CRRT对重症急性胰腺炎患者脂联素TNF-α和CRP的影响

目的探讨重症急性胰腺炎（SAP）患者脂联素、TNF-α和CRP水平的变化特点及连续性肾脏替代疗法（CRRT）对其影响。方法按照平行对照设计原理，将所有66例患者分为对照组和CRRT组。对两组患者的相关临床资料及脂联素、TNF-α和CRP水平进行比较。结果与CRRT组患者比较，对照组患者第1天TNF-α和CRP水平均明显升高（均P〈0．05），脂联素水平明显降低（P〈0．05）；与CRRT组患者比较，对照组患者第2、3天TNF-α和CRP水平均明显升高（均P〈0．01），脂联素水平明显降低（均P〈0．01）；治疗前两组患者脂联素、TNF-α和CRP水平，差异无统计学意义（均P〉0．05）；在年龄、性别、APACHEII评分等方面两组差异无统计学意义（均P〉0．05）。结论CRRT能通过降低TNF-α和CRP水平及升高脂联素水平，对SAP患者起到较好的治疗作用。

急性胰腺炎的类型和预后的判断

探讨判断急性胰腺炎预后的指标。结果显示患者阳性指标少于4项者主要为水肿型 ,预后较好 ;患者有5～8项阳性指标。主要为出血坏死型 ,预后欠佳 ,病死率增加 ,宜早期手术治疗 ;阳性指标超过8项者预后极差。

急性出血坏死性胰腺炎的临床病理与治疗出院后生存质量的研究

研究急性出血坏死性胰腺炎 (AHNP)的临床病理分型及生存及死亡的转归 ,指导临床诊断与治疗。

急性胰腺炎患者血浆leptin和血清hs-CRP、IL-6和IL-8检测的临床意义

目的:探讨了急性胰腺炎患者血浆leptin和血清hs-CRP、IL-6和IL-8水平的变化及临床意义。方法:应用放射免疫分析和免疫比浊法对30例急性胰腺炎患者进行了血浆leptin和血清hs-CRP、IL-6和IL-8检测,并与35名正常健康人作比较。结果:急性胰腺炎患者血浆leptin和血清hs-CRP、IL-6和IL-8水平均非常显著地高于正常人组(P<0.01)且急性胰腺炎患者血浆leptin和血清hs-CRP、IL-6和IL-8水平呈正相关(r=0.6132、0.5786、0.6218,P<0.01)。结论:检测急性胰腺炎患者血浆leptin与血清hs-CRP、IL-6和IL-8水平的变化对观察病情发展及预后判断均有重要的临床价值。

重症急性胰腺炎的早期危险因素—血液浓缩

目的 研究血液浓缩能否作为急性坏死性胰腺炎和多器官功能不全综合征 (MODS)的早期预测指标。方法 1997～ 2 0 0 0年住院的急性胰腺炎病人 ,分轻重两型进行比较。胰腺坏死的诊断根据临床表现、增强CT扫描或术中典型改变。结果 符合要求者 115例 ,48例为重症 ,Logistic回归确定 ,入院时对红细胞压积 (HCT)≥43%和 (或 )入院至 2 4h未见下降可作为预测重症急性胰腺炎 (SAP)的最好指标。入院时 ,坏死型胰腺炎病人HCT≥ 43%的比例显著高于间质型胰腺炎 (36 /4 8∶11/6 7;P <0 0 0 1)。 9例并发多器官功能不全者中 7例HCT≥ 43% ,而 10 6例未发生多器官功能不全者中有 40例HCT≥ 43% (P <0 .0 5 )。 2 4h两指标预测SAP的敏感性 ,特异性及阴性预测值分别为 81 2 % ,79 1%和 78 5 %。结论 入院HCT≥ 43%或入院至 2

