 49 strains of microorganisms were isolated from the manure both in the control and the basic (experimental) group. For the treatment of acute necrotic pancreatitis, antibiotics were used in conjunction with polyvalent pyobacteriofag (main group). Only antibiotics were used to treat patients in the control group.Main results. In the experimental group of patients with acute necrotic pancreatitis, associations of microorganisms that were acting together with antibiotics and polyvalent pyobacteriophag were isolated.According to the data obtained, the use of antibiotics, in combination with polyvalent pyobacteriophage in the complex treatment of purulent necrotic pancreatitis, accelerated healing of surgical wounds and recovery of patients.Thus, the data that were obtained as a result of the complex treatment of acute necrotic pancreatitis with the use of antibiotics and polyvalent pyobacteriophag purified, indicate that the treatment of patients in the main group, compared with the control, was more effective.Conclusions. The use of the complex therapy with an antibiotic with polyvalent piobacteriofag reduces the cost of the treatment, which has an important social and economic significance.It has been proved that the use of polyvalent piobactyrophag, together with antibiotics in the complex treatment of acute necrotic pancreatitis, reduced the duration of the treatment to 39 ± 4, and with the use of antibiotics alone, treatment continued for 42 ± 6 years.With the use of this technique, patients' wound healing was at 6 ± 2 days, while at the treatment with antibiotics only wound was cleared by 12 ± 3

Multimodal video-endoscopic and transcutaneous interventions in surgical treatment of infected acute necrotizing pancreatitis

Background: Recent researches improves understanding of natural course of acute necrotizing pancreatitis (ANP). Today there are no disagreements on timing and indications for surgical treatment, but different approaches still exist. Our aim was to establish the efficacy of multimodal video-endoscopic (VE) and transcutaneous interventions (TI) in surgical treatment of infected ANP. Methods: We performed retrospective study of step-up surgical ttreatment of 173 patients with ANP. As a first step VE were used in 69, TI - 99 cases. In 31 patients with extended necrosis their multimodal application were performed. Duration of in-hospital treatment, complications, amount of procedures and necessarily for open necrosectomy were studied. Results: From 52 patients with acute necrotizing collections (ANC) separate application of VE or TI was final method of treatment in 74.0% patients, video-assisted retroperitoneal debridement (VARD) we performed in 13.5%, mini-laparotomic necrosectomies - 5.8%, open necrosectomies -19.2% observations. Their application in 102 patients with walled off pancreatic necrosis (WOPN) was followed by VARD in 10.8%, mini-laparotomic necrosectomies - 3.9%, open necrosectomies - 16.8% cases. Total number of invasive procedures reached 2.5±0.24, complication rate - 12.3% (pancreatic fistula -7.2%), overall mortality - 2%. Multimodal VE and PTI approach was applied in 9 ANC and 32 WOPN observations with no mortality cases. Necessary of additional intervention occurred in 12.9% (p<0.05), open necrosectomies - 6.4% (p<0.05), there were no procedure-related immediate and long-term complications. Conclusions: Multimodal application of video-endoscopic and transcutaneous interventions is effective approach as first step for surgical treatment of patients with extended infected ANP.

Inhibition of 5-lipoxygenase represses neutrophils activation and activates apoptosis in pancreatic tissues during acute necrotizing pancreatitis

Pancreatic glandular necrosis is rapid inflammation of the pancreas and contributes to severe acute pancreatitis in humans. The pathogenesis of pancreatic tissue inflammation during acute pancreatitis is still largely unknown. Recent studies suggest that 5-lipoxygenase (5-LOX) is an essential mediator in modulating cell death pathways in human diseases. In this study, we aimed to evaluate the effects of a 5-LOX inhibitor, zileuton, on tissue apoptosis and neutrophils activation in pancreatic tissues during acute necrotizing pancreatitis (ANP) in a rat model. In this present study, both mRNA and protein levels of 5-LOX are upregulated during ANP and zileuton treatment is shown to repress ANP-induced upregulation of 5-LOX levels. In addition, zileuton treatment is found to repress blood biomarkers of neutrophils activation such as soluble intercellular adhesive molecular 1 (ICAM-1), soluble E-selectin (E-selectin), soluble P-selectin (P-selectin), leukotriene B4 (LTB4), and myeloperoxidase (MPO). Also, zileuton treatment attenuates pancreatic tissue pathology, upregulates caspase-3, downregulates B-cell lymphoma 2 (Bcl-2), and activates tissue apoptosis evaluated by TUNEL staining. Our results show that 5-LOX plays an important role in activating apoptosis and repressing neutrophils activation during ANP. The current study suggests that 5-LOX can be used as a potential target for the treatment of ANP.

