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。     

复杂胆囊结石患者行腹腔镜胆囊次全切除术的临床疗效观察

目的 观察复杂胆囊结石患者行腹腔镜胆囊次全切除术的临床疗效.方法 按入院先后顺序将186例复杂性胆囊结石患者随机分为观察组与对照组,每组93例.观察组给予腹腔镜下胆囊次全切除术,对照组给予腹腔镜下逆行胆囊切除术.统计并比较两组患者的手术时间、术中出血量、中转开腹率、腹腔引流量、住院时间及术后并发症发生情况等各项临床指标.结果 观察组的手术时间[（83.6±17.8）min]短于对照组[（115.2±19.7）min],术中出血量[（91.4±21.5）ml]也少于对照组[（112.0±38.6）ml],组间比较,差异具有统计学意义（均P＜0.05）;观察组的中转开腹率（3.2％）、腹腔引流量[（116.5±32.1）ml]、住院时间[（6.1±1.1）d]、并发症发生率（7.5％）,与对照组的中转开腹率（2.1％）、腹腔引流量[（110.3±30.5）ml]、住院时间[（6.7±1.2）d]、并发症发生率（8.6％）相似,组间比较,差异无统计学意义（P＞0.05）.结论 腹腔镜下次全胆囊切除术治疗复杂胆囊结石的手术效果与腹腔镜下逆行胆囊切除术相仿,但手术时间更短,术中出血量更少,疗效显著,值得临床推广应用.     

Acute papillary stone impaction: An ideal indication for upfront needle knife papillotomy (“needle knife excision”)

Needle knife papillotomy (NKP) is still considered a rescue technique after conventional access failure due to traditional high complication rates, albeit data are maturing for early use of NKP in standard endoscopic retrograde cholangiopancreatography indications. By contrast, in certain settings NKP should be prioritized to a first‐class indication, such as in choledochocele management and/or, more often encountered in clinical practice, true papillary stone impaction with or without gallstone pancreatitis. The latter results in prompt stone release; thus, the procedure might become alternatively designated as “needle knife excision.”     

The relationship between juxtapapillary duodenal diverticula and the presence of bacteria in the bile

A total of 432 patients with gallstone disease were studied with respect to the existence of juxtapapillary duodenal diverticula and their relationship to the presence of bacteria in the bile. A total of 63 patients were found to have diverticula with an incidence of 14.6 per cent, being significantly higher in the elderly group aged 60 years or older (p<0.01), and no sex difference was noted. Among the patients with diverticula, positive bacterial cultures of bile were recognized at a significantly higher frequency, being found in 49 of the 63 patients (77.8 per cent; p<0.01), and the probability of bilirubinate stones was also higher, being found in 35 of 37 patients (94.6 per cent; p<0.01). The presence of a diverticulum bore significant relation to a higher positive bile bacterial culture (p<0.05), dilatation of the common bile duct (p<0.05), and elevation of the bile duct pressure (p<0.05), even when the conditions were divided into cholecystolithiasis or choledocholithiasis. It was suggested that the presence of a diverticulum affected the flow in the bile duct by narrowing it from the outside and chronically stimulating the papilla, inducing biliary tract infection and/or the formation of gallstones. As the surgical procedures for juxtapapillary duodenal diverticula, including its indications, have not been established, long term follow up investigations seem necessary.     

The efficacy of extracorporeal shock wave lithotripsy on single dense calcified gallstones according to computed tomography

The efficacy and complications of extracorporeal shock wave lithotripsy (ESWL) for single gallstones were compared between 15 patients with a CT-lucent stone and 18 patients with a dense calcified stone. In all of five patients with a stone smaller than 10 mm in diameter, complete or sufficient clearance was observed, regardless of calcification. However, in 28 patients with a stone larger than 11 mm in diameter, the rates of complete or sufficient clearance were lower in those with a dense calcified stone (64%) than in those with a computed tomography (CT) lucent stone (93%). There was no difference in the rate of complications between patients with a CT-lucent stone and those with a dense calcified stone. These results thus suggest that extracorporeal shock wave lithotripsy may be safely employed for patients with a single calcified gallstone.     

套式聚合酶链反应扩增胆固醇结石中细菌DNA及其临床意义研究

为探讨细菌在胆固醇结石发病机理中的作用，从３０例胆汁细菌培养阴性的胆囊胆固醇结石中提取ＤＮＡ，应用套式聚合酶链反应扩增细菌１６ＳｒＲＮＡ基因片段作为有细菌存在的分子证据。结果显示，２６例胆固醇结石中有细菌ＤＮＡ存在。提示细菌可能在胆固醇结石的形成中具有一定的作用。