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.

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.

Different dosages of methylprednisolone therapy for acute necrotizing encephalopathy of childhood:a 6-year multicenter retrospective study

To the Editor:Acute necrotizing encephalopathy(ANE)is a rare but often devastating neurologic disorder in children.[1]Hereditary susceptibility and cytokine storm play important roles in ANE pathogenesis,[2,3]but the specific molecular biological mechanism is unclear.

Acute pancreatitis in the critical care setting:A review of assessment and intervention strategies

The incidence of acute pancreatitis(AP),a condition characterized by inflammation in the pancreas,has been increasing globally and is associated with several complications.This review elaborated on the etiology,clinical presentation,severity assessment,and treatment modalities of AP,mainly in the critical care setting.Patients with severe AP,as indicated by organ failure(>48 hours from onset),warrant treatment in the intensive care unit setting.The most common etiologies,biliary disease and alcohol consumption,and the advanced diagnostic tools used for the identification of the cause are highlighted.Different severity assessment tools are utilized for grading the severity of the disease,predicting patient outcomes,determining the associated risk,and guiding treatment decisions.The treatment interventions comprise various approaches,such as anti-infective therapy enteral nutrition,analgesics for pain,or minimally invasive surgical procedures,thereby demonstrating an evolving landscape of AP management.Furthermore,various complications such as necrosis,organ failure,and hemorrhage,necessitate disease monitoring and differential diagnosis and are crucial for optimal management of patients.Novel treatment modalities and advancements in multidisciplinary care emphasize the potential for reducing the burden of AP in critical care settings.

Early endoscopic management of an infected acute necrotic collection misdiagnosed as a pancreatic pseudocyst: A case report

BACKGROUND Infected acute necrotic collection(ANC)is a fatal complication of acute pancre-atitis with substantial morbidity and mortality.Drainage plays an exceedingly important role as the first step in invasive intervention for infected necrosis;however,there is great controversy about the optimal drainage time,and better treatment should be explored.CASE SUMMARY We report the case of a 43-year-old man who was admitted to the hospital with severe intake reduction due to early satiety 2 wk after treatment for acute pancre-atitis;conservative treatment was ineffective,and a pancreatic pseudocyst was suspected on contrast-enhanced computed tomography(CT).Endoscopic ultra-sonography(EUS)suggested hyperechoic necrotic tissue within the cyst cavity.The wall was not completely mature,and the culture of the puncture fluid was positive for A-haemolytic Streptococcus.Thus,the final diagnosis of ANC in-fection was made.The necrotic collection was not walled off and contained many solid components;therefore,the patient underwent EUS-guided aspiration and lavage.Two weeks after the collection was completely encapsulated,pancreatic duct stent drainage via endoscopic retrograde cholangiopancreatography(ERCP)was performed,and the patient was subsequently successfully discharged.On repeat CT,the pancreatic cysts had almost disappeared during the 6-month fo-llow-up period after surgery.CONCLUSION Early EUS-guided aspiration and lavage combined with late ERCP catheter drainage may be effective methods for intervention in infected ANCs.

Clinical features of acute esophageal mucosal lesions and reflux esophagitis Los Angeles classification grade D: A retrospective study

BACKGROUND Acute esophageal mucosal lesions(AEMLs)are an underrecognized and largely unexplored disease.Endoscopic findings are similar,and a higher percentage of AEML could be misdiagnosed as reflux esophagitis Los Angeles classification grade D(RE-D).These diseases could have different pathologies and require different treatments.AIM To compare AEML and RE-D to confirm that the two diseases are different from each other and to clarify the clinical features of AEML.METHODS We selected emergency endoscopic cases of upper gastrointestinal bleeding with circumferential esophageal mucosal injury and classified them into AEML and RE-D groups according to the mucosal injury’s shape on the oral side.We examined patient background,blood sampling data,comorbidities at onset,endoscopic characteristics,and outcomes in each group.RESULTS Among the emergency cases,the AEML and RE-D groups had 105(3.1%)and 48(1.4%)cases,respectively.Multiple variables exhibited significantly different results,indicating that these two diseases are distinct.The clinical features of AEML consisted of more comorbidities[risk ratio(RR):3.10;95%confidence interval(CI):1.68–5.71;P<0.001]and less endoscopic hemostasis compared with RE-D(RR:0.25;95%CI:0.10–0.63;P<0.001).Mortality during hospitalization was higher in the AEML group(RR:3.43;95%CI:0.82–14.40;P=0.094),and stenosis developed only in the AEML group.CONCLUSION AEML and RE-D were clearly distinct diseases with different clinical features.AEML may be more common than assumed,and the potential for its presence should be taken into account in cases of upper gastrointestinal bleeding with comorbidities.

