Stage Of Severe Acute Pancreatitis Research Articles

“PERFUSION CT IN PREDICTING THE DEVELOPMENT OF PANCREATIC NECROSIS IN EARLY STAGE OF SEVERE ACUTE PANCREATITIS”

PURPOSE: To evaluate the role of perfusion CT (PCT) scan in predicting the development of pancreatic necrosis (PN) in early stage of severe acute pancreatitis (SAP). MATERIALS AND METHODS: A total of 20 adult patients with a clinical diagnosis of SAP presenting within 72 hours of onset of symptoms with a positive SIRS criteria were included in the study. All the patients underwent PCT on a 128 slice MDCT scannerusing 40 ml of non-ionic iodinated contrast followed by post processing using vendor provided CT perfusion software whereby perfusion parameters were calculated. Perfusion defect (PD) was dened as pancreatic BF and/or BV qualitatively less than hepatic BF and/or BV respectively on the color coded maps. A follow up CECT abdomen was done after 2 weeks as a 'gold standard' to assess whether PN developed in the corresponding region of PD. RESULTS: 8 out of 20 patients developed perfusion defect (PD) on the PCT, of which 6 patients developed PN on the follow up scan. Patients who did not show any PD on the PCT (12 out of 20) did not develop necrosis on the follow up CECT. The sensitivity, specicity, PPV, NPV and accuracy of PCT in predicting necrosis was 100%, 85.71%, 75%, 100% and 90% respectively. The cut off values of pancreatic BF and BV in predicting the development of PN were 34.87 ml/100ml/min and 11.70ml/100ml respectively based on the ROC curve. CONCLUSION: PCT is a useful technique that can predict development of PN in the early stage of SAP so that early aggressive management can be initiated.

Intestinal bacterial overgrowth in the early stage of severe acute pancreatitis is associated with acute respiratory distress syndrome.

BACKGROUNDIn the early stage of acute pancreatitis (AP), a large number of cytokines induced by local pancreatic inflammation seriously damage the intestinal barrier function, and intestinal bacteria and endotoxins enter the blood, causing inflammatory storm, resulting in multiple organ failure, infectious complications, and other disorders, eventually leading to death. Intestinal failure occurs early in the course of AP, accelerating its development. As an alternative method to detect small intestinal bacterial overgrowth, the hydrogen breath test is safe, noninvasive, and convenient, reflecting the number of intestinal bacteria in AP indirectly. This study aimed to investigate the changes in intestinal bacteria measured using the hydrogen breath test in the early stage of AP to clarify the relationship between intestinal bacteria and acute lung injury (ALI)/acute respiratory distress syndrome (ARDS). Early clinical intervention and maintenance of intestinal barrier function would be highly beneficial in controlling the development of severe acute pancreatitis (SAP).AIMTo analyze the relationship between intestinal bacteria change and ALI/ARDS in the early stage of SAP.METHODSA total of 149 patients with AP admitted to the intensive care unit of the Digestive Department, Xuanwu Hospital, Capital Medical University from 2016 to 2019 were finally enrolled, following compliance with the inclusion and exclusion criteria. The results of the hydrogen breath test within 1 wk of admission were collected, and the hydrogen production rates at admission, 72 h, and 96 h were calculated. The higher the hydrogen production rates the more bacteria in the small intestine. First, according to the improved Marshall scoring system in the 2012 Atlanta Consensus on New Standards for Classification of Acute Pancreatitis, 66 patients with a PaO2/FiO2 score ≤ 1 were included in the mild AP (MAP) group, 18 patients with a PaO2/FiO2 score ≥ 2 and duration < 48 h were included in the moderately SAP (MSAP) group, and 65 patients with a PaO2/FiO2 score ≥ 2 and duration > 48 h were included in the SAP group, to analyze the correlation between intestinal bacterial overgrowth and organ failure in AP. Second, ALI (PaO2/FiO2 = 2) and ARDS (PaO2/FiO2 > 2) were defined according to the simplified diagnostic criteria proposed by the 1994 European Union Conference. The MSAP group was divided into two groups according to the PaO2/FiO2 score: 15 patients with PaO2/FiO2 score = 2 were included in group A, and three patients with score > 2 were included in group B. Similarly, the SAP group was divided into two groups: 28 patients with score = 2 were included in group C, and 37 patients with score > 2 were included in group D, to analyze the correlation between intestinal bacterial overgrowth and ALI/ARDS in AP.RESULTSA total of 149 patients were included: 66 patients in the MAP group, of whom 53 patients were male (80.3%) and 13 patients were female (19.7%); 18 patients in the MSAP group, of whom 13 patients were male (72.2%) and 5 patients were female (27.8%); 65 patients in the SAP group, of whom 48 patients were male (73.8%) and 17 patients were female (26.2%). There was no significant difference in interleukin-6 and procalcitonin among the MAP, MSAP, and SAP groups (P = 0.445 and P = 0.399, respectively). There was no significant difference in the growth of intestinal bacteria among the MAP, MSAP, and SAP groups (P = 0.649). There was no significant difference in the growth of small intestinal bacteria between group A and group B (P = 0.353). There was a significant difference in the growth of small intestinal bacteria between group C and group D (P = 0.038).CONCLUSIONIntestinal bacterial overgrowth in the early stage of SAP is correlated with ARDS.

