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.

Endoscopic transluminal drainage and necrosectomy for infected necrotizing pancreatitis:Progress and challenges

Infected necrotizing pancreatitis(INP)represents a severe condition in patients with acute pancreatitis.Invasive interventions are recommended in symptomatic INP.Growing evidence has suggested interventional strategies of INP evolving from traditional surgery to minimally invasive step-up endoscopic procedures.However,there is still no standardized protocol for endoscopic interventions.Recently,various studies have been published about the endoscopic management of INP.This article reviews published articles and guidelines to present the progress and challenges of endoscopic transluminal drainage and necrosectomy in INP.

Management of infected acute necrotizing pancreatitis

Necrotizing or severe pancreatitis represents approximately 10%-20%of acute pancreatitis.30%-40%of patients with acute necrotizing pancreatitis(ANP)will develop debris infection through translocation of intestinal microbial flora.Infected ANP constitutes a serious clinical condition and is complicated by severe sepsis with high mortality rates of up to 40%despite progress in current intensive care.The timely detection of sepsis is crucial.The Quick Sequential Organ Failure Assessment score,procalcitonin levels>1.8 ng/mL and increased lactates>2 mmol/L(>18 mg/dL),indicate the need for urgent management.The escalated step-by-step management protocol starts with broad-spectrum antibiotics,percutaneous drainage or endoscopic management,and ends with surgical management if needed.The latter includes necrosectomy(either laparoscopic or traditional open surgery),peritoneal lavage and extensive drainage.This management protocol increases the chance of survival to approximately 60%in patients with otherwise fatal cases.Any treatment choice must be individualized,and the timing is critical.

Mortality and morbidity in necrotizing pancreatitis managed on principles of step-up approach:7 years experience from a single surgical unit

AIM To determine percentage of patients of necrotizing pancreatitis(NP) requiring intervention and the types of interventions performed. Outcomes of patients of step up necrosectomy to those of direct necrosectomy were compared. Operative mortality, overall mortality, morbidity and overall length of stay were determined. METHODS After institutional ethics committee clearance and waiver of consent, records of patients of pancreatitis were reviewed. After excluding patients as per criteria, epidemiologic and clinical data of patients of NP was noted. Treatment protocol was reviewed. Data of patients in whom stepup approach was used was compared to those in whom it was not used. RESULTS A total of 41 interventions were required in 39% patients. About 60% interventions targeted the pancreatic necrosis while the rest were required to deal with the complications of the necrosis. Image guided percutaneous catheter drainage was done in 9 patients for infected necrosis all of whom required further necrosectomy and in 3 patients with sterile necrosis. Direct retroperitoneal or anterior necrosectomy was performed in 15 patients. The average time to first intervention was 19.6 d in the non step-up group(range 11-36) vs 18.22 d in the Step-up group(range 13-25). The average hospital stay in non step-up group was 33.3 d vs 38 d in step up group. The mortality in the step-up group was 0%(0/9) vs 13%(2/15) in the non step up group. Overall mortality was 10.3% while post-operative mortality was 8.3%. Average hospital stay was 22.25 d.CONCLUSION Early conservative management plays an important role in management of NP. In patients who require intervention, the approach used and the timing of intervention should be based upon the clinical condition and local expertise available. Delaying intervention and use of minimal invasive means when intervention is necessary is desirable. The step-up approach should be used whenever possible. Even when the classical retroperitoneal catheter drainage is not feasible, there should be an attempt to follow principles of step-up technique to buy time. The outcome of patients in the step-up group compared to the non stepup group is comparable in our series. Interventions for bowel diversion, bypass and hemorrhage control should be done at the appropriate times.

Outcome of patients with acute, necrotizing pancreatitis requiring drainage-does drainage size matter?

