Low-dose heparin for the prevention of post-ERCP pancreatitis: a randomized placebo-controlled trial

Background  As suggested by observational and animal studies, heparin has antiinflammatory effects that could prevent acute post–endoscopic retrograde cholangiopancreatography (ERCP) pancreatitis. Low-molecular-weight heparin did not reduce the incidence of post-ERCP pancreatitis in a controlled study. The current study aimed to determine whether prophylactic administration of low-dose unfractionated heparin, which has potentially more antiinflammatory capability, can prevent acute post-ERCP pancreatitis. Methods  Patients scheduled for ERCP in the authors’ department were randomized to receive unfractionated heparin (5,000 IU) or placebo (saline solution 0.5 ml) administered subcutaneously 20 to 30 min before the ERCP. Patients who had undergone endoscopic sphincterotomy in the past were excluded from the study. Post-ERCP pancreatitis was defined according to criteria established by Cotton: abdominal pain combined with a threefold elevation of blood amylase 24 h after the ERCP. Results  The study enrolled 106 patients. One patient was excluded from the analysis due to inaccessible papilla of Vater, leaving 51 patients in the heparin group and 54 in the placebo group, for a total of 105 patients (62 women and 43 men) with a mean age of 64.6 years. The rate of post-ERCP pancreatitis was not different between the groups (heparin, 4 patients, 7.8%; placebo, 4 patients, 7.4%). Two patients in each group experienced mild bleeding. Conclusions  The study did not demonstrate a significant effect of low-dose unfractionated heparin in the prevention of post-ERCP pancreatitis. A multicenter trial with a larger number of patients is needed to demonstrate a benefit from this drug.     

Pancreatic duct stenting for the duration of ERCP only does not prevent pancreatitis after accidental pancreatic duct cannulation: a prospective randomized trial

Background

Pancreatic duct stent placement during endoscopic retrograde cholangiopancreatography (ERCP) has been recommended in patients at risk for post-ERCP pancreatitis. However, the optimal duration of stent placement remains an open question. Our aim was to compare the efficacy of pancreatic stenting for the duration of ERCP only with spontaneous dislodgment/deferred endoscopic removal in preventing post-ERCP pancreatitis after accidental wire-guided pancreatic duct cannulation.

Methods

All patients in whom accidental wire-guided pancreatic duct cannulation had occurred during ERCP underwent immediate 5-Fr unflanged pigtail pancreatic duct stenting before attempting any other endoscopic maneuver. At the end of the ERCP, patients were randomly assigned to immediate stent removal (group A) or to leaving the stent in place (group B). Assessment of post-ERCP pancreatitis was blind.

Results

Post-ERCP pancreatitis occurred in 6/21 (29 %) patients in group A and in 0/19 patients in group B (P = 0.021); the two groups were well matched for their baseline characteristics. Post-ERCP pancreatitis was mild in two patients, moderate in two patients, and severe in two patients. Stents dislodged spontaneously in 14/19 (74 %) patients within 24–96 h; uneventful endoscopic removal was carried out after 96 h in 5 cases. Proximal stent migration did not occur in any case.

Conclusions

Pancreatic duct stent placement for the duration of ERCP only does not prevent post-ERCP pancreatitis. Pancreatic stents should be left in place until spontaneous dislodgment occurs or endoscopic removal is deemed timely. 5-Fr unflanged pigtail stents remain in place for a period sufficient to prevent post-ERCP pancreatitis and do not migrate proximally.     

Cholecystokinin in the early course of acute post-ERCP pancreatitis

Background: A high dose of cholecystokinin (CCK) agonist cerulein can induce acute pancreatitis in animals. The role of CCK in the induction of acute pancreatitis in humans is unclear. We investigated basal plasma CCK levels before and after induction of post-ERCP pancreatitis to determine CCK levels in the early course of the disease.