Экскреция азота с мочой в раннюю фазу острого тяжелого панкреатита

Aim. To study urinary nitrogen excretion at the early stage of severe acute pancreatitis. Materials and methods. Prospective, single-center, cohort study. Inclusion criteria: diagnosis of acute pancreatitis and presence of at least one of the predictors of severe course. Among all patients (n = 72), a cohort of patients with severe acute pancreatitis (n = 32) was allocated. Three groups were formed in it: the first one – all patients, the second one – survivors (n = 24), the third one – deceased (n = 8). Urinary nitrogen excretion was determined using the Deacon formula. Measurements were performed on the first, third and fifth days of the disease. Statistical processing of the material was carried out by the SPSS software package. The null hypothesis was rejected at p &lt; 0.05. Results. In the first week of the disease in all groups, the maximum urinary nitrogen excretion occurs on the 3rd day. When comparing the results of the second and third groups, it was found that the urinary nitrogen excretion on the first and fifth days did not have a statistically significant difference between the groups (respectively, p = 0.138, p = 0.572), and the results of the third day have (p = 0.014). A similar pattern remains when recalculating the nitrogen loss in the urine to the ideal weight; for the third day, the differences between the second and third groups were statistically significant (p = 0.007). ROC analysis of urinary nitrogen excretion of the third day calculated to the ideal body weight showed an area under the curve of 0.813 (p &lt; 0.009). The value at the cut-off point is defined as 0.65 g/kg/day. The sensitivity of the model was 0.75%, specificity – 0.83%. Conclusion. If in a patient with acute pancreatitis, there is urinary nitrogen excretion on the third day from the onset of the disease, calculated to an ideal body weight of ≥ 0.65 g/kg/day, an unfavorable outcome of the disease is predicted.

The Immunomodulatory Effects and Mechanisms of Tim-3 Action in the Early Stage of Mice with Severe Acute Pancreatitis.

Tim-3 has been considered as an ideal target for the immunotherapy of inflammation, but it is unclear whether Tim-3 also plays an important role in acute pancreatitis (AP), as well. To identify the immunomodulatory effects and mechanisms of Tim-3 action in the early stages of severe acute pancreatitis in mice. Male BALB/c mice were randomly divided into sham injection group, severe acute pancreatitis group, and anti-Tim-3 treated group. Histopathological scores of the pancreas were calculated, pancreatic myeloperoxidase (MPO) activity was assessed. The concentrations of serum IL-6, IL-10, and TNF-α were evaluated by ELISA method. Quantitative RT-PCR was performed to detect the transcripts of Tim-3, IL-6, IL-10, TNF-α, and TLR4 in peritoneal macrophages. The levels of peritoneal macrophages Tim-3, TLR4, MyD88, and NF-kB p65 were measured by western blot analysis. The pathological scores of the anti-Tim-3 treated group (11.5 ± 1.3) significantly increased compared with the sham (1.3 ± 0.5) and SAP groups (6.9 ± 1.0). Furthermore, the downregulation of Tim-3 significantly aggravated mouse pancreatic tissue damage. It was further shown that Tim-3 negatively regulated the production of pro-inflammatory cytokines, IL-6 and TNF-α, as well as anti-inflammatory cytokine IL-10. Of note, the negative regulation of inflammatory cytokines by Tim-3 was mediated by the activation of TLR4/MyD88 NF-kB signaling pathway. Our study showed that Tim-3 might play an important role in the development of AP through regulating the inflammatory response.

