胆汁内外引流术对梗阻性黄疸大鼠肝脏诱导型一氧化氮合酶表达的影响

目的 探讨胆汁引流方法对梗阻性黄疸大鼠肝脏诱导型一氧化氮合酶(iNOS)表达的影响.方法 将42只成年雄性SD大鼠随机分为四组,采用我们既往建立的二次手术方法分别建立梗阻性黄疸(OJ,n=12)、胆汁内引流术(ID,n=10)、胆汁外引流术(ED,n=10)及假手术(SH,n=10)模型.于第二次术后7 天留取肝脏标本.通过SABC免疫组化方法测定肝脏组织iNOS的表达情况.结果 假手术组大鼠肝组织几乎无iNOS表达.梗阻性黄疸时,大鼠肝组织iNOS表达增强,阳性面积增加(30.539±6.255),平均光密度升高(0.296±0.055).通过胆汁内引流术解除黄疸后,肝脏iNOS表达明显受到抑制,阳性表达面积减少(16.571±2.044)(P=0.017),平均光密度下降(0.204±0.029)(P<0.01).但通过胆汁外引流术后,肝组织iNOS表达阳性面积(38.186±7.495)及平均光密度(0.399±0.086)非但不减少,反而显著增加(P<0.01,P＝0.004).结论 梗阻性黄疸时,大鼠肝脏iNOS表达增强,胆汁内引流术可明显抑制肝脏iNOS表达,而胆汁外引流术却使其表达增强,提示在抑制诱导型一氧化氮合酶的表达方面胆汁内引流术优于外引流术.     

胆汁内外引流术对梗阻性黄疸大鼠血内毒素、IL-2及IL-6的影响

目的 研究胆汁内外引流方法对梗阻性黄疸大鼠血内毒素及IL-2、IL-6水平的影响,探讨胆汁内引流术解除术前黄疸优于外引流术的机制.方法 60只成年SD雄性大鼠,随机分为4组,分别建立梗阻性黄疸(OJ)、胆汁内引流术(ID)、胆汁外引流术(ED)及假手术(SH)模型.于二次术后第7 d留取血液标本.通过鲎试验动态浊度法测定大鼠血浆内毒素水平,采用双抗体夹心酶联免疫吸附法(ELISA)检测血清IL-2及IL-6水平.结果 成功建立了大鼠梗阻性黄疸及内外引流术模型.梗阻性黄疸时大鼠形成严重的内毒素血症(42.463 pg/mL±3.486 pg/mL),血清IL-6及IL-2水平明显升高(212.949 pg/mL-I-56.546 pg/mL,212.718 pc/mL±62.419 pg/mL).行胆汁外引流术后,大鼠内毒素血症得到改善(P≤0.01),血清IL-2及IL-6水平却持续上升(P≤0.05,P≤0.01).而通过胆汁内引流术解除黄疸后,大鼠血内毒素、IL-6及IL-2浓度均几乎恢复至正常水平,与假手术对照组相比无明显差异(P>0.05).结论 胆汁内引流术可明显改善梗阻性黄疸时内毒素血症及细胞因子分泌紊乱,而胆汁外引流术作用不明显,甚至使病情加重,提示术前利用胆汁内引流术解除黄疸优于外引流术.     

