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Alanyl-glutamine Dipeptide for Severe Acute Pancreatitis: A Systematic Review

Objective　To systematically review the effectiveness and safety of alanyl-glutamine dipeptide for severe acute pancreatitis (SAP). Methods　Such databases as MEDLINE, EMbase, CENTRAL, VIP, WanFang Data, CBM and CNKI were electronically searched from inception to October, 2012 for randomized controlled trials on alanyl-glutamine dipeptide for SAP. Two reviewers independently screened literature according to the inclusion and exclusion criteria, extracted data, and assessed methodological quality. Then, meta-analysis was performed using RevMan 5.2. Results　Five trials were included involving a total of 227 patients. The results of meta-analysis showed that: compared with the control group, the alanyl-glutamine dipeptide group had the lower incidence of SAP complications (RR=0.41, 95%CI 0.20 to 0.82), the lower incidence of infected pancreatic necrosis (RR=0.12, 95%CI 0.02 to 0.89), less time for alleviating bellyache (MD= –0.90, 95%CI –1.72 to –0.08). There was a tendency in decreasing SAP mortality (RR=0.15, 95%CI 0.02 to 1.19) and lessening the recovery time of blood amylase (SMD=0.37, 95%CI –0.04 to 0.79). Conclusion　Current evidence shows that, alanyl-glutamine dipeptide can lower the incidence of complications and the incidence of infected pancreatic necrosis, and shorten the time for alleviating bellyache in SAP patients. Due to the limited quality of the included studies, the above conclusion needs to be verified by more high quality studies.

Somatostatin with Traditional Chinese Medicine for Acute Pancreatitis: A Systematic Review

【摘要】　目的　评价生长抑素联合中药在治疗重症急性胰腺炎中的有效性。　方法　应用国际Cochrane协作网系统评价方法对生长抑素联合中药治疗重症急性胰腺炎的随机对照试验（RCT）进行系统评价。计算机检索MEDLINE（Ovid）、PubMed数据库、中文科技期全文数据库（VIP）、万方数据库、中国期刊全文数据库（CNKI）、中国生物医学文献数据库（CBM）。检索时间均为建库至2009年9月。文献检索语种为英语和中文。　结果　共纳入8个RCT，436例患者，所有纳入试验在治疗末均未进行随访。Meta分析结果显示，生长抑素联合中药治疗组（治疗组）的病死率（13/188，6.9%）明显低于单纯生长抑素治疗组（对照组）（24/174，13.7%），差异有统计学意义[Peto OR=0.46，95%CI（0.22，0.94），Plt;0.05]。治疗组平均住院日低于对照组[WMD=-7.01，95%CI（-7.89，-6.13），Plt;0.000 01]。治疗组腹痛缓解时间明显低于对照组，其差异有统计学意义[WMD=-0.77，95%CI（-0.82，-0.72），Plt;0.000 01]。治疗组与对照组治疗第7天APACHE Ⅱ评分均下降，治疗组下降幅度大于对照组，两组比较差异有统计学意义（Plt;0.05）。治疗组并发症发生率（26/91，28.6%）与对照组（35/88，39.8%）相比，其差异无统计学意义[Peto OR=0.61，95%CI（0.32，1.13），P=0.12]。　结论　生长抑素联合中药治疗在改善重症急性胰腺炎的病死率、平均住院时间、腹痛缓解时间、APACHE Ⅱ评分下降幅度优于单纯生长抑素治疗。

Effect of Early Application of Traditional Chinese Medicine in Treating Severe Acute Pancreatitis with Paralytic Intestinal Obstruction by Retention Enema Catharsis

目的：观察柴芩承气汤治疗重症急性胰腺炎(SAP)并发麻痹性肠梗阻 (Paralytic Intestinal Obstruction)的疗效。方法:依据纳入和排除标准,选取四川大学华西医院中西医结合科收治的SAP患者40例,按1∶1比例随机分成试验组(20例)和对照组(20例),试验组入院时即给予柴芩承气汤灌肠治疗,对照组使用安慰剂灌肠治疗;两组入院时基线资料差异无统计学意义(Pgt;005)，且两组均给予相同常规西医治疗。观察入院后其首次自行排便排气时间,入院时、入院后第3天、第7天APACHEⅡ评分及住院病程。结果:入院后首次自行排便排气时间试验组（302±154）天,低于对照组（453±241）天;入院后第3天APACHEⅡ评分试验组（925±184）分，低于对照组（1163±222）分;入院后第7天APACHEⅡ评分试验组（624±247）分，低于对照组（881±325）分。住院时间试验组（2453±426）天,低于对照组（3032±589）天。结论:早期应用柴芩承气汤灌肠治疗SAP并发麻痹性肠梗阻,可缩短麻痹性肠梗阻的持续时间及减轻其危害,减少住院病程。

Establishment of Lung Injury Model Caused by Severe Acute Pancreatitis in Rats with Ligated Pancreatic Duct