Portosplenomesenteric vein thrombosis in patients with early-stage severe acute pancreatitis.

AIMTo investigate the incidence and risk factors of portosplenomesenteric vein thrombosis (PSMVT) in the early stage of severe acute pancreatitis (SAP).METHODSPatients with SAP in a tertiary care setting from January 2014 to December 2016 were retrospectively reviewed. All contrast-enhanced computed tomography (CT) studies were reassessed and reviewed. Clinical outcome measures were compared between SAP patients with and without PSMVT in the early stage of the disease. Univariate and multivariate logistic regression analyses were sequentially performed to assess potential risk factors for the development of PSMVT in SAP patients. A receiver operating characteristic (ROC) curve was generated for the qualifying independent risk factors.RESULTSTwenty-five of the one hundred and forty (17.86%) SAP patients developed PSMVT 6.19 ± 2.43 d after acute pancreatitis (AP) onset. PSMVT was confirmed by contrast-enhanced CT. Multivariate stepwise logistic regression analyses showed that Balthazar’s CT severity index (CTSI) scores [odds ratio (OR): 2.742; 95% confidence interval (CI): 1.664-4.519; P = 0.000], hypoalbuminemia (serum albumin level < 25 g/L) (OR: 32.573; 95%CI: 2.711-391.353; P = 0.006) and gastrointestinal wall thickening (OR: 4.367, 95%CI: 1.218-15.658; P = 0.024) were independent risk factors for PSMVT developed in patients with SAP. The area under the ROC curve for Balthazar’s CTSI scores was 0.777 (P = 0.000), the sensitivity was 52%, and the specificity was 93% at a cut-off value of 5.5.CONCLUSIONHigh Balthazar’s CTSI scores, hypoalbuminemia and gastrointestinal wall thickening are independent risk factors for PSMVT developed in the early stage of SAP.

Early diagnosis of pancreatic necrosis based on perfusion CT to predict the severity of acute pancreatitis.

Perfusion CT can diagnose pancreatic necrosis in early stage of severe acute pancreatitis, accurately. However, no study to date has examined whether early diagnosis of pancreatic necrosis is useful in predicting persistent organ failure (POF). We performed a multi-center prospective observational cohort study to investigate whether perfusion CT can predict the development of POF in the early stage of AP, based on early diagnosis of the development of pancreatic necrosis (PN). From 2009 to 2012, we examined patients showing potential early signs of severe AP (n=78) on admission. Diagnoses for the development of PN were made prospectively by on-site physicians on the admission based on perfusion CT (diagnosis 1). Blinded retrospective reviews were performed by radiologists A and B, having 8 and 13years of experience as radiologists (diagnosis 2 and 3), respectively. Positive diagnosis for the development of PN were assumed equivalent to positive predictions for the development of POF. We then calculated the area under the curve (AUC) of the receiver operating characteristic for POF predictions. Fourteen (17.9%) and 23 patients (29.5%) developed PN and POF, respectively. For diagnoses 1, 2, and 3, AUCs for POF predictions were 74, 68, and 73, respectively. Perfusion CT diagnoses pancreatic necrosis and on that basis predicts the development of POF; http://www.umin.ac.jp/ctr/index-j.htm,UMIN000001926 .

