胰腺创伤的诊断和治疗进展

胰腺创伤的早期诊断是根据详细的询问病史、全面的体格检查,结合淀粉酶指标、B超、CT扫描、逆行胰胆管造影（ERCP）及磁共振下胰胆管成像（MRCP）等检查做出诊断,必要时应及时行剖腹探查,剖腹探查术是最可靠的早期诊断方法。依据损伤部位及严重程度,选择最佳的手术方式,可提高治愈率,减少并发症的发生,通畅引流是改善预后的关键措施,本文对胰腺创伤的诊治进展作一综述。     

低剂量灌注CT成像诊断胰腺癌的研究进展

随着MSCT的不断发展以及检查技术的不断完善,胰腺疾病的诊断率也不断进步。CT可以对胰腺进行普通平扫、多期增强扫描及CT灌注扫描(CTPI)。其中,普通平扫及增强扫描对小的胰腺癌病灶诊断率较低;普通灌注扫描可以通过监测胰腺组织血流动力学评价胰腺功能,对于早期胰腺癌的诊断率较高,但辐射剂量也较高,因此对患者的远期影响较大。因此,在满足对胰腺癌疾病诊断条件的前提下,减少CT扫描对患者的辐射剂量是目前临床研究的热点。灌注扫描通过监测患者血流量(BF)、血容量(BV)对正常胰腺及胰腺癌病灶进行观察,能够在减少辐射剂量的同时获得灌注数据,从而提供更多的诊断信息,进而满足临床诊断的要求。     

胰腺星状细胞的调控及转归

活化的胰腺星状细胞(pancreatic stellate cells,PSCs)是胰腺炎致胰腺纤维化的主要效应细胞。近年来,学者普遍认为,胰腺纤维化早期阶段是动态可逆的,因此,若在胰腺损伤的早期阶段,抑制PSCs的增殖、迁移,减少损伤部位PSCs的数目,降低细胞外基质(extracellular matrix,ECM)的生成,将可能逆转胰腺纤维化。该文以PSCs为靶点阐述了抗胰腺纤维化的新策略。     

电视腹腔镜胆囊切除术中器械改良的设想

电视腹腔镜自90年代初引进以来,便得到全国各级医院的青睐。几年间,电视腹腔镜在外科领域的开展业已取得眩目的成果．甚至涉及到对疾病更客观的诊断。利用电视腹腔镜探查诊断疾病、设计和决定手术方式、让病人更多地减轻身心痛苦和经济上的负担,赢得诊治的条件等,均是传统的剖腹探查术所不能及的。因此其得到了越来越多的同行及患者的认可,同时也充分表明了其令人鼓舞的发展前景。     

胸部创伤患者早期血清PTX3和αMSH及 CRP水平与创伤后细菌感染的相关性分析

目的 探讨胸部创伤患者早期血清正五聚蛋白(PTX3)、α黑素细胞刺激素(αMSH)及CRP水平与创伤后细菌感染的相关性分析。 方法 选取2017年3月至2019年5月本院收治的96例胸部创伤或以胸部创伤为主的多发伤患者作为创伤组,分为感染组34例和非感染组62例;同期健康体检者100例作为对照组。采用ELISA法检测血清PTX3、α黑素细胞刺激素(αMSH)水平;免疫比浊法检测血清CRP水平;ROC曲线评估血清PTX3、αMSH、CRP水平对胸部创伤并发细菌感染的诊断价值。Logistic回归分析创伤后细菌感染的影响因素。 结果 创伤组患者血清PTX3、CRP表达水平高于对照组(P结论 胸部创伤及创伤后细菌感染发生过程中血清PTX3、CRP水平上升,血清αMSH水平下降,三者联合检测对胸部创伤并发细菌感染具有一定诊断价值。     