Study Design: We determined plasma CCK concentrations in four groups of patients who underwent ERCP: (1) post-ERCP pancreatitis patients (n = 23); (2) patients with post-ERCP hyperamylasemia without pancreatitis (n = 5); (3) patients with post-ERCP abdominal pain without hyperamylasemia (n = 18); and (4) patients with an uneventful post-ERCP period (n = 43). Plasma samples were taken before ERCP, 4 to 8 hours, 10 to 16 hours, and 24 hours after ERCP. Plasma CCK concentrations were determined by a specific and sensitive radioimmunoassay using CCK antiserum (Euro-Diagnostica, Malmö, Sweden).

Results: Plasma CCK levels increased five-fold early in the course in post-ERCP pancreatitis patients, but not in post-ERCP hyperamylasemia patients or in uncomplicated ERCP patients, where CCK levels temporarily decreased after ERCP. In patients with abdominal pain, CCK levels did not change. After the early increase, plasma CCK levels declined to almost unmeasurable levels one day after the onset of symptoms in post-ERCP pancreatitis. In other groups CCK levels were close to the pre-ERCP level.

Conclusions: It remains to be shown whether CCK is important in the pathogenesis of post-ERCP pancreatitis or merely a secondary phenomenon. There is a rationale to test CCK antagonists in preventing post-ERCP pancreatitis.     

Post-ERCP acute necrotizing pancreatitis

An analysis of acute necrotizing pancreatitis (ANP) after endoscopic retrograde cholangiopancreatography (ERCP) was carried out. The incidence of ANP was 0.5% (5/914) for ERCP and 0.5% (2/370) for endoscopic sphincterotomies (EST). All the five patients were obese, middle-aged or older women. Four had a suspicion of common bile duct stones and the fifth a pancreatic tumour as an indication for ERCP. Two had most probably a functional sphincteric disorder and the third was without clear pathological findings. In the remaining two cases the bile duct cannulation failed and repeated pancreatic duct cannulation occurred; while in one case the pancreatic duct was not cannulated. The four pancreatographies were normal and without parenchymal opacification. Symptoms of acute pancreatitis started within 6 hours after ERCP. The pancreatitis was severe by Ranson criteria and necrotizing by evaluation at laparotomy. All the patients showed bacterial growth either in bile, blood or ascitic fluid early in the course of pancreatitis (E. coli, Str. faecalis or Klebsiella pneumoniae). The possible pathogenetic factors of post-ERCP ANP are discussed.     

Time course of bacterial infection of the pancreas and its relation to disease severity in a rodent model of acute necrotizing pancreatitis.

BACKGROUND: Bacterial infection of pancreatic necrosis is thought to be a major determinant of outcome in acute necrotizing pancreatitis. The determinants and possibilities for prophylaxis are unknown and difficult to study in humans. OBJECTIVE: The time course of bacterial infection of the pancreas in a rodent model of acute necrotizing pancreatitis was characterized. The authors ascertained if there is a correlation with the degree of necrosis. METHODS: Acute pancreatitis (AP) of graded severity was induced under sterile conditions by an intravenous infusion of cerulein (5 micrograms/kg/hr) for 6 hours (mild AP), or a combination of intravenous cerulein with an intraductal infusion of 10-mM glycodeoxycholic acid (0.2 mL for 2 min for moderate AP, 0.5 mL for 10 min for severe AP). Sham-operated animals (intravenous and intraductal NaCl 0.9%) served as controls. Ninety-six hours after induction, animals were killed for quantitative bacterial examination and histologic scoring of necrosis. In addition, groups of animals with severe AP were investigated at 12, 24, 48, 96, and 144 hours. RESULTS: No significant pancreatic necrosis was found in control animals (0.3 +/- 0.1) or animals with mild AP (0.6 +/- 0.1) killed at 96 hours. Necrosis scores were 1.1 +/- 0.2 for animals with moderate AP and 1.9 +/- 0.2 for animals with severe AP. Control animals did not develop significant bacterial infection of the pancreas (> or = 10(3) CFU/g). At 96 hours, the prevalence of infection was 37.5% in animals with mild AP and 50% in animals with moderate AP. In animals with severe AP, infection of the pancreas increased from 33% in the first 24 hours to 75% between 48 and 96 hours (p < 0.05). The bacterial counts and the number of different species increased with time and was maximal (> 10(11) CFU/g) at 96 hours. CONCLUSION: Bacterial infection of the pancreas in rodent AP increases during the first several days, and its likelihood correlates with the severity of the disease. This model, which closely mimics the features of human acute pancreatitis, provides a unique opportunity to study the pathogenesis of infected necrosis and test therapeutic strategies.     

