阻止急性胰腺炎由轻型向重症发展的非手术治疗172例报告

目的 探讨阻止急性胰腺炎（ＡＰ）由轻型向重症发展的非手术治疗方法。方法 总结分析了１９９４～１９９６年和１９９６～１９９８年两个阶段共收治的１７２例ＡＰ患者的治疗效果。第１阶段采取常规保守治疗,第２阶段采取改善微循环和防止细胞钙超负荷的措施。结果 第１阶段共收治的ＡＰ患者７８例,轻型ＡＰ７６例,其中有转化为重症ＡＰ８例;重症ＡＰ１０例,出现全身性并发症９例,局部并发症７例,死亡３例。第２阶段共收治     

异搏定对胰腺腺泡细胞内游离钙离子浓度的影响

目的:探讨细胞内钙超负荷在急性胰腺炎(AP)发生发展中的作用.方法:使用140只SD大白鼠胆胰管逆行加压注射4.5%牛磺胆酸钠制成AP模型,用荧光指示剂Fura-2/Am测定游离胰腺腺泡细胞内游离钙离子浓度([Ca~(2 )]i).结果:注射后2小时和3小时胰腺呈急性出血坏死性炎症早期改变,制AP模型后AP组[Ca~(2 )]i较对照组明显增高(P<0.001),AP组胰腺腺泡细胞内[Ca~(2 )]i增高值与胰腺病理变化程度呈正相关关系(r_s=0.9727,P<0.001),异搏定治疗可明显提高病鼠生存率和改善胰腺组织出血坏死程度和腺泡细胞超微结构损害.结论:胰腺腺泡细胞内钙超负荷在胆汁性急性水肿性胰腺炎向出血坏死性胰腺炎转变中起明显作用,钙通道阻滞剂异搏定可明显阻止胰腺细胞内钙离子超负荷,是其治疗急性胰腺炎的主要机理之一.     

遏制轻型急性胰腺炎向重症转化的非手术 治疗策略

目的 ：探讨遏制急性胰腺炎向重症转化的非手术治疗策略。方法 ：将4年间收治的286例轻型急性胰腺炎分为对照组和治疗观察组。对照组采取常规非手术治疗措施;观察组加用改善胰腺微循环，防治细胞钙超载和抑制胰酶的治疗方法。结果 ：对照组144轻型有20例转化为重症胰腺炎，14例发生全身性并发症;观察组142例轻型有8例转化为重症，2例出现全身性并发症。观察组重症患者血C-反应蛋白和Balthazar CT严重度指数在治疗后各时点较对照组明显降低。结论 ：在常规治疗的基础上加用改善胰腺微循环，防治细胞钙超载和抑制胰酶的治疗措施可能有助于阻止轻型急性胰腺炎向重症化发展。     

改善胰腺缺血和钙拮抗剂在急性重症胰腺炎治疗中的保护作用

目的 探讨改善胰腺缺血和钙通道阻断剂在急性重症胰腺炎治疗中的保护作用。方法 将24例轻型急性胰腺炎患者随机分为对照组和治疗组,对照组采取常规保守治疗,治疗组重点改善胰腺缺血并使用钙拮抗剂。测定两组患者血液流变学变化及血液肿瘤坏死因子（TNFα）、白介素（IL-1β）、C-反应蛋白（CRP）、血栓素（TXB2）及前列腺素（6-酮-PGF1α）含量变化。结果 治疗组血液流变学异常得到明显改善。血TNFα）、白但纱（IL-1β）、C-反应蛋白（CRP）、血栓素（TXB2）及前列腺素（6-酮-PGF1α）含量变化。结果 治疗组血液流变学异常得到明显改善,血TNFα、IL-1β、CRP、TXB2和6-酮-PGF1α含量均较对照组显著降低。结论 重点改善胰腺缺血和使用钙通道阻断剂在阻止急性胰腺炎重症化治疗中有明显保护作用。     

早期改善胰腺微循环对重症急性胰腺炎的影响

目的　探讨早期改善胰腺微循环对治疗重症急性胰腺炎 (SAP)的疗效。方法　回顾性分析对比 1995～ 1998年 44例 (前期 )和 1998～ 2 0 0 1年 40例 (后期 )SAP患者的治疗效果。前期采取常规统一治疗 ,后期增加改善胰腺缺血及防止细胞钙超负荷的措施。结果　后期患者治愈率(85 .0 % )显著高于前期SAP患者治愈率 (68.2 % ) (P <0 .0 5 ) ;后期死亡率 (15 .0 % )、中转手术率(2 2 .5 % )、并发症率 (3 5 .0 % )明显地低于前期 (3 1.8%、40 .9%、5 4.5 % ) (P <0 .0 5 )。后期平均住院日 (2 2± 4)d ,较前期平均住院日 (3 2± 7)d明显缩短 (P <0 .0 5 )。结论　改善胰腺缺血和防止细胞钙超负荷有助于限制SAP恶化进程 ,改善SAP的预后     

