Cholesterol Nucleation Time in Gallbladder Bile of Patients With Solitary or Multiple Cholesterol Gallstones

Jüngst, Dieter; Lang, Thomas; Ritter, Christoph von; Pratschke, E.; Paumgartner, Gustav

doi:10.1002/hep.1840150510

Cited by 37 publications

(21 citation statements)

References 24 publications

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“…44 There was no indication of a relation between levels of total or individual proteins in bile and speed of crystallization in the group of solitary cholesterol stone patients. In contrast, for multiple cholesterol stone patients, levels of total protein and all individual proteins were much lower in the subgroup with slow crystallization than in the subgroup with fast crystallization (Figs.…”

Section: Discussionmentioning

confidence: 92%

“…We divided patients into subgroups with slow and fast crystallization (crystal observation time Ͼ4 days and Յ4 days, respectively) according to previously published criteria. 44 All 7 patients with multiple stones and slow crystallization invariably had low levels of total as well as various individual proteins, in general significantly lower than the 18 fast-nucleating multiple cholesterol stone patients (Figs 1-4). Gallstone cholesterol content was also lower in case of slow crystallization (85 Ϯ 3.0% and 94 Ϯ 1.8%, respectively; P ϭ .02).…”

Section: Comparison Of Solitary and Multiple Cholesterol Stone Patientsmentioning

confidence: 86%

“…43 Patients were divided in fast and slow nucleators (crystal observation time Յ4 days and Ͼ4 days, respectively) according to previously published criteria. 44 Extent of crystallization was also evaluated daily in a whole drop of bile (without coverslide at 100ϫ magnification: means of five counted fields) with the aid of a semiquantitative scoring system: 0 ϭ no crystals; 1ϩ ϭ 1 crystal/field; 2ϩ ϭ 2-5 crystals/field; 3ϩ ϭ 6-10 crystals/field; 4ϩ ϭ more than 10 crystals/field. 3 A cumulative score was obtained at the end of the 21-day observation period (maximal score ϭ 22 ϫ 4 ϭ 88).…”

Section: Patientsmentioning

confidence: 99%

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Cholesterol crystallization in human gallbladder bile: Relation to gallstone number, bile composition, and apolipoprotein E4 isoform

Erpecum¹,

Berge‐Henegouwen²,

Eckhardt³

et al. 1998

Hepatology

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Patients with multiple cholesterol gallstones are at increased risk of recurrence after nonsurgical therapy, possibly because of fast biliary cholesterol crystallization. Serum apolipoprotein E4 (apo E4) is a risk factor for primary cholesterol gallstone formation as well as recurrence. We examined potential effects of stone number and apolipoprotein E genotype on crystallization and on various crystallization-influencing factors in gallbladder biles of 36 cholesterol stone patients (25 multiple stones: 10 carrying the ⑀4 allele). Biliary cholesterol saturation, bile salt composition or concentrations of total protein, immunoglobulin (Ig)A, IgG, ␣ 1 -acid glycoprotein, haptoglobin, or mucin-all crystallization promoters-did not differ between multiple and solitary stone patients, apparently not explaining different speed of crystallization (crystal observation time 3.5 ؎ 0.6 days vs. 12.7 ؎ 2.4 days, respectively; P ‫؍‬ .0003). In contrast, biliary aminopeptidase-N activities (2,607 ؎ 592 mU/mL vs. 947 ؎ 185 mU/mL; P ‫؍‬ .04) were higher and IgM levels (179 ؎ 39 vs. 65 ؎ 8 mg/L; P ‫؍‬ .09) tended to be higher in the case of multiple stones. Although patients carrying the ⑀4 allele had similar stone numbers and crystallization as patients without the ⑀4 allele, their cholesterol saturation index (CSI) was lower (1.08 ؎ 0.09 vs. 1.54 ؎ 0.13; P ‫؍‬ .01), whereas total protein and bile salt concentrations tended to be higher with preferential taurineconjugation. In conclusion, fast cholesterol crystallization is associated with multiple stones but not with apolipoprotein E4. Whereas fast crystallization may contribute to high recurrence rates after nonsurgical therapy in case of multiple gallstones, the mechanism for increased risk of gallstone formation in patients carrying the ⑀4 allele remains unknown. (HEPATOLOGY 1998;27:1508-1516.)Patients with multiple cholesterol gallstones have a higher risk of gallstone recurrence after successful nonsurgical treatment than patients with solitary stones. 1 Biliary cholesterol crystallization is much faster in the case of multiple than solitary cholesterol stones, 2,3 thus offering a potential explanation for high recurrence rates. In line with this finding, in a recent prospective study in gallstone patients treated by cholecystotomy with concomitant stone removal, fast crystallization in gallbladder bile obtained during the procedure was the only major risk factor for recurrence during follow-up. 4 Several factors may contribute to fast crystallization, such as biliary cholesterol supersaturation, increased concentration of bile in the gallbladder, 2,5 increased amounts of the hydrophobic bile salt deoxycholate, 6 a shortage of crystallizationinhibiting proteins, 7 or excessive crystallization promoting proteins. 8 The crystallization-promoting proteins have been partly isolated by means of lectin chromatography with concanavalin A-Sepharose. 8 This lectin binds glucose-and mannose-containing glycoproteins, which comprise about 10% of total biliary proteins. Increased tota...

