难取性胆道结石的微创治疗

目的：探讨胆道难取性结石微创治疗的方法、疗效和安全性。方法：回顾分析2005年12月至2010年11月采用腹腔镜、胆道镜、体内微爆破碎石仪联合治疗难取性胆道结石72例患者的临床资料,观察碎石成功率、结石取净率和并发症发生率。结果：碎石成功率100%,结石取净率97.2%,无胆道大出血、穿孔及胆漏等严重并发症发生。结论：腹腔镜、胆道镜、体内微爆破碎石仪可显著提高胆道难取性结石的治疗效果,安全可靠,为临床治疗胆道结石提供了更多选择。     

胆道镜结合微爆破碎石治疗复杂性胆道结石

目的:探讨微爆破碎石用于治疗复杂胆道结石的治疗体会。方法:在胆道镜直视下,分别在术中和术后对158例复杂的胆道结石患者进行微爆破碎石,然后用取石网取出碎石,泥沙状结石随液体流出或让其自行流入肠道。结果:158例患者156例取石成功。取石成功率98.73%。明显提高了胆道取石的成功率。无1例出现胆道穿孔、瘘道穿孔及胆道出血等严重并发症。结论:在胆道镜下,采用微爆破碎石术治疗复杂的胆道结石是一种安全、可靠、高效的方法,可以明显提高结石的取净率。     

胆道镜结合微爆破碎石治疗复杂性胆道结石

目的：探讨微爆破碎石用于治疗复杂胆道结石的治疗体会。方法：在胆道镜直视下,分别在术中和术后对158例复杂的胆道结石患者进行微爆破碎石,然后用取石网取出碎石,泥沙状结石随液体流出或让其自行流入肠道。结果：158例患者156例取石成功。取石成功率98.73%。明显提高了胆道取石的成功率。无1例出现胆道穿孔、瘘道穿孔及胆道出血等严重并发症。结论：在胆道镜下,采用微爆破碎石术治疗复杂的胆道结石是一种安全、可靠、高效的方法,可以明显提高结石的取净率。     

腹腔镜联合胆道镜治疗胆总管结石行胆管一期缝合的可行性研究

目的:探讨应用腹腔镜联合胆道镜胆总管切开取石并行一期缝合胆总管的方法治疗胆总管结石病的可行性。方法:采用前瞻性研究方法,将我院2013年6月~2016年6月收治的76例胆总管结石患者随机分成A、B两组,A组给予腹腔镜联合胆道镜胆总管切开取石后行胆管一期缝合;B组给予腹腔镜联合胆道镜胆总管切开取石后留置T管引流。比较分析两组术中、术后及并发症情况。结果:胆总管一期缝合组较留置T管组住院时间更短,住院费用更低,且术后出现的并发症几率更小。结论:腹腔镜联合胆道镜胆总管切开取石后一期缝合胆总管是治疗胆总管结石病的安全可行的方法,既为患者节省了费用又避免留置T管带来的并发症,在合适的适应症下可行此手术方法治疗胆总管结石病。     

