胆结石溶石疗法现状

胆结石溶石疗法现状李可为综述施维锦审校我国胆石症的发病率至少为自然人群的７％（１），近年有上升趋势。手术虽然有效，但大多数人更愿意接受保守治疗，其中溶石疗法历史最长，研究最多，在实验与临床上都已有了较为系统的了解。口服溶石１胆固醇结石溶解剂１．１胆酸...     

复方MTBE桔皮油乳剂对胆结石溶石的实验研究

本实验拟探讨自制复方MTBE桔皮油乳剂(COMO)对胆囊结石的溶石效果.实验方法 1.COMO由甲基三丁乙醚(MTBE)、环已烷二胺四乙酸(CDTA)及桔皮油为主要成分组成之复方乳剂.2.体外实验:将胆固醇和胆色素结石分为A、B、C三组,分别加入COMO、复方桔皮油乳剂Ⅱ及石蜡油乳剂,置室温下观察1周.3.动物实验:将健康家兔20只随机分为两组,将人胆色素钙结石植入兔胆囊内,通过胆囊置管A组注入COMO、B组注入复方桔皮油乳剂Ⅱ.观察各组实验前后结石重量变化,形态结构变化及毒副作用.     

肝内结石灌注溶石系列研究（20年科研总结）

本文对历经20年三代胆道结石灌注溶石药剂研究进行小结。采用一至三代药物复方胆汁酸钠、复方桔油乳剂及复方甲基叔丁醚对576例胆道结石进行灌注溶石治疗。结石消失率分别为43.41%、49.17%及41.72%。有效率分别为63.56%、86.95%和85.05%;副作用发生率分别为22.48%、11.39%和14.94%。溶石途径经过了初期的“T管”、T管(?)道改置“F管”发展至后期经皮肝穿留置气囊导管和十二指肠镜留置气囊鼻胆管等方法,全组随访438例(随访率76.04%)。结果表明:三代溶石药物均具有溶解胆固醇和色素结石的特点;置管方式和药物、结石特征等有关;ERBD气囊导管被认为是目前无损伤性理想的灌注溶石途径。     

胆结石碎石和溶石治疗现状

随着各种新技术的应用 ,胆结石的各种碎石和溶石方法相继问世。经过十多年的临床实践 ,在胆囊结石治疗上的应用已逐渐减少 ,而在胆管结石治疗上的应用 ,治疗方法日趋增多 ,适应证逐渐扩大 ,治疗病例越来越多 ,这是总的趋势。国内外文献上有关胆囊结石的碎石和溶石治疗的报道正在逐渐减少 ,除了各种治疗方法的本身缺点以外 (如口服药物溶石目前对中国人的疗效极差 ,灌注药物溶石的溶石剂对胆囊粘膜和肺有损伤、操作相当费时间 ,经皮胆镜碎石取石需行硬膜外麻醉 ,体外冲击波碎石需严格挑选病例、疗效较长等 ) ,结石复发问题是一大障碍。上海市…     

舒胆合剂对胆囊胆固醇结石的防治作用及机理

目的研究舒胆合剂对胆囊胆固醇结石有无预防及溶解作用,并初步探讨其机理。方法建立豚鼠胆囊胆固醇结石模型时,给予舒胆合剂,研究防石作用;建立模型后给予舒胆合剂,研究溶石作用。测定血、胆汁生化及肝、胆囊病理,探讨作用机理。结果防石组成石率（２１％）显著低于致石组（６７％）（Ｐ＜０．０１）;溶石组成石率（６０％）与致石组（６７％）无显著差异。防石及溶石组的肝脂肪变性均显著低于致石组。结论舒胆合剂有防石及缓解肝脂肪变性作用,但短期应用无溶石作用。     

电动振荡仪和溶石剂联合治疗胆道残石的护理

肝胆结石症是一种常见的多发病,以胆色素混合结石为主的胆石类型,手术常难以清除于净,术后胆道残余结石发生率国内达32.9～59.5％。我院消化外科1984～1988年应用电动振荡仪和溶石剂联合治疗胆道残石     

肝内胆管结石的溶石研究

肝内胆管结石的溶石研究大连医科大学（１１６０２７）裴德恺肝内胆管结石的治疗是甚为棘手的难题之一，其溶石研究虽受到一定的关注，但迄今仍处于探索阶段。近３０年来，国外有关胆石的溶石工作，曾取得了较大的进展。一系列的实验室及临床研究相继揭示，口服鹅去氧胆酸...     