Surveillance of Intra-Abdominal Pressure and Intestinal Barrier Function in a Rat Model of Acute Necrotizing Pancreatitis and Its Potential Early Therapeutic Window

ObjectivesTo monitor intra-abdominal pressure (IAP) and intestinal barrier function in a rat model of acute necrotizing pancreatitis (ANP) to elucidate a potential relevant therapeutic window.MethodsSprague-Dawley rats were randomly divided into experimental or control groups. The ANP group (n = 40) was injected with 4.5% sodium taurocholate into the pancreatic duct to induce ANP. The controls received only abdominal opening surgery (sham-operated, SO; n = 40) or no treatment or surgery (baseline; 0 h, n = 20). The SO and ANP groups were then randomly subdivided into 3, 6, 12 and 24 h groups (n = 10 each). IAP was measured at each time point and the rats were sacrificed to measure the weight of accumulated ascites fluid and the amylase, endogenous creatinine (Cr), total bilirubin (TB), tumor necrosis factor- alpha (TNF-alpha), diamine oxidase (DAO), and D-lactate. Mortality and the development of pathological changes in the pancreas and intestines were also monitored.ResultsIAP showed a continuous upward trend in the ANP group, with values 2 to 3 times higher than those in the SO group at the corresponding time points and the rising rate was peaking at 6 h. The levels of plasma amylase, TNF-alpha, Cr, TB, DAO, and D-lactate also gradually increased in the ANP group over time and were significantly higher than in the SO group at 3, 6, 12 and 24 h (all P<0.05). Moreover, the rising rate of TNF-alpha, DAO, and D-lactate also peaked at 6 h.ConclusionsThe ANP-induced changes in IAP, inflammatory factors and intestinal barrier that we observed in the rat model were especially obvious at 6 h post-induction, suggesting an early therapeutic window for the treatment of ANP in humans.

The role of tumor suppressor factor CYLD in lung injury associated with acute necrotizing pancreatitis

Objective Acute necrotizing pancreatitis (ANP) may cause lung injury.This study explores two factors that are associated with lung damage from ANP,the expression of tumor suppressor factor CYLD and nuclear factor-kappa B (NF-κB).Methods 72 adult Sprague-Dawley rats were randomly divided into 3 groups:sham operation,ANP,and GdCl3 treatment groups (n=24 for each group).A retrograde injection of 5％ sodium taurocholate into the biliopancreeatic duct of rats induced ANP,and the animals were killed 1,3,6,and 12 hours after the ANP induction.AMs were harvested by bronchoalveolar lavage technique,and TNF-a and IL-1β levels in bronchoalveolar lavage fluid (BALF) were evaluated.Lung tissue was checked with histological examinations,and the activity of NF-κB and CYLD in AM were measured by western blot.Results TNF-α and IL-1β secreted by AM were gradually elevated,peaked on the sixth hour,had maximums of (491.3 ±20.3)ng/L and (178.83±11.32)ng/L respectively,and decreased on the twelfth hour.The levels of TNF-α and IL-1β in the ANP group were significantly higher than the sham operation group (P＜0.05),and the GdC13 group levels were obviously lower than ANP group.In the sham operation group,the expression of NF-κB was low and CYLD was high.In the ANP group,when compared to the sham operation group,the expression of NF-κB rose after 3 hours and continued to rise with time progression (P＜0.05).In contrast,CYLD protein expression in the ANP group dropped after 3 hours and continued to gradually decrease (P＜0.05).The CYLD and NF-κB protein expression in GdCl3 groups had similar trends as the ANP group.GdCl3 group CYLD levels began to rise at 6 hours (P＜0.05),and NF κB levels began to fall at 1 hour (P＜0.05).The expression of NF-κB and CYLD possessed a negative correlation in both the ANP and GdCl3 groups (r =-0.918,r=-0.723,P＜ 0.01).Conclusions Therefore,in acute lung injury associated with acute pancreatitis,CYLD expression decreased with evident phases,such as a decrease in levels after 3 hours,and NF κB expression increased.Also,GdCl3 may be responsible for upregulation of CYLD expression and downregulation of NF-κB expression,and confirmed that CYLD had a negative effect on NF-κB.Perhaps GdCl3 could be used in the future to ameliorate the lung injury associated with ANP. Key words: Pancreatitis, acute necrotizing; Tumor suppressor proteins; Lung; Wounds and injuries