The uncommon syndrome of pancreatic encephalopathy

Even though first described in 1923, the syndrome of pancreatic encephalopathy is an uncommon complication of acute pancreatitis. A multiple organ dysfunction syndrome, it generally occurs in early stage of severe acute pancreatitis and carries a high mortality of up to 57% and more. The syndrome must be distinguished from Wernicke encephalopathy, which may follow as a part of neurological complications in the last or restoration stage of acute pancreatitis, and occurs as a result of long fasting, hyperemesis and total parenteral nutrition without thiamine. Poorly recognized by clinicians, a large dose of Vitamin B1 is effective in the management of Wernicke encephalopathy. The present article draws attention to the two lesser recognized complications of acute pancreatitis and briefly dwells on their pathogenesis and management.

Utilization of glucocorticoids in early stage of severe acute pancreatitis: Analysis of seven cases

Objective: To discuss the characteristics of lymph node aversion, and analysis the influence to prognosis, which can provide theory foundation for the surgery of carcinoma of head of pancreas patients. Methods: Retrospectively analyzed the lymph node aversion and influence to prognosis of 298 carcinoma of head of pancreas cases, who did radical resection in West China Hospital and Deyang People's Hospital during Jan, 2007 to May, 2010. Among them, there were 206 male cases, 92 female cases, and the sex ratio were 2.24:1; the ages were from 41 to 79, and the ms-age was 62, 103 cases were younger than 60, 297 cases were older than 60; before surgery, CA-19-9 37 were 83 cases, U/ ml>37 U/ml were 215 cases; the maximum diameter 2 cm were 46 cases, 2-5 cm were 187cases, >5 cm were 65 cases; 32 cases were welldifferentiated, 108 cases were moderately differentiated, 158 cases were poorly differentiated; 192 cases had venous tumor embolus, 106 cases had no venous tumor embolus; the tumor was limited in pancreas in 56 cases, encroached outside the pancreas in 242 cases. In radical resection, despite the size, location, staging and histological differentiate degree of tumor, standard duodenopancreatectomy was done, and the area absorbent gland clearing. Dilatation radical resection was only needed according to the surgery, when the patients safety was ensured and the margin of negative excision can be reached. No matter it was radical resection or dilatation radical resection, total number of intragroup lymph node was cleared. Results: Patients having lymph node aversion were 201 cases, 67%(201/298); the high aversion rate of which in turnwere 13 group (32%), 14 group (27.4%), 8 group (17.5%), 17 group (16.1%), 12 group (13.8%), 16 group (11.6%). The 5-year survival rate of negative lymph node patient was 29%, median survival time was 23 months; the 5-year survival rate of positive lymph node patient was 13%, median survival time was 14 months, comparing the two groups, there was significant differences(p<0.0.5). Conclusion: There is certain regular pattern of lymph node aversion for carcinoma of head of pancreas patients, in which 13, 14, 12, 8, 16 group of lymph node have high rate of aversion, which should be cleared in lymph node clearing during carcinoma of head of pancreas surgery. Comparing to the carcinoma of head of pancreas patients having no lymph node, the patients with lymph node aversion are obviously worse, which means the lymph node aversion is one of the important factors for prognosis of carcinoma of head of pancreas patients. The lymph node aversion of carcinoma of head of pancreas patients has a high rate, less time cost, and area lymph node clearing should be done for those who can has carcinoma of head of pancreas resection.

Perfusion CT: can it predict the development of pancreatic necrosis in early stage of severe acute pancreatitis?