输尿管镜钬激光碎石术和后腹腔镜输尿管切开取石术治疗输尿管上段结石的临床疗效比较

目的:比较输尿管镜钬激光碎石术(USL)和后腹腔镜输尿管切开取石术(RLU)治疗输尿管上段结石的疗效,探讨治疗输尿管上段结石的最佳方法.方法:回顾性分析115例输尿管上段结石患者临床资料,其中71例采用输尿管镜术治疗,44例采用后腹腔镜术治疗,比较两种手术方法的临床治疗效果.结果:后腹腔镜组的手术成功率(97.7％)明显高于输尿管镜组(83.1％)(P＜0.05).输尿管镜组和后腹腔镜组手术时间分别为(43.2± 14.7)min和(79.6± 24.1)min,术中出血量分别为(3.1±0.8)ml和(36.4± 3.7)ml,术后住院天数分别为(3.3±2.1)d和(6.7±1.3)d,差异均具有显著统计学意义(P＜0.01),输尿管镜组均优于后腹腔镜组.输尿管镜组手术后并发症6例,后腹腔镜组5例,两组并发症的发生率比较差异无统计学意义(P＞0.05).术后1个月复查腹部X线平片(KUB),输尿管镜组17例有结石残留,后腹腔镜组均无结石残留,输尿管镜组的结石残留率明显高于腹腔镜组(P＜0.01).结论:输尿管上段结石采用输尿管镜钬激光碎石术和后腹腔镜输尿管切开取石术治疗各有其优缺点.RLU具有安全、高效、创伤小、并发症少、结石清除率高的优点;而USL相对具有出血少、手术时间及住院时间短等优点,但手术成功率和结石清石率低,需其他辅助方式治疗结石.因此,泌尿外科医师应根据结石大小、位置、有无炎性息肉包裹、梗阻程度、肾积水量等术前检查结果及所拥有的设备与技术熟练程度选择最合适的治疗方法.     

侧卧位经皮肾微造瘘输尿管镜下取石治疗上尿路结石56例报道

目的:探讨侧卧位施行经皮肾微造瘘输尿管镜下取石(MPCNL)治疗上尿路结石方法及疗效。方法:回顾分析56例上尿路结石侧卧位施行PCNL治疗的临床资料,其中肾铸形结石33例,输尿管上段结石23例。结果:56例均手术成功,无穿刺失败或中转开放手术。一次结石取净率80%,两次手术合计达96%。术中均无输血,无肠道损伤等并发症。结论:侧卧位施行MPCNL手术患者易耐受,手术更安全,术中碎石易排出。效果良好。     

经皮肾微造瘘输尿管镜取石术治疗复杂鹿角形肾结石

目的:探讨经皮肾穿刺微通道法(MPCNL-mini percutaneous nephrolithotomy)在治疗复杂鹿角形肾结石的临床应用价值.方法:使用F16-F18左右的肾筋膜扩张器建立经皮肾微通道,通过气压弹道碎石及输尿管镜取石治疗复杂鹿角形肾结石,并对采用此法手术的478名患者的治疗效果进行回顾性分析.结果:通过经皮肾穿刺建立微通道(M PCNL)治疗复杂鹿角形肾结石的478名患者,术中及术后均无严重并发症发生,结石取净率达93.143%.结论:经皮肾穿刺微通道技术治疗复杂鹿角形肾结石具有创伤小、出血少、并发症少、住院时间短的优点,具有良好的临床应用价值.     

经皮肾微造瘘输尿管镜取石术治疗复杂鹿角形肾结石

目的:探讨经皮肾穿刺微通道法(M PCNL-mini percutaneous nephrolithotomy)在治疗复杂鹿角形肾结石的临床应用价值.方法:使用F16-F18左右的肾筋膜扩张器建立经皮肾微通道,通过气压弹道碎石及输尿管镜取石治疗复杂鹿角形肾结石,并对采用此法手术的478名患者的治疗效果进行回顾性分析.结果:通过经皮肾穿刺建立微通道(M PCNL)治疗复杂鹿角形肾结石的478名患者,术中及术后均无严重并发症发生,结石取净率达93.143%.结论:经皮肾穿刺微通道技术治疗复杂鹿角形肾结石具有创伤小、出血少、并发症少、住院时间短的优点,具有良好的临床应用价值.     

