Unconjugated bilirubin in hepatic bile with brown pigment gallstones and cholangitis

To investigate the role of cholangitis in hydrolysis of bilirubin in bile with brown pigment gallstones, bilirubin composition and bacterial growth in hepatic bile with and without cholangitis were studied. The study included 38 brown pigment gallstone cases (28 without cholangitis and 10 with cholangitis). The proportion of unconjugated bilirubin in hepatic bile with cholangitis (16.9±8.5%, mean ± SD) was significantly higher than that without cholangitis (3.7±1.8%, P<0.001. A positive correlation was found between bacterial population with -glucuronidase activity and the proportion of unconjugated bilirubin in bile in cases of brown pigment stones with cholangitis P<0.05) but not in those without cholangitis despite the fact that bacterial species and population are similar regardless of the presence of cholangitis. In cholangitis, pH of bile becomes lower toward the optimal pH of bacterial -glucuronidase. Together the lower concentration of bile acid and the lower pH in bile result in lower solubility of unconjugated bilirubin, promoting its precipitation. Thus occasional bouts of cholangitis may result in periodic deposition of bilirubinate on brown pigment stones with layered structures by inducing cyclic changes of bile composition in situ.     

胆囊胆固醇结石患者肝脏受体类似物1基因表达差异的研究

目的研究胆囊胆固醇结石患者肝脏受体类似物1(LRH-1)表达,探讨其与胆固醇结石病发病的关系。方法27例胆囊胆固醇结石患者,男6例,女21例,平均年龄52．44岁。14例无胆石症者为对照(肝脏肿瘤2例,胆囊息肉患者12例),男9例,女5例,平均年龄47．50岁。测定胆汁脂类成分和计算胆汁胆固醇饱和指数。实时定量PCR法测定肝脏LRH-1 mRNA的表达量。结果胆石组LRH-1表达14．18±9．37,高于对照组7．86±6．19,(P＜0．05),胆石组胆汁呈胆固醇过饱和(1．17±0．27)。结论本研究提示肝脏LRH-1表达增高与胆囊胆固醇结石病有关。     

Bile acid synthesis is increased in Chilean Hispanics with gallstones and in gallstone high-risk Mapuche Indians

BACKGROUND & AIMS: Gallstone disease is an important, costly health-care problem in Western societies. It is still unclear whether hepatic lipid regulatory enzymes play primary or secondary roles in gallstone formation. In this study, the aim was to investigate whether the synthesis of bile acids and cholesterol is increased in gallstone disease and to test whether such a metabolic change, if present, might occur before gallstone formation. METHODS: A total of 125 Chilean Hispanic women (80 without gallstones and 45 with gallstones) matched for age and body mass index were investigated, along with 40 Chilean Mapuche Indian women (20 without gallstones and 20 with gallstones), a population group in which the prevalence for gallstone disease is very high. Fasting blood plasma samples were assayed for 7 alpha-hydroxy-4-cholesten-3-one and lathosterol, 2 strong indicators for hepatic bile acid and body cholesterol synthesis, respectively. RESULTS: Plasma 7 alpha-hydroxy-4-cholesten-3-one levels, corrected for plasma cholesterol, were significantly increased by 50% in Hispanic women with gallstones as compared with gallstone-free Hispanics (P < 0.006). As compared with Hispanic women without gallstones, plasma 7 alpha-hydroxy-4-cholesten-3-one levels were increased by > or =100% (P < 0.002) in Mapuche Indian women, independently of whether gallstones were present. Plasma lathosterol, corrected for plasma cholesterol, was significantly increased by 22% in Hispanic women with gallstones and in Mapuche Indian women compared with Hispanic women. CONCLUSIONS: The results indicate that the synthesis of bile acids and cholesterol is induced in gallstone disease and precedes gallstone development. These inductions presumably occur as a response to an increased intestinal loss of bile acids.     