Pancreatic necrosis is an important determinant of patient outcome in severe acute pancreatitis (SAP). This prospective study was conducted to evaluate if perfusion CT (PCT) can predict the development of necrosis at an early stage in SAP. PCT was performed within 72 h of abdominal pain in 57 consecutive admitted patients of acute pancreatitis, out of which four patients were excluded. Thirty-two patients were classified as SAP and 21 as mild acute pancreatitis (MAP) on the basis of APACHE II or SIRS criteria or presence of organ failure. All patients underwent a follow-up CECT at 3 weeks to look for pancreatic necrosis. Out of 32 patients of SAP, 14 patients showed perfusion defects. The mean blood flow (BF) in these areas was 11.47 ± 5.56 mL/100 mL/min and median blood volume (BV) was 3.92 mL/100 mL (0.5-8.49 mL/100 mL). All these patients developed necrosis on follow-up scan. Two patients who did not show perfusion defects also developed necrosis. Remaining 37 patients (16 SAP and 21 MAP) did not show perfusion defect and did not develop necrosis on follow-up. All regions showing BF less than ≤23.45 mL/100 mL/min and BV ≤8.49 mL/100 mL developed pancreatic necrosis. The values of perfusion parameters may vary with the scanner, mathematical model and protocol used. The sensitivity and specificity of PCT for predicting pancreatic necrosis were 87.5% and 100%, respectively. The cut off values of BF and BV for predicting the development of pancreatic necrosis were 27.29 mL/100 mL/min and 8.96 mL/100 mL, respectively, based on ROC curve. PCT is a reliable tool for early prediction of pancreatic necrosis, which may open new avenues to prevent this ominous complication.

The effects of fluid resuscitation on oxygenation index and prognosis in early stage of severe acute pancreatitis

To analyze the correlation between fluid equilibrium and oxygen index in patients at early stage (within 2 weeks) of severe acute pancreatitis (SAP), and to discuss the effects of fluid equilibrium after resuscitation on the prognosis. A clinical study was conducted. Ninety-seven patients with SAP admitted into Shengjing Hospital of China Medical University directly or transferred into intensive care unit (ICU) in 24 hours after admission between March 2011 to October 2013 were studied. Finally, 65 patients were enrolled in statistical analysis, and those with termination of treatment prematurely were excluded. The patients received treatment protocol formulated by the same physician in ICU. Patients were divided into improved group and death group according to the outcome. The differences in fluid equilibrium on 1, 2, 3, 7, 14 days after admission of ICU between the two groups were compared. The correlation between fluid equilibrium and oxygen index was analyzed with curve fitting. Among 65 patients enrolled, 53 of them were improved after intensive care and were transferred into ordinary wards. However, 12 patients died in ICU. Patients in the improved group showed delayed positive fluid equilibrium, and some patients even showed negative fluid equilibrium. Patients in death group needed more fluid to achieve fluid equilibrium. There was a significant difference in the need of fluid to reach an equilibrium between improved group and death group [1 day: 1 814.5 (905.2, 2 152.8) mL vs. 3 891.0 (2 524.2, 5 714.5) mL, Z=-3.303, P=0.001; 2 days: 2 469.0 (1 456.0, 3 696.0) mL vs. 6 498.0 (4 617.8, 8 763.5) mL, Z=-4.431, P<0.001; 3 days: 3 234.0 (1 098.0, 4 295.5) mL vs. 9 533.5 (6 748.8, 10 689.0) mL, Z=-4.684, P<0.001; 7 days: 3 234.0 (1 033.0, 5 162.0) mL vs. 13 986.5 (8 045.8, 14 518.0) mL, Z=-4.718, P<0.001; 14 days: 3 234.0 (978.5, 4 924.0) mL vs. 13 436.5 (8 045.8, 14 518.0) mL, Z=-4.769, P<0.001]. There was no correlation between fluid equilibrium and oxygen index in improved patients within 3 days of ICU admission (R² = 0.000, P=0.827), and it fit the logistic curve in a relatively low level after 3 days of ICU admission (R² = 0.036, P<0.001). Early fluid resuscitation could help maintain hemodynamics stability in SAP patients. Those SAP patients who showed a negative equilibrium in early stage showed a better prognosis, and the fluid equilibrium and oxygen index in improved patients fit the logistic curve after 3 days of ICU admission.