基于TLR4/MYD88信号通路探讨大黄牡丹汤对急性胰腺炎大鼠模型的保护作用

目的基于TLR4/MYD88信号通路研究大黄牡丹汤对逆行性胰胆管注射法制作急性胰腺炎(acute pancreatitis,AP)大鼠模型的保护作用。方法 SPF级Wistar大鼠96只,按照随机数字表法分为:假手术组、AP模型观察组、奥曲肽阳性对照组、大黄牡丹汤高、中、低剂量组,除假手术组经胰胆管逆行注射生理盐水,其余各组均采用经胰胆管逆行注射5%牛磺胆酸钠溶液造模,给与药物干预6 d。观察大鼠一般生存状况;测定血清淀粉酶(AMS)、谷丙转氨酶(ALT)、谷草转氨酶(AST)含量; HE观察胰腺病理组织改变; RT-PCR、Westen Blot、IHC法检测胰腺组织TLR4、MYD88、IRAK-2、IRAK-4基因蛋白表达水平; ELISA法检测胰腺组织中炎性因子IL-2、iNOS、IFN-γ含量。结果 (1)与假手术组比较,AP模型观察组大鼠一般生存状况相对较差,血清淀粉酶(AMS)、谷丙转氨酶(ALT)、谷草转氨酶(AST)均显著升高,镜下可见胰腺组织结构散乱,坏死、充血严重,胰腺组织中TLR4、MYD88、IRAK-2、IRAK-4基因蛋白表达水平均显著升高,胰腺组织匀浆液中IL-2、iNOS、IFN-γ含量均显著升高,差异具有统计学意义(P0.05);(2)干预后,各治疗组大鼠一般生存状况有不同程度改善,血清淀粉酶(AMS)、谷丙转氨酶(ALT)、谷草转氨酶(AST)均下降,镜下间质性水肿以及坏死灶明显改善,胰腺组织中TLR4、MYD88、IRAK-2、IRAK-4基因蛋白表达水平均下降,胰腺组织匀浆液中IL-2、iNOS、IFN-γ含量均下降,其中尤以大黄牡丹汤高剂量组显著,差异具有统计学意义(P0.05)。结论大黄牡丹汤改善急性胰腺炎大鼠胰腺损伤,其作用机制可能与抑制TLR4/MYD88信号通路有关。     

内镜下逆行胰胆管造影术的护理

内镜下逆行性胰胆管造影术（endoscopic retrograde cholangiopancreatography,简称ERCP）是近10年来逐渐发展的一项医疗新技术,该术通过十二指肠镜将造影剂从导管注入胰管和胆管使其显影。适用于疑有胆道、胰腺疾病和疑难性腹痛等患者的诊断及进一步的治疗,具有安全、有效、痛苦少等优点,是当前辅助诊断和治疗胰胆管疾病的一种重要的方法之一。随着消化内镜性能的不断改进和插管造影技术的提高,还可以在诊断的基础上进行其他相关的内镜治疗,如内镜下十二指肠乳头括约肌切开术（EST）、内镜鼻胆引流术（ENDB）等。我科自1998年7月开展此项技术,取得了良好的效果,现将护理总结如下。     

非闭塞性肠系膜缺血致肠坏死的临床分析(附11例报道)

目的:探讨非闭塞性肠系膜缺血所致肠坏死的临床表现和结局。方法:回顾性总结青岛大学附属医院11例非闭塞性肠系膜缺血所致肠坏死的病例,评估分析其临床表现、实验室检查、腹部CT影像和手术过程。结果:所有病人均在全麻下行剖腹探查术,实施肠管切除术并一期吻合术或肠造口术,7例病人恢复良好,2例住院期间死亡,2例放弃治疗回家后死亡。结论:非闭塞性肠系膜缺血临床罕见,术前难以诊断,具有较高的病死率,血管造影可以作为NOMI早期诊断及治疗的有效手段,对于怀疑有肠坏死发生的患者需及早行手术治疗。     

多镜联合治疗胆总管结石合并胆囊结石的技术优势

目的探讨十二指肠镜、胆道镜、腹腔镜等多镜联合治疗胆总管结石合并胆囊结石的技术优势。方法采用腹腔镜胆总管探查术+腹腔镜胆囊切除术(LCBDE+LC)和内窥镜逆行胰胆管造影术+内窥镜下括约肌切开取石术+腹腔镜胆囊切除术(ERCP+EST+LC)两种术式治疗胆总管结石合并胆囊结石患者。结果有两组病例,其中LCBDE+LC组36例,本组术后胆道残余结石2例,后经T管窦道行胆道镜取石治愈。ERCP+EST+LC组54例,本组术后并发一过性高淀粉酶血症3例,发生急性轻型胰腺炎2例。结论多镜联合治疗胆总管结石合并胆囊结石具有创伤小、效果好、并发症少、恢复快的优点,多镜联合发挥出其独特技术优势,避免了因接受传统开腹手术而造成较大创伤的不合理治疗模式。     

