腹腔镜联合胆道镜与小切口微创保胆手术治疗胆囊结石的对照研究

目的:探讨腹腔镜联合胆道镜与小切口微创保胆手术治疗胆囊结石的疗效。方法:选择2013年1月-2013年10月我院胆囊结石患者80例为研究对象,其中采用腹腔镜联合胆道镜治疗40例设为腹腔镜组,采用小切口微创保胆手术40例设为小切口组,比较2组术中、术后恢复情况。结果:腹腔镜组切口小、术中出血量少、术后胃肠功能恢复快、疼痛轻、术后住院时间短,与对照组比较,差异均有统计学意义(P0.05)。结论:腹腔镜联合胆道镜下保胆取石术具有伤小、恢复快、并发症少等优点,临床应优先于小切口手术使用。     

腹腔镜联合胆道镜微创手术与开腹手术治疗胆囊结石合并胆总管 结石的疗效比较

目的:比较分析腹腔镜联合胆道镜微创手术与开腹手术治疗胆囊结石合并胆总管结石的疗效。方法:将2009年10月-2011年5月因胆囊结石合并胆总管结石行手术治疗的100例患者,分为微创手术组和开腹手术组,分析比较微创手术组与开腹手术组之间患者的手术时间、术后通气所需时间与镇痛药使用情况、住院时间与完全康复时间。结果:与开腹组相比:微创组患者的手术时间之间无明显差异;但微创组术后通气时间。住院时间与完全康复时间、镇痛药的使用率均明显短于或低于开腹组(P<0.05)。结论:对合适的患者,腹腔镜联合胆道镜微创手术入路治疗胆囊结石合并胆总管结石能够获得良好的效果,值得借鉴。     

腹腔镜联合胆道镜治疗胆囊息肉合并胆囊结石的临床效果

目的:探讨腹腔镜联合胆道镜治疗胆囊息肉并发胆囊结石的临床成效及并发症。方法:选取我院肝胆外科收治的胆囊息肉并发胆囊结石患者92例,随机分为两组。其中对照组46例,行传统开腹手术治疗;实验组46例,行腹腔镜联合胆道镜保胆手术治疗。对比两组患者手术平均时间、术中出血量、术后排气时间、术后下床活动时间、平均住院时间以及术后并发症发生率。结果:1实验组手术时间明显长于对照组,实验组患者术中出血量、术后排气时间、术后下床活动时间、平均住院时间明显较对照组明显缩短,差异有统计学意义(P0.05);2实验组术后并发症发生率(6.52%)明显低于对照组(16.67%),差异有统计学意义(P0.05)。结论:腹腔镜联合胆道镜治疗胆囊息肉并发胆结石能够明显减少患者术中出血量,缩短术后排气时间、术后下床活动时间、平均住院时间,降低术后并发症发生率,有利于提高临床疗效,改善预后,对临床具有指导意义。     

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。     

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。     

腹腔镜和胆道镜及十二指肠镜联合治疗急性梗阻性化脓性胆管炎的临床研究

目的:探讨腹腔镜和胆道镜及十二指肠镜联合治疗急性梗阻性化脓性胆管炎(AOSC)的临床效果。方法:选取2007年3月~2014年3月我院收治的100例AOSC患者,根据手术方法的不同与患者的意愿分为研究组50例与对照组50例,研究组采用腹腔镜和胆道镜及十二指肠镜联合治疗,对照组采用开腹胆囊切除及胆道探查术。观察两组的生化指标、术后并发症、切口感染率、术后残石率。结果:研究组白细胞计数(WBC)、血直接胆红素(DBIL)、丙氨酸转氨酶(ALT)、谷氨酰转肽酶(GT)、天冬氨酸转氨酶(AST)明显低于对照组(P0.05)。研究组术后并发症、切口感染明显少于对照组(P0.05)。两组术后1年残石比较差异无统计学意义(P0.05)。结论:腹腔镜和胆道镜及十二指肠镜联合治疗AOSC患者具有创伤小、愈合恢复快、并发症发生率低、预后好等优点。     