重症急性胰腺炎胰腺感染的综合性预防及治疗

目的 探讨重症急性胰腺炎 (SAP)继发胰腺感染的综合预防措施及治疗。方法 本组 2 2 3例SAP均先行非手术治疗 ,采取促进胃肠道功能的恢复、应用抗生素、抗休克、预防多器官组织低灌注及低氧血症等多种措施预防胰腺感染。 1990～ 1994年 ,将胰腺感染作为手术指征并立即进行手术 ;1995～ 1999年 ,加强对胰腺感染的预防 ,特别注意早期促进胃肠道功能的恢复。延期手术 ,将晚期局限性胰腺感染作为手术指征。结果 本组 2 2 3例SAP中发生胰腺感染 2 3例 ( 10 3 % )。两个阶段的胰腺感染率分别为 12 4 %及 8 7%。胰腺感染局限者的病死率为 8% ( 1/ 13 ) ,低于胰腺感染未局限者的 5 0 % ( 5 / 10 ) ,P =0 0 3 5。结论 积极、有效的综合性预防措施及延期手术治疗有助于降低SAP继发性胰腺感染率及胰腺感染的病死率。

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.

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.

Heparin improves organ microcirculatory disturbances in caerulein-induced acute pancreatitis in rats

AIM:Microcirculatory disturbances are important early pathophysiological events in various organs during acute pancreatitis.The aim of the study was to evaluate changes in microperfusion of the pancreas,liver,kidney,stomach, colon,skeletal muscle,and to investigate the influence of heparin on the organ microcirculation in caerulein-induced experimental acute pancreatitis. METHODS:Acute pancreatitis was induced by 4 intraperitoneal injections of caerulein(Cn)(15 μg/kg).The organ microcirculation was measured by laser Doppler flowmetry.Serum interleukin 6 and hematocrit levels were analysed. RESULTS:Acute pancreatitis resulted in a significant drop of microperfusion in all examined organs.Heparin administration(2×2.5 mg/kg)improved the microcirculation in pancreas(36.9±4% vs 75.9±10%),liver(56.6±6% vs 75.2±16%),kidney (45.1±6% vs 79.3±5%),stomach (65.2±8% vs 78.1±19%),colon(69.8±6% vs 102.5±19%), and skeletal muscle (59.2±6% vs 77.9±13%).Heparin treatment lowered IL-6(359.0±66 U/mL vs 288.5±58 U/mL) and hematocrit level(53±4% vs 46±3%). CONCLUSION:Heparin administration has a positive influence on organ microcirculatory disturbances accompanying experimental Cn-induced acute pancreatitis.

Relaxin prevents the development of severe acute pancreatitis

AIM： TO investigate the severity of acute pancreatitis （AP） is associated to the intensity of leukocyte activation, inflammatory up-regulation and microcirculatory disruption associated to ischernia-reperfusion injury. Hicrovascular integrity and inhibition of pro-inflammatory mediators are key-factors in the evolution of AP. Relaxin is an insulin-like hormone that has been attributed vasorelaxant properties via the nitric oxide pathway while behaving as a glucocorticoid receptor agonist. METHODS： AP was induced by the bilio-pancreatic duct-outlet-exclusion closed-duodenal-loops model. Treatment with relaxin was done at different timepoints. Nitric oxide synthase inhibition by L-NAME and glucocorticoid receptor （GR） blockage by mifepristone was considered. AP severity was assessed by biochemical and histopathological analyses. RESULTS： Treatment with relaxin reduced serum amylase, lipase, C-reactive protein, IL-6, IL-10, hsp72, LDH and 8-isoprostane as well as pancreatic and lung myeloperoxidase. Acinar and fat necrosis, hemorrhage and neutrophil infiltrate were also decreased. ATP depletion and ADP/ATP ratio were reduced while caspases 2-3-8 and 9 activities were increased. L-NAME and mifepristone decreased the efficiency of relaxin. CONCLUSION： Relaxin resulted beneficial in the treatment of AP combining the properties of a GR agonist while preserving the microcirculation and favoring apoptosis over necrosis.