沙漠干热环境创伤失血性休克猪模型的氧代谢特点

目的:探讨沙漠干热环境创伤失血性休克猪的氧代谢特点。方法:选择长白仔猪40头,随机分为四组:常温假手术组(NS)、常温创伤失血性休克组(NTHS)、干热假手术组(DS)、干热创伤失血性休克组(DTHS),分别置于相应的环境暴露3小时后,进行麻醉,动静脉置管,NTHS组和DTHS组分别自剖腹术后,行左下叶1/4肝脏切除及脾切除术后,再快速放血至平均动脉压(MAP)降至45±5mmHg;NS组和DS组仅行腹中线剖腹术。持续检测计算动脉、混合静脉氧饱和度、氧含量及氧输送(DO_2)、氧耗(VO_2)、氧摄取率(O_2ER)和动脉血乳酸(Lac)。结果:整个病程中,各组动脉氧饱和度均无显著变化。DTHS组混合静脉氧饱和度和氧含量均较相同时间点的其他各组低,DO_2、VO_2、O_2ER均显著高于常温环境组(P0.05)。模型成功后,NTHS组和DTHS组DO_2均经历"下降-代偿-稳定"的过程,但DTHS组短暂稳定后立即呈进行性快速下降至到动物死亡。在实验过程中,DTHS组各时间点氧摄取率(O_2ER)均高于相同时间点的其他组,差异具有统计学意义(P0.05)。NTHS组和DTHS组氧O_2ER均在休克后0 h出现明显变化,而动脉血乳酸(Lac)在休克后1.5 h才出现明显变化,但DTHS组动脉Lac增高较NTHS组升高更加明显(P0.05),且进展迅速。结论:(1)沙漠干热环境创伤失血性休克较高的氧代谢,是机体代偿能力弱、病程变化快的重要原因之一;(2)VO_2、O_2ER等直接氧代谢指标可作为早期评估监测机体氧代谢的敏感指标;(3)血Lac浓度可能是反映干热环境创伤失血性休克严重程度的重要指标。     

Interaction of complement and leukocytes in severe acute pancreatitis: potential for therapeutic intervention

In acute pancreatitis, local as well as systemic organ complications are mediated by the activation of various inflammatory cascades. The role of complement in this setting is unclear. The aim of the present study was to determine the level of complement activation in experimental pancreatitis, to evaluate the interaction of complement and leukocyte-endothelium activation, and to assess the effects of complement inhibition by soluble complement receptor 1 (sCR1) in this setting. Necrotizing pancreatitis was induced in Wistar rats by the combination of intravenous cerulein and retrograde infusion of glycodeoxycholic acid into the biliopancreatic duct; edematous pancreatitis was induced by intravenous cerulein only. In control animals, a sham operation (midline laparotomy) was performed. Complement activation, leukocyte sequestration, and pancreatic as well as pulmonary injury were assessed in the presence/absence of sCR1. Increased levels of C3a were found in necrotizing but not in edematous pancreatitis. When complement activation in necrotizing pancreatitis was blocked by sCR1, levels of C3a and total hemolytic activity (CH50) were decreased. Leukocyte-endothelial interaction, as assessed by intravital microscopy, and pancreatic as well as pulmonary organ injury (wet-to-dry weight ratio, MPO activity, and histology) were ameliorated by sCR1. As a result of the present study, necrotizing but not edematous pancreatitis is characterized by significant and early complement activation. Based on the interaction of complement and leukocytes, complement inhibition by sCR1 may be a valuable option in the treatment of leukocyte-associated organ injury in severe pancreatitis.     

SELEX技术在胰腺癌分子诊断及靶向治疗中应用的研究进展

胰腺癌由于起病隐匿,早期诊断率较低,临床治疗效果差,是目前预后最差的恶性肿瘤之一。目前,临床上尚缺乏有效的非创伤早期筛查胰腺癌的手段,因而胰腺癌的早期诊断和治疗显得尤为重要。近年来,指数富集配基的系统进化(SELEX)技术以其在其他疾病中所表现的应用价值为疾病的诊治提供了一个新的途径。对于缺乏有效确诊手段,发病隐匿且病死率高的胰腺癌而言,SELEX技术基于胰腺癌发病的分子机制,可以筛选出特异结合于胰腺癌分子靶标的适配体,对筛选所得适配体进一步化学修饰,可以实现分子水平成像及靶向治疗,进而达到胰腺癌早期诊治的目的,具有重要的临床意义。本文就SELEX技术在胰腺癌分子诊断及靶向治疗中的应用研究进展进行了综述。     