重症胰腺炎胰供血动脉改变的观察与防护

随着急性胰腺炎(AP)发病机制的深入研究,以缺血、血栓阻塞为特征的胰腺供血不足所导致的胰腺缺血,组织灌注不足,微循环障碍被认为是AP的发病机制之一。但临床上还难以用胰腺供血改变的客观指标来判断AP病程演变及预后转归。我院1999年12月至2001年12月采用区域动脉灌注(RAI)治疗重症急性胰腺炎(SAP)47例,通过数字式减影血管造影(DSA)作胰腺血管造影,观察胰腺供血动脉的改变,探讨胰腺血供异常改变的程度与SAP病情严重程度、并发症和预后的关系及防护。     

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。     

IL-10区域动脉灌注减轻急性胰腺炎大鼠肺损伤的实验研究

为探讨IL-10区域动脉灌注（LAI）对急性胰腺炎（AP）大鼠肺损伤的保护作用。笔者以5%牛磺胆酸钠胰胆管注射(1mL/kg )制成大鼠急性胰腺炎模型，IL-10（40 000UI/kg）LAI，以生理盐水为对照，取大鼠肺组织、胰腺组织进行病理学比较。结果示,AP组大鼠肺泡结构破坏，可见明显出血和白细胞浸润;胰腺细胞坏死，大片液化，粒细胞浸润。IL-10治疗组大鼠肺出血和白细胞浸润较AP组明显改善;胰腺细胞坏死、液化，血管周围可见粒细胞浸润。两组动物肺和胰腺病理损害评分AP组显著高于LAI组（P<0.05）。提示IL-10 LAI能显著减轻AP动物的胰腺和肺组织损害，IL-10有望成为AP综合治疗的药物之一。     

一种研究急性胰腺炎加重病理机理的动物模型

介绍一种急性水肿性胰腺炎（ＡＥＰ）向坏死性胰腺炎（ＡＮＰ）转变的大鼠模型。１０７只ＳＤ大鼠随机分为假手术组、ＡＥＰ组和ＡＮＰ组。ＡＥＰ通过胰管结扎、外分泌刺激诱发。在ＡＥＰ模型基础上静注大剂量Ｄｅｘｔｒａｎ１１０诱发ＡＮＰ。结果显示：血清淀粉酶水平在ＡＥＰ、ＡＮＰ组明显增高，胰腺泡细胞胞浆游离钙离子浓度在ＡＮＰ诱发后持续增高；胰腺出血、实质坏死、钙沉积在ＡＮＰ组常见。超微结构显示ＡＮＰ组胰毛细血管内皮剥脱、坏死。由此表明，胰腺缺血可能通过腺泡细胞钙超负荷的作用促发ＡＥＰ向ＡＮＰ转变。该大鼠模型因临床联系较好、病变渐进，不失为一种从细胞和分子水平研究急性胰腺炎加重病理机理的动物模型     

缬沙坦治疗大鼠急性胰腺炎的实验研究

急性胰腺炎（AP）因其发病机理复杂而治疗棘手。新近研究发现，血管紧张素Ⅱ水平在AP病程中异常升高，并加重胰腺持续缺血，机体微循环紊乱，使AP病情进一步恶化。据此，本研究通过复制大鼠AP模型，探讨血管紧张素Ⅱ受体拮抗剂缬沙坦（valsartan）对大鼠AP的治疗作用。     

Effects of heparin in experimental models of acute pancreatitis and post-ERCP pancreatitis