胆汁内外引流术对梗阻性黄疸大鼠肺肿瘤坏死因子α、中性粒细胞弹性蛋白酶的影响

目的研究胆汁内外引流方法对梗阻性黄疸大鼠肺肿瘤坏死因子α(TNF-α)、中性粒细胞弹性蛋白酶(NE)水平的影响。方法将64只成年SD雄性大鼠随机分为4组,分别建立梗阻性黄疸(OJ)、胆汁内引流术(ID)、胆汁外引流术(ED)及假手术(SH)4组模型。于2次术后第14天留取肺组织匀浆液标本。采用双抗体夹心酶联免疫吸附法(ELISA)检测10%肺匀浆液TNF-α水平,生化法检测10%肺匀浆液NE水平。结果成功建立了大鼠梗阻性黄疸及内外引流术模型。梗阻性黄疸时大鼠肺TNF-α、NE水平较假手术对照组明显升高(100.893 pg/mL±21.271 pg/mL vs 64.091 pg/mL±13.034 pg/mL,P<0.01;50.396μg/mL±17.388μg/mL vs 39.718μg/mL±9.625μg/mL,P<0.05)。通过胆汁内引流术解除黄疸后,大鼠肺TNF-α浓度(75.141 pg/mL±15.849 pg/mL)与梗阻性黄疸组相比下降明显(P<0.01);而通过胆汁外引流术解除黄疸后,大鼠肺TNF-α浓度仍较高(112.129 pg/mL±36.886 pg/mL),与梗阻性黄疸组相比无差异(P>0.05)。行胆汁内、外引流术后,大鼠肺NE水平均降低(39.390μg/mL±12.410μg/mL、44.790μg/mL±16.681μg/mL),但与梗阻性黄疸组相比内引流明显(P<0.05)、外引流无差异(P>0.05),且内引流恢复至正常水平,与假手术对照组相比无差异(P>0.05)。结论梗阻性黄疸可导致肺组织炎症细胞因子升高,胆汁内引流术可明显改善梗阻性黄疸时肺组织炎症细胞因子水平、甚至接近正常,而胆汁外引流术没有改善肺炎症细胞因子水平,提示术前利用胆汁内引流术解除梗阻性黄疸缓解肺部炎症反应优于外引流术。     

胆汁内、外引流术对梗阻性黄疸大鼠血清肿瘤坏死因子和肝脏库普弗细胞诱导型一氧化氮合酶表达的影响

目的 研究胆汁内、外引流术对梗阻性黄疸大鼠血清肿瘤坏死因子-α(TNF-α)水平和肝脏库普弗细胞诱导型一氧化氮合酶(iNOS)表达的影响.方法 采用成年雄性Sprague-Dawley大鼠48只,分成梗阻性黄疸、胆汁外引流、内引流和假手术四组,每组12只.采用原位灌注消化肝脏及贴壁培养方法 分离并纯化库普弗细胞,采用逆转录(RT)-PCR方法 检测库普弗细胞iNOS mRNA表达.用ELlSA方法 测定血清TNF-α含量.结果 梗阻性黄疸组血清TNF-α水平为(110.8±26.3)pg/ml,与假手术组的(88.4±17.9)pg/ml比较,差异有统计学意义(P=0.045).内引流组解除胆道梗阻后,血清TNF-α水平受到抑制,为(89.84±28.3)pg/ml,而胆汁外引流组却无此作用,为(118.6±22.7)Pg/ml,后者与梗阻性黄疸组比较差异无统计学意义(P=0.059).胆道梗阻形成后,梗阻性黄疸组库普弗细胞iNOSmRNA表达增强(0.82±0.24),显著高于假手术组(0.38±0.35,P=0.005).胆汁内引流术解除黄疸后,内引流术组的库普弗细胞iNOS mRNA表达受到抑制(0.59±0.35),但与梗阻性黄疸组比较差异无统计学意义(P=0.139),外引流组iNOSmRNA表达并未受抑制(0.974±0.48),与梗阻性黄疸组比较差异无统计学意义(P=0.321),但显著高于胆汁内引流组(P=0.016).结论 胆汁内引流术在逆转梗阻性黄疸大鼠升高的血清TNF-α水平和肝脏库普弗细胞iNOS mRNA的表达方面优于胆汁外引流术.     

术前不同引流方式减黄对梗阻性黄疸大鼠部分肝切除术后肝功能和肝再生的影响

目的 了解术前不同引流方式减黄对梗阻性黄疸(OJ) SD大鼠部分肝切除术(PH)术后肝功能和肝再生的影响.方法 建立OJ不同引流方式减黄70％部分肝切除SD大鼠动物模型.并在术后0、1、2、4、12、24、48和72h收集大鼠血液及肝脏组织标本,测定血清TBIL、ALB、ALT、AST水平,计算残肝重量、肝再生率,免疫组化法观察肝脏组织PCNA表达,ELISA法检测血清TNF-α水平.结果 PH术后各时段内引流(ID)组和外引流(ED)组TBIL、ALT、AST水平较OJ组均偏低.各时段ID组ALB水平较OJ组、ED组偏高.72 h肝再生率ID组高于ED组,ED组高于OJ组.3组PCNA水平均于12 h明显升高,ID组于24 h达高峰,OJ组、ED组高峰延迟至48 h且峰值偏低.PH术后各组血清TNF-α水平均呈上升趋势,ID组于12 h达高峰,OJ组、ED组均于24 h达高峰,各时段OJ组、ED组血清TNF-α水平较ID组均偏高.结论 内外引流术均可改善OJ所致的高胆红素血症和肝功能,并改善OJ大鼠残肝再生能力,但内引流效果更明显,且内引流术可以有效降低血清TNF-α水平.     