净石灵胶囊联合体外冲击波碎石术治疗复杂性肾结石临床疗效分析

目的:探讨净石灵胶囊联合体外冲击波碎石术治疗复杂性肾结石临床疗效。方法:选取2010年1月-2011年12月在我院就诊的复杂性肾结石患者83例,随机分为体外冲击波碎石术组、经皮肾镜碎石取石组、净石灵胶囊联合体外冲击波碎石术组。观察两组间的手术时间、碎石率、疗效以及组内之间不同直径的结石的碎石率。结果:ESWL组碎石成功率85.3%,PCNL组碎石成功率90.0%,净石灵胶囊联合体外冲击波碎石术组碎石成功率89.7%,三组比较无统计学意义(P>0.05);ESWL组手术时间(40.2±6.3)min,PCNL组手术时间(46.6±4.1)min,净石灵胶囊联合体外冲击波碎石术组手术时间(42.2±5.7)min,三组比较无统计学意义(P>0.05);ESWL组、PCNL组、净石灵胶囊联合体外冲击波碎石术组治疗复杂性肾结石的有效率依次为75.0%、80.0%、97.4%,组间比较,差异具有统计学意义(P<0.05);ESWL组5<10mm、10<15mm、15<20mm直径的肾结石的粉碎率依为100%、85.7%、40%,组内比较具有统计学意义(P<0.01),PCNL组5<10mm、10<15mm、15<20mm直径的肾结石的粉碎率依次为100%、83.3%、75%,组内比较具有统计学意义(P<0.05),净石灵胶囊联合体外冲击波碎石术组5<10mm、10<15mm、15<20mm直径的肾结石的粉碎率依次为100%、88.9%、57.1%,组内比较具有统计学意义(P<0.01)。结论:体净石灵胶囊联合体外冲击波碎石术治疗复杂性肾结石的临床疗效优于单纯运用体外冲击波碎石术或经皮肾镜碎石取石术。     

胆道镜联合腹腔镜治疗胆总管结石的疗效及预后

目的:观察胆道镜联合腹腔镜治疗胆总管结石的临床疗效以及预后情况,探讨胆道镜联合腹腔镜在胆总管结石治疗中的意义。方法:选择我院收治的胆总管结石患者共106例,根据手术方案分为两组,其中实验组共53例,采取胆道镜联合腹腔镜手术治疗;对照组共53例,给予腹腔镜手术治疗,记录两组的手术相关情况、术后并发症以及住院情况,应用统计学软件对两组数据进行分析。结果:1实验组的手术时间短于对照组,术中出血少于对照组,术后胃肠功能恢复正常时间短于对照组,差异具有统计学意义(P0.05);2实验组住院时间与住院费用均少于对照组,差异具有统计学意义(P0.05);3实验组术后并发症发生率为18.87%,显著低于对照组(35.85%),差异具有统计学意义(P0.05)。结论:胆道镜联合腹腔镜能够安全有效的治疗胆总管结石。     

Endotoxin-induced reduction in biliary indocyanine green excretion rate in a chronically catheterized rat model

Using a nonstressed chronically catheterized rat model in which the common bile duct was cannulated, we studied endotoxin-induced alterations in hepatic function by measuring changes in the maximal steady-state biliary excretion rate of the anionic dye indocyanine green (ICG). Biliary excretion of ICG was calculated from direct measurements of biliary ICG concentrations and the bile flow rate during a continuous vascular infusion of ICG. Despite significant elevations in mean peak serum tumor necrosis factor-alpha (TNF-alpha) concentrations (90.9 +/- 16.2 ng/ml), there was no effect on mean rates of bile flow or biliary ICG clearance after administration of 100 microg/kg endotoxin at 6 or 24 h. Significant differences from mean baseline rates of bile flow and biliary ICG excretion did occur after administration of 1,000 microg/kg endotoxin (mean peak TNF-alpha 129.6 +/- 24.4 ng/ml). Furthermore, when rats were treated with up to 16 microg/kg of recombinant TNF-alpha, there was no change in mean rates of bile flow or ICG biliary clearance compared with baseline values. These data suggest that the complex regulation of biliary excretion is not mediated solely by TNF-alpha.     