Objective　To establish a stable and reliable lung injury model caused by severe acute pancreatitis（SAP）in rats， which is helpful to study the acute lung injury （ALI）and acute respiratory distress syndrome （ARDS） induced by SAP.Methods　Sixty Sprague-Dawley rats were randomized into ligature group （n=20）， traditional group （n=20），and sham operation group （n=20）. SAP model was established through retrograde injection of 5% taurocholic acid. After injection， the pancreatic duct of rats was ligated in ligature group， but not in traditional group. The lung damage and edema at 24 h after operaton and natural course of rats were observed.Results　The ALI model of rats induced by SAP was established successfully in ligature group. The rats died of acute respiratory failure within 48 h in ligature group， the mortality was significantly higher than that in traditional group （100% vs.20%），P＜0.05. Pleural effusion occurred in four rats in ligature group， while no pleural effusion was found in rats in other two groups. The volume of ascites of rats in ligature group was （21.15±5.33） ml， which was more than that in traditional group 〔（7.75±2.66） ml〕，P＜0.05， while no ascites was found in rats in sham operation group. The level of serum amylase of rats in ligature group was （2 470.70±399.73） U/L，which was significantly higher than that in traditional group 〔（1 528.40±289.54） U/L〕 and sham operation group 〔（831.10±93.26） U/L〕，P＜0.001. The level of serum albumin of rats in ligature group was （6.90±1.66）g/L， which was significantly lower than that in traditional group 〔（13.10±0.99） g/L〕 and sham operation group 〔（16.20±0.92） g/L〕，P＜0.001.The lung wet-to-dry weight ratio （W/D） of rats in ligature group was 6.50±0.23， which was greater than that in traditional group （4.92±0.18） and sham operation group （4.61±0.16）， P＜0.001. The score of lung histopathologic of rats in ligature group was 29.25±1.07， which was significantly higher than that in traditional group （12.65±1.98） and sham operation group （0），P＜0.001. The score of pancreas histopathologic of rats in ligature group was 15.95±0.15，which was significantly higher than that in traditional group （13.75±0.66） and sham operation group （0.13±0.29），P＜0.001. Under transmission electron microscope， basement membrane of pulmonary capillary of rats in ligation group was destructive， the nuclei was dissolved， endothelial pinocytotic vesicles was functional active， and tight junctions between capillary endothelial cells were blurred and even ruptured. Moreover， tight junctions between alveolar epithelial cells were destructive. Pathological changes of lung ultrastructure of rats in ligation group were more severe than that in traditional group， while no pathological change of lung ultrastructure was observed in rats in sham operation group. Conclusions　Injury process and pathogenesis of ALI or ARDS clinically caused by acute gallstone pancreatitis can be reproduced in this animal model， which is suitable to explore the related mechanisms of ALI caused by SAP and provides good animal model for the study of ALI caused by SAP.

Research of Continuous Regional Arterial Infusion of Dexamethasone Treatment for Severe Acute Pancreatitis

ObjectiveTo study the effects of continuous regional arterial infusion (CRAI) of dexamethasone on plasma inflammatory factors of severe acute pancreatitis (SAP) rabbits. MethodsTwentyfour rabbits were randomly divided into sham operation group, SAP group, intravenous infusion of dexamethasone group and CRAI of dexamethasone group (each group 6 rabbits) by random number table. The serum tumor necrosis factor (TNF)-α, interleukin (IL)-6, IL-10, and amylase (AMY) levels in rabbits were tested at hour 0.5, 3, 6, 9, and 12 after modeling succeed. The pathological changes of pancreas and the survival were observed on day 3 after modeling succeed. ResultsCompared with the sham operation group, the serum levels of IL-6 significantly increased at 3 h and reached the peak at 6 h, decreased at 9 h (all Plt;0.05); levels of IL-10 significantly increased at 6 h, continuously elevated at 9 h and 12 h (all Plt;0.001); levels of TNF-α significantly increased at 0.5 h (Plt;0.001), reached the peak at 6 h (Plt;0.001) and decreased at 9 h (Plt;0.05); levels of AMY significantly increased at 9 h, continuously elevated at 12 h (all Plt;0.05) in the SAP group. Compared with the SAP group, the serum levels of IL-6 and IL-10 in the CRAI of dexamethasone group all significantly decreased at 6 h, 9 h, and 12 h (Plt;0.001); levels of IL6 significantly decreased only at 6 h in the intravenous infusion of dexamethasone group; levels of TNF-α in the CRAI of dexamethasone group significantly decreased at 3 h, 6 h, 9 h, and 12 h (all Plt;0.001), which in the intravenous infusion of dexamethasone group significantly decreased only at 6 h (Plt;0.05); levels of AMY in the CRAI of dexamethasone group and intravenous infusion of dexamethasone group all significantly decreased at 12 h (Plt;0.05). Compared with the intravenous infusion of dexamethasone group, the serum levels of IL-6 and IL-10 in the CRAI of dexamethasone group all significantly decreased at 6 h (Plt;0.05) and 12 h (Plt;0.001); levels of TNF-α all significantly decreased at 3 h, 6 h, 9 h, and 12 h (all Plt;0.001); levels of AMY were not significantly different (Pgt;0.05). The pathological changes of pancreas in the CRAI of dexamethasone group were obvious, the death of rabbits reduced on day 3 after modeling succeed. ConclusionCRAI dexamethasone can effectively reduce the systemic inflammatory response and pancreatic inflammation, and reduce mortality.