不同胆道引流方式对梗阻性黄疸大鼠肠屏障功能的影响

目的:探讨不同胆道引流方式对梗阻性黄疸大鼠肠屏障功能的影响.方法:60只SD大鼠随机分为假手术组(shame operation,SO组)、梗阻性黄疸组(obstructive jaundice,OJ组)、内引流组(internal biliary drainage,ID组)和外引流组(enternal biliary drainage,ED组).制备OJ模型,SO组、OJ组在术后第7天处死大鼠并采集标本,ID组、ED组则行不同引流手术,在引流术后第7天处死大鼠并采集标本.检测血清丙氨酸氨基转移酶(alanine aminotransferase,ALT)、总胆红素(total bilirubin,TBIL)、直接胆红素(direct bilirubin,DBIL)、胆汁酸(totalbileacide,TBA)及小肠黏液sIgA含量,并对结果进行统计学分析.结果:OJ组较SO组血清ALT、TBIL、DBIL、TBA均明显升高,小肠黏液sIgA含量(0.160±0.150)明显减少.ED、ID组血清中ALT、TBIL、DBIL、TBA明显低于OJ组;ID组小肠黏液sIgA含量明显高于OJ组及ED组(0.272±0.182vs0.160±0.150,0.191±0.113,均P<0.05).结论:胆道内、外引流均能有效解除胆道梗阻,改善肝功能.但内引流可明显增加肠道黏液sIgA,其改善肠道屏障功能的效果优于外引流.     

梗阻性黄疸大鼠血清IL-6、TNF-α及肝脏Kuppfer细胞CD14表达变化

目的观察梗阻性黄疸（0J）大鼠血清IL-6、TNF-α及肝脏Kuppfer细胞CD14表达变化,探讨黄疸性肝损伤的免疫机制。方法将60只成年雄性sD大鼠随机分为三组各20只,其中黄疸组结扎切断胆管制备OJ模型,假手术组仅行胆管分离而不结扎切断,对照组不行特殊处理。三组均于7d后留取下腔静脉血及肝组织标本,采用EusA法检测血清IL-6、TNF-仪水平,采用免疫组化法检测肝脏CD,。表达。结果与假手术组及对照组比较,黄疸组血清IL-6及TNF-α均显著升高（P均〈0．05）、肝脏Kuppfer细胞CD14表达明显增多（P〈0．01）,前两组比较无显著差异（P〉0．05）。结论OJ大鼠肝脏Kuppfer细胞被激活、CD14表达增强并导致炎症因子血清IL-6及TNF-α大量表达,此可能为0J引起肝损伤及机体免疫功能下降的机制之一。     

梗阻性黄疸大鼠胆道外引流术前术后肝脏中转化生长因子β1表达

目的探讨转化生长因子(TGF)-β1在梗阻性黄疸大鼠胆道外引流术前后肝脏中的表达。方法监测梗阻性黄疸大鼠胆道外引流术前及术后不同时间组及假手术组TGF-β1的表达强度。结果 TGF-β1在梗阻性黄疸大鼠胆道外引流术前表达强度较高,术后3、6、9 d表达强度逐渐下降,与假手术组有明显差异(P<0.05)。结论 1TGF-β1在梗阻性黄疸大鼠胆道外引流术前术后肝脏中的表达存在显著差异,术后不同时段差异不同,术后随时间推移TGF-β1表达减弱。2胆道外引流术可改善梗阻性黄疸大鼠肝损伤,越早引流肝损伤恢复越快。     