腹腔镜胆囊切除术治疗复杂性胆囊结石的评价

为了评价腹腔镜胆囊切除术（ＬＣ）治疗复杂性胆囊结石的有效性和安全性，本文对比分析了手术时间、中转开腹手术率、并发症发生率和住院时间等项指标。结果表明，单纯组和复杂组平均手术时间分别为３１．６和４５．７分钟（Ｐ＜０．０５）；中转开腹手术率分别为１．０％和７．４％（Ｐ＜０．０１）；住院时间复杂组长于单纯组。单纯组９９％的病人、复杂组９０％以上的患者能够采用ＬＣ治愈。两组术后并发症发生率无显著差异。两组总中转开腹手术率为２．７％。本文结果提示，ＬＣ用于治疗伴有各种并发症的复杂性胆囊结石是可行的，同样可以保留和体现出它的优越性。     

用Logistic回归模型预测胆固醇结石易患人群

采用Ｌｏｇｉｓｔｉｃ回归模型对胆固醇结合高危人群的筛选进行了初步的尝试。对胆囊的形态学和动力学以及血清生化各种指标进行优化组合。５７例胆固醇结石病人和１７２例健康对照者用作建立模型，对有高血压史但无胆石的６８例，用来作胆固醇结石前瞻性预测。根据模型判别得出，男组５２例中有成石危险的３３例，女且１６例中有危险的计划１０例。２４至３０个月后Ｂ超复查发现其中７例新发胆石，发病率为１０％，预测正确率达７１     

Effect of laser fragmentation of cholesterol and mixed gallstones onin vitro dissolution in methyltert-butyl ether

This study examined cholesterol and mixed gallstone dissolution in vitroby methyltert-butyl ether (MTBE) after gallstone fragmentation. Three morphologically identical gallstones were obtained from 42 patients. One stone from each patient was fragmented with laser energy at a wavelength of 504 nm delivered to the stone surface with a 320-m quartz fiber. Intact and fragmented stones from the same patient were incubated without stirring in MTBE and dissolution was expressed as the percent of initial stone weight remaining after 2 hr. Stone composition did not correlate with the amount of laser energy required for stone fragmentation. Fragmented stones dissolved faster than intact stones in MTBE with 13.97%±0.37% vs 31.0%±0.51% respectively (mean±SEM) of initial stone weight remaining at 2 hr (P<0.0001). Initial stone weight and stone matrix content significantly predicted dissolution of intact (P=0.0033 and P=0.0483, respectively) and fragmented stones (P=0.003 and P=0.0001, respectively) in MTBE. These data suggest that the gallstone matrix may inhibit stone dissolution even after stone fragmentation.Dr. Smith was supported by NIH grant DK39107.A portion of this work appeared in abstract form in Gastroenterology 94:A577, 1988, and was presented at the annual meeting of the American Gastroenterological Association in New Orleans, May 1988.     

Investigation of the Lith6 candidate genes APOBEC1 and PPARG in human gallstone disease.

BACKGROUND: Genetic susceptibility contributes to the aetiology of gallbladder diseases as shown by multiple epidemiological studies. A major gallstone susceptibility locus (Lith6) was identified in 2003 by quantitative trait locus mapping in mice. Two attractive positional and functional candidate genes in apolipoprotein B mRNA-editing protein (APOBEC1) and peroxisome proliferator-activated receptor gamma (PPARG) are located in this interval. AIMS: To investigate APOBEC1 and PPARG as candidate genes for common symptomatic gallstone disease in humans. PATIENTS AND METHODS: Eight hundred and ten patients who underwent cholecystectomy for symptomatic gallstone disease (median age of onset 50) were compared with 718 sex-matched control individuals. An independent additional sample included 368 gallstone patients and 368 controls. Control individuals were sonographically free of gallstones. Haplotype tagging and all known coding single nucleotide polymorphisms were genotyped for PPARG (N=32) and APOBEC1 (N=11). RESULTS: The investigated high-risk patient sample provides a power of greater than 80% for the detection of odds ratios down to 1.45. No evidence of association of the two genes in the single-point tagging markers, coding variants and in the sliding window haplotype analysis was detected (all nominal single point P-values >0.04). A logistic regression analysis including age, sex and BMI as covariates was also negative (nominal P-values > or =0.08). CONCLUSIONS: In the investigated German samples, no evidence of association of APOBEC1 and PPARG with gallstone susceptibility was detected. Systematic fine mapping of the complete Lith6 region is required to identify the causative genetic variants for gallstone in mice and humans.     