AIM:To assess the outcome of patients with acute necrotizing pancreatitis treated by percutaneous drainage with special focus on the influence of drainage size and number. METHODS:We performed a retrospective analysis of 80 patients with acute pancreatitis requiring percutaneous drainage therapy for infected necroses. Endpoints were mortality and length of hospital stay. The influence of drainage characteristics such as the median drainage size, the largest drainage size per patient and the total drainage plane per patient on patient outcome was evaluated. RESULTS:Total hospital survival was 66%. Thirty-four patients out of all 80 patients (43%) survived acute necrotizing pancreatitis with percutaneous drainage therapy only. Eighteen patients out of all 80 patients needed additional percutaneous necrosectomy (23%). Ten out of these patients required surgical necrosectomy in addition, 6 patients received open necrosectomy without prior percutaneous necrosectomy. Elective surgery was performed in 3 patients receiving cholecystectomy and one patient receiving resection of the parathyroid gland. The number of drainages ranged from one to fourteen per patient. The drainage diameter ranged from 8 French catheters to 24 French catheters. The median drainage size as well as the largest drainage size used per patient and the total drainage area used per patient did not show statistically significant influence on mortality. CONCLUSION:Percutaneous drainage therapy is an effective tool for treatment of necrotizing pancreatitis.Large bore drainages did not prove to be more effective in controlling the septic focus.

Surgical management of necrotizing pancreatitis:An overview

Necrotizing pancreatitis is an uncommon yet serious complication of acute pancreatitis with mortality rates reported up to 15%that reach 30%in case of infection.Traditionally open surgical debridement was the only tool in our disposal to manage this serious clinical entity.This approach is however associated with poor outcomes.Management has now shifted away from open surgical debridement to a more conservative management and minimally invasive approaches.Contemporary approach to patients with necrotizing pancreatitis and/or infectious pancreatitis is summarized in the 3Ds:Delay,Drain and Debride.Patients can be managed in the intensive care unit and any intervention should be delayed.Percutaneous drainage can be utilized first and early in the course of the disease,followed by endoscopic drainage or video assisted retroperitoneoscopic drainage if necrosectomy is deemed necessary.Open surgery is now less frequently performed and should be reserved for cases refractory to any other approach.The management of necrotizing pancreatitis therefore requires a multidisciplinary dynamic model of approach rather than being a surgical disease.

Changes of gastric and intestinal blood flow, serum phospholipase A_2 and interleukin-1β in rats with acute necrotizing pancreatitis

AIM:To explore the relationship between gastric and intestinal microcirculatory impairment and inflammatory mediators released in rats with acute necrotizing pancreatitis (ANP). METHODS: A total of 64 rats were randomized into control group and ANP group. ANP model was induced by injection of 5% sodium taurocholate under the pancreatic membrane. Radioactive biomicrosphere technique was used to measure the gastric and intestinal tissue blood flow at 2 and 12 h after the induction of ANP, meanwhile serum phospholipase A2 (PLA2) activities and interleukin-1β levels were determined. Pathologic changes in pancreas, gastric and intestinal mucosae were studied. RESULTS: The gastric blood flow in ANP group (0.62±0.06 and 0.35±0.05) mL/(min·g) was significantly lower than that in control group (0.86±0.11 and 0.85±0.06) mL/(min·g) (P<0.01) at 2 and 12 h after induction of ANP. The intestinal blood flow in ANP group (0.80±0.07 and 0.50±0.06) mlV(min·g) was significantly lower than that in control group (1.56±0.18 and 1.61±0.11) mL/(min·g) (P<0.01). Serum PLA2 activities (94.29±9.96 and 103.71± 14.40) U/L and IL-1β levels (0.78±0.13 and 0.83±0.20)μg/L in ANP group were higher than those in control group (65.27±10.52 and 66.63±9.81) U/L, (0.32±0.06 and 0.33±0.07)μg/L (P<0.01). At 2 and 12 h after introduction of the model, typical pathologic changes were found in ANP. Compared with control group, the gastric and intestinal mucosal pathologic changes were aggravated significantly (P<0.01) at 12 h after induction of ANP. Gastric and intestinal mucosal necrosis, multiple ulcer and hemorrhage occurred. CONCLUSION: Decrease of gastric and intestinal blood flow and increase of inflammatory mediators occur simultaneously early in ANP, both of them are important pathogenic factors for gastric and intestinal mucosal injury in ANP.