胆总管巨大结石胆道塑料内支架"搅动溶石"作用临床研究

目的 评价胆道塑料内支架置入对胆总管巨大结石的搅动溶石作用.方法 常规方法行ERCP,对45例胆总管巨大结石病人(8例结石伴下端胆管狭窄、5例结石伴乳头过小),在导丝引导下放置8.5 Fr胆道塑料内支架治疗.结果 3个月后第2次ERCP检查时发现,10例结石消失;22例结石直径变小1/2以上或成碎片状经网篮或气囊扩张顺利取出;13例结石无明显变化,行更换塑料内支架治疗并每月腹部B型超声随访,一旦发现结石明显变小,即再次行ERCP+取石.经平均2.4次内镜下联合治疗,95.6%(43/45)病人结石取净.期间未发生与ERCP或放置胆道塑料内支架相关的严重并发症.结论 放置胆道塑料内支架是治疗胆总管巨大结石简便、有效方法,尤其适用于高危老年胆总管结石病人.     

临床预测胆石化学类型研究的进展

随着非手术疗法胆石症的进展,治疗前确定胆石化学类型变得十分重要。口服鹅去氧胆酸(CDCA)/熊去氧胆酸(UDCA)溶石,胆囊/胆道内灌注甲基叔丁基醚溶石都仅适用于胆固醇类结石;而有些溶石剂只适用于胆色素结石。经皮经肝穿刺胆囊/胆道插管溶石是一种侵入性治疗,治疗前必需对胆石性质了解清楚。为提高体外冲击波碎石的疗效,在碎石前后辅以CDCA/CDCA口服溶石,也只对胆固醇类结石起作用。治疗失败的主要原因是治疗前未能确切了解胆结石的化学类型。随着医学影象技术的发展,很多学者正在各领域寻求一种准确而又简便的方法,以便在溶石、碎石治疗前能判断患者结石化学类型,选择病例,以提高疗效。兹分别综述如下:     

"友来特"对输尿管尿酸结石的排石促进作用

目的探讨尿液碱化剂"友来特"对输尿管尿酸结石排石治疗的促进作用.方法输尿管尿酸结石45例,其中男28例,女17例.结石大小为0.5～1.0 cm,平均0.7 cm.经腹部平片、静脉肾盂造影、逆行肾盂造影、螺旋CT及血、尿生化检查确诊.随机分成溶石排石组和单纯排石组.前者23例,口服"排石冲剂"的同时加服"友来特"(枸橼酸氢钾钠颗粒剂),调整尿液pH值至6.8,每日监测尿液pH值3次;后者22例,单纯服用"排石冲剂",疗程均为1个月.比较两组的排石成功率和平均排石时间.结果溶石排石组和单纯排石组分别排石18例和11例,排石成功率分别为78.3%和50.0%,两组排石成功率差异有统计学意义(P<0.05).溶石排石组平均排石时间(17±6)d较单纯排石组(22±7)d明显缩短,差异有统计学意义(P<0.05).结论尿液碱化剂"友来特"能显著提高输尿管尿酸结石的排石成功率,缩短排石时间.作用机制可能与"友来特"对尿酸结石的溶解作用有关.     