Accumulation of 7α-hydroxycholesterol in liver tissue of patients with cholesterol gallstones

Patients with cholesterol gallstones have a reduced pool of bile acids. This study was undertaken to clarify the mechanism by which bile acid biosynthesis does not increase to supranormal levels to cause a reexpansion of the pool. We investigated the first two steps of the bile acid biosynthesis pathway by assaying the activities of cholesterol 7α-hydroxylase, the rate-limiting enzyme in this pathway, and 3β-hydroxy-Δ⁵-C₂₇-steroid dehydrogenase/isomerase, and by measuring the concentrations of 7α-hydroxycholesterol and 7α-hydroxy-4-cholesten-3-one in liver specimens from ten patients with cholesterol gallstones and ten gallstone-free controls. In the patients with gallstones, cholesterol 7α-hydroxylase activity, 3β-hydroxy-Δ⁵-C₂₇ dehydrogenase/isomerase activity, and hepatic 7α-hydroxy-4-cholesten-3-one concentration did not significantly different from levels in controls, but hepatic 7α-hydroxycholesterol concentration was more than twofold that of controls (12.9 ± 2.6 vs 5.3 ±1.2 nmol/g liver,P<0.01). The concentration of 7α-hydroxycholesterol positively correlated with the ratio of cholesterol 7α-hydroxylase activity to 3β-hydroxy-Δ⁵-C₂₇ dehydrogenase/isomerase activity (r=0.93;P<0.005) in the gallstone-free controls. In contrast, this correlation disappeared in the patients with gallstones. These results suggest a derangement of the normal 7α-hydroxycholesterol metabolism in the patients with gallstones. The reason for the accumulation of 7α-hydroxycholesterol remains unclear; however, it is possible that, in patients with cholesterol gallstones, the accumulated 7α-hydroxycholesterol causes inappropriate suppression of cholesterol 7α-hydroxylase activity by product inhibition.     

Gallbladder stone recurrence after medical treatment do gallstones recur true to type?

Medical treatments that dissolve or remove gallbladder stones but leave the gallbladder in situ have the disadvantage of gallstone recurrence. Little is known about the composition of recurrent stones or whether they recur true to type. In 21 patients with recurrent stones detected 5–74 months (mean ±sem, 26±4 months) after being rendered stone-free with dissolution therapy (N=15) or percutaneous cholecystolithotomy (N=6), we compared pretreatment and postrecurrence gallstone number, maximum gallstone attenuation scores measured by computed tomography (CT) and, in 13, the dissolvability of the recurrent stones with oral bile acids ± extracorporeal shock-wave lithotripsy. Before treatment, five patients had solitary and 16 had multiple stones but on recurrence, the gallstones differed in number from the primary stones in 10 of the 21 patients. As a result of patient selection, before dissolution, the primary stones were all radiolucent with maximum CT scores of <100 Hounsfield units (HU) (mean 45, range 10–84 HU). On recurrence, the stones were again CT-lucent in 13 of the 15 patients but were CT-dense in the remaining two (118 and 176 HU). Initially, all six patients treated by percutaneous cholecystolithotomy had radio-opaque stones, with a mean CT score of 459 (range 100–969) HU. However, on recurrence, only one had calcified stones (HU 140); the remaining five had CT-lucent stones (16–98 HU,P<0.05). Of the 13 patients whose recurrent, plain x-ray-lucent and CT-lucent stones were treated with oral bile acids ± lithotripsy, 12 (92%) showed evidence of gallstone dissolution. We conclude that gallbladder stones do not recur true to type in up to two thirds of patients. However, irrespective of original gallstone composition, recurrent stones are usually radio- and CT-lucent, presumed cholesterol-rich, and therefore potentially dissolvable with oral bile acids.     

腹腔镜逆行胆囊切除术和次全胆囊切除术治疗复杂性胆囊结石疗效比较

目的比较腹腔镜逆行胆囊切除术与次全胆囊切除术治疗复杂性胆囊结石的效果。方法选择复杂性胆囊结石患者75例,分别行腹腔镜逆行胆囊切除术(A组,37例)与次全胆囊切除术(B组,38例);比较2组患者手术指标及术后康复情况。结果 B组患者手术时间(86.47±17.95)min、术中出血量(82.58±34.84)mL、术中补液量(786.57±128.65)mL显著低于A组的(103.72±22.56)min、(108.23±41.46)mL和(975.68±151.36)mL,差异均有统计学意义(P<0.05);2组患者中转开腹率、术后体温、腹腔引流量、术后通气时间及住院时间比较差异均无统计学意义(P>0.05)。2组患者均无明显并发症发生。结论腹腔镜逆行胆囊切除术与次全胆囊切除术疗效相当,但后者操作简便,手术时间短,对于耐受性差的患者更为适合。