Preventive effect of tetramethylpyrazine on intestinal mucosal injury in rats with acute necrotizing pancreatitis

AIM： To evaluate the role of microcirculatory disorder （MCD） and the therapeutic effectiveness ;of tetramethylpyrazine （TMP） on intestinal mucosa injury in rats with acute necrotizing pancreatitis （ANP）.METHODS： A total of 192 Sprague-Dawley rats were randomly divided into three groups： normal control group （C group）, ANP group not treated with TMP （P group）, ANP group treated with TMP （T group）. An ANP model was induced by injection of 50 g/L sodium taurocholate under the pancreatic membrane （4 mL/kg）. C group received isovolumetric injection of 9 g/L physiological saline solution using the same method. T group received injection of TMP （10 mL/kg） via portal vein. Radioactive biomicrosphere technique was used to measure the blood flow at 0.5, 2, 6 and 12 h after the induction of ANP. Samples of pancreas, distal ileum were collected to observe pathological changes using a validated histology score. Intestinal tissues were also used for examination of myeloperoxidase （MPO） expressed intraceUularly in azurophilic granules of neutrophils.RESULTS： The blood flow was significantly lower in P group than in C group （P 〈 0.01）. The pathological changes were aggravated significantly in P group. The longer the time, the severer the pathological changes. The intestinal MPO activities were significantly higher in P group than in C group （P 〈 0.01）. The blood flow of intestine was significantly higher in T group than in P group after 2 h （P 〈 0.01）. The pathological changes were alleviated significantly in T group. MPO activities were significantly lower in T group than in P group （P 〈 0.01 or P 〈 0.05）. There was a negative correlation between intestinal blood flow and MPO activity （r = -0.981, P 〈 0.01） as well as between intestinal blood flow and pathologic scores （r = -0.922, P 〈 0.05）.CONCLUSION： MCD is an important factor for intestinal injury in ANP. TMP can ameliorate the condition of MCD and the damage to pancreas and intestine.

Ligustrazine alleviates gastric mucosal injury in a rat model of acute necrotizing pancreatitis

BACKGROUND: Acute necrotizing pancreatitis (ANP) leads to a systemic inflammatory response characterized by widespread leukocyte activation and, as a consequence, distant organ injury. The aim of this study was to explore the relationship between gastric microcirculatory impairment and inflammatory mediators released in rats and to evaluate the therapeutic effect of ligustrazine extracted from Rhizoma ligusticum wallichii on gastric mucosa injury in a rat model of ANP. METHODS: Ninety-six Sprague-Dawley rats were randomly divided into three groups: normal control (group Q; ANP without treatment (group P); and ANP treated with ligustrazine (group T). The ANP model was induced by injection of 50 g/L sodium taurocholate under the pancreatic membrane (4 ml/kg). Group C was given isovolumetric injection of 9 g/L physiological saline by the same route. Group T was injected with ligustrazine (10 ml/kg) via the portal vein. The radioactive biomicrosphere technique was used to measure the blood flow 2 and 12 hours after the induction of ANP. Samples of the pancreas and stomach were taken to assess pathological changes by a validated histology score; meanwhile, the levels of serum interleukin-1 beta (IL-1 beta) were determined. Gastric tissues were also used to measure the level of myeloperoxidase (MPO), which is expressed intracellularly in the azurophilic granules of neutrophils. RESULTS: Blood flow in group P was significantly lower than that in group C (P < 0.01). Pathological changes were significantly aggravated in group P. The gastric MPO activity in group P was significantly higher than that in group C (P < 0.01). The level of serum IL-1 beta in group P increased more significantly than that in group C (P < 0.01). Blood flow of the stomach in group T was significantly higher than that in group P after 2 hours (P < 0.01). The pathological changes were significantly alleviated in group T. The MPO activity of group T was significantly lower than that of group P (P < 0.01). Although serum IL-1 beta level of group T, was higher than of group C (P < 0.01), it was lower than that of group P (P < 0.01). There was a negative correlation between gastric blood flow and MPO activity (r=-0.983, P < 0.01), and between gastric blood flow and pathological score (r=-0.917, P < 0.05). CONCLUSIONS: Decreased gastric blood flow and increased inflammatory mediators can be seen early in ANP, and both are important factors for gastric and mucosal injury. Ligustrazine can ameliorate microcirculatory disorder and alleviate the damage to the pancreas and stomach.