Effect of melatonin on the severity of L-arginine-induced experimental acute pancreatitis in rats

AIM： To determine the effect of melatonin pre- and post-treatment on the severity of L-arginine （L-Arg） -induced experimental pancreatitis in rats. METHODS： Male Wistar rats （25） were divided into five groups. Those in group A received two injections of 3.2 g/kg body weight L-Arg i.p. at an interval of 1 h. In group MA, the rats were treated with 50 mg/kg body weight melatonin i.p. 30 min prior to L-Arg administration. In group AM, the rats received the same dose of melatonin 1 h after L-Arg was given. In group M, a single dose of melatonin was administered as described previously. In group C the control animals received physiological saline injections i.p. All rats were exsanguinated 24 h after the second L-Arg injection. RESULTS： L-Arg administration caused severe necrotizing pancreatitis confirmed by the significant elevations in the serum amylase level, the pancreatic weight/body weight ratio （pw/bw）, the pancreatic IL-6 content and the myeloperoxidase activity, relative to the control values. Elevation of the serum amylase level was significantly reduced in rats given melatonin following L-Arg compared to rats injected with L-Arg only. The activities of the pancreatic antioxidant enzymes （Cu/Zn-superoxide dismutase （CulZn-SOD） and catalase （CAT）） were significantly increased 24 h after pancreatitis induction. Melatonin given in advance of L-Arg significantly reduced the pancreatic CAT activity relative to that in the rats treated with L-Arg alone. In the liver, L-Arg significantly increased the lipid peroxidation level, and the glutathione peroxidase and Cu/Zn-SOD activities, whereas the Mn-SOD activity was reduced as compared to the control rats. Melatonin pre-treatment prevented these changes. CONCLUSION： Melatonin is an antioxidant that is able to counteract some of the L-Arg-induced changes during acute pancreatitis, and may therefore be helpful in the supportive therapy of patients with acute necrotizing pancreatitis.

Oral allopurinol to prevent hyperamylasemia and acute pancreatitis after endoscopic retrograde cholangiopancreatography

AIM:To assess the efficacy of allopurinol to prevent hyperamylasemia and pancreatitis after endoscopic retrograde cholangiopancreatography(PEP).METHODS:One hundred and seventy patients were enrolled and randomized to two groups:a study group(n=85)who received 300 mg of oral allopurinol at 15 h and 3 h before endoscopic retrograde cholangiopancreatography(ERCP)and a control group(n=85)receiving an oral placebo at the same times.Main Outcome Measurements included serum amylase levels and the number severity of the episodes of pancreatitis.Serum amylase levels were classified as normal(<150 IU/L)or hyperamylasemia(>151 IU/L).Episodes of PEP were classified following Ranson's criteria and CT severity index.RESULTS:Gender distribution was similar between groups.Mean age was 53.5±18.9 years for study group and 52.8±19.8 years for controls.Also,the distribution of benign pathology was similar between groups.Hyperamylasemia was more common in the control group(P=0.003).Mild PEP developed in two patients from the study group(2.3%)and eight(9.4%) from control group(P=0.04),seven episodes were observed in high-risk patients of the control group(25%) and one in the allopurinol group(3.3%,P=0.02).Risk factors for PEP were precut sphincterotomy(P=0.02),pancreatic duct manipulation(P=0.002)and multiple procedures(P=0.000).There were no deaths or side effects.CONCLUSION:Oral allopurinol before ERCP decreased the incidences of hyperamylasemia and pancreatitis in patients submitted to high-risk procedures.

Continuous regional arterial infusion therapy with gabexate mesilate for severe acute pancreatitis

AIM： To evaluate the efficacy of continuous regional arterial infusion therapy （CRAI） with gabexate mesilate and antibiotics for severe acute pancreatitis （SAP）. METHODS： We conducted a prospective study on patients who developed SAP with or without CRAI. Out of 18 patients fulfilled clinical diagnostic criteria for SAP in Japan, 9 patients underwent CRAI, while 9 patients underwent conventional systemic protease inhibitor and antibiotics therapy （non-CRAI）. CRAI was initiated within 72 h of the onset of pancreatitis. Gabexate mesilate （2400 mg/d） was continuously administered for 3 to 5 d. The clinical outcome including serum inflammation-related parameters were examined. RESULTS- The duration of abdominal pain in the CRAI group was 1.9 =1：0.26 d, whereas that in the non-CRAI group was 4.3 ±0.50. The duration of SIRS in the CRAI group was 2.2 ± 0.22 d, whereas that in the non- CRAI group was 3.2 ± 0.28. Abdominal pain and SIRS disappeared significantly in a short period of time after the initiation of CRAI using gabexate mesilate. The average length of hospitalization significantly differed between the CRAI and non-CRAI groups, 53.3 ± 7.9 d and 87.4± 13.9 d, respectively. During the first two weeks, levels of serum CRP and the IL6/IL10 ratio in the CRAI group tended to have a rapid decrease compared to those in the non-CRAI group. CONCLUSION： The present results suggest that CRAI using gabexate mesilate was effective against SAP.