Methyl-tert-butyl-ether for treating bile duct stones: the British experience

Methyl-tert-butyl-ether (MTBE), infused via a nasobiliary catheter, was used to treat 33 patients with bile duct stones in nine units around Britain. MTBE contributed to success in 12 (36 per cent) cases: seven passed stones spontaneously during MTBE infusion and five had partial stone dissolution allowing subsequent endoscopic extraction. MTBE was non-contributory in 21 (64 per cent) cases: four passed stones after MTBE was stopped, six were treated by subsequent endoscopic techniques without evidence of dissolution, seven underwent surgery, and four were treated conservatively (with one death). In at least ten of the 21 cases in which MTBE was non-contributory, pigment stones were present. Forty-two complications occurred in 26 (79 per cent) patients. The efficacy of MTBE for treating bile duct stones might be improved by better methods of instillation and, since success may be related to technique, the use of MTBE should be restricted to units familiar with this chemical.     

人两种胆囊结石的胆汁差异蛋白质组学研究

目的 比较胆固醇性与胆色素性胆囊结石患者的胆囊胆汁蛋白质表达谱差异,寻找两种不同胆囊结石形成及调控相关的蛋白质.方法 采集胆囊结石患者胆囊胆汁及结石,结石胆固醇比例＞70%入选胆固醇结石组,胆色素比例＞40%入选胆色素结石组.胆汁予脱盐、脱脂等预处理后,二维色谱/串联质谱分析,Mascot检索数据库.结果 分别从胆固醇和胆色素结石胆汁中鉴定出495和511种蛋白质.两组共检测到抗成核因子1种,促成核因子12种,其中Mucin-5B等两种蛋白在胆固醇组高表达,载脂蛋白A-I等11种蛋白在胆色素组高表达.结论 二维色谱/串联质谱技术是高效的人胆汁蛋白质组研究技术.两组胆汁的蛋白质差异表达提示两种结石的形成机制差异,胆色素结石形成与促成核因子密切相关,载脂蛋白A-I抗成核作用减弱参与胆固醇结石形成.

Abstract：

Objective By comparing gallbladder bile samples from cholesterol cholelithiasis patients with pigment cholelithiasis patients, we try to find out proteins participating in gallstone formation for revealling two kinds of stone formation mechanisms. Methods Gallstones and bile were collected from cholelithiasis patients. These patients were divided into two groups by stone chemical compositon analysis.Patients with stone cholesterol levels greater than 70% were assigned into cholesterol stone group, and those with bilirubin levels greater than 40% into pigment stone group. After removing the bile salt and lipid, peptide fragments were separated by 2D-LC, analysed by MS/MS, and searched against Swiss Prot database by Mascot. Results There were 495 and 511 proteins identified from cholesterol stone group and pigment stone group respectively. There was 1 anti-nucleation factor and 12 pro-nucleation factors, including 2 proteins up-regulated in cholesterol stone group and 11 proteins down-regulated in pigment stone group. Conclusion 2D-LC/MS/MS is an efficient technology in bile proteomics research. Differentially expressed proteins reveal 2 kinds of different stone formation mechanisms. Pro-nucleation factors are closely related with pigment stone formation, while down-regulation of apolipoprotein A- I is closely related with cholesterol stone formation.     

Fragmentation of biliary stones with a 308 nm excimer laser

The use of a XeCl excimer laser (308 nm) for biliary stone fragmentation is reported. Laser energy is delivered via UV grade fused silica fibers to the target stones immersed in normal saline solution. Sixty biliary calculi--pigment (n = 40), and cholesterol (n = 20)--were fragmented in vitro. The total energy delivered per unit mass of the stone is kept constant. Two energy fluences (80 and 110 mJ/mm2) at two repetition rates (5 and 20 Hz) delivered through fibers of two core sizes (300 and 600 microns) are utilized to study the effect of different laser parameters on the fragmentation process. Although both pigment and cholesterol stones are susceptible to excimer laser fragmentation, higher fragmentation efficiency is obtained for the pigment stones than for the cholesterol stones. Our study suggests that higher energy fluence and larger fiber core size result in higher fragmentation efficiency for pigment stones. Fragmentation thresholds at stone surface for a variety of biliary calculi of known composition were measured. The threshold energy fluence is approximately 3 mJ/mm2 and 17 mJ/mm2 for pigment and cholesterol stones, respectively. Our study indicates that the 308 nm excimer laser may be effective as a laser lithotriptor with low threshold and good efficiency for biliary stone fragmentation.     