Beneficial effects of recombinant platelet-activating factor acetylhydrolase and BN 52021 on bacterial translocation in cerulein-induced pancreatitis

BACKGROUND: Bacterial translocation (BT) has been suggested to be responsible for the high incidence of infections occurring after acute pancreatitis (AP). The aim of this study was to investigate the effects of the platelet-activating factor (PAF) inactivator, recombinant PAF-acetylhydrolase (rPAF-AH), and the PAF receptor antagonist, BN 52021, in AP. METHODS: Forty-eight male Wistar rats were divided into 4 groups: the sham group received saline intraperitoneally every hour for 6 h; the control group received cerulein 50 g/kg i.p. every hour for 6 h; the rPAF-AH group received AP plus rPAF-AH (5 mg/kg i.v. bolus), and the BN52021 group received AP plus BN 52021 (5 mg/kg i.v. bolus). The animals were sacrificed 12 h after the first cerulein injection. RESULTS: Supramaximal cerulein stimulation induced an increase in serum pancreatic enzymes, interleukin (IL)-6, pancreatic edema, and produced histologic evidence of AP. Compared with the control group, the addition of PAF receptor antagonists had a significant effect on serum pancreatic enzymes, pancreatic edema, and the histologic score of the pancreatitis. AP caused significant increases in BT in mesenteric lymph nodes (MLNs), pancreas, liver, spleen and blood. Compared with the control group, both rPAF-AH and BN 52021 decreased BT in the pancreas and blood. In addition, rPAF-AH decreased BT in the MLNs. We also found that PAF receptor antagonists suppressed the elevation in IL-6 levels. CONCLUSION: PAF antagonists attenuated the severity of experimental AP and reduced pancreatitis-induced BT to distant sites.     

Rescue ERCP and insertion of a small-caliber pancreatic stent to prevent the evolution of severe post-ERCP pancreatitis: a case-controlled series

Introduction  Recently prophylactic placement of a trans-sphincteric pancreatic stent has successfully been applied to prevent post-endoscopic retrograde cholangiopancreatography (ERCP) pancreatitis. Rescue ERCP and emergency application of small-caliber pancreatic stents during the early course of post-ERCP pancreatitis as a possible endoscopic therapy has not been reported yet. Methods  All patients who underwent ERCP were hospitalized for at least 24 h, with routine laboratory testing of amylase levels. Out of 1,225 ERCPs, evolution of severe post-ERCP pancreatitis was anticipated in six consecutive patients, based on severe pancreatic pain attack, more than tenfold elevation of serum amylase levels at 8 and 24 h, and moderate rise of white blood cell (WBC) and C-reactive protein (CRP) levels. Rescue ERCP and emergency application of small-caliber (4-5F, 4-cm, Geenen stent) pancreatic stents were successfully performed in all patients within 8–20 h after the initial ERCP. Results  Moderate to severe papillary oedema was observed in all patients during the rescue ERCP. Pancreatic pain was promptly reduced after the rescue pancreatic drainage procedure and completely diminished within 24 h after pancreatic stenting. Serum amylase levels were exponentially reduced and normalized within 72 h in all patients; no pancreatic necrosis or any other late complications were observed. Pancreatic stents could be safely removed a few days later. Conclusion  Rescue pancreatic stenting with small-caliber prophylactic pancreatic stents seems to be a safe and effective procedure that might be feasible to stop the evolution of severe post-ERCP pancreatitis, but prospective controlled studies are clearly demanded to support this innovative approach.     