肝外胆管结石微创治疗的研究进展

肝外胆管结石是肝胆外科临床常见病,严重威胁患者健康。目前该病治疗主要以手术治疗为主,以往的手术方式主要以剖腹胆总管切开取石为主,但创伤较大,恢复较慢,后遗症较多。随着微创技术的发展,腹腔镜、胆道镜及十二指肠镜等微创治疗技术以其创伤小、恢复快等优势越来越多的被肝外胆管结石患者采用。微创治疗肝外胆管结石的方法也日趋多样化,如经消化内镜治疗,经腹腔镜治疗,腹腔镜联合消化内镜治疗及腹腔镜、胆道镜、十二指肠镜三镜联合治疗等。本文就肝外胆管结石治疗中各种微创技术的研究进展做一综述。     

腹腔镜治疗胆囊结石合并胆总管结石的临床研究

目的:探讨腹腔镜手术治疗胆囊及胆总管结石的应用价值.方法:90例胆囊结石合并胆管结石患者按手术方式随机分为腹腔镜胆道探查术组(简称:腹腔镜组)和常规开腹胆道探查T管引流术组(简称:常规开腹组).观察两组手术切口大小、并发症、胃肠道功能恢复时间和平均住院时间等指标.结果:腹腔镜组术后并发症发生率为2.2%,显著低于常规开腹组(15.9%)(P<0.05);腹腔镜组手术切口显著小于常规开腹组(P<0.05);腹腔镜组术后胃肠道功能恢复时间和平均住院时间与对照组比较显著缩短,相比较有显著性差异(P<0.05).结论:应用腹腔镜治疗胆囊结石合并胆总管结石是一种安全、有效、可行的微创手术方式.     

依泽替米贝辅助腹腔镜微创术联合治疗胆囊结石患者对炎性因子及血清CCK-A表达的影响

目的:探讨依泽替米贝辅助腹腔镜微创术联合治疗胆囊结石患者对炎性因子及胆囊收缩素A(Cholecystokinin-A,CCK-A)表达的影响。方法:以2016年2月-2018年2月我院收治的100例胆囊结石患者作为研究对象,按随机数字表法分为对照组(腹腔镜微创术)和观察组(腹腔镜微创术+依泽替米贝),每组各50例。观察并比较治疗前后两组患者临床疗效、胆囊结石数量和直径的变化、炎性因TNF-α、IL-1水平以及血清CCK-A水平的变化。结果:术后观察组感染2例,胰腺炎1例,观察组发生感染3例,两组患者并发症发生情况差异无统计学意义(P<0.05),观察组患者的治疗有效率明显高于对照组(94.0%vs 58.0%)(P<0.05);治疗前两组患者胆囊结石平均数量、直径差异无统计学意义(P>0.05),治疗后观察组和对照组患者胆囊结石数量(5.16±2.35 vs9.18±2.82)、直径(0.78±0.29 cm vs 1.26±0.36 cm)明显降低,观察组低于对照组(P<0.05);治疗前两组患者血清TNF和IL-1水平无明显差异(P>0.05),治疗后观察组和对照组患者血清TNF-α[15.28±4.28(ng/mg)vs 22.19±5.02(ng/mg)]、IL-1[63.38±8.27(μg/mg)vs 89.59±7.39(μg/mg)]水平明显降低,且观察组明显低于对照组(P<0.05);治疗前两组患者血清CCK-A水平无明显差异(P>0.05),治疗后观察组和对照组患者血清CCK-A水平[121.36±10.47(ng/mg)vs 115.39±10.39(ng/mg)]明显升高,且观察组高于对照组(P<0.05)。结论:依泽替米贝辅助腹腔镜微创术能有效减少胆囊结石患者的结石数量、降低结石直径,并且可以降低患者血清炎性因子水平,促进CCK-A表达,减轻胆囊炎症反应,缓解患者痛苦,有较好的临床效果。     

腹腔镜联合硬质胆道镜治疗复发性肝胆管结石的临床应用

目的:观察腹腔镜联合硬质胆道镜治疗复发性肝胆管结石的临床应用。方法:选取2013年1月-2014年1月期间在广州医科大学附属第一医院治疗的复发性肝胆管结石患者64例,随机分为研究组和对照组,研究组患者给予腹腔镜联合硬质胆道镜治疗,对照组患者采取开腹治疗。观察并比较两组患者的临床效果。结果:研究组患者手术出血量、手术时间、肛门排气时间、术后胆红素恢复时间、平均住院时间和抗生素应用时间均少于或短于对照组,差异均有统计学意义(均P0.05);研究组患者术后发生感染、胆漏、出血、结石残余与对照组比较差异均无统计学意义(均P0.05);研究组患者术后疼痛3例显著高于对照组的15例(P0.05)。结论:腹腔镜联合硬质胆道镜治疗复发性肝胆管结石对患者损伤小、手术过程中出血量少、结石取出率高、残留可能性小、结石复发率低、术后恢复快、并发症发生率低,其可行性和安全性高,适应范围广,值得推广应用。     