血流から見た急性膵炎の初期病態：Perfusion CTによる検討

1993年のアトランタ基準では"重症急性膵炎"は，膵壊死か多臓器不全をきたした場合と定義された．一方，近年，欧米のガイドラインが改訂され，膵壊死合併膵炎は中等度重症，膵壊死の合併にかかわらず48時間以上継続する臓器不全を有した場合を重症急性膵炎とした．発症早期の膵壊死は，多臓器不全を予測するための予後因子の一つということになり，初療時に壊死診断・予測を行うことの重要性は決して損なわれてはいない．こうした観点から，本稿では，重症急性膵炎における初期病態，とくに発症早期の膵壊死の形成と，その背景としての循環不全・血管内皮障害の関係について，新しいModalityであるPerfusion CTで得られた知見を交えながら概説する．

Pancreatic Perfusion CT in Early Stage of Severe Acute Pancreatitis

Early intensive care for severe acute pancreatitis is essential for improving SAP mortality rates. However, intensive therapies for SAP are often delayed because there is no ideal way to accurately evaluate severity in the early stages. Currently, perfusion CT has been shown useful to predict prognosis of SAP in the early stage. In this presented paper, we would like to review the clinical usefulness and limitations of perfusion CT for evaluation of local and systemic complications in early stage of SAP.

The roles of C-reactive protein and pleural effusion in prognosis evaluation in the early stage of acute pancreatitis

Objective To investigate the values of C-reactive protein (CRP) and pleural effusion in predicting the severity in the early stage of severe acute pancreatitis (SAP) . Methods A total of 89patients with acute pancreatitis were collected from October 2008 through October 2010 for retrospective analysis. Patients were divided into two groups, namely mild acute pancreatitis (MAP) group and SAP group as per the Guidelines for Clinical Diagnosis and Classification of Acute Pancreatitis set by the Society of Chinese Medical Association in 2003. The levels of CRP were measured on the 1st, 2nd, 3rd and 7th days after admission. Pleural effusion was also observed on the 1 st day after admission. The data of two groups were analyzed and compared. Results There were significant differences in CRP at all intervals between SAP group and MAP group (P ＜0.05) . The relative risk of increase in CRP ( ＞ 150 mg/L),pleural effusion and increase in CRP along with pleural effusion were analyzed, and each of these three markers can be used as an independent severity factor of SAP. Particularly, increase in CRP along with pleural effusion could be most sensitive in predicting the severity of SAP with relative risk (RR) to be 4. 8 and specificity of predictive value to be 100％. Conclusions C-reactive protein and pleural effusion are available, simple and economic biomarkers which can help us predict the risk of acute pancreatitis in the early stage. Key words: C-reactive protein; Pleural effusions; Acute pancreatits; Mild acute panereatitis1; Severe acute pancreatitis

Dynamic changes of cytokines and the effect of pioglitazone on them in early stage of severe acute pancreatitis

Objective To observe the dynamic changes and significances of TNF-α， IL-6 and IL-10 in severe acute pancreatitis (SAP) rats， and assess the effect of pretreatment with pioglitazone on them.Methods 54 male Sprague-Dawley(SD) rats were randomly divided into sham group(C group)， SAP group， and pioglitazone group(P group). (1) SAP group was induced by the retrograde injection of sodium taurocholate (STC) in the pancreatic duct (n＝18)； (2) P group (same as SAP group， but pioglitazone(50 mg/kg) was injected intraperitoneally two hours prior to STC(n＝18)； (3) Sham operation group. Sham-operated animals served as control. Operation was executed， STC was not injected， but pancreas was flipped and striked gently three times. Rats were killed by abdominal aorta exsanguination at 3 h， 6 h and 12 h after the induction of pancreatitis. Serum activities of amylase were measured， the concentrations of inflammatory cyctokines (TNF-α，IL-6 and IL-10) of the blood were measured by ELISA and pancreatic histologic score were assessed.Results Compared with C group， pancreatic histologic score， serum amylase， TNF-α and IL-6 in SAP group were increased significantly (P<0.01) except IL-10 level(P＞0.05). Pretreatment with pioglitazone obviously decreased histologic score and the serum level of amylase， TNF-α， IL-6， and the level of IL-10 was higher than SAP group in early SAP(P<0.05). Conclusions Cytokines play an important role in early progress of SAP； pioglitazone could attenuate the severity of inflammatory response through regulating the balance of pro- and anti-inflammatory cytokines.