Temporary pancreatic stent to prevent post endoscopic retrograde cholangiopancreatography pancreatitis: a preliminary, single-center, randomized controlled trial

Background Post endoscopic retrograde cholangiopancreatography (post-ERCP) pancreatitis is the most common complication of ERCP, which can occasionally become serious or fatal. This preliminary study was to prospectively evaluate the efficacy of a temporary unflanged pancreatic duct stent (PS) to prevent post-ERCP pancreatitis. Methods A total of 64 patients were randomly divided into a control group, which did not undergo stenting, and a stent group. The stent used was a 5-Fr pigtail PS without an inner flange. Results Placement of an unflanged PS was successful and without complications in all 32 patients. The rates of hyperamylasemia were 50.0% and 34.4% in the control and stent groups, respectively (P > 0.05), and the mean serum amylase levels were 456.2 and 257.9 IU/l, respectively (P = 0.035). The overall rates of post-ERCP pancreatitis diagnosed according to Cotton's criteria were 12.5% and 3.1% in the control and stent groups, respectively (P > 0.05). The severity of pancreatitis was severe in one patient, moderate in one, and mild in two in the control group, whereas in the stent group, the single case of pancreatitis was mild. Conclusions Placement of an unflanged 5-Fr PS may be useful in preventing post-ERCP pancreatitis.     

胰管塑料支架预防ERCP术后胰腺炎的临床应用

目的探讨胰管塑料支架预防内镜下逆行性胰胆管造影（ERCP）术后胰腺炎的临床效果。方法对我院2009年10月～2010年11月期间37例胆管炎或胆管结石患者在ERCP术中胆管插管困难患者的临床资料进行回顾性分析。这些患者均采用胰管括约肌小切口,并置入胰管塑料支架,观察是否并发术后胰腺炎或其他并发症。结果在接受ERCP的37例患者中,3例卅现高淀粉酶及高脂肪酶血症,其中1例淀粉酶高于正常值的3倍,余两例淀粉酶值分别为132和312IU／I,脂肪酶324和523IU／1。72小时后复查,上述结果均恢复正常。患者无腹痛,恶心呕吐等症状,胰腺周围无渗出或假性囊肿的出现。术后3～4周,电子胃镜下取出支架。除2例支架轻度外移1．0cm外,其余均放置良好,未见堵塞。结论ERCP胆管插管困难患者放置胰管塑料支架可以预防术后胰腺炎的发生。     

Platelet Function in Acute Experimental Pancreatitis

Acute pancreatitis (AP) is characterized by disturbances of pancreatic microcirculation. It remains unclear whether platelets contribute to these perfusion disturbances. The aim of our study was to investigate platelet activation and function in experimental AP. Acute pancreatitis was induced in rats: (1) control (n = 18; Ringer’s solution), (2) mild AP (n = 18; cerulein), and (3) severe AP (n = 18; glycodeoxycholic acid (GDOC) + cerulein). After 12 h, intravital microscopy was performed. Rhodamine-stained platelets were used to investigate velocity and endothelial adhesion in capillaries and venules. In addition, erythrocyte velocity and leukocyte adhesion were evaluated. Serum amylase, thromboxane A2, and histology were evaluated after 24 h in additional animals of each group. Results showed that 24 h after cerulein application, histology exhibited a mild AP, whereas GDOC induced severe necrotizing AP. Intravital microscopy showed significantly more platelet–endothelium interaction, reduced erythrocyte velocity, and increased leukocyte adherence in animals with AP compared to control animals. Thromboxane levels were significantly elevated in all AP animals and correlated with the extent of platelet activation and severity of AP. In conclusion, platelet activation plays an important role in acute, especially necrotizing, pancreatitis. Mainly temporary platelet–endothelium interaction is observed during mild AP, whereas severe AP is characterized by firm adhesion with consecutive coagulatory activation and perfusion failure. Parts of the results of this study were presented at the congress of the German Surgical Society, Berlin (May 2004), the Digestive Disease Week (May 2004), and the Annual Meeting of the American Pancreatic Association, Chicago (November 2004).     