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Section: Discussionmentioning

confidence: 92%

Section: Comparison Of Solitary and Multiple Cholesterol Stone Patientsmentioning

confidence: 86%

Section: Patientsmentioning

confidence: 99%

See 1 more Smart Citation

Cholesterol crystallization in human gallbladder bile: Relation to gallstone number, bile composition, and apolipoprotein E4 isoform

Erpecum¹,

Berge‐Henegouwen²,

Eckhardt³

et al. 1998

Hepatology

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“…Ultrafiltration, as used in the present study, may decrease the amount of bile lipids considerably, with potential influences on the process of nucleation [42]. On the other hand, ultracentrifugation also leads to a decrease of bile lipids [43], and there is a strong correlation between nucleation time determined in the same biles after ultrafiltration and ultracentrifugation [42,44]. In addition, we found exactly the same biliary bile salt composition and hydrophobicity index in gallbladder bile before and after ultrafiltration, thus excluding an effect of this procedure on hydrophobicity.…”

Section: Discussionmentioning

confidence: 94%

Effects of bile salt and phospholipid hydrophobicity on lithogenicity of human gallbladder bile

Erpecum¹,

Portincasa

Stolk

et al. 1994

Eur J Clin Investigation

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Abstract. Increased biliary bile salt and phospholipid hydrophobicity may promote nucleation of cholesterol crystals and gallstone formation. We therefore compared bile salt composition (determined by gasliquid chromatography) in patients with cholesterol (n = 35) and pigment (n = 16) gallstones (group A). Bile salt composition and cumulative bile salt hydrophobicity index were not different between both stone types. Hydrophobicity index or YO of individual bile salts did not correlate with cholesterol saturation index or nucleation time. In an additional 21 cholesterol stone patients (group B) biliary bile salt and phospholipid hydrophobicity as determined by highpressure liquid chromatography did not correlate with cholesterol saturation index or nucleation time. In both group A and group B, cholesterol stone patients with cholesterol crystals in their fresh biles had a higher % deoxycholic acid, a lower YO cholic acid and a higher bile salt hydrophobicity index than crystal-negative patients. This study indicates the need for further research on the role of bile salt hydrophobicity in the pathogenesis of gallstones.

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“…33 In both studies the rate of recurrence was significantly higher in patients treated for multiple stones, and it has been shown that those patients have a greater degree of nucleating defects. 34 The rate of stone recurrence within 5 years after ESWL combined with bile acid therapy has been studied by Sackmann et al 8 A total of 100 consecutive patients were followed up for a median of 4.3 years after stone disappearance and after discontinuation of bile-acid therapy. Eighty-nine of these patients had single stones, and only 11 patients had two or three stones prior to lithotripsy.…”

Section: Resultsmentioning

confidence: 99%

Rapid Formation of Cholesterol Crystals in Gallbladder Bile Is Associated With Stone Recurrence After Laparoscopic Cholecystotomy

et al. 1997

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it avoids injury to the common biliary duct and leaves the Laparoscopic cholecystotomy (LCT) with subsequent gallbladder in situ after the removal of stones. extraction of gallstones and primary closure of the gall-The technique can be used in patients with a functioning bladder has been introduced as an alternative therapy gallbladder irrespective of the composition or number of for patients with cholecystolithiasis and preserved gallstones. However, stone recurrence has to be considered a bladder function. However, stone recurrence has to be major drawback. Postdissolution trials have shown that considered as a major drawback that might be related when gallbladder stones have been completely dissolved and to lithogenic factors of gallbladder bile or the composibile-acid treatment is withdrawn, stones recur in 28% to 61% tion of gallbladder stones. Therefore, these were studied of patients after 2 to 12 years. [3][4][5] Comparable results were in relation to stone recurrence within an observation obtained after successful treatment of gallbladder stones by period of 1 to 5 years (median, 3.6 years) in 50 patients extracorporeal shock wave lithotripsy (ESWL). 6-8 Therefore, after LCT. The concentrations of total and individual the study of factors associated with recurrent stones is of bile acids, phospholipids, cholesterol, total lipids, mucin, crucial importance. The impact of impaired motility of the protein, and the cholesterol saturation indices in gallgallbladder on gallstone recurrence after ESWL has been bladder bile were not significantly different between 10 demonstrated recently. 9 However, nothing is known whether patients with and 40 patients without stone recurrence.lithogenic factors of gallbladder bile or the composition of However, the crystal observation time was significantly stones might affect recurrence rates after successful gallstone (P õ .02) shorter (range, 1-2 days; median, 1.5) in the treatment that leaves the gallbladder in situ. The introducbile of patients with stone recurrence compared to those tion of LCT as an alternative treatment of gallstones allows without (range, 1-21 days, median 3.5). Moreover, all 10 for the first time a prospective study of these relationships. stone recurrences were observed in the 28 patients withThis prompted us to analyze gallbladder bile and stones cola crystal observation time in the bile of less than or equal lected at the time of LCT and to compare these data with the to 2 days (approximate annual risk: 12%-15%), and no rate of stone recurrence as determined by repeated ultrasorecurrences were observed in the 22 patients with a crysnography. tal observation time greater than 2 days (P õ .0001) or in patients with pigment stones. The rapid formation of PATIENTS AND METHODS cholesterol monohydrate crystals in bile seems to be the major risk factor for recurrent stones after LCT. These Patients and Collection of Bile. Fifty patients, 38 women (mean are most likely cholesterol stones and, therefore, are age range, 47.8 { 10.5 years) and 12 men (mean...

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Cholesterol Nucleation Time in Gallbladder Bile of Patients With Solitary or Multiple Cholesterol Gallstones

Cited by 37 publications

References 24 publications

Cholesterol crystallization in human gallbladder bile: Relation to gallstone number, bile composition, and apolipoprotein E4 isoform

Cholesterol crystallization in human gallbladder bile: Relation to gallstone number, bile composition, and apolipoprotein E4 isoform

Effects of bile salt and phospholipid hydrophobicity on lithogenicity of human gallbladder bile

Rapid Formation of Cholesterol Crystals in Gallbladder Bile Is Associated With Stone Recurrence After Laparoscopic Cholecystotomy

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