Traumatic pancreatitis

Traumatic pancreatitis should be considered as a diagnostic possibility when trauma to the epigastrium is followed by phenomena suggestive of intra-abdominal injury. The presence or absence of hyperamylasemia should be established immediately. Even when traumatic pancreatitis is believed to exist, any suggestion of injury to other viscera should indicate laparotomy. Retroperitoneal rupture of the duodenum may simulate traumatic pancreatitis in all respects, including hyperamylasemia. X-ray studies may be of value in differentiation.Non-complicated traumatic pancreatitis is best treated conservatively. Gunshot and knife wounds of the pancreas should be drained.     

Endoplasmic Reticulum Stress Is Chronically Activated in Chronic Pancreatitis

The pathogenesis of chronic pancreatitis (CP) is poorly understood. Endoplasmic reticulum (ER) stress has now been recognized as a pathogenic event in many chronic diseases. However, ER stress has not been studied in CP, although pancreatic acinar cells seem to be especially vulnerable to ER dysfunction because of their dependence on high ER volume and functionality. Here, we aim to investigate ER stress in CP, study its pathogenesis in relation to trypsinogen activation (widely regarded as the key event of pancreatitis), and explore its mechanism, time course, and downstream consequences during pancreatic injury. CP was induced in mice by repeated episodes of acute pancreatitis (AP) based on caerulein hyperstimulation. ER stress leads to activation of unfolded protein response components that were measured in CP and AP. We show sustained up-regulation of unfolded protein response components ATF4, CHOP, GRP78, and XBP1 in CP. Overexpression of GRP78 and ATF4 in human CP confirmed the experimental findings. We used novel trypsinogen-7 knock-out mice (T^−/−), which lack intra-acinar trypsinogen activation, to clarify the relationship of ER stress to intra-acinar trypsinogen activation in pancreatic injury. Comparable activation of ER stress was seen in wild type and T^−/− mice. Induction of ER stress occurred through pathologic calcium signaling very early in the course of pancreatic injury. Our results establish that ER stress is chronically activated in CP and is induced early in pancreatic injury through pathologic calcium signaling independent of trypsinogen activation. ER stress may be an important pathogenic mechanism in pancreatitis that needs to be explored in future studies.     

Alcoholic pancreatitis in rats: injury from nonoxidative metabolites of ethanol

The mechanism by which alcohol injures the pancreas remains unknown. Recent investigations suggest a role for fatty acid ethyl ester (FAEE), a nonoxidative metabolite of ethanol, in the pathogenesis of alcohol pancreatitis. In this study, we characterized ethanol-induced injury in rats and evaluated the contribution of oxidative and nonoxidative ethanol metabolites in this form of acute pancreatitis. Pancreatic injury in rats was assessed by edema, intrapancreatic trypsinogen activation, and microscopy after infusing ethanol with or without inhibitors of oxidative ethanol metabolism. Plasma and tissue levels of FAEE and ethanol were measured and correlated with pancreatic injury. Ethanol infusion generated plasma and tissue FAEE and, in a dose-dependent fashion, induced a pancreas-specific injury consisting of edema, trypsinogen activation, and formation of vacuoles in the pancreatic acini. Inhibition of the oxidation of ethanol significantly increased both FAEE concentration in plasma and pancreas and worsened the pancreatitis-like injury. This study provides direct evidence that ethanol, through its nonoxidative metabolic pathway, can produce pancreas-specific toxicity in vivo and suggests that FAEE are responsible for the development of early pancreatic cell damage in acute alcohol-induced pancreatitis.     

ERCP-Guided Percutaneous Fine-Needle Pancreatic Biopsy

In patients with a radiologic diagnosis of unresectable pancreatic carcinoma, exploratory laparotomy for tissue diagnosis is no longer required. Histologic confirmation of the diagnosis may be obtained safely and accurately with percutaneous fine-needle aspiration biopsy. Endoscopic retrograde cholangiopancreatography (ERCP) precisely localized the biopsy site for cytologic diagnosis of adenocarcinoma in 13 of 14 patients (93 percent) with pancreatic carcinoma.     