Dynamic changes of IL-2/IL-10, sFas and expression of Fas in intestinal mucosa in rats with acute necrotizing pancreatitis

AIM:To investigate dynamic changes of serum IL-2, IL-10, IL-2/IL-10 and sFas in rats with acute necrotizing pancreatitis. To explore the expression of Fas in intestinal mucosa of rats with acute necrotizing pancreatitis (ANP). METHODS:A total of 64 Sprague-Dawley (SD) rats were randomly divided into two groups:normal control group (C group), ANP group (P group). An ANP model was induced by injection of 50 g/L sodium taurocholate under the pancreatic membrane. Normal control group received isovolumetric injection of 9 g/L physiological saline solution using the same method. The blood samples of the rats in each group were obtained via superior mesenteric vein to measure levels of IL-2, IL-10, sFas and calculate the value of IL-2/IL-10. The levels of IL-2, IL-10 and sFas were determined by ELISA. The severity of intestinal mucosal injury was evaluated by pathologic score. The expression of Fas in intestinal mucosal tissue was determined by immunohistochemistry staining. RESULTS:Levels of serum IL-2 were significantly higher in P group than those of C group (2.79 ± 0.51 vs 3.53 ± 0.62, 2.93 ± 0.89 vs 4.35 ± 1.11, 4.81 ± 1.23 vs 6.94 ± 1.55 and 3.41 ± 0.72 vs 4.80 ± 1.10, respectively, P < 0.01, for all) and its reached peak at 6 h. Levels of serum IL-10 were significantly higher in P group than those of C group at 6 h and 12 h (54.61 ± 15.81 vs 47.34 ± 14.62, 141.15 ± 40.21 vs 156.12 ± 43.10, 89.18 ± 32.52 vs 494.98 ± 11.23 and 77.15 ± 22.60 vs 93.28 ± 25.81, respectively, P < 0.01, for all). The values of IL-2/IL-10 were higher significantly in P group than those of C group at 0.5 h and 2 h (0.05 ± 0.01 vs 0.07 ± 0.02 and 0.02 ± 0.01 vs 0.03 ± 0.01, respectively, P < 0.01, for all), and it were significantly lower than those of C group at 6 h (0.05 ± 0.02 vs 0.01 ± 0.01, P < 0.01) and returned to the control level at 12 h (0.04 ± 0.01 vs 0.05 ± 0.02, P > 0.05). In sFas assay, there was no significant difference between P group and C group (3.16 ± 0.75 vs 3.31 ± 0.80, 4.05 ± 1.08 vs 4.32 ± 1.11, 5.93 ± 1.52 vs 5.41 ± 1.47 and 4.62 ± 1.23 vs 4.44 ± 1.16, respectively, P > 0.05, for all). Comparison of P group and C group, the pathological changes were aggravated significantly in P group. Immunohistochemistry staining show the expression of Fas was absent in normal intestinal tissues, however, it gradually increased after induction of pancreatitis in intestinal tissue, then reached their peaks at 12 h.CONCLUSION:Fas were involved in the pathogenesis of pancreatitis associated intestinal injury. The mechanisms of Fas may be associated to Fas mediated T helper cell apoptosis.