Effects of Ulinastatin on Renal Apoptosis and Expression of bcl-2 in Rats with Severe Acute Pancreatitis

Objective　To explore the effects of ulinastatin (UTI) on renal apoptosis and expression of bcl-2 in rats with severe acute pancreatitis (SAP). Methods　Sixty rats weighing 250-300 g were randomized divided into 3 groups: pseudo-operation group (SO group, n=20), SAP group (n=20) and UTI treated group (UTI group, n=20). The model of SAP was established by retrograde injection of 5% sodium taurocholate solution into the biliopancreatic duct in the rats. Serum Cr and BUN were determined. The left kidneys were resected for light and electronic microscopic study. Renal cell apoptosis was determined by TUNEL. Expression of bcl-2 was detected by immunohistochemical staining of SABC. Results　Serum Cr, BUN, renal cell apoptotic index and bcl-2 expression were markedly increased in SAP group compared with SO group （P＜0.05， P＜0.01）, Renal tissue injuries were aggravated in SAP group under light and electronic microscopic study as well. In UTI group, serum Cr, BUN and renal cell apoptotic index were decreased significantly while the expression of bcl-2 increased remarkably and renal tissue injuries relieved compared with SAP group （P＜0.05）. Positive correlations were found between the renal cell apoptotic index and BUN as well as Cr (r=0.807, P＜0.05; r=0.812, P＜0.05). Conclusion　The protective effect of UTI on SAP renal injury is probably through increasing bcl-2 expression and decreasing apoptosis.

Effects of Early Hemofiltration on TNF-α and IL-1β in Pigs with Severe Acute Pancreatitis

【Abstract】Objective To study the influence of early hemofiltration on plasma concentrations of proinflammatory cytokines TNF-α and IL-1β and their transcription levels in severe acute pancreatitis (SAP) pigs. Methods The model of SAP was induced by retrograde injection of artificial bile into pancreatic duct in pigs. Animals were divided randomly into two groups: SAP hemofiltration treatment group (HF group, n=8) and SAP no hemofiltration treatment group (NHF group, n=8). TNF-α and IL-1β plasma concentrations were measured by ELISA. Their transcription levels in the tissues of pancreas, liver and lung were assayed by semi-quantitative reverse transcription polymerase chain reaction. Results After hemofiltration treatment, the plasma concentrations of TNF-α and IL-1β increased gradually but were lower than those of NHF group at the same time spot 〔at 6 h after hemofiltration treatment, (618±276) pg/ml vs (1 375±334) pg/ml and (445±141) pg/ml vs (965±265) pg/ml, P＜0.01〕. At 6 h after hemofiltration treatment, the transcription levels of TNF-α and IL-1β in tissues of pancreas, liver and lung were lower than in NHF group (57.8±8.9 vs 85.7±17.4, 48.0±8.1 vs 78.1±10.2, 46.2±9.6 vs 82.4±10.5; 55.9±9.0 vs 82.2±15.7, 40.6±9.2 vs 60.0±10.6, 35.7±9.8 vs 58.1±9.3, P＜0.01). Conclusion Early hemofiltration can reduce TNF-α and IL-1β plasma concentrations and transcription levels in SAP pigs.

Nutritional Supart in Patients with Severe Acute Pancreatitis

Effect of Complications on Prognosis in Patients with Severe Acute Pancreatitis

目的 分析重症急性胰腺炎（SAP）并发症发生的原因，拟定最佳治疗方案，减少对预后的影响。方法 对1992～2001年收治的35例SAP进行回顾性分析，观察其胰腺病理改变、治疗方式、并发症及其预后间的关系。结果 ①胰周积液者无死亡； ②胰腺组织坏死伴感染时易发生胃肠瘘，创面开放和闭合引流与胃肠瘘的发生无明显关系（Pgt;0.05）； ③4例胰周积液者有胰腺假性囊肿形成； ④胰周积液无感染者平均住院时间为19 d，胰腺及胰周组织坏死者住院时间gt;49 d。结论 急性呼吸窘迫综合征、腹腔脓肿、肠瘘及胰瘘是SAP的主要并发症，可影响其预后。

The Treatment of Severe Acute Pancreatitis by Using Somatostatin and Parenteral Nutrition

目的探讨生长抑素和肠外营养对重症急性胰腺炎的治疗作用。方法采用生长抑素和肠外营养支持对15例重症急性胰腺炎患者进行治疗（实验组），并与同期22例未采用上述治疗措施者（对照组）进行比较分析。生长抑素用思他宁，并按6 mg/d持续静脉滴注； 肠外营养支持视临床情况按常规给予。结果实验组并发症发生率、手术率和死亡率均显著低于对照组（P＜0.01）。结论生长抑素和肠外营养支持对重症急性胰腺炎具有较佳的治疗效果。