Recurrent acute pancreatitis and its relative factors

AIM: To evaluate the causes and the relative factors of recurrent acute pancreatitis.METHODS: From 1997 to 2000, acute pancreatitis relapsed in 77 of 245 acute pancreatitis patients. By reviewing the clinical treatment results and the follow-up data, we analyzed the recurrent factors of acute pancreatitis using univariate analysis and multivariate analysis.RESULTS: Of the 245 acute pancreatitis patients, 77 were patients with recurrent acute pancreatitis. Of them, 56 patients relapsed two times, 19 relapsed three times, each patient relapsed three and four times. Forty-seven patients relapsed in hospital and the other 30 patients relapsed after discharge. Eighteen patients relapsed in 1 year, eight relapsed in 1-3 years, and four relapsed after 3 years. There were 48 cases of biliary pancreatitis, 3 of alcohol pancreatitis, 5 of hyperlipidemia pancreatitis, 21 of idiopathic pancreatitis. Univariate analysis showed that the patients with local complications of pancreas, obstructive jaundice and hepatic function injury were easy to recur during the treatment period of acute pancreatitis (P = 0.022＜0.05, P = 0.012＜0.05 and P = 0.002＜0.05, respectively). Multivariate analysis showed that there was no single factor related to recurrence. Of the 47 patients who had recurrence in hospital, 16 had recurrence in a fast period, 31 after refeeding. CONCLUSION: Acute pancreatitis is easy to recur even during treatment. The factors such as changes of pancreas structure and uncontrolled systemic inflammatory reaction are responsible for the recurrence of acute pancreatitis. Early refeeding increases the recurrence of acute pancreatitis. Defining the etiology is essential for reducing the recurrence of acute pancreatitis.

Comparison of integrated Chinese and Western medicine with and without somatostatin supplement in the treatment of severe acute pancreatitis

AIM: To evaluate the therapeutic effect of the combined use of early short-term somatostatin and conventional integrated Chinese and Western medicine in treating severe acute pancreatitis. METHODS: Sixty patients with severe acute pancreatitis were divided at random into a somatostatin group and a basic treatment group. Both groups received integrated traditional Chinese and Western medicine without surgery. For patients in the somatostatin group, somatostatin was infused intravenously 250 μg/h for 72 h; other medications were the same as in the basic treatment group. In both groups, comparisons of therapeutic effectiveness were made in terms of morbidity of organic dysfunction and mortality rate, and severity of the disease according to serum levels of C-reaction protein, scores of acute physiology and chronic health evaluation (APACHE Ⅱ), and scores of Balthazar-CT. RESULTS: The indexes for C-reaction protein levels on the fourth and seventh clays, and APACHE II scores on the seventh day after treatment, were significantly improved in the somatostatin group than in the basic treatment group. The morbidity of organic dysfunction was lower in the somatostatin group than in the basic treatment group, although the difference was not statistically significant. There was no significant difference in mortality between the two groups. CONCLUSION: We conclude that combined traditional Chinese and Western medicines with an early short-term use of somatostatin can improve the condition of patients with severe acute pancreatitis.