Role of nitric oxide in Toll-like receptor 2 and 4 mRNA expression in liver of acute hemorrhagic necrotizing pancreatitis rats

AIM： To investigate the role of nitric oxide （NO） in Tolllike receptor 2 （TLR2）/4mRNA expression in livers of acute hemorrhagic necrotizing pancreatitis （AHNP） rats. METHODS： One hundred and ten SD male rats were randomly divided into sham-operated group （n = 10）, AHNP group （n = 30）, chloroquine （CQ）-treated group （n = 30） and L-Arg-treated group （n = 40）. TLR2/4mRNA expression in the liver of AHNP rats was measured by RT-PCR. RESULTS： Expression of TLR2/4mRNA could be detected in the liver of AHNP rats in sham-operated group （0.155E-5±0.230E-6 and 0.115E-2±0.545E-4）, but was markedly increased at 3 h in AHNP group （0.197E-2±0.114E-3 and 0.175±0.349E-2） peaking at 12 h （0.294E-2 ± 0.998E-4 and 2.673 ± 2.795E-2, P〈 0.01）. Hepatic injuries were aggravated, TNF-α concentration in the liver was increased and NO concentration was decreased （P〈 0.05 or P〈 0.01）. When TLR2/4mRNA expression was inhibited by CQ （3 h： 1.037E-4±3.299E-6 and 0.026±3.462E-3; 6 h： 1.884E-4±4.679E-6 and 0.108±6.115E-3; 12 h： 2.443E-4±7.714E-6 and 0.348±6.807E-3; P 〈 0.01）, hepatic injuries were relieved, NO concentration in the liver was increased and TNF-α concentration was decreased （P〈0.05 or P〈0.01）. When rats with AHNP were treated with L-Arg, TLR2/4mRNA expression in the liver could be effectively inhibited （50 mg-T： 0.232E-2±0.532E-4 and 0.230±6.883E-3; 100 mg-T： 0.210E-2± 1.691E-4 and 0.187±0.849E-2; 200 mg-T： 0.163E-2±0.404E-4 and 0.107±0.195E-2; 400 mg-T： 0.100E-2±0.317E-4 and 0.084±0.552E-2; P〈0.01） and hepatic injuries were relieved. At the same time, NO concentration in the liver was markedly increased and TNF-α concentration was decreased （P〈0.05 or P〈O.OI）, CONCLUSION： The expression of TLR2/4mRNA is increased and hepatic injuries are aggravated in the liver of AHNP rats. TLR2/4mRNA gene expression in the liver of AHNP rats can be markedly inhibited by NO, leading to the relief of hepatic injuries.

Effect of nitric oxide on toll-like receptor 2 and 4 gene expression in rats with acute lung injury complicated by acute hemorrhage necrotizing pancreatitis