Contraceptive steroids increase cholesterol in bile: mechanisms of action

Contraceptive steroids increase the risk of acquiring cholesterol gallstones. The factors responsible include an increase in cholesterol saturation of bile and an increase in rate of secretion of cholesterol into bile. The goal of this study was to investigate the mechanism(s) of these increases in biliary cholesterol. During the use of contraceptive steroids, cholesterol saturation of gallbladder bile and the amount of cholesterol secreted per mole of bile acid increased (P less than 0.05 and P less than 0.02, respectively). Cholesterol absorption, cholesterol synthesis, chylomicron remnant clearance, and the concentration of plasma and lipoprotein lipids were not altered by contraceptive steroids. Despite this apparent lack of effect, important correlations were present during steroid use. LDL (low density lipoprotein) cholesterol increased as dietary cholesterol increased (r = 0.58, P less than 0.025). Cholesterol synthesis correlated directly with VLDL cholesterol concentration (r = 0.64, P less than 0.01), biliary cholesterol secretion (r = 0.68, P less than 0.01) and with molar percent cholesterol in bile (r = 0.49, P = 0.06). Chylomicron remnant clearance also correlated with cholesterol secretion (r = 0.85, P less than 0.001). As either remnant uptake or synthesis increased, the effect of the other source of hepatic cholesterol on biliary cholesterol secretion diminished. These relationships were not observed in the same subjects when they were not taking the hormones. The findings suggest that both newly synthesized and dietary cholesterol contribute to the cholesterol secreted in bile. This is consistent with the hypothesis that cholesterol for secretion into bile and VLDL is derived from a common metabolic pool of free cholesterol. It is proposed that contraceptive steroids exert their effect on biliary cholesterol by increasing cholesterol entering the pool and/or by inhibiting hepatic ACAT (acylcoenzyme A:cholesterol acyltransferase) activity, a known effect of progesterone, so that an increase in free cholesterol entering the pool leads to an increase in output.     

Liver uptake and hepato-biliary transfer of galactosylated proteins in rats are determined by the extent of galactosylation

The effect of molecular mass and surface density of galactose residues on hepatic uptake and subsequent biliary excretion of galactosylated proteins was investigated in rats. Several proteins with different molecular weights (15-70 kDa) and different numbers of galactose units were synthesized and radiolabeled with 111In. Galactosylated proteins were administered i.v. to anaesthetized rats and samples of plasma and bile were collected for 3 h. Liver was harvested at the end of the experiments and the radioactivity of all samples was measured. Galactosylated proteins accumulated primarily in the liver and 2-10% of the administered dose appeared in the bile, mainly in undegraded form. The hepatic uptake clearance (Cl liver) and biliary excretion rate constant (kbile) of galactosylated proteins were calculated. No direct effect of molecular weight was observed, however, on increasing the galactose density, Cl liver increased from about 4 to 400 ml/h whereas kbile gradually decreased from about 0.057 to 0.007 (h-1). In conclusion, both hepatic uptake and biliary excretion of galactosylated proteins were found to be affected by the extent of galactosylation.     

Chronokinetics of Active Biliary Ampicillin Secretion in Rats

The existence of temporal variation in biliary excretion has been demonstrated for dibromosulfophthalein and ampicillin (AMP). This study was performed to investigate if the 24h rhythm of active AMP biliary secretion could be attributed to circadian rhythms in the capacity and/or binding affinity of the active secretion mechanism. In this study, 12 Sprague-Dawley rats, housed under a 12h light/12h dark environment, were used. Each rat four lh infusions of incremental doses of AMP during either the active (24: 00 group) or rest phase (12: 00 group) under pentobarbital anesthesia. High doses of AMP were administered to saturate the biliary secretion of AMP via the anion carrier system. Bile and plasma were collected at steady stale for each infusion and analyzed by a microbiological assay. The systemic clearance of AMP was increased approximately twofold during the active phase (24: 00 group) compared to the resting phase (12: 00 group). Plots of bile excretion rate versus plasma concentration indicated saturation of the anion carrier system. Analysis of the data using the Michaelis-Menten model revealed no significant difference in the binding affinity (1/Km) of the biliary anion carrier system between the 12: 00 and 24: 00 groups. However, the maximum AMP excretion rate attained in the bile (maximum transport or Vmax) showed a 50% increase during the active phase, thus implicating a day-night variation in transport capacity of the anionic pathway. Therefore, temporal variation in the capacity of the secretory mechanisms is a determinant contributor to the proposed circadian rhythm observed in the biliary elimination of AMP.     