Prophylactic antibiotic treatment in acute necrotizing pancreatitis: Results from a meta-analysis

Objective. The effect of prophylactic antibiotic treatment on infection and survival of acute necrotizing pancreatitis (ANP) remains uncertain. The aim of this study was to assess the long-term efficacy of prophylactic antibiotic treatment for ANP. Material and methods. Searches were carried out of electronic databases including Medline, EMBASE, the Cochrane Controlled Trials Register, the Science Citation Index, and PubMed (updated to December 2007), and manual bibliographical searches were also conducted. A meta-analysis of all randomized controlled trials (RCTs) comparing prophylactic antibiotic treatment with placebo or no treatment was performed. Results. Eight RCTs including 540 patients were assessed. The outcomes included infected necrosis, death, non-pancreatic infection, surgical intervention, and length of hospital stay. Prophylactic antibiotic use leads to a significant reduction of infected necrosis (relative risk (RR) 0.69, 95% CI, 0.50–0.95; p=0.02), non-pancreatic infections (RR 0.66 95% CI, 0.48–0.91; p=0.01), and length of hospital stay (p=0.004) but was not associated with a statistically significant reduction in mortality (RR 0.76 95% CI, 0.50–1.18; p=0.22) and surgical intervention (RR 0.90 95% CI, 0.66–1.23; p=0.52). In a subgroup analysis, carbapenem was associated with a significant reduction in infected necrosis (p=0.009) and non-pancreatic infections (p=0.006), whereas other antibiotics were not. Conclusions. Prophylactic antibiotic treatment is associated with a significant reduction of pancreatic or peripancreatic infection, non-pancreatic infection, and length of hospital stay, but cannot prevent death and surgical intervention in acute necrotizing pancreatitis.

Effects of Caffeic Acid Phenethyl Ester on Pancreatitis in Rats

This study investigated the effect of caffeic acid phenethyl ester (CAPE) on acute necrotizing pancreatitis (ANP) induced by glycodeoxycholic acid in rats. CAPE, an active component of honeybee propolis, has previously been determined to have antioxidant, anti-inflammatory, antiviral, and anticancer activities. Forty-eight rats were divided into four groups of 12. Group 1 animals received intraductal saline and intravenous saline infusion treatment. Group 2 was given intraductal saline and intraperitoneal CAPE infusion treatment. ANP was induced in the animals in group 3 (ANP with saline infusion), and group 4 had induced ANP plus CAPE infusion treatment (ANP with CAPE infusion). Sampling was performed 48 h after treatment. ANP induction significantly increased mortality rate, pancreatic necrosis, and bacterial infection in pancreatic and extrapancreatic organs. ANP also increased levels of amylase and alanine aminotransferase (ALT) in serum, increased levels of urea and lactate dehydrogenase in bronchoalveolar lavage fluid (BAL LDH), increased the activities of myeloperoxidase (MPO) and malondialdehyde (MDA) in pancreas and lung tissue, and decreased the serum calcium levels. The use of CAPE did not significantly reduce the mortality rate but significantly reduced the ALT and BAL LDH levels, the activities of MPO and MDA in the pancreas, the activity of MDA in the lungs, and pancreatic damage. The administration of CAPE did not reduce the bacterial infection. These results indicate that CAPE had beneficial effects on the course of ANP in rats and suggest that CAPE shows promise as a treatment for ANP.

Changes in somatostatin receptor expression of the pancreas and effectiveness of octreotide in rats with acute necrotizng pancreatitis

To investigate changes in the expression of the somatostatin receptor (SSTR) of the pancreas and of pancreatic blood flow, and its relationship to the metabolism of eicosanoids in order to elucidate the effectiveness of octreotide, an analog of somatostatin, in acute necrotizing pancreatitis (ANP). A model of ANP was induced in rats with injection of sodium taurocholate via the pancreaticobiliary duct. The SSTR was detected using a radioligand binding assay (RBA) with 125I-somatostatin-14, and the SSTR2 mRNA of the pancreas was analyzed using in situ hybridization. Pancreatic blood flow and the metabolites of eicosanoids were also determined. The SSTR of the pancreas was 109.70 +/- 58.32 fmol/mg protein in normal rats. A significant decrease in the SSTR, together with the signals of SSTR2 mRNA, was shown at 3, 6 and 12 h after onset of ANP. Pancreatic blood flow was reduced and thromboxin-2 was increased significantly in the course of ANP. In the ANP group treated with octreotide, both the decrease in pancreatic blood flow and the abnormal metabolism of eicosanoids were corrected, and the pathological damage was relieved. SSTR expression of the pancreas is significantly reduced in ANP. Correction of the abnormal metabolism of eicosanoids and improvement in pancreatic microcirculation may be the major mechanism of somatostatin analogs in the treatment of ANP and inhibition of pancreatic enzymes via their receptors plays a minor role.