BACKGROUND: Toll-like receptor (TLR) 2/4 might play important roles in mediating proinflammatory cytokine synthesis and release. And nitric oxide (NO) has been used to treat acute respiratory distress syndrome (ARDS). This study aimed to investigate the changes in TLR2/4 gene expression in the lungs of rats with acute lung injury (ALI) complicated by acute hemorrhage necrotizing pancreatitis (AHNP) and the effect of NO on the TLR2/4 gene expression. METHODS: One hundred and ten SD male rats were randomly divided into sham-operated group ( n = 10) , AHNP group (n = 30) , chloroquine-treated group ( n = 30) , and L-Arg-treated group (n =40). The lungs were dissected for lung histological scoring, and bronchoalveolar lavages were harvested for lung injury indexing. TLR2/4 mRNA expression in the lungs was measured by RT-PCR. RESULTS: TLR2/4mRNA was detected in the lungs with low values in the sham-operated group (0.016±0. 210E-2, 0.112 ±0.750E-2) , but it was markedly increased at 3 hours in the AHNP group (0.787±0.751E-2, 1.512 ±1.794E-2) , peaking at 12 hours (1.113 ±6.141E-2, 2.957±2.620E-2; P <0.05 or P <0.01). When lung injuries were aggravated, TNF-α concentrations in the lungs were increased, but NO concentrations were decreased ( P < 0.05 or P < 0.01 ) . When TLR2/4mRNA was inhibited by CQ (3h: 0.313 ± 5.491E-2, 0.005 ±1.419E-3 ; 6h: 0.488 ±7.442E-2, 0.010 ± 1.518E-3; 12h: 0.883 ± 8.911E-2, 0.024 ± 2.760E-3; P< 0.05 or P <0.01) , lung injuries were relieved. NO concentrations in the lungs were increased but TNF-α concentrations were decreased (P <0. 05 or P <0.01). When the rats with AHNP were treated with L-Arg, TLR2/4mRNA expression in the lungs could be effectively inhibited (50mg-T: 0.656 ±3. 977E-2, 1. 501 ±6.111E-2; 100mg-T: 0.260± 0.891E-2, 0.732 ±5.135E-2; 200mg-T: 0.126 ±0.914E-2, 0.414 ± 1.678E-2; 400mg-T: 0.091 ±0.399E-2, 0.287 ± 0.176E-2; P <0.05 or P <0. 01) and lung injuries were relieved. At the same time, NO concentrations in the lungs were markedly increased, but TNF-α concentrations were decreased (P <0.05 or P <0.01). CONCLUSIONS: The expression of TLR2/4mRNA is increased in the lungs in rats with AHNP and lung injuries are aggravated. TLR2/4mRNA gene expression of the lungs of rats with AHNP could be markedly inhibited by NO, leading to the relief of lung injuries.

Effects of Chai-Qin-Cheng-Qi Decoction on cefotaxime in rats with acute necrotizing pancreatitis

AIM:To investigate the effect of Chai-Qin-Cheng-Qi Decoction(CQCQD)on cefotaxime(CTX)concentration in pancreas of rats with acute necrotizing pancreatitis (ANP). METHODS:Sixty healthy male Sprague-Dawley rats were divided randomly into an ANP group(ANP model +CTX,n=20),treatment group(ANP model+CTX +CQCQD,n=20)and control group(normal rats+ CTX,n=20).ANP models were induced by retrograde intraductal injection of 3.5%sodium taurocholate (1 mL/kg),and the control group was injected intraductally with normal saline.All rats were injected introperitoneally with 0.42 g/kg CTX(at 12-h intervals for a continuous 72 h)at 6 h after intraductal injection. Meanwhile,the treatment group received CQCQD (20 mL/kg)intragastrically at 8-h intervals,and the ANP and control group were treated intragastrically with normal saline.At 15 min after the last CTX injection,blood and pancreas samples were collected for the determination of CTX concentration using validated high-performance liquid chromatography. Pathological changes and wet-to-dry-weight(W/D) ratio of pancreatic tissue were examined. RESULTS:Serum CTX concentrations in three groups were not significantly different.Pancreatic CTXconcentration and penetration ratio were lower in ANP group vs control group(4.4±0.6μg/mL vs 18.6± 1.7μg/mL,P=0.000;5%vs 19%,P=0.000),but significantly higher in treatment group vs ANP group (6.4±1.7μg/mL vs 4.4±0.6μg/mL,P=0.020;7% vs 5%,P=0.048).The histological scores and W/D ratio were significantly decreased in treatment group vs ANP and control group. CONCLUSION:CQCQD might have a promotive effect on CTX concentration in pancreatic tissues of rats with ANP.