梗阻性黄疸大鼠NF-κB的变化及其对免疫应答的影响

目的:探讨梗阻性黄疸(obstructive jaundice,OJ)时NF-KB的变化及其对免疫应答的影响.方法:60只Wistar♂大鼠随机分成3组:假手术组(SHAM组)、梗阻性黄疸组(CBDL组)和梗阻性黄疸+NF-kB抑制剂脯氨酸二硫化氨基甲酸酯(PDTC)组(PDTC组).每组术后7、14 d分批(n=10)检测光镜下肝脏病理组织学,血清总胆红素(TB),谷丙转氨酶(ALT),内毒素(LPS)水平,肝组织促炎因子IL-1β、IL-6,抑炎因子IL-10以及NF-kB蛋白表达.结果:CBDL组7、14 d大鼠均出现肝组织病理损伤,CBDL组较SHAM组血清TB、ALT、LPS增高(7 d:140.14±10.17 vs 7.309±1.04,134.479±10.20 vs 35.79±3.76.189.33±11.05 vs 2.816±0.58;14 d:194.608±12.73 vs 36.142±3.51.217.797±12.37 vs 7.321±1.03.292.816±14.53vs 2.664±0.53,均P＜0.01),肝组织IL-1β,IL-6,IL-10和NF-kB表达增强(均P＜0.01),且14 d较7 d变化更为显著.PDTC组大鼠血清TB、ALT和肝组织IL-1β、IL-6、NF-kB表达在7 d时相点时比CBDL组显著下降(P＜0.01),而到14 d时相点时比较CBDL组无明显变化;LPS和IL-10表达与CBDL组各时相点相比无明显差异.结论:梗阻性黄疸大鼠早期(7 d)通过PDTC抑制NF-kB活化表达,可下调促炎因子的表达,减轻肝损.后期(14 d)作用不明显,其机制可能是通过LPS、IL-10等其他途径所致.     

ROLE OF ENDOSCOPIC NASOBILIARY DRAINAGE INDICATION AND BASIC TECHNIQUE

Endoscopic nasobiliary drainage (ENBD) plays an important role in the treatment of patients with obstructive jaundice. Nowadays, ENBD is widely performed for not only biliary drainage, but also for gallbladder, pancreatic duct, and pancreatic cyst drainage. Herein is presented the indications for ENBD and its technique.     

A Comparison of Preoperative Biliary Drainage Methods for Perihilar Cholangiocarcinoma: Endoscopic versus Percutaneous Transhepatic Biliary Drainage

Background/Aims

Controversy remains over the optimal approach to preoperative biliary drainage in patients with resectable perihilar cholangiocarcinoma. We compared the clinical outcomes of endoscopic biliary drainage (EBD) with those of percutaneous transhepatic biliary drainage (PTBD) in patients undergoing preoperative biliary drainage for perihilar cholangiocarcinoma.

Methods

A total of 106 consecutive patients who underwent biliary drainage before surgical treatment were divided into two groups: the PTBD group (n=62) and the EBD group (n=44).

Results

Successful drainage on the first attempt was achieved in 36 of 62 patients (58.1%) with PTBD, and in 25 of 44 patients (56.8%) with EBD. There were no significant differences in predrainage patient demographics and decompression periods between the two groups. Procedure-related complications, especially cholangitis and pancreatitis, were significantly more frequent in the EBD group than the PTBD group (PTBD vs EBD: 22.6% vs 54.5%, p<0.001). Two patients (3.8%) in the PTBD group experienced catheter tract implantation metastasis after curative resection during the follow-up period.

Conclusions

EBD was associated with a higher risk of procedure-related complications than PTBD. These complications were managed properly without severe morbidity; however, in the PTBD group, there were two cases of cancer dissemination along the catheter tract.     

Preoperative biliary drainage for hilar cholangiocarcinoma

Hilar cholangiocarcinomas grow slowly, and metastases occur late in the natural history. Surgical cure and long-term survival have been demonstrated, when resection margins are clear. Preoperative biliary drainage has been proposed as a way to improve liver function before surgery, and to reduce post-surgical complications. Percutaneous transhepatic biliary drainage (PTBD) with multiple drains was previously the preferred method for the preoperative relief of obstructive jaundice. However, the introduction of percutaneous transhepatic portal vein embolization (PTPE) and wider resection has changed preoperative drainage strategies. Drainage is currently performed only for liver lobes that will remain after resection, and for areas of segmental cholangitis. Endoscopic biliary drainage (EBD) is less invasive than PTBD. Among EBD techniques, endoscopic nasobiliary drainage (ENBD) is preferable to endoscopic biliary stenting (EBS), because secondary cholangitis (due to the retrograde flow of duodenal fluid into the biliary tree) does not occur. ENBD needs to be converted to PTBD in patients with segmental cholangitis, those with a prolonged need for drainage, or when the extent of longitudinal tumor extension is not sufficiently well characterized.     