BACKGROUND: Acute pancreatitis (AP) is a complication of diagnostic or therapeutic endoscopic retrograde cholangiopancreatography (ERCP). In a recent clinical trial, a decreased rate of post-ERCP pancreatitis was shown after prophylactic heparin treatment. The aim of this study was to evaluate the effects of prophylactic heparin application in various experimental models of AP and pancreatic duct obstruction and to assess the underlying mechanisms. METHODS: In various experimental models, pancreatic injury of graded severity was induced in Wistar rats: (1) mild pancreatitis by IV cerulein infusion over 6 hours; (2) severe pancreatitis by infusion of glycodeoxycholic acid into the pancreatic duct plus IV cerulein application over 6 hours. The clinical ERCP situation was imitated in groups (3) obstruction of the pancreatic duct and (4) infusion of contrast medium into the pancreatic duct plus obstruction. In every group the animals received either no heparin (n=six per group) or continuous IV heparin (n=six per group) starting before pancreatic injury. Histologic changes, amylase, and lipase in plasma were evaluated 12 hours after induction of pancreatic injury. Additional animals were treated to investigate pancreatic microcirculation by intravital microscopy (n=six per group). RESULTS: In groups 1, 3, and 4 (mild AP/duct obstruction/duct obstruction plus contrast medium), IV heparin-treated animals showed reduced edema, inflammation, and peak amylase values compared with the corresponding non-heparin-treated animals (P<.05). Moreover, mean erythrocyte velocity was significantly higher and leukocyte-endothelium interaction was reduced in these groups after prophylactic administration of heparin. In contrast, group 2 (severe AP) did not show any difference between control animals and animals that received heparin as assessed by histology and intravital microscopy. CONCLUSIONS: Prophylactic systemic application of heparin provides a protective effect in mild AP and in experimental post-ERCP pancreatitis. The mechanism of the protective effects of heparin seems to be the reduction of leukocyte-endothelium interaction and the normalization of pancreatic microcirculation.     

Potential harmful effect of iodinated intravenous contrast medium on the clinical course of mild acute pancreatitis

HYPOTHESIS: A worse clinical outcome might be expected in patients with acute pancreatitis (AP) who receive intravenous contrast medium for a nondynamic contrast-enhanced computed tomographic (CECT) study early during hospital admission. DESIGN: Cohort analytic study. SETTING: Tertiary care center. PATIENTS: Of 126 patients with mild AP, 52 patients underwent CECT to establish AP diagnosis (group 1), and the remaining 74 did not (group 2). MAIN OUTCOME MEASURES: Survival and development of local or systemic complications during the hospital stay. Potential confounders were demographic, clinical, and biochemical data, as well as therapeutic measures. The Atlanta classification was used to define local and systemic complications. RESULTS: Mean age, etiology of AP, prognostic score on admission, and pharmacologic treatment were similar between groups. Local and systemic complications were more frequently observed in patients who underwent CECT (odds ratio, 11.4; 95% confidence interval, 2.0-64.8; P =.008). Six patients, all in group 1, developed a pancreatic abscess (odds ratio, 20.8; P =.004). In 5 of them, a second CECT showed more severe AP changes. The association between CECT and abscess development was more apparent in patients with a body mass index of 25 or more and/or nasogastric suction. Six patients in group 1 and 1 in group 2 had systemic complications (odds ratio, 9. 5; P =.01). There were no deaths. CONCLUSIONS: The observed increased incidence of local and systemic complications in patients with mild AP who undergo CECT, particularly in those with a body mass index of 25 or more, suggests a potentially harmful effect of intravenous contrast medium. Until this issue is clarified, it seems reasonable to restrict the use of dynamic CECT to patients with severe AP, protracted clinical course, or suspected local septic complication.     

Acute pancreatitis after aortic surgery

Acute pancreatitis (AP) after aortic surgery has rarely been reported. A retrospective review of all abdominal and thoracoabdominal aortic operations complicated with AP from January 1982 to March 1992 was performed to study the presentation and outcome of this infrequently recognized complication. Thirteen cases of AP were found among 1965 abdominal aortic operations (0.7% incidence). The distribution of the original aortic operations was as follows: eight elective abdominal aortic aneurysm repairs, two aortoiliac grafts for aortoiliac occlusive disease, and three aortorenal bypasses. Two cases of pancreatitis complicated 170 thoracoabdominal aortic operations (1.2% incidence). Ten patients had mild pancreatitis, nine were discharged without any pancreatic complications after receiving supportive treatment. Five patients with severe AP died of multisystem organ failure despite aggressive surgical treatment; 4 had infected necrosis. The overall mortality was 40 per cent; severe AP resulted in a 100 per cent mortality. The diagnosis of severe AP was usually made in the second postoperative week, significantly later (P < 0.01) than for patients with mild disease. Typically, patients with mild AP presented with hyperamylasemia at a median of 5 postoperative days, and severe AP was found at reoperation or autopsy after a period of unexplained sepsis. Five patients with mild AP were found to have biliary tract stones, with one requiring endoscopic stone extraction. In conclusion, pancreatitis is an uncommon, although perhaps underreported complication. Underreporting may be due to a lack of hyperamylasemia when severe pancreatitis is diagnosed. The severe form is diagnosed late in patients with postoperative sepsis, associated with infected necrosis, and lethal. The complication may be reduced by incidental cholecystectomy for cholelithiasis.     