Prospective randomized double-blind placebo-controlled trial of glyceryl trinitrate in endoscopic retrograde cholangiopancreatography-induced pancreatitis

BACKGROUND: One possible aetiology of pancreatitis following endoscopic retrograde cholangio pancreatography (ERCP) is cannulation-induced spasm of the sphincter of Oddi and consequent pancreatic duct obstruction. Sublingual glyceryl trinitrate (GTN) has been shown to produce periampullary sphincter relaxation. The aim of this study was to determine whether prophylactic long-acting GTN could reduce the incidence of ERCP-induced pancreatitis. METHODS: In a randomized double-blind study, prophylactic treatment with GTN (2 mg given sublingually 5 min before endoscopy) was compared with placebo in 186 patients who presented for elective ERCP. The primary endpoint was the occurrence of pancreatitis within 24 h, defined as a serum amylase concentration greater than 1000 units/ml in association with a visual analogue pain score of more than 5. RESULTS: The incidence of pancreatitis was lower in the GTN group compared with placebo (seven of 90 versus 17 of 96; P < 0.05). Mean serum amylase values were similar in the two groups. The protective effect of GTN appears to be highest in the diagnostic ERCP group (one of 54 versus ten of 66; P = 0.012) and in the group in which cholangiography alone was performed (one of 54 versus eight of 57; P = 0.032). CONCLUSION: Prophylactic treatment with GTN reduces the incidence of pancreatitis following ERCP but does not seem to reduce the extent of hyperamylasaemia or the severity of pancreatitis.     

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对于急性胆源性胰腺炎,内镜治疗具有重要的地位。行内镜逆行胰胆管造影术(ERCP)及内镜超声检查可明确诊断,指导进一步治疗。早期行经内镜鼻胆管引流(ENBD)、经内镜乳头括约肌切开术(EST)、胰管支架置入可及时解除梗阻,降低胆管、胰管压力,引流胆汁及胰液,缓解胰腺炎,降低并发症的发生率。内镜治疗可能导致出血、穿孔、胰腺炎加重、腹膜后感染等严重并发症,因此应严格掌握适应证,对于伴有急性胆管炎的急性胆源性胰腺炎,早期内镜治疗是绝对适应证;对于不伴有急性胆管炎的重症急性胰腺炎,应严密观察,除留置空肠营养管之外的早期内镜治疗并没有明显益处。     

Role of pancreatic duct occlusion with prolamine (Ethibloc) in necrotizing pancreatitis

There is evidence that the pancreatic duct plays an important role in the evolution of necrotizing pancreatitis. We hypothesized that occlusion of the pancreatic duct and its smaller ductules with prolamine (Ethibloc) in opossums at risk of severe necrotizing pancreatitis would have a beneficial effect on the progression of the disease. Sixteen opossums underwent bile duct ligation below the entrance of the pancreatic duct. They were divided into four groups at 6 days. Group I (control, n = 5) opossums were killed for histologic observation of the degree of necrosis of the pancreas; group II (n = 5) underwent external drainage of the pancreatic biliary duct; group III (n = 4) had external biliary drainage and ligation of the pancreatic duct; group IV (n = 7) was treated with external biliary drainage and ligation of the main pancreatic duct after instillation of prolamine. Serum amylase, lipase, and calcium values were determined. The pancreas was examined by inspection and histologically at the time of death, and the severity of the disease was determined by quantitation of pancreatic tissue necrosis. All animals in groups II and III died 8 to 14 days after bile duct ligation, and all had severe necrotizing pancreatitis. All animals in group IV survived and were killed at 2 to 10 weeks after prolamine (Ethibloc) injection into the pancreatic duct. A mild edematous pancreatitis was observed in all seven animals. Prolamine (Ethibloc) provided dramatic protection from progressive necrosis. This study does not provide an explanation, but it allows for speculation that ductal injection interrupted the deleterious effect of proteolytic enzymes and their leakage into the interstitial space of the pancreas.     