Pathogenesis of pancreatic encephalopathy in severe acute pancreatitis

BACKGROUND: Pancreatic encephalopathy (PE) is a serious complication of severe acute pancreatitis (SAP). In recent years, more and more PE cases have been reported worldwide, and the onset PE in the early stage was regarded as a poor prognosis sign of SAP, but the pathogenesis of PE in SAP still has not been clarified in the past decade. The purpose of this review is to elucidate the possible pathogenesis of PE in SAP. DATA SOURCES: The English-language literature concerning PE in this review came from the Database of MEDLINE (period of 1991-2005), and the keywords of severe acute pancreatitis and pancreatic encephalopathy were used in the searching. RESULTS: Many factors were involved in the pathogenesis of PE in SAP. Pancreatin activation, excessive release of cytokines and oxygen free radicals, microcirculation abnormalities of hemodynamic disturbance, ET-1/NO ratio, hypoxemia, bacterial infection, water and electrolyte imbalance, and vitamin B1 deficiency participated in the development of PE in SAP. CONCLUSIONS: The pathogenesis of PE in SAP has not yet been fully understood. The development of PE in SAP may be a multi-factor process. To find out the possible inducing factor is essential to the clinical management of PE in SAP.

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.

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.

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.

Splanchnic vein thrombosis in necrotizing acute pancreatitis: Detection by computed tomographic venography

AIM: To assess the diagnostic accuracy of computed tomographic venography(CTV) for splanchnic vein thrombosis(SVT) detection in necrotizing acute pancreatitis(AP) patients.METHODS:Forty-three patients with necrotizing AP who underwent both CTV and digital subtraction angiography(DSA)within 3 d were analyzed in this retrospective comparative study.All CTV procedures were performed with a dual-source CT scanner.The presence and location of SVT were determined via blinded imaging data analyses.RESULTS:According to the DSA results,17(39.5%)of the total 43 patients had SVT.The sensitivity,specificity,positive and negative predictive values of CTV for SVT detection were 100%(95%CI:77.1%-100%),92.3%(95%CI:73.4%-98.7%),89.5%(95%CI:65.5%-98.2%)and 100%(95%CI:82.8%-100%),respectively.CONCLUSION:CTV is an effective examination for SVT detection in patients with necrotizing AP with high positive and negative predictive values.

Pancreatic encephalopathy and Wernicke encephalopathy in association with acute pancreatitis: A clinical study

AIM： To investigate clinical characteristics and therapy of pancreatic encephalopathy （PE） and Wernicke encephalopathy （WE）. METHODS： In a retrospective study of 596 patients with acute pancreatitis （AP）, patients with PE were compared to those with WE in regards to history, clinical manifestation, diagnosis, treatment and outcome. RESULTS： There were 93 patients with severe acute pancreatitis （SAP）. Encephalopathies were discovered in 10 patients （1.7%）. Six patients with PE all developed in SAP （6.5%）, and three of them died （3% of SAP, 50% of PE）. Four patients with WE developed in AP （0.7%）, and two of them died （0.3% of AP, 50% of WE）. Two patients with WE were treated with parenteral thiamine and survived. Global confusions were seen in all patients with encephalopathy. Ocular abnormalities were found. Conjugate gaze palsies were seen in 1 of 6 （16.7%） patients with PE. Of 4 patients with WE, one （25%） had conjugate gaze palsies, two （50%） had horizontal nystagmus, three （75%） had diplopia, and one （25%） had myosis. Ataxia was not seen in all patients. None of patients with WE presented with the classic clinical triad. CSF examinations for 2 patients with WE showed lightlyincreased proteins and glucose. CT and MRI of the brain had no evidence of characteristic abnormalities. CONCLUSION： PE occurs in early or reiteration stage of SAP, and WE in restoration stage of SAP/AP. Ocular abnormalities are the hallmarks of WE, and horizontal nystagmus is common. It is difficult to diagnose earlier an encephalopathy as PE or WE, as well as differentiate one from the other. Long fasting, hyperemesis and total enteral nutrition （TPN） without thiamine are main causes of thiamine deficiency in the course of pancreatitis.