Histone H3K4 trimethylation by MLL3 as part of ASCOM complex is critical for NR activation of bile acid transporter genes and is downregulated in cholestasis

The nuclear receptor Farnesoid x receptor (FXR) is a critical regulator of multiple genes involved in bile acid homeostasis. The coactivators attracted to promoters of FXR target genes and epigenetic modifications that occur after ligand binding to FXR have not been completely defined, and it is unknown whether these processes are disrupted during cholestasis. Using a microarray, we identified decreased expression of mixed lineage leukemia 3 (MLL3), a histone H3 lysine 4 (H3K4) lysine methyl transferase at 1 and 3 days of post-common bile duct ligation (CBDL) in mice. Chromatin immunoprecipitation analysis (ChIP) analysis revealed that H3K4me3 of transporter promoters by MLL3 as part of activating signal cointegrator-2 -containing complex (ASCOM) is essential for activation of bile salt export pump (BSEP), multidrug resistance associated protein 2 (MRP2), and sodium taurocholate cotransporting polypeptide (NTCP) genes by FXR and glucocorticoid receptor (GR). Knockdown of nuclear receptor coactivator 6 (NCOA6) or MLL3/MLL4 mRNAs by small interfering RNA treatment led to a decrease in BSEP and NTCP mRNA levels in hepatoma cells. Human BSEP promoter transactivation by FXR/RXR was enhanced in a dose-dependent fashion by NCOA6 cDNA coexpression and decreased by AdsiNCOA6 infection in HepG2 cells. GST-pull down assays showed that domain 3 and 5 of NCOA6 (LXXLL motifs) interacted with FXR and that the interaction with domain 5 was enhanced by chenodeoxycholic acid. In vivo ChIP assays in HepG2 cells revealed ligand-dependent recruitment of ASCOM complex to FXR element in BSEP and GR element in NTCP promoters, respectively. ChIP analysis demonstrated significantly diminished recruitment of ASCOM complex components and H3K4me3 to Bsep and Mrp2 promoter FXR elements in mouse livers after CBDL. Taken together, these data show that the "H3K4me3" epigenetic mark is essential to activation of BSEP, NTCP, and MRP2 genes by nuclear receptors and is downregulated in cholestasis.     

Vectorial transport of unconjugated and conjugated bile salts by monolayers of LLC-PK1 cells doubly transfected with human NTCP and BSEP or with rat Ntcp and Bsep

Na(+)-taurocholate-cotransporting peptide (NTCP)/SLC10A1 and bile salt export pump (BSEP)/ABCB11 synergistically play an important role in the transport of bile salts by the hepatocyte. In this study, we transfected human NTCP and BSEP or rat Ntcp and Bsep into LLC-PK1 cells, a cell line devoid of bile salts transporters. Transport by these cells was characterized with a focus on substrate specificity between rats and humans. The basal to apical flux of taurocholate across NTCP- and BSEP-expressing LLC-PK1 monolayers was 10 times higher than that in the opposite direction, whereas the flux across the monolayer of control and NTCP or BSEP single-expressing cells did not show any vectorial transport. The basal to apical flux of taurocholate was saturated with a K(m) value of 20 microM. Vectorial transcellular transport was also observed for cholate, chenodeoxycholate, ursodeoxycholate, their taurine and glycine conjugates, and taurodeoxycholate and glycodeoxycholate, whereas no transport of lithocholate was detected. To evaluate the respective functions of NTCP and BSEP and to compare them with those of rat Ntcp and Bsep, we calculated the clearance by each transporter in this system. A good correlation in the clearance of the examined bile salts (cholate, chenodeoxycholate, ursodeoxycholate, and their taurine or glycine conjugates) was observed between transport by human and that of rat transporters in terms of their rank order: for NTCP, taurine conjugates > glycine conjugates > unconjugated bile salts, and for BSEP, unconjugated bile salts and glycine conjugates > taurine conjugates. In conclusion, the substrate specificity of human and rat NTCP and BSEP appear to be very similar at least for monovalent bile salts under physiological conditions.     