Endothelin inhibition delays onset of hyperglycemia and associated vascular injury in type I diabetes: evidence for endothelin release by pancreatic islet beta-cells

This study investigated the role of endothelin-1 for hyperglycemia, vascular, and pancreatic injury in early type I diabetes in non-obese-diabetic (NOD) mice. Endothelium dependent relaxation to acetylcholine and vascular gene expression of endothelin converting enzyme (ECE) isoforms 1 and 2 were studied as indicators of vascular injury. Endothelial NO bioactivity in the aorta was reduced in diabetic NOD mice while vascular expression of ECE-1 and ECE-2 mRNA was increased compared with controls (all p<0.05). Vascular histology was normal in all animals. Unexpectedly, treatment of prediabetic NOD mice for 6 weeks with the orally active ET(A) receptor antagonist BSF461314 prevented onset of diabetes without affecting insulitis severity. ET(A) receptor blockade also restored abnormal endothelial NO bioactivity and reduced ECE-1 and ECE-2 gene expression in NOD mice to levels comparable with healthy controls (p<0.05). Moreover, secretion of endothelin-1 in a time-dependent fashion was observed by pancreatic islet beta-cells cultured in vitro. These data suggest a critical role for ET(A) receptor signaling in the development of autoimmune forms of diabetes and the early vascular injury associated with it.     

Prophylactic and therapeutic treatments with AT 1 and AT 2 receptor antagonists and their effects on changes in the severity of pancreatitis

Previous studies showed that a local pancreatic renin-angiotensin system (RAS) was upregulated in experimental acute pancreatitis. RAS inhibition could attenuate pancreatic inflammation and fibrosis, which casts a new light on the role of the pancreatic RAS in pancreatitis. The present study explores the prophylactic and therapeutic potentials, and possible molecular mechanism for the antagonism of angiotensin II receptors on the changes in the severity of pancreatic injury induced by acute pancreatitis. Experimental pancreatitis was induced by an intraperitoneal injection of supra-maximal dose of cerulein. The differential effects of angiotensin II receptors inhibitors losartan and PD123319 on the pancreatic injury were assessed by virtue of using the pancreatic water content, biochemical and histological analyses. Blockade of the AT(1) receptor by losartan at a dose of 200microg/kg could markedly ameliorate the pancreatic injury induced by cerulein, as evidenced by biochemical and histopathological studies. However, blockade of the AT(2) receptor by PD123319 appeared not to provide any beneficial role in cerulein-induced pancreatic injury. Both prophylactic and therapeutic treatments with losartan were effective against cerulein-induced pancreatic injury. The protective action of losartan was linked to an inhibition of NAD(P)H oxidase activity, thus consequential oxidative modification of pancreatic proteins in the pancreas. Inhibition of the AT(1) receptor, but not AT(2) receptor, may play a beneficial role in ameliorating the severity of acute pancreatitis. The differential effects of AT(1) and AT(2) inhibitors on cerulein-induced pancreatic injury might be due to the distinctive mechanism of the AT(1) and AT(2) receptors on the activation of NAD(P)H oxidase. Thus the protective role of AT(1) receptor antagonist, losartan, could be mediated by the inhibition of NAD(P)H oxidase-dependent generation of reactive oxygen species (ROS).     

Relationship between NF-kappaB and trypsinogen activation in rat pancreas after supramaximal caerulein stimulation

Intra-acinar cell nuclear factor-kappaB (NF-kappaB) and trypsinogen activation are early events in secretagogue-induced acute pancreatitis. We have studied the relationship between NF-kappaB and trypsinogen activation in rat pancreas. CCK analogue caerulein induces early (within 15 min) parallel activation of both NF-kappaB and trypsinogen in pancreas in vivo as well as in pancreatic acini in vitro. However, NF-kappaB activation can be induced without trypsinogen activation by lipopolysaccharide in pancreas in vivo and by phorbol ester in pancreatic acini in vitro. Stimulation of acini with caerulein after 6 h of culture results in NF-kappaB but not trypsinogen activation. Protease inhibitors (AEBSF, TLCK, and E64d) inhibit both intracellular trypsin activity and NF-kappaB activation in caerulein stimulated acini. A chymotrypsin inhibitor (TPCK) inhibits NF-kappaB activation but not trypsin activity. The proteasome inhibitor MG-132 prevents caerulein-induced NF-kappaB activation but does not prevent trypsinogen activation. These findings indicate that although caerulein-induced NF-kappaB and trypsinogen activation are temporally closely related, they are independent events in pancreatic acinar cells. NF-kappaB activation per se is not required for the development of early acinar cell injury by supramaximal secretagogue stimulation.