Stereoselective biliary elimination of disopyramide and mono-N-desisopropyldisopyramide in humans.

The results of a previous pharmacokinetic study of disopyramide (DP) enantiomers in humans suggested that DP and/or mono-N-desisopropyldisopyramide (MND) may show stereoselective extrarenal elimination. Thus, the present study investigates the biliary elimination of DP and MND enantiomers in three patients who had undergone cholecystectomy for cholelithiasis. DP and MND enantiomers displayed biliary elimination. In both subjects, this elimination pathway showed the same characteristics: (1) biliary elimination of DP and MND was stereoselective, (2) the stereoselectivity was opposite to that observed for the metabolic and renal elimination pathways, i.e., the elimination of the (-)-(R)-enantiomer was higher than that of the (+)-(S)-enantiomer, and (3) biliary elimination of MND was higher than that of DP, for both enantiomers. Estimates of the relative contribution of the biliary clearance in the total clearance of DP and MND indicated that this elimination pathway was secondary, especially for DP. The biliary clearance (expressed as % of total clearance) was 1.9 to 4.0% for (-)-(R)-DP, 1.2 to 1.7% for (+)-(S)-DP, 7.8 to 22.9% for (-)-(R)-MND, and 5.2 to 10.5% for (+)-(S)-MND.     

Inhibition of the biosynthesis of uroporphyrinogen and heme in rat liver during obstructive jaundice produced by bile duct ligation

Altered hepatic microsomal drug metabolism has been reported to occur in afflicted with hyperbilirubinemia. Similarities of the chemical structures of hydroxymethylbilane, an intermediate in the biosynthesis of uroporphyrinogen, to bilirubin prompted investigations of the effect of bilirubin on the activity of uroporphyrinogen I synthase (porphobilinogen deaminase, EC 4.3.1.8) and the biosynthesis of heme. Bilirubin was found to be a reversible, noncompetitive inhibitor of uroporphyrinogen I synthase. The inhibition constant (Ki) for bilirubin was 1.5 microM. Bile acids had no effect on rat hepatic uroporphyrinogen I synthase activity. Hyperbilirubinemia was achieved in rats by biliary ligation in order to investigate whether elevated levels of bilirubin impair the biosynthesis of hepatic heme in vivo. The relative rate of heme biosynthesis, as measured by the rate of incorporation of delta-[4-14C]aminolevulinic acid into heme, was decreased 59% 24 h after biliary obstruction. The levels of hepatic microsomal heme and cytochrome P-450 were decreased by 43 and 40%, respectively, 72 h after biliary obstruction. The activities of hepatic delta-aminolevulinic acid synthase and uroporphyrinogen I synthase were increased by 39 and 46%, respectively, 72 h after biliary obstruction. During the 48- to 72-h period following biliary obstruction, the urinary excretion of porphobilinogen and uroporphyrin was increased 3.0- and 3.5-fold, respectively, whereas, the urinary excretion of delta-aminolevulinic acid was not altered. During this 48-to 72-h time interval following biliary obstruction, 100% of the uroporphyrin was excreted as isomer I. These results indicate that bilirubin is capable of depressing the biosynthesis of rat hepatic heme and thus cytochrome P-450-mediated drug metabolism by inhibition of the formation of uroporphyrinogen. These findings are a plausible mechanism for reports of impaired clearance of various drugs in patients afflicted with hyperbilirubinemic disease states.     

Dehydrophenylalanine derivatives as VLA-4 integrin antagonists

We describe a series of dehydrophenylalanine derivatives where the Z isomers are potent VLA-4 antagonists but are subject to rapid biliary clearance and the E isomers have poor activity but have a slower rate of clearance. These configurationally constrained molecules have led to the design of a novel class of benzodiazepine VLA-4 antagonists.