腹腔镜下胆道镜经胆囊管行胆道探查取石术的临床分析

目的：探讨腹腔镜下胆道镜经胆囊管行胆道探查取石术（LTCBDE）的可行性以及安全性。方法：124 例胆囊合并胆总管结石 患者,根据手术方式分为LTCBDE 组和腹腔镜胆总管切开取石T管引流术（LCTD组）,各62 例,比较两组的手术情况、疗效及安 全性。结果：LTCBDE 的手术时间、术后引流时间、肛门排气时间、术后住院时间及补液量较LCTD 组显著减少（P<0.05）;LTCBDE 组并发症发生率及复发率分别为3.23%、1.61%,显著低于LCTD 组的20.97%、11.29%（P<0.05）。结论：LTCBDE 创伤小、患者痛 苦少、术后恢复快、并发症少且复发率低,是治疗胆囊结石合并胆总管结石的一种安全可行的微创治疗手段,值得在临床中推广 应用。     

Suppression of BSEP and MRP2 in mouse liver by miroestrol and deoxymiroestrol isolated from Pueraria candollei

Miroestrol and deoxymiroestrol are highly active phytoestrogens isolated from the tuberous root of Pueraria candollei var. mirifica (Leguminosae). Modulatory effects of miroestrol and deoxymiroestrol on the mRNAs of BSEP and MRP2 genes involved in bile salt transportation, in C57BL/6 mice were investigated. In contrast to estradiol, miroestrol and deoxymiroestrol suppressed the expression of BSEP and MRP2 mRNA in both male and female mice. The results suggest for the first time that the use of miroestrol and deoxymiroestrol-containing products as alternative medicines or health supplements should be concerned according to their effects on key genes that regulate the bile salt export pump, which could result in the risk of hepatotoxicity and intrahepatic cholestasis.     

Evaluation of the Endothelin Receptor Antagonists Ambrisentan,Bosentan, Macitentan,and Sitaxsentan as Hepatobiliary Transporter Inhibitors and Substrates in Sandwich-Cultured Human Hepatocytes

Background

Inhibition of the transporter-mediated hepatobiliary elimination of bile salts is a putative mechanism for liver toxicity observed with some endothelin receptor antagonists (ERAs).

Methods

Sandwich-cultured human hepatocytes were used to study the hepatobiliary distribution and accumulation of exogenous taurocholate, ERAs and endogenous bile acids. The molecular mechanisms for findings in hepatocytes or clinical observations were further explored using either vesicular assays (efflux transporters) or transfected cell-lines (uptake transporters). Inhibition constants (IC₅₀) were measured for the human hepatobiliary transporters bile salt export pump (BSEP), sodium taurocholate cotransporting polypeptide (NTCP), multidrug resistance protein 2 (MRP2), P-glycoprotein (Pgp), breast cancer resistance protein (BCRP), organic anion-transporting polypeptide 1B1 (OATP1B1) and OATP1B3.

Results

The ERAs showed dose-dependent reductions in exogenous taurocholate cellular accumulation in human hepatocytes, with macitentan having the greatest effect. Consistent with their effects on bile acids, the ERAs inhibited bile transporters. IC₅₀ values for OATP1B1 and OATP1B3 ranged from 2 µM for macitentan to 47 µM for ambrisentan. Macitentan and bosentan also inhibited NTCP with IC₅₀ values of 10 and 36 µM, respectively. Similar to previously reported findings with sitaxsentan, BSEP inhibition was observed for bosentan and macitentan with IC₅₀ values of 42 and 12 µM, respectively. In contrast, ambrisentan showed little or no inhibition of these transporters. Other transporters tested were weakly inhibited by the ERAs. Accumulation in hepatocytes was also a factor in the effects on bile transport. Macitentan demonstrated the greatest accumulation in human hepatocytes (∼100x) followed by sitaxsentan (∼40x), bosentan (∼20x) and ambrisentan (∼2x).

Conclusions

Significant differences in the inhibition of hepatic transporters were observed between the evaluated ERAs in vitro. Macitentan had the highest level of cellular accumulation and caused the greatest effects on bile acid distribution in human hepatocytes followed by sitaxsentan and bosentan. Ambrisentan showed a low potential to affect bile acids.