基于胆汁泡相糖蛋白特征而研制诊断胆结石ELISA药盒的可行性分析

目的:分析胆汁泡相糖蛋白的特征并评估其ELISA药盒临床应用的可行性。方法:应用凝集素探针介导的点印迹法分析泡蛋白糖链的组成与结构,利用酶解方法测定泡蛋白各组分的构成,并分析其氨基酸组成。利用Westernblot法分析胆汁与血清泡蛋白的同源性,根据ELISAkit测定泡蛋白的含量分布,并以ROC曲线判别ELISAkit的临床应用价值。结果:化学分析泡蛋白由多肽和寡糖组成,其中多肽分子量约为21u,糖链约占总蛋白含量的37.3%,为核心岩藻糖丰富的多天线复杂型聚糖。泡蛋白具胆汁与血清分布两相性,胆固醇性结石组胆囊胆汁和血清33.5u泡蛋白含量分别为(213.4±70.1)μg/ml、(179.8±97.9)μg/ml,明显高于胆色素性结石症组和正常对照组(P<0.05),而后两者间差异无显著性(P>0.05)。ELISAkit判断胆固醇性结石的胆汁相敏感度和特异度分别为85%和90%,而血清相为61.7%和93.3%。结论:胆汁泡蛋白是一种新认识的胆结石促成核因子,其在不同人群中具有表达谱的异质性,ELISAkit辅助诊断胆石症具有一定的临床应用价值,但尚需更多病例的积累和验证。     

Bacteria Entombed in the Center of Cholesterol Gallstones Induce Fewer Infectious Manifestations than Bacteria in the Matrix of Pigment Stones

Purpose The clinical significance of bacteria in the pigment centers of cholesterol stones is unknown. We compared the infectious manifestations and characteristics of bacteria from pigment stones and predominantly cholesterol stones. Methods Three hundred forty patients were studied. Bile was cultured. Gallstones were cultured and examined with scanning electron microscopy. Level of bacterial immunoglobulin G (bile, serum), complement killing, and tumor necrosis factor-alpha production were determined. Results Twenty-three percent of cholesterol stones and 68% of pigment stones contained bacteria (P < 0.0001). Stone culture correlated with scanning electron microscopy results. Pigment stone bacteria were more often present in bile and blood. Cholesterol stone bacteria caused more severe infections (19%) than sterile stones (0%), but less than pigment stone bacteria (57%) (P < 0.0001). Serum and bile from patients with cholesterol stone bacteria had less bacterial-specific immunoglobulin G. Cholesterol stone bacteria produced more slime. Pigment stone bacteria were more often killed by a patient’s serum. Tumor necrosis factor-alpha production of the groups was similar. Conclusions Bacteria are readily cultured from cholesterol stones with pigment centers, allowing for analysis of their virulence factors. Bacteria sequestered in cholesterol stones cause infectious manifestations, but less than bacteria in pigment stones. Possibly because of their isolation, cholesterol stone bacteria were less often present in bile and blood, induced less immunoglobulin G, were less often killed by a patient’s serum, and demonstrated fewer infectious manifestations than pigment stone bacteria. This is the first study to analyze the clinical relevance of bacteria within cholesterol gallstones. This paper was presented at the American Hepato-Pancreato-Biliary Association meeting last March 2006.     

Computed tomographic analysis of gallstones. An in vitro study

The chemical dissolution of gallstones cannot be accurately predicted since available biliary studies often do not distinguish stone types. To elucidate the predictive value of computed tomography (CT), 65 gallstones were studied in vitro. Thirty stones were analyzed by both CT and infrared spectroscopy. The CT number (Hounsfield unit [HU]) was significantly different for cholesterol and pigment stones (-87.3 +/- 14.5 vs 162 +/- 27.6 HU) and demonstrated a linear correlation with cholesterol content. Another 35 gallstones were tested for dissolution in a 200 mM chenodeoxycholate solution after CT analysis. Thirteen stones (50%) with CT values less than 50 HU completely dissolved in three weeks, whereas none of the stones with CT numbers greater than 50 HU dissolved. These findings suggest that the CT analysis of gallstones allows accurate gallstone classification and is useful in predicting solubility.     