Acute necrotizing pancreatitis as fi rst manifestation of primary hyperparathyroidism

We report the case of a female patient with severe acute necrotizing pancreatitis associated with hypercalcemia as first manifestation of primary hyperparathyroidism caused by a benign parathyroid adenoma.Initially the acute pancreatitis was treated conservatively.The patient subsequently underwent surgical resection of the parathyroid adenoma and surgical clearance of a large infected pancreatic pseudocyst.Although the association of parathyroid adenoma-induced hypercalcemia and acute pancreatitis is a known medical entity,it is very uncommon.The pathophysiology of hypercalcemia-induced acute pancreatitis is therefore not well known,although some mechanisms have been proposed.It is important to treat the provoking factor.Therefore,the cause of hypercalcemia should be identif ied early.Surgical resection of the parathyroid adenoma is the ultimate therapy.

Is necrosectomy obsolete for infected necrotizing pancreatitis? Is a paradigm shift needed?

In 1886,Senn stated that removing necrotic pancreatic and peripancreatic tissue would benefit patients with severe acute pancreatitis.Since then,necrosectomy has been a mainstay of surgical procedures for infected necrotizing pancreatitis(NP).No published report has successfully questioned the role of necrosectomy.Recently,however,increasing evidence shows good outcomes when treating walled-off necrotizing pancreatitis without a necrosectomy.The literature concerning NP published primarily after 2000 was reviewed;it demonstrates the feasibility of a paradigm shift.The majority(75%)of minimally invasive necrosectomies show higher completion rates:between 80%and 100%.Transluminal endoscopic necrosectomy has shown remarkable results when combined with percutaneous drainage or a metallic stent.Related morbidities range from 40%to 92%.Single-digit mortality rates have been achieved with transluminal endoscopic necrosectomy,but not with video-assisted retroperitoneal necrosectomy series.Drainage procedures without necrosectomy have evolved from percutaneous drainage to transluminal endoscopic drainage with or without percutaneous endoscopic gastrostomy access for laparoscopic instruments.Most series have reached higher success rates of 79%-93%,and even 100%,using transcystic multiple drainage methods.It is becoming evident that transluminal endoscopic drainage treatment of walledoff NP without a necrosectomy is feasible.With further refinement of the drainage procedures,a paradigm shift from necrosectomy to drainage is inevitable.

Chloroquine Relieves Acute Lung Injury in Rats with Acute Hemorrhagic Necrotizing Pancreatitis

Summary： This study preliminarily investigated the mechanism by which chloroquine （CQ） relieves acute lung injury （ALI） complicated in acute hemorrhagic necrotizing pancreatitis （AHNP）. Sixty male Wistar rats were randomized into sham-operated group （group A, n=10）, AHNP group （group B, n=10）, L-arginine-treated group （group C, n=10）, L-N-nitro-L-arginine methyl ester （NAME）-treated group （group D, n=10）, CQ-treated group （group E, n=10） and CQ＋L-NAME-treated group （group F, n=10）. TLR4 expression was measured by using real time-PCR and Western blotting respectively. The results showed that, in the group B, the expression of TLR4 and the levels of TNF-α and IL-6 in the lungs were significantly increased, and the nitric oxide （NO） concentration was reduced, as compared with those in the group A （P〈0.05 or P〈0.01）. Lung injury was aggravated with the increased expression of TLR4. When the inhibitor and stimulator of TLR4, namely L-Arg and L-NAME, were added respectively, lung injury was correspondingly relieved or aggravated （P〈0.05 or P〈0.01）. In the group E, TLR4 expres- sion was substantially lower and NO concentration higher than those in the group B （P〈0.05 or P〈0.01）. However, in the group F, NO concentration was markedly decreased, and the inhibitory effect of CQ on TLR4 expression and the relief of lung injury were weakened when compared with those in the group E （P〈0.05 or P〈0.01）. It was concluded that TLR4 may play an important role in the pathogenesis and development of ALl complicated in AHNP. CQ could relieve ALl by decreasing the TLR4 expression and increasing the NO release.

