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Bile composition in inflammatory bowel disease: ileal disease and
colectomy, but not colitis, induce lithogenic bile.Aliment
Pharmacol Ther. 2003 Apr
1;17(7):923-33.
BACKGROUND:
Inflammatory bowel disease is a risk factor for gall-bladder stones,
but there is controversy about the composition of these stones and
whether such patients develop lithogenic bile. METHODS: In 54
gallstone-free inflammatory bowel disease patients and 13
non-inflammatory bowel disease patients with cholesterol-rich
gallstones, we measured the biliary cholesterol saturation indices,
nucleation times and bilirubin concentrations, and determined the
bile acid composition and molecular species of phosphatidylcholine,
in gall-bladder bile. RESULTS: Patients with Crohn's colitis or
ulcerative colitis had less saturated bile (mean cholesterol
saturation index, 0.9) and longer nucleation times (median, 21 days)
than those with ileal Crohn's disease (1.5; 14 days) or those who
had undergone colectomy (1.6; 5 days). In patients with ileal
Crohn's disease, the mean biliary bilirubin concentration was two-
to three-fold higher than that in the other groups, and was
associated with a decrease in the percentage of biliary deoxycholate
and an increase in the percentage of ursodeoxycholate, compared with
disease controls, but phosphatidylcholine species were similar.
CONCLUSIONS: Patients with small bowel Crohn's disease, or who have
undergone colonic resection, have supersaturated bile and an
increased risk of cholesterol gallstone formation. In patients with
ileal disease, the presence of high biliary bilirubin concentrations
and low percentage of deoxycholic acid may also favour the formation
of mixed, pigment-rich, gallstones.
The role of
bacteria in gallstone pathogenesis.Front
Biosci. 2001 Oct 1;6:E93-103.
Bacteria are
often found in high concentrations in brown pigment and less so in
cholesterol gallstones. Although it is intriguing to hypothesize
that cholesterol stone formation is non-bacterial in nature and
principally different from the pathogenesis of "infectious" brown
pigment gallstones, it is more likely that significant overlap
exists between the two processes. Most gallstones are composite in
nature. Using molecular-genetic methods, bacteria can be found in
most pure cholesterol gallstones (i.e. those whose structure
consists of more than 90% cholesterol). The natural history of the
gallstones development is unknown. It is likely that brown pigment
stones can evolve in their chemical composition after the
termination of the infectious process that initiate their formation,
and may further develop into either mixed or nearly pure cholesterol
stones. In a similar fashion, cholesterol-poor or black pigment
gallstones may act as foreign bodies to enhance the propensity of
bacterial colonization in the presence of pre-existing gallstones or
cholangitis, thereby activating pathways of bacterial lithogenesis
and resulting in the encasement of cholesterol nuclei with pigment
shells and/or in the internal remodeling of extant stones. It is
often difficult, if not impossible, to ascertain whether bacterial
infection of bile arose before stone formation or vice-versa. The
development of gallstones (nucleation, assembly of microcalculi,
growth, remodeling) includes the interaction of both bacterial and
non-bacterial mechanisms, working discontinuously over years and
decades and shaping the structural individuality of each stone. At
cholecystectomy, the gallstone removed from the patient represents
the end product of a long pathologic process. Although our
understanding of the exact temporal contribution of bacteria in
lithogenesis is incomplete, it is important for the clinician to
realize that most gallstones are colonized by a bacterial biofilm,
even though the bile may be culture-negative.
Histopathological
changes in gallbladder mucosa in cholelithiasis: correlation with
chemical composition of gallstones.Trop
Gastroenterol. 2002 Jan-Mar;23(1):25-7.
BACKGROUND:
Cholelithiasis produces diverse histopathological changes in
gallbladder mucosa namely acute inflammation, chronic inflammation,
glandular hyperplasia, granulomatous inflammation, cholesterosis,
dysplasia, and carcinoma. Gallstones have different chemical
composition. They may be cholesterol, pigment or mixed stones. The
aim of this prospective study was to see if any correlation existed
between the chemistry of gallstones and any particular
histopathologic picture. METHODS: Between May 1997 and December 1997
we diagnosed and operated on 40 patients with cholelithiasis.
Diagnosis was established by ultrasound. After operation gallstones
were sent for chemical analysis to detect presence of calcium
bilirubinate and cholesterol. Serial sections of gallbladder from
fundus to neck were stained by haematoxylin and eosin, and studied.
RESULTS: Out of 40 patients (n = 40) 29 were females and 11 were
males. The mean age of our patients was 38 +/- 21 years with a
median of 40 years. Median age of males was 48 years compared to 38
years for females. Twenty-eight patients had mixed stones, 8 had
pigment stones and 4 had cholesterol stones. Out of 28 patients with
mixed stones 14 had histological picture of chronic cholecystitis, 8
had granulomatous cholecystitis, 4 had adenomatous hyperplasia, 1
had dysplasia and 1 had carcinoma. All 8 patients having pigment
gallstones had chronic cholecystitis. Out of 4 patients with
cholesterol gallstones, 2 had chronic cholecystitis, 1 had
adenomatous hyperplasia and 1 had cholesterosis. Gallbladder having
pigment stones were devoid of Rokitansky-Aschoff sinuses.