Acute necrotizing pancreatitis: Surgical indications and technical procedures

Necrosis of pancreatic parenchyma or extrapancreatic tissues is present in 10%-20% of patients with acute pancreatitis, defining the necrotizing presentation frequently associated with high morbidity and mortality rates. During the initial phase of acute necrotizing pancreatitis the most important pillars of medical treatment are fluid resuscitation, early enteral nutrition, endoscopic retrograde colangiopancreatography if associated cholangitis and intensive care unit support. When infection of pancreatic or extrapancreatic necrosis occurs, surgical approach constitutes the most accepted therapeutic option. In this context, we have recently assited to changes in time for surgery(delaying the indication if possible to around 4 wk to deal with "walledoff" necrosis) and type of access for necrosectomy: from a classical open approach(with closure over large-bore drains for continued postoperative lavage or semiopen techniques with scheduled relaparotomies), trends have changed to a "step-up" philosophy with initial percutaneous drainage and posterior minimally invasive or endoscopic access to the retroperitoneal cavity for necrosectomy if no improvement has been previously achieved. These approaches are progressively gaining popularity and morbidity and mortality rates have decreased significantly. Therefore, a staged, multidisciplinary, step-up approach with minimally invasive or endoscopic access for necrosectomy is widely accepted nowadays for management of pancreatic necrosis.

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.

Nuclear factor-kappaB activation on the reactive oxygen species in acute necrotizing pancreatitic rats

AIM： To investigate the potential role of nuclear factor kappa-B （NF-κB） activation on the reactive oxygen species in rat acute necrotizing pancreatitis （ANP） and to assess the effect of pyrrolidine dithiocarbamate （PDTC, an inhibitor of NF-κB）.METHODS： Rat ANP model was established by retrograde injection of 5% sodium taurocholate into biliopancreatic duct. Rats were randomly assigned to three groups （10 rats each）： Control group, ANP group and PDTC group. At the 6^th of the model, the changes of the serum amylase,nitric oxide （NO）, malondialdehyde （MDA）, superoxide dismutase （SOD） and pancreatic morphological damage were observed. The expressions of inducible nitric oxide （iNOS） were observed by SP immunohistochemistry. And bhe expressions of NF-κB p65 subunit mRNA were observed by hybridization in situ.RESULTS： Serum amylase and NO level decreased significantly in ANP group as compared with PDTC administrated group [（7 170.40＋1 308.63） U/L vs（4 074.10＋1 719.78） U/L,P〈0.05], [（76.95±9.04） μmol/L vs （65.18±9.02） μmol/L,P〈0.05] respectively. MDA in both ANP and PDTC group rose significantly over that in control group [（9.88＋1.52）nmol/L, （8.60±1.41） nmol/L, vs （6.04：hl.78） nmol/L,P〈0.05], while there was no significant difference between them. SOD levels in both ANP and PDTC group underwent a significant decrease as compared with that in control[（3 214.59±297.74） NU/mL, （3 260.62±229.44） NU/mL,vs（3 977.80＋309.09） NU/mL, P〈0.05], but there was no significant difference between them. Though they were still higher bhan those in Control group, pancreas destruction was slighter in PDTC group, iNOS expression and NF-κB p65 subunit mRNA expression were lower in PDTC group as compared with ANP group.CONCLUSION： We conclude that correlation among NF-κB activation, serum amylase, reactive oxygen species level and tissue damage suggests a key role of NF-κB in the pathogenesis of ANP. Inhibition of NF-κB activation may reverse the pancreatic damage of rat ANP and the production of reactive oxygen species.

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.

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.

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.

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.