Efficacy of preoperative endoscopic nasobiliary drainage for hilar cholangiocarcinoma

Background/Purpose

Although percutaneous transhepatic biliary drainage has previously been recommended as a primary preoperative step, endoscopic nasobiliary drainage (ENBD) is prevalent as an alternative procedure. Few reports assess the efficacy and safety of ENBD in a substantial patient cohort.

Methods

Of 116 patients with hilar cholangiocarcinoma who underwent surgery, 62 (43 men and 19 women, median age 69 years) underwent preoperative ENBD. After classification of lesions according to Bismuth–Corlette (B–C) criteria, we evaluated efficacy and safety with respect to B–C type.

Results

Patients were classified as B–C types I (n = 5), II (n = 21), IIIa (n = 23), IIIb (n = 5), and IV (n = 8). Preoperative single ENBD was effective in 46/62 patients (74%) including 5/5 (100%) B–C type I, 20/21 (94%) type II, 16/23 (70%) type IIIa, 4/5 (80%) type IIIb, and 1/8 (13%) type IV. Sixteen cases (26%) required additional drainages with ENBD or endoscopic biliary stenting (EBS) in 8/16 (50%), and with PTBD in 8/16 (50%). Mild acute pancreatitis (n = 1, 2%), segmental cholangitis (n = 2, 3%), and acute cholangitis with catheter obstruction (n = 7, 11%) occurred with ENBD.

Conclusions

Preoperative single ENBD in the future remnant lobe is effective treatment for B–C type I–III hilar cholangiocarcimona. Preoperative ENBD was rarely complicated with segmental cholangitis.     

经内镜胆管内引流治疗恶性胆道梗阻的探讨

为缓解胆道梗阻，对２８例恶性胆道梗阻（ＭＢＯ）患者行经内镜胆管内引流术（ＥＢＤ）。结果２５例（８９％）插管成功，共插管４４次，７Ｆ管３次，１０Ｆ２５次，１２Ｆ１６次。２３例（９２％）减黄有效，ＥＢＤ后第３天胆红素平均下降４６．３％，肝外胆管径平均回缩５８．６％，减黄有效者腹胀迅速消失或减轻。首次插管维持有效引流时间１４１．５±１５１．２天，早、中期并发胆管炎４０％，１年以上生存１７％。结果表明ＥＢＤ减黄效果和症状改善是显著的，胆红素下降与胆管径回缩相平行。认为胆管是否屈曲及乳头括约肌切开术的好坏是ＥＢＤ成败的关键；腹胀再现，有胆道感染症状及Ｂ超见肝外胆管扩张为通管的指征。ＥＢＤ适合高龄或高危人群的ＭＢＯ患者，对延长生存期有重要的价值。     

Endoscopic Biliary Drainage for Acute Obstructive Cholangitis: Analysis of 100 Consecutive Patients

Abstract: Acute obstructive suppurative cholangitis is a life-threatening condition and prompt biliary decompression is essential if the patient is to survive. One hundred patients with acute obstructive (suppurative) cholangitis were treated by simple endoscopic cannulation for biliary drainage. Forty-eight patients had common duct stones alone, 33 patients had additional stones in the gallbladder, and 18 patients had stones in the intrahepatic ducts. Another patient had a confluence stone. Twenty-six patients had undergone endoscopic sphincterotomy. Bile duct dilatation was present in only 25 of 47 patients (53%) studied by ultrasound tomography. Biliary decompression was achieved in 98 patients. One tortuous distal bile duct and one oversized stone were the causes of failure in two patients. Forty-seven patients proved to have suppurative cholangitis. Most patients felt instant and dramatic relief of their syniptoms. Bleeding at sphinctetomy was the only complication associated with the decompression ocurring in 2 patients. Bending (2 patients) and withdrawal (2 patients) of a nasobiliary catheter, and nasal bleeding (1 patient) were the complications related to nasobiliary drainage. Two patients with suppurative cholangitis died despite successful decompression performed 3 and 5 days after the onset of cholangitis. This delay seemed responsible for their deaths. Thus the mortality rate was 2.0% for all the patients arid 4.3% for those with suppurative cholangitis. These results suggest that endoscopic cannulation, which is feasible even in the absence of bile duct dilatation, is a prompt, safe, and effective procedure for emergency biliary decompression for the treatment of acute obstructive (suppurative) cholangitis.     