Co-localization hypothesis:A mechanism for the intrapancreatic activation of digestive enzymes during the early phases of acute pancreatitis

Acute pancreatitis is generally believed to be a disease in which the pancreas is injured by digestive enzymes that it normally produces. Most of the potentially harmful digestive enzymes produced by pancreatic acinar cells are synthesized and secreted as inactive zymogens which are normally activated only upon entry into the duodenum but, during the early stages of acute pancreatitis, those zymogens become prematurely activated within the pancreas and, presumably, that activation occurs within pancreatic acinar cells. The mechanisms responsible for intracellular activation of digestive enzyme zymogens have not been elucidated with certainty but, according to one widely recognized theory （the ＂co-localization hypothesis＂）, digestive enzyme zymogens are activated by lysosomal hydrolases when the two types of enzymes become co-localized within the same intracellular compartment. This review focuses on the evidence supporting the validity of the m-localization hypothesis as an explanation for digestive enzyme activation during the early stages of pancreatitis. The findings, summarized in this review, support the conclusion that co-localization of lysosomal hydrolases with digestive enzyme zymogens plays a critical role in permitting the intracellular activation of digestive enzymes that leads to acinar cell injury and pancreatitis.

Present and future of prophylactic antibiotics for severe acute pancreatitis

AIM: To investigate the role of prophylactic antibiotics in the reduction of mortality of severe acute pancreatitis (SAP) patients, which is highly questioned by more and more randomized controlled trials (RCTs) and metaanalyses. METHODS: An updated meta-analysis was performed. RCTs comparing prophylactic antibiotics for SAP with control or placebo were included for meta-analysis. The mortality outcomes were pooled for estimation, and re-pooled estimation was performed by the sensitivity analysis of an ideal large-scale RCT. RESULTS: Currently available 11 RCTs were included. Subgroup analysis showed that there was significant reduction of mortality rate in the period before 2000, while no significant reduction in the period from 2000 [Risk Ratio, (RR ) = 1.01, P = 0.98]. Funnel plot indi-cated that there might be apparent publication bias in the period before 2000. Sensitivity analysis showed that the RR of mortality rate ranged from 0.77 to 1.00 with a relatively narrow confidence interval (P < 0.05). However, the number needed to treat having a minor lower limit of the range (7-5096 patients) implied that certain SAP patients could still potentially prevent death by antibiotic prophylaxis. CONCLUSION: Current evidences do not support prophylactic antibiotics as a routine treatment for SAP, but the potentially benefited sub-population requires further investigations.

α-Lipoic acid protects against cholecystokinin-induced acute pancreatitis in rats

AIM: α-Lipoic acid (ALA) has been used as an antioxidant.The aim of this study was to investigate the effect of α-lipoic acid on cholecystokinin (CCK)-octapeptide induced acute pancreatitis in rats.METHODS: ALA at 1 mg/kg was intra-peritoneally injected, followed by 75 μg/kg CCK-octapeptide injected thrice subcutaneously after 1, 3, and 5 h. This whole procedure was repeated for 5 d. We checked the pancreatic weight/body weight ratio, the secretion of pro-inflammatory cytokines and the levels of lipase,amylase of serum. Repeated CCK octapeptide treatment resulted in typical laboratory and morphological changes of experimentally induced pancreatitis.RESULTS: ALA significantly decreased the pancreatic weight/body weight ratio and serum amylase and lipase in CCK octapeptide-induced acute pancreatitis. However,the secretion of IL-1β, IL-6, and TNF-α were comparable in CCK octapeptide-induced acute pancreatitis.CONCLUSION: ALA may have a protective effect against CCK octapeptide-induced acute pancreatitis.

Role of genetic disorders in acute recurrent pancreatitis

There was remarkable progress in the understanding of the role genetic risk factors in chronic pancreatitis. These factors seem to be much more important than thought in the past. The rare autosomal-dominant mutations N29I and R122H of PRSS1 (cationic trypsinogen) as well as the variant N34S of SPINK1 (pancreatic secretory trypsin inhibitor) are associated to a disease onset in childhood or youth. Compared to chronic alcoholic pancreatitis the progression is slow so that for a long time only signs of acute-recurrent pancreatitis are found. Only at later time points (more than 10-15 years) there is evidence for chronic pancreatitis in the majority of patients. Acute recurrent pancreatitis may therefore be regarded as a transition state until definite signs of chronic pancreatitis are detectable.