Pioglitazone: A Promising Therapeutic Tool in Sodium Taurocholate-Induced Severe Acute Pancreatitis

Studies suggest that peroxisome proliferator-activated receptor γ(PPARγ) ligands may represent a therapeutic option in acute pancreatitis, yet most of them have been prophylactic administrated. To evaluate the therapeutic effect of pioglitazone in rats with severe acute pancreatitis induced by sodium taurocholate. Severe acute pancreatitis (SAP) was induced in male Sprague-Dawley rats by the retrograde injection of 5% sodium taurocholate into the pancreatic duct. After SAP was induced, pioglitazone was injected intraperitoneally and its role on the severity of inflammatory response and pancreatic injury was investigated. Amylase activity, inflammatory cytokines production, pathological changes of pancreas, PPARγ mRNA expression, and the survival rate were examined. Treatment with pioglitazone decreased the level of amylase activity, proinflammatory factors IL-6 and TNF-α, ameliorated pancreatic histological score, and upregulated the expression of PPARγ mRNA. The survival rate in the early stage of severe acute pancreatitis was also improved. Pioglitazone can be used as a therapeutic drug and relieve the damages caused by SAP, which suggests PPARγ ligand-pioglitazone offers a potent approach for the treatment of severe acute pancreatitis.

Role of macrophages in the progression of acute pancreatitis

In addition to pancreatic cells, other inflammatory cell populations contribute to the generation of inflammatory mediators during acute pancreatitis. In particular, macrophages could be activated by mediators released during pancreatitis by a damaged pancreas. It has been reported that peritoneal macrophages, alveolar macrophages and Kupffer cells become activated in different stages of severe acute pancreatitis. However, macrophages display remarkable plasticity and can change their physiology in response to environmental cues. Depending on their microenvironmental stimulation, macrophages could follow different activation pathways resulting in marked phenotypic heterogeneity. This ability has made these cells interesting therapeutical targets and several approaches have been assayed to modulate the progression of inflammatory response secondary to acute pancreatitis. However, despite the recent advances in the modulation of macrophage function in vivo, the therapeutical applications of these strategies require a better understanding of the regulation of gene expression in these cells.

Regulation of ω-3 fish oil emulsion on the SIRS during the initial stage of severe acute pancreatitis

The aim of this study was to explore the effects of parenteral supplementation with omega-3 fish oil emulsion (Omegaven) on systemic inflammatory response syndrome (SIRS) during the initial stage of severe acute pancreatitis (SAP). In a prospective, randomized and controlled trial, 60 patients with SAP were randomized either to treat with conventional therapy (Con group, n=30) or conventional therapy plus intravenous supplementation with omega-3 fish oil emulsion 0.2 g/kg every day (FO group, n=30). The effects were analyzed by the SIRS-related indexes. The results showed that APACHE-II scores in FO group were significantly lower, and the gap increased much farther after the 4th day than those in Con group (P<0.05). Fluid equilibrium time became shorter markedly in FO group than in Con group (5.1+/-2.2 days vs 8.4+/-2.3 days). In FO group, SIRS scores were markedly decreased and the SIRS state vanished after the 4th day; Plasma level of TNF-alpha was significantly reduced, while IL-10 decreased markedly, most prominently between the 4th and 7th day, and the ratio of IL-10/TNF-alpha raised as compared with Con group (P<0.05). During the initial stage of SAP, parenteral supplementation with omega-3 fish oil emulsion could efficiently lower the magnitude and persistence time of the SIRS, markedly retrieve the unbalance of the pro-/anti-inflammatory cytokines, improve severe condition of illness and may provide a new way to regulate the SIRS.