CONCLUSION: Adenomatous hyperplasia and Rokitansky-Aschoff sinuses
were not seen in gallbladder containing pigment stones but seen in
gallbladders containing mixed and cholesterol stones in our study.
Cholesterol may be a more potent stimulus for glandular hyperplasia
or glandular hyperplasia may responsible for formation of
cholesterol rich stones.
Composition
and immunofluorescence studies of biliary "sludge" in patients with
cholesterol or mixed gallstones.J
Hepatol. 2000;33(3):352-60.
BACKGROUND/AIMS: Gallbladder bile from patients with cholesterol or
mixed gallstones frequently contains biliary "sludge", a suspension
of cholesterol monohydrate crystals and pigment granules embedded in
mucin and proteins. The composition of biliary "sludge" and the
preferential localization of mucin and proteins could be an
indicator for its potential role in gallstone formation. METHODS:
Ultracentrifugation (100000 g/l h) was used to precipitate "sludge"
from bile, and the concentration difference of its main components
between native bile and ultracentrifuged bile samples was
calculated. After purification of the sediment, immunolocalization
was performed for the detection of mucin, IgA, albumin,
aminopeptidase, and anionic polypeptide fraction using polyclonal
and monoclonal antibodies. RESULTS: The amount of sludge in
gallbladder bile was 4.26 mg/ml-0.78 (mean+/-SEM) in patients with
cholesterol and 2.51 mg/ml+/-0.39 in patients with mixed stones and
cholesterol was the main component (48.9+/-4.6% and 44.4+/-7.1%).
The sediment appeared as a mixture of vesicular aggregates and
pigment particles which were linked by a gel matrix of mucin
containing cholesterol crystals. While anionic polypeptide fraction
and aminopeptidase were associated to pigments, IgA was uniformly
spread in the crystalline parts of "core-like" structures, and
albumin, when it was present, appeared as randomly located small
spots. CONCLUSIONS: Our study demonstrates that the cholesterol
content and the distribution pattern of mucin and different proteins
is similar in the sediments of biliary "sludge" to that previously
shown in cholesterol and mixed gallstones. This suggests that
biliary "sludge" represents an early stage of gallstone formation in
these patients.
Bacterial
DNA in mixed cholesterol gallstones.Am
J Gastroenterol. 1999
Dec;94(12):3502-6.
OBJECTIVE: Numerous investigators have proposed a role for bacteria
in biliary lithogenesis. We hypothesized that bacterial DNA is
present in gallstones, and that categorical differences exist
between gallstone type and the frequency of bacterial sequences.
METHODS: Polymerase chain reaction (PCR) was used to amplify
bacterial 16S rRNA and uidA (encoding Escherichia coli [E. coli]
beta-glucuronidase) genes in different types of gallstones. PCR
products were sequenced. RESULTS: Bacterial 16S rRNA and uidA DNA
sequences in E. coli were detected in all brown pigment, common bile
duct, and mixed cholesterol gallstones (n = 14). In contrast, only
one (14%) of seven pure cholesterol gallstones yielded a PCR
product. Most (88%) mixed cholesterol gallstones yielded PCR
amplification products from their central, as well as their outer,
portions. Sequenced products possessed 88-98% identity to 16S rRNA
genes of E. coli and Pseudomonas species. CONCLUSIONS: Bacterial DNA
sequences are usually present in mixed cholesterol (to 95%
cholesterol content), brown pigment, and common bile duct, but
rarely in pure cholesterol gallstones. The presence of bacterial
beta-glucuronidase is also suggested. The role of bacteria and their
products in the formation of mixed cholesterol gallstones, which
comprise the majority of cholesterol gallstones, warrants further
study.
The classification of biliary calculi and the clinico-therapeutic
implications.Ann
Ital Chir. 1998 Nov-Dec;69(6):701-8.
A new
classification of gallstones is reported, which has interesting
implications for diagnostic and therapeutic purposes. Gallstones
have been divided according to "type" into the following categories:
cholesterol (single, multiple), mixed, black pigment, brown pigment,
combination and composite. In addition, gallstones primarily formed
within the gallbladder have been distinguished from those initially
formed in the common duct (before and after surgery) and within the
intrahepatic ducts. Stone type and composition have been related to
symptoms, on the basis of a new view, according to which gallstones
are not a unique entity, but a heterogeneous disease including
different entities, each of which has its own pathogenesis, clinical
manifestations, biological behaviour and also deserves a different
treatment. The proper treatment should be appropriate to the
individual and his stones. Therapeutic guide-lines are suggested for
each type of stones, in particular for stones complicated by
cholangitis, pancreatitis, or for common duct stones concomitantly
found with gallbladder stones. For the last group, techniques and
therapeutic options preserving the function of the sphincter of Oddi
are recommended. Suggestions are also reported concerning the
treatment of various types of hepatolithiasis: primary, i.e.
associated with cystic intrahepatic bile duct dilatation;
post-surgical, i.e. occurring cranially to a biliary enteric
anastomosis: secondary, i.e. associated with concomitant gallbladder
and common duct stones.
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