Laparoscopic Treatment of Acute Necrotizing Pancreatitis.

Laparoscopic debridement and necrosectomy are described for the treatment for acute necrotizing pancreatitis. Three techniques are described: (1) retrogastric retrocolic debridement; (2) a full retroperitoneoscopic approach; and (3) a transgastric drainage. These three techniques were performed for necrotizing pancreatitis in a group of patients from 1993 to 1994. These techniques have resulted in 75% success of drainage and debridement of necrotizing pancreatitis. No mortalities were encountered during this time period, and reintervention was necessary in 25% of patients. Apart from a cosmetic advantage, less stress has resulted from the procedure, therefore promoting earlier recovery with potentially less fistula complications, which are often observed after open drainage.

Nonsurgical Treatment of Acute Necrotizing Pancreatitis

Our objective was to analyze conservative management in a large series of acute necrotizing pancreatitis (ANP) patients in a specialized center for pancreatic disease in the Internal Medicine and Emergency Department of a 1,500-bed hospital. One hundred ninety-nine patients with ANP were considered (mean age, 55.4 +/- 18.2 years; biliary etiology, 60.3%). Identification of necrotizing forms of acute pancreatitis was obtained by ultrasonography, computed tomography scan, and surgery (53 cases). Exclusion of infection of the necrosis was based on clinical findings and percutaneous aspiration with bacteriological sampling. Medical treatment was started in all cases; 37 patients required ICU treatment; 87 patients underwent early endoscopic cholangiopancreatography (ERCP), and endoscopic sphincterotomy was performed in 61 cases; and percutaneous guided aspiration of necrosis and fluid collections was performed in 78 cases and in 9 patients with acute pseudocysts. Fifty-three patients (26.6%) underwent surgery; all patients (n = 30) with infected necrosis were in this group. One hundred forty-six patients were unoperated (73.3%): clinical resolution of ANP and biochemical normalization was achieved in 132 cases (66.3%) at discharge. Ultrasonographic follow-up documented morphological resolution of necrosis and fluid collections in 84 cases (57.5%) at different periods from the onset of ANP (range, 2.2-63.5 weeks); 16 patients dropped out and seven patients are still being followed. Spontaneous regression of acute pseudocysts was observed in 59.2%; percutaneous/endoscopic aspiration was successful in 33.3%. Mortality was 9.5%, significantly lower than the mortality observed in operated patients (28.3%; p = 0.002). Conservative treatment of ANP with sterile necrosis may allow healing in most cases, independent of the extent of necrosis or its association with major complications.

Genetic determinants of mortality in acute necrotizing pancreatitis

Acute necrotizing pancreatitis (ANP), which often progresses to infection, sepsis, and multisystem organ failure, runs a course remarkably similar to that seen frequently after severe burns, massive physical trauma, or major surgery. There is extensive evidence that the development of the sepsis response is mediated by immunocytes, particularly activated polymorphonuclear leukocytes (PMNLs) and their secretions (reactive oxygen species, lysosomal hydrolases, cytokines, and so on). Some years ago it was suggested that the high mortality of ANP may be related to an overaggressive immunological defense system of the host rather than to autodigestion of the gland. Recent investigations of the immunoregulatory responses following surgery or other trauma have not only furnished additional support for this concept, but also revealed some genetic factors that may critically influence the outcome of posttraumatic illness including ANP. The prognostic significance of abnormal, early polymorphonuclear leukocyte (PMNL) activation in the development of sepsis, high neutrophil expression of certain receptor molecules, low monocyte and lymphocyte expression of major histocompatibility antigen MHC-class II, and the influence of the genetically encoded TNF and IL-1 secretion on the course of the illness are discussed and related to ANP. Evidence is presented for the potential usefulness of some of these parameters in the prognosis and future treatment of ANP.