Cardiovascular Homeostasis in Hypotension Associated With Initial Stages of Severe Acute Pancreatitis

To identify the mechanisms underlying hypotension during the early phase of severe acute pancreatitis (SAP) by analyzing whether an impaired response to vasoactive substances occurs in this pathological process. Experimental SAP was induced by infusing 5% sodium taurocholate through the main pancreatic duct in rats. Once mean arterial pressure (MAP) in animals with pancreatitis was reduced, different vasoactive substances and inhibitors were administered. Administration of the nonspecific nitric oxide synthase inhibitor N omega-nitro-L-arginine methyl ester caused a similar increase in MAP in rats with pancreatitis and control rats, whereas inducible nitric oxide synthase inhibition did not cause changes in MAP. Moreover, the hypertensive response to endothelin and angiotensin II was lower in pancreatitis. Inhibition of angiotensin II synthesis by the angiotensin-converting enzyme inhibitor perindopril in animals with pancreatitis caused severe hypotension, causing death in 40% of them. Finally, pressor hyporesponsiveness to angiotensin II in animals with pancreatitis was avoided by previous administration of perindopril and N omega-nitro-L-arginine methyl ester. The SAP-induced hypotension is associated with a deficient pressor responsiveness to angiotensin II and endothelin-1. The renin-angiotensin system plays an important role in the control of MAP in animals with pancreatitis.

Perfusion Computerized Tomography Can Predict Pancreatic Necrosis in Early Stages of Severe Acute Pancreatitis

The mortality rate associated with severe acute pancreatitis (SAP) with necrosis remains high because early prediction of pancreatic necrosis is difficult. We evaluated whether perfusion computerized tomography (CT), which is used to identify early stage ischemia in the brain, could detect ischemic changes in the pancreas in the early stages of SAP and predict development of necrosis. Thirty consecutive patients with a diagnosis of SAP according to the Atlanta criteria and whose score was greater than 6 were enrolled in this study. All patients were hospitalized within 3 days after onset of symptoms indicative of acute pancreatitis and underwent perfusion CT. Three weeks later, all patients underwent conventional contrast-enhanced CT to detect progression of their disease. Perfusion CT showed that 10 of the 30 patients had pancreatic ischemia at the time of diagnosis. Contrast-enhanced CT disclosed that pancreatic necrosis developed in 9 of these 10 patients, but not in the 20 patients who did not have pancreatic ischemia. The sensitivity and specificity of perfusion CT for predicting pancreatic necrosis was calculated to be 100% and 95.3%, respectively. Perfusion CT is a useful tool for early detection of ischemic changes in the pancreas that lead to pancreatic necrosis.

The role of CD4+/CD25+T cell and altered immune responses in rats with the early stage of severe acute pancreatitis

目的 研究急性胰腺炎时调节性T细胞(CD4+CD25+T细胞)的变化规律及其与胰腺炎发病初期时免疫状态的关系.方法 36只Sprague-Dawley大鼠分为对照组(n=6)和急性坏死性胰腺炎组(n=30),后者胰管内注射胆酸钠造模后分别在2、6、12、24、48 h处死,每次6只大鼠.酶联免疫吸附法测定肿瘤坏死因子(TNF)α水平,流式细胞仪测定外周血中CD4+CD25+T细胞占淋巴细胞的百分比, 胰腺病理损伤程度根据胰腺水肿、白细胞浸润、出血和坏死评分.结果 与对照组(2.842%)相比,坏死性胰腺炎各组调节性T细胞的比例明显下降(2、6、12、24、48 h时分别为1.838%、1.373%、1.063%、1.055%和0.748%),差异有统计学意义(P值均＜0.01).TNFα水平除SAP 48 h组外均明显上升,2、6、12、24、48 h组分别为43.32、28.02、32.45、29.98、21.70 pg/ml,与对照组(15.00pg/ml)相比,除SAP 48 h组外,其他各组差异均有统计学意义(P值均＜0.05).相关分析提示调节性T细胞与TNFα水平呈明显负相关(Pearson相关系数=-0.398,P=0.022),与SAP的病理评分亦呈负相关(Pearson相关系数=-0.759,P＜0.01).结论 急性坏死性胰腺炎时调节性T细胞水平下降,可能是引起急性胰腺炎免疫过度活化并发展为SAP的原因之一。