Disturbances of the microcirculation in acute pancreatitis

BACKGROUND: Severe acute pancreatitis is characterized by pancreatic necrosis, resulting in local and systemic inflammation. Pancreatitis affects both the systemic and pancreatic vasculature. This review focuses on the underlying processes involved in the changes of microvascular anatomy following acute pancreatitis. METHODS: A Medline/PubMed search (January 1966 to December 2005) with manual cross-referencing was conducted. All relevant articles investigating the pancreatic microcirculatory anatomy and the effect of pancreatitis on the microcirculation were included. RESULTS: The pancreas is susceptible to ischaemic insult, which can exacerbate acute pancreatitis. There is also increasing evidence of pancreatic and systemic microvascular disturbances in the pathogenesis of pancreatitis, including vasoconstriction, shunting, inadequate perfusion, and increased blood viscosity and coagulation. These processes may be caused or exacerbated by ischaemia-reperfusion injury and the development of oxygen-derived free radicals. CONCLUSION: Acute pancreatitis impairs the pancreatic and systemic microcirculation, which is a key pathological process in the development of severe necrotizing disease.     

Management of infection in acute pancreatitis

The clinical course of acute pancreatitis varies from a mild, transitory illness to a severe, rapidly fatal disease. In about 80% to 90% of cases pancreatitis presents as a mild, self-limiting disease with low morbidity and mortality. Unlike mild pancreatitis, necrotizing pancreatitis develops in about 15% of patients, with infection of pancreatic and peripancreatic necrosis representing the single most important risk factor for a fatal outcome. Infection of pancreatic necrosis in the natural course develops in the second and third week after onset of the disease and is reported in 40% to 70% of patients with necrotizing pancreatitis. Just recently, prevention of infection by prophylactic antibiotic treatment and assessment of the infection status of pancreatic necrosis by fine-needle aspiration have been established in the management of severe pancreatitis. Because medical treatment alone will result in a mortality rate of almost 100% in patients with signs of local and systemic septic complications, patients with infected necrosis must undergo surgical intervention, which consists of an organ-preserving necrosectomy combined with a postoperative closed lavage concept that maximizes further evacuation of infected debris and exudate. However, intensive care treatment, including prophylactic antibiotics, reduces the infection rate and delays the need for surgery in most patients until the third or fourth week after the onset of symptoms. At that time, debridement of necrosis is technically easier to perform, due to better demarcation between viable and necrotic tissue compared with necrosectomy earlier in the disease. In contrast, surgery is rarely needed in the presence of sterile pancreatic necrosis. In those patients the conservative approach is supported by the present data. Received: March 20, 2002 / Accepted: April 15, 2002 Offprint requests to: W. Uhl     

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.     

急性胰腺炎的依治现状

目的 介绍急性胰腺炎（AP）诊断与治疗的近视。方法 参阅本期有关来稿结合作者专业知识和临床经验予以小结。结果及结论 AP病理变化多端,在分型上有轻、重二型。轻型占90%,可行非手术治疗：重型占10%,常因胰腺坏死合并感染需行手术治疗。但有一个原则“不早作不大作”。在诊治方法上均有进展。因此提高了AP治愈率。但在广大基层医院常因某些原因还不能按全国统一规范实行,基层医院在治疗上应用中草药也有效果。故总结有4条经验,即早期诊断,区别轻重程度,提高疗效;合理治疗,缩短疗程;并发症的预防和中西医药的结合治疗,这是目前我国诊治AP的现状。     

JPN Guidelines for the management of acute pancreatitis: medical management of acute pancreatitis

The basic principles of the initial management of acute pancreatitis are adequate monitoring of vital signs, fluid replacement, correction of any electrolyte imbalance, nutritional support, and the prevention of local and systemic complications. Patients with severe acute pancreatitis should be transferred to a medical facility where adequate monitoring and intensive medical care are available. Strict cardiovascular and respiratory monitoring is mandatory for maintaining the cardiopulmonary system in patients with severe acute pancreatitis. Maximum fluid replacement is needed to stabilize the cardiovascular system. Prophylactic antibiotic administration is recommended to prevent infectious complications in patients with necrotizing pancreatitis. Although the efficacy of the intravenous administration of protease inhibitors is still a matter of controversy, there is a consensus in Japan that a large dose of a synthetic protease inhibitor should be given to patients with severe acute pancreatitis in order to prevent organ failure and other complications. Enteral feeding is superior to parenteral nutrition when it comes to the nutritional support of patients with severe acute pancreatitis. The JPN Guidelines recommend, as optional measures, blood purification therapy and continuous regional arterial infusion of a protease inhibitor and antibiotics, depending on the patient's condition.