Fragmentation of human gallstones using ultrasound and electrohydraulic lithotripsy: experimental and clinical experience

In vitro fragmentation of gallstones was performed by means of ultrasound (n = 89) and electrohydraulic lithotripsy (n = 83) with success rates of 100% and 93%, respectively. The fragmentation time was 21.9 +/- 52 seconds (mean +/- SEM) for ultrasound and 2.5 +/- 3.4 seconds for electrohydraulic lithotripsy. The energies required were similar to those used safely in the fragmentation of renal and bladder stones. Fragmentation was not related to the composition of the gallstones; there was no statistical difference between the fragmentation times or rates (p greater than 0.05) in cholesterol stones and pigment stones by either method. Fragmentation time was linearly related to gallstone weight for both methods. Comparison of ultrasound and electrohydraulic lithotripsy, using the two-way analysis of variance model, revealed no statistical difference between the two methods in times and rates of fragmentation (p greater than 0.05). Both ultrasound and electrohydraulic lithotripsy offer distinct advantages over the dissolution of gallstones by chemical methods because they are rapid and independent of gallstone composition. In vivo fragmentation of a large pigment common duct stone was also accomplished by means of an electrohydraulic lithotriptor. The stone was discovered in a 79-year-old patient on post-operative T-tube cholangiogram. Chemical analysis of the gallstones removed from the patient during cholecystectomy had revealed a very low cholesterol content. Since the remaining stone could not be dissolved and was too large to be mechanically extracted, it was fragmented through a T-tube, under fluoroscopic guidance and the small fragments were extracted with a dormia basket. The electrohydraulic lithotriptor was selected because it has a flexible probe.     

检测胆囊结石胆汁中L型细菌的研究及其意义

目的 探讨L型细菌在胆囊结石、胆囊炎发病中的意义。方法 应用高渗培养技术对130例胆囊结石、胆囊炎及20例非胆道疾病的患者胆囊胆汁标本进行普通菌及L型菌联合培养。结果 L型菌总检出率胆囊疾病组为59.2%,对照组为5.0%;胆囊结石胆汁中,检出率最高为胆色素类结石（88.9%),其次为混合性胆石（80.0%)、胆固醇结石（54.8%)和黑色结石（50.0%);多发结石明显高于单个结石,随年龄增加,其感染检出率增高。结论 L型菌感染可能在胆囊结石、胆囊炎发生发展中有重要意义。临床上应重视其检测和治疗。     

Percutaneous catheter dissolution of cystine calculi

In 11 kidneys with presumed cystine stones that were symptomatic and obstructing, percutaneous nephrostomy and stone lavage with either acetylcysteine-bicarbonate solution or tromethamine-E were performed. There were 7 complete stone dissolutions: 2 of 6 attempts with acetylcysteine-bicarbonate alone, 3 of 5 with tromethamine-E, 1 partial with acetylcysteine-bicarbonate, which was completed with tromethamine-E, and 1 proved mixed stone (cystine and calcium phosphate) that required acetylcysteine-bicarbonate and hemiacidrin. In 1 case tromethamine-E irrigation was 97 per cent complete but a few tiny caliceal fragments remained. There were 3 failures of chemolysis: 2 pure cystine stones (1 each acetylcysteine-bicarbonate and tromethamine-E) and 1 mixed calculus with a surface shell of calcium oxalate. Irrigation time was 6 to 42 days for the 7 unoperated kidneys. Tromethamine-E appears to be a more effective agent for cystine stone dissolution. Percutaneous nephrostomy and dissolution are an alternative to an operation in patients with cystine calculous disease.