Interventional strategies in infected necrotizing pancreatitis:Indications,timing,and outcomes

Acute pancreatitis(AP)is one of the most common gastrointestinal diseases and remains a life-threatening condition.Although AP resolves to restitutio ad integrum in approximately 80%of patients,it can progress to necrotizing pancreatitis(NP).NP is associated with superinfection in a third of patients,leading to an increase in mortality rate of up to 40%.Accurate and early diagnosis of NP and associated complications,as well as state-of-the-art therapy are essential to improve patient prognoses.The emerging role of endoscopy and recent trials on multidisciplinary management of NP established the“step-up approach”.This approach starts with endoscopic interventions and can be escalated to other interventional and ultimately surgical procedures if required.Studies showed that this approach decreases the incidence of new multiple-organ failure as well as the risk of interventional complications.However,the optimal interventional sequence and timing of interventional procedures remain controversial.This review aims to summarize the indications,timing,and treatment outcomes for infected NP and to provide guidance on multidisciplinary decision-making.

Effects of chondroitin sulfate on alteration of actin cytoskeleton in rats with acute necrotizing pancreatitis

BACKGROUND: In experimental acute pancreatitis, a large amount of reactive oxygen species are produced, and in turn cytoskeletal changes may be induced in pancreatic tissue. These changes contribute to an imbalance of digestive enzyme segregation, transport, exocytosis and activation, resulting in cell injury. In this study, we assessed the effects of chondroitin sulfate (CS) on attenuation of oxidative damage and protection of F-actin in rats with acute necrotizing pancreatitis (ANP). METHODS: Ninety male Wistar rats were divided randomly into three groups. Group A was infused with 5% sodium taurocholate; group B was treated with CS; and group C served as control. Rats from the three groups were killed at 1, 3 or 8 hours. The levels were measured of malonyl dialdehyde (MDA), total superoxide dismutase (SOD), glutathione synthetase (GSH), serum amylase (SAM) and adenosine triphosphate (ATP). F-actin immunostained with rhodamine-phalloidin was analyzed using a confocal laser scanning system and the content of F-actin protein was determined. RESULTS: The levels of SAM increased in groups A and B, whereas the levels of GSH, SOD and ATP in group A decreased markedly during pancreatitis, and MDA increased significantly. The levels of GSH, SOD and ATP in group B were higher than those in group A, but the level of MDA was lower than in group A. At the same time, ANP resulted in early disruption of the cytoskeleton with dramatic changes and a loss of F-actin. Administration of CS moderated the damage to the actin cytoskeleton. CONCLUSIONS: Retrograde infusion of sodium taurocholate via the pancreatic duct may produce pancreatic necrosis and a marked increase in serum amylase activity, induce a severe depletion of ATP level, prime lipid peroxidation, and damage F-actin. Treatment with CS can ameliorate pancreatic cell conditions, limit cell membrane peroxidation, protect F-actin, and attenuate pancreatitis.

Acute necrotizing pancreatitis complicated with pancreatic pseudoaneurysm of the superior mesenteric artery: A case report

Acute necrotizing pancreatitis complicated with pancreatic pseudoaneurysm is a rare emergency associated with high mortality that demands immediate treatment to save the patient’s life. We treated a 64-year-old man who presented with a bleeding pseudoaneurysm of the superior mesenteric artery caused by acute pancreatitis, using interventional embolizing therapy. In the present report we show that interventional treatment is an effective therapeutic modality for patients with acute necrotizing pancreatitis complicated with intra-abdominal bleeding.

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

BACKGROUND Timing 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.AIM To evaluate laboratory variables in ANP patients in the preoperative period for the purpose of their use in the timing of surgery.METHODS A 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.RESULTS Seven 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.CONCLUSION Multifactorial analysis of dynamic changes of routine laboratory variables can be useful for a person-tailored timing of surgical intervention in ANP patients.