Post-ERCP pancreatitis: Reduction by routine antibiotics

Cholangitis and pancreatitis are severe complications of endoscopic retrograde cholangiopancreatography (ERCP). Antibiotics have been considered important in preventing cholangitis, especially in those with jaundice. Some have suggested that bacteria may play a role in the induction of post-ERCP pancreatitis. It is not clear, however, whether the incidence of post-ERCP pancreatitis could be reduced by antibiotic prophylaxis, as is the case with septic complications. In this prospective study, a total of 321 consecutive patients were randomized to the following two groups: (1) a prophylaxis group (n = 161) that was given 2 g of cephtazidime intravenously 30 minutes before ERCP, and (2) a control group (n = 160) that received no antibiotics. All patients admitted to the hospital for ERCP who had not taken any antibiotics during the preceding week were included. Patients who were allergic to cephalosporins, patients with immune deficiency or any other condition requiring antibiotic prophylaxis, patients with clinical jaundice, and pregnant patients were excluded. In the final analysis six patients were excluded because of a diagnosis of bile duct obstruction but with unsuccessful biliary drainage that required immediate antibiotic treatment. The diagnosis of cholangitis was based on a rising fever, an increase in the C-reactive protein (CRP) level, and increases in leukocyte count and liver function values, which were associated with bacteremia in some. The diagnosis of acute pancreatitis was based on clinical findings, and increases in the serum amylase level (>900 IU/L), CRP level, and leukocyte count with no increase in liver chemical values. The control group had significantly more patients with post-ERCP pancreatitis (15 of 160 in the prophylaxis group vs. 4 of 155 in the control group; P = 0.009) and cholangitis (7 of 160 vs. 0 of 155; P = 0.009) compared to the prophylaxis group. Nine patients in the prophylaxis group (6%) and 15 patients in the control group (9%) had remarkably increased serum amylase levels (>900 III/L) after ERCP, but clinical signs of acute pancreatitis with leukocytosis, CRF’ reaction, and pain developed in four of nine patients in the prophylaxis group compared to 15 of 15 patients with hyperamylasemia in the control group (P = 0.003). In a multivariate analysis, the lack of antibiotic prophylaxis (odds ratio 6.63, P = 0.03) and sphincterotomy (odds ratio 5.60, P = 0.05) were independent risk factors for the development of post-ERCP pancreatitis. We conclude that antibiotic prophylaxis effectively decreases the risk of pancreatitis, in addition to cholangitis after ERCP, and can thus be routinely recommended prior to ERCP These results suggest that bacteria could play a role in the pathogenesis of post-ERCP pancreatitis.     

胆管超选技术降低ERCP术后胰腺炎发生率的对照研究

目的 探讨应用导丝超选胆管技术在减少ERCP术后相关胰腺炎中的价值.方法 随机抽取术者1998-2001年间以乳头直接插入法行诊断性及治疗性ERCP术病人共78例,及2007-2008年间应用导丝超选技术行ERCP术病人112例,回顾性对比研究了两组插管成功率、胰管显影率,以及ERCP术后血淀粉酶的动态变化、相关胰腺炎的发生情况,并进行胰管显影分级与胰腺炎并发症之间的单因素相关分析.结果 乳头直接插入法的胆管插管成功率仅42.30 %(33/78例),约61.53%(16/26例)的病人因插管失败,不能进一步行ERCP相关治疗;而近年采用导丝超选胆管技术显著提高了插管成功率94.64%(106/112例,P<0.01).前后两组术中胰管显影率分别为58.97 %(46/78例)及8.04%(9/112例)(P<0.01);术后相关胰腺炎发生率分别为21.79%(17/78例)及3.57%(4/112例)(P<0.01),其中直接插管组有3例发生重症胰腺炎,导丝超选组无一例发生重症胰腺炎;两组ERCP术后高淀粉酶血症发生率分别为65.38%(51/78例)及61.61%(69/112例)(P>0.05).胰管显影程度与ERCP术后胰腺炎的发生之间有显著的正相关性(P<0.01).结论 借助导丝引导的胆管超选技术明显提高了插管成功率,显著降低了ERCP术后相关胰腺炎并发症,并可降低操作过程中胰管的显影率;胰管显影分级可预测ERCP术后胰腺炎的发生,是导致其发生的重要的但非单一因素.     