Preoperative biliary drainage in hilar cholangiocarcinoma: When and how?

Hilar cholangiocarcinoma is a tumor of the extrahepatic bile duct involving the left main hepatic duct, the right main hepatic duct, or their confluence. Biliary drainage in hilar cholangiocarcinoma is sometimes clinically challenging because of complexities associated with the level of biliary obstruction. This may result in some adverse events, especially acute cholangitis. Hence the decision on the indication and methods of biliary drainage in patients with hilar cholangiocarcinoma should be carefully evaluated. This review focuses on the optimal method and duration of preoperative biliary drainage(PBD) in resectable hilar cholangiocarcinoma. Under certain special indications such as right lobectomy for Bismuth type ⅢA or Ⅳ hilar cholangiocarcinoma, or preoperative portal vein embolization with chemoradiation therapy, PBD should be strongly recommended. Generally, selective biliary drainage is enough before surgery, however, in the cases of development of cholangitis after unilateral drainage or slow resolving hyperbilirubinemia, total biliary drainage may be considered. Although the optimal preoperative bilirubin level is still a matter of debate, the shortest possible duration of PBD is recommended. Endoscopic nasobiliary drainage seems to be the most appropriate method of PBD in terms of minimizing the risks of tract seeding and inflammatory reactions.     

CURRENT STATUS AND FUTURE EXPECTATIONS FOR ENDOSCOPIC BILIARY DRAINAGE IN 16 HOSPITALS

The authors examined the performance of endoscopic biliary drainage (EBD) in 16 hospitals. The examination was in the form of a questionnaire given between 1 June and 20 July 2005 to clarify the status of 369 patients who had undergone EBD. A total of 124 patients underwent endoscopic nasobiliary drainage (ENBD), 224 patients underwent endoscopic biliary drainage (EBS), and one patient underwent simultaneous ENBD and EBS. With regard to the underlying diseases, 227 patients had malignant disease and 142 had benign disease. A total of 244 patients underwent EBS. Plastic stent (PS) was used in 200 cases, and metal stent (MS) in 44 cases. One stent was used in 89% of cases, two stents in 10%, three or more stents in 1%. Metal stent was used in 44 patients (23 were covered and 21 uncovered) with unresectable biliary stenosis. One stent was used in 33 patients, two stents in 10 patients, and three stents in one patient. For treating middle and inferior common bile duct stenosis, PS having a caliber of 10 Fr is too soft; newer tubes should be developed utilizing materials that provide longer stent patency. Longer patency can be achieved now by applying EBS using a covered MS. Improving the materials will also improve stent flexibility and the smoothness of the coating film. When treating superior common bile duct and porta hepatic bile duct stenosis, the stent is placed in both lobes of the liver.     

经内镜胆管内引流治疗恶性胆道梗阻的探讨

为缓解胆道梗阻，对２８例恶性胆道梗阻（ＭＢＯ）患者行经内镜胆管内引流术（ＥＢＤ）。结果２５例（８９％）插管成功，共插管４４次，７Ｆ管３次，１０Ｆ２５次，１２Ｆ１６次。２３例（９２％）减黄有效，ＥＢＤ后第３天胆红素平均下降４６．３％，肝外胆管径平均回缩５８．６％，减黄有效者腹胀迅速消失或减轻。首次插管维持有效引流时间１４１．５±１５１．２天，早、中期并发胆管炎４０％，１年以上生存１７％。结果表明ＥＢＤ减黄效果和症状改善是显著的，胆红素下降与胆管径回缩相平行。认为胆管是否屈曲及乳头括约肌切开术的好坏是ＥＢＤ成败的关键；腹胀再现，有胆道感染症状及Ｂ超见肝外胆管扩张为通管的指征。ＥＢＤ适合高龄或高危人群的ＭＢＯ患者，对延长生存期有重要的价值。