Enterokinase induces severe necrosis and rapid mortality in cerulein pancreatitis: characterization of a novel noninvasive rat model of necro-hemorrhagic pancreatitis

BACKGROUND: Unlike edematous pancreatitis, induction of severe necrotizing pancreatitis in rats generally requires an invasive laparotomy with infusion and/or ligation of the pancreatic duct or duodenal or arterial occlusion. The aim of this study was to establish and characterize a noninvasive model of severe acute pancreatitis in rats. METHODS: Wistar rats were infused intravenously with cerulein or a combination of cerulein and enterokinase. Saline (154-mmol/L NaCl) or enterokinase only was infused in controls. In a first set of experiments, intrapancreatic protease activation and the release of cytokines were correlated with the severity of organ injury. Pancreatic and pulmonary injuries were determined at 6 h. In a second set of experiments, we assessed 24-h survival, serum parameters possibly reflecting the course of the disease, and morphologic changes later in the course of the disease. RESULTS: The severity of pancreatic injury and survival were correlated strongly with the amount of enterokinase infused simultaneously with cerulein. Trypsin as well as elastase and cathepsin B activity in pancreatic tissue samples were increased markedly in these animals. Marked pancreatic hemorrhage, necrosis, and leukocyte infiltration were present in animals with the greatest amounts of enterokinase infused. IL-6 and LDH, but not IL-1beta, CRP, and amylase, in serum correlated with the severity of pancreatitis. CONCLUSIONS: This noninvasive rat model of acute pancreatitis is characterized by major pancreatic necrosis, hemorrhage, and fatality. The simple and noninvasive induction technique may have advantages for future studies on inflammatory changes and sepsis in necrotizing pancreatitis compared with other currently available invasive models.     

高脂血症对大鼠急性胰腺炎影响及白蛋白的干预效应

目的探讨高脂血症对急性胰腺炎的影响及白蛋白的干预效应。方法分别用Triton WR1339、Cerulein制作大鼠高脂血症和急性胰腺炎（acute pancreatitis，AP）模型，同时应用两者制作伴有高脂血症的AP模型．应用白蛋白治疗伴有高脂血症的AP．比较各组胰腺病理损害评分、腹水量、胰腺湿／干比、血清淀粉酶和胰腺组织的凋亡：Western blot检测胰腺组织PKC的膜转位。结果Triton WR1339诱导大鼠高脂血症以TG升高为主．6h达高峰．升高达20倍，使部分大鼠出现轻型急性胰腺炎。伴有高脂血症的AP组病理评分、腹水量、胰腺湿／干比和血清淀粉酶较Cerulein胰腺炎组均显著升高（P〈0．05），白蛋白治疗后均有所下降，但差异无统计学意义。TUNEL法测得伴有高脂血症的AP腺泡出现凋亡数量最多，白蛋白治疗后无明显的变化。合并高脂血症胰腺炎组PKC膜转位比例最高．白蛋白治疗后显著下降（P〈0．05）。结论高脂血症可以诱导AP或加重AP的胰腺损伤．白蛋白治疗不能减轻胰腺的病变。PKC的活化可能是高脂血症加重急性胰腺炎的机制之一。     

Pancreatic tissue perfusion in experimental acute pancreatitis.

OBJECTIVE: To investigate pancreatic tissue perfusion and oxygenation in severe and mild experimental acute pancreatitis in pigs. DESIGN: Randomised controlled experiment. SETTING: Animal laboratory, Finland. ANIMALS: 24 domestic pigs weighing 21-27 kg. INTERVENTIONS: 24 pigs were randomised into severe acute pancreatitis, mild acute pancreatitis and control groups (n = 8 in each). The pancreatic duct of eight anaesthetised and mechanically ventilated pigs was cannulated and taurocholic acid was infused into the pancreatic duct to induce severe acute pancreatitis. Eight animals received intraductally infused saline and developed mild acute pancreatitis. Eight pigs had their ducts cannulated alone, and served as controls. MAIN OUTCOME MEASURES: Pancreatic tissue oxygenation, laser Doppler red cell flux, central haemodynamics. RESULTS: Intraductally infused taurocholic acid rapidly induced macroscopically and histologically proven severe necrotising acute pancreatitis. Histological changes characterising mild acute pancreatitis were seen in animals after intraductal saline infusion. Pancreatic tissue oxygen tension decreased in the severe group and increased in the mild group during the six-hour study period. Laser Doppler red cell flux decreased in the severe group. Central haemodynamics, arterial blood gases, and acid base balances were stable throughout the study period in all groups. CONCLUSION: The present model of severe acute pancreatitis significantly impairs pancreatic oxygenation in the early phase. In mild acute pancreatitis, pancreatic oxygenation increases.     

ERCP findings and the role of endoscopic sphincterotomy in acute gallstone pancreatitis

A total of 131 patients with acute pancreatitis (of whom 100 had gallstones) underwent endoscopic retrograde cholangiopancreatography (ERCP) during the same hospital admission. Urgent ERCP (less than 72 h) was performed in 68 cases and early ERCP (3-30 days) in 63 cases; 47 had predicted severe attacks and 84 had predicted mild attacks (modified Glasgow criteria). The highest incidence of common bile duct stones occurred in those with predicted severe attacks and those who had urgent ERCP. Highly significant correlations were found between age and common bile duct and pancreatic duct diameters. Significant correlations were also found between the common bile duct and pancreatic duct (correcting for age) and between these and the admission serum bilirubin. The common bile duct diameter was greatest in those with common bile duct stones and predicted severe attacks. A considerably lower incidence of pancreatic duct filling occurred in those with predicted severe attacks and common bile duct stones; in predicted mild attacks the pancreatic duct diameter was greater in those with common bile duct stones. In gallstone patients complications were highest in those with predicted severe attacks but more significantly in those with common bile duct stones. Endoscopic sphincterotomy was undertaken in 37 patients with common bile duct stones without mortality. The overall complication rate in gallstone patients was 19 per cent and the mortality rate was 2 per cent. These findings suggest that common bile duct stones cause acute common bile duct and pancreatic duct obstruction and are closely associated with complications. Urgent ERCP for detection of common bile duct stones, and endoscopic sphincterotomy for treatment, is strongly recommended for patients with predicted severe attacks due to gallstones and should also be considered for others who fail to show clinical improvement.     

Pulmonary microcirculation in mild and severe experimental pancreatitis

BACKGROUND: Research aimed at elucidating the pathogenesis of pancreatitis-associated lung injury and evaluating novel strategies for preventing respiratory complications in acute pancreatitis (AP) has not yet involved intravital microscopic (IVM) studies of pulmonary microcirculation in animals with severe disease. OBJECTIVE: To characterize and compare pulmonary microcirculation in severe/necrotizing (NP) and mild/edematous pancreatitis (EP) in the rat. METHODS: EP was induced by intravenous cerulein infusion (n = 10) and NP by a standardized intraductal infusion of glycodeoxycholic acid followed by intravenous cerulein (n = 10). After 24 h a left-sided thoracotomy was performed for IVM examination of pulmonary capillary blood flow, permeability, leukocyte sticking and the thickness of alveolar septi. Further measurements included monitoring of arterial blood gases and histological evaluation of lung injury. RESULTS: In animals with NP, histology revealed severe pulmonary edema together with clustering of polymorphonuclear leukocytes in pulmonary microvessels and alveoli. IVM showed a greater number (n) of leukocytes sticking on the endothelium of pulmonary capillaries (9.4 +/- 0.7 vs. 1.8 +/- 0.2 in healthy control animals) and increased capillary permeability (260 +/- 14 vs. 136 +/- 6% relative fluorescein intensity) while capillary blood flow was decreased (0.41 +/- 0.05 vs. 0.57 +/- 0.03 mm/s). In comparison, changes in EP were significantly less pronounced (flow 0.5 +/- 0.04 mm/s, permeability 156 +/- 4%, leukocyte sticking n = 4.6 +/- 0.7). CONCLUSIONS: These findings suggest that deterioration of pulmonary microcirculation in AP correlates with disease severity and that a model featuring NP may therefore be more suitable to further study pancreatitis-associated pulmonary injury.