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Susceptibility of the liver and biliary tract to anaerobic infection in extrahepatic biliary tract obstruction. II. Liver function and morphology of the liver and biliary tract--an experimental study in rabbits.

Biliary tract infection with anaerobic bacteria (B. fragilis or Fusobacterium mortiferum) was produced in rabbits by common duct ligation (c.d.l.) 3 days prior to intravenous bacterial inoculation. Animals were investigated 1, 4 or 7 days after inoculation. Histopathological investigations included the liver, the common duct, and the gallbladder, while liver function was evaluated by bilirubin, alkaline phosphatase (AP), and L-alanine aminotransferase (GPT) in serum. Rabbits with c.d.l. and biliary tract infection were compared to rabbits with c.d.l. in which bacterial inoculation failed to produce infection, to inoculated rabbits without c.d.l., and to uninoculated rabbits with c.d.l. Anaerobic biliary tract infection in rabbits with c.d.l. caused a significant increase in liver abscesses, a significant increased infiltration with granulocytes in the gallbladder, and a significant increase in serum levels of bilirubin, AP, and GPT, but failed to produce signs of cholangitis in the liver and intramural abscesses in the gallbladder. A material is presented of normal values for bilirubin, AP, and GPT in serum in rabbits.

Alkaline Phosphatase

[Atypical anatomical variants and anomalies of the biliary tract in patients with biliary tract and pancreatic diseases. II. Endoscopic treatment].

Results are reported of endoscopic treatment of 79 patients with atypical anatomical variants and anomalies of the bile ducts: common bile duct calculosis (54), stenosing papillo-odditis (8), indurative pancreatitis (2) and bile duct cancer (15). The following endoscopic manipulations have been performed: endoscopic sphincterotomy (72); hydrostatic balloon extraction of calculi (27); hydrostatic balloon dilatation of constricted segments (29); mechanical lithotripsy (15); nasolabial drainage (17) and endoprosthesis (15). Much more difficult was the extraction of calculi from the common bile in the event of atypical anatomical variants and anomalies of the distal portion of the common bile duct (chi 2 = 14.55; p less than 0.001). Treatment resulted in significant reduction of the bilirubin levels (t = 4.13; p less than 0.001), of AP (t = 4.47; p less than 0.001), GGTP (t = 4.07; p less than 0.001); AcAT (t = 5.75; p less than 0.001) and AlAT (t = 5.63; p less than 0.001). Complications occurred in 6 per cent of the patients (acute pancreatitis, cholangitis, hemorrhage). Mortality from endoscopic treatment was 1.3 per cent. Endoscopic methods for treatment are advised as alternative to operative treatment for patients in advanced age and high operative risk.

Adult

[Atypical anatomical variants and anomalies of the biliary tract in patients with biliary tract and pancreatic diseases. I. The incidence according to ERCP].

Of 570 patients with clinical manifestations of bile duct and pancreas diseases, examined by ERCP, 122 had different atypical anatomical variants (142 in 114 patients) and anomalies of the biliary passages (8 patients). The incidence of the individual atypical anatomical variants of the bile ducts was, as follows: 1. variants in the entry of the common bile duct in the duodenum--3.3 per cent (19 of 570 patients); 2. variants in the entry of ductus cysticus in the common bile duct--11.1 per cent (63 of 570 patients); 3. variants of the ramifications of the hepatic canals--10.5 per cent (60 of 570 patients). Of the bile duct anomalies, choledochocele was the most common--in 5 of the 8 patients in this group. In addition, there was a double gall bladder, gall bladder atresia and cysts of the intrahepatic bile ducts in one case each. High was the incidence of choledocholithiasis (63 per cent) and especially of primarily formed calculi in the common bile duct (20 per cent), as well as bile duct cancer (11 per cent). Cancer of the biliary passages was significantly commoner in atypical anatomical variants of ductus hepaticus (18 per cent) vs. 8 per cent in atypical variants of ductus cysticus and none in the common bile duct variants (chi 2 = 4.06; p less than 0.05). Cancer of the common bile duct was found also in 1 of the eight patients with anomalies of the biliary passages.

Age Factors

Susceptibility of the liver and biliary tract to anaerobic infection in extrahepatic biliary tract obstruction. III. Possible synergistic effect between anaerobic and aerobic bacteria. An experimental study in rabbits.

The pathogenicity of single anaerobic, single aerobic, and mixed anaerobic and aerobic bacterial inocula was studied in 3 groups of 12 rabbits with biliary tract obstruction. B. fragilis, ss. fragilis and E. coli serotype 01: K1: H7 were used. The investigation was made 7 days after bacterial inoculation and included bacteriological studies of the liver and bile as well as studies of liver function and morphology of the liver and biliary tract. Inoculation of 10(5)-10(6) E. coli did not cause biliary tract infection, liver abscesses or death. Inoculation of 10(9) B. fragilis caused biliary tract infection in 83% and liver abscesses in 17% of the animals inoculated, without any mortality. Combined inoculation with B. fragilis and E. coli in reduced doses significantly increased mortality (42%) and frequency of liver abscesses in surviving animals (86%). All abscesses, however, yielded pure culture of B. fragilis only. 84% of the animals inoculated with B. fragilis alone or with B. fragilis in combination with E. coli developed biliary tract infection with B. fragilis, the bile yielding from 10(7)-10(9) B. fragilis per ml, gallbladder bile yielding significantly higher bacterial counts than common duct bile. E coli was never recovered from bile in surviving animals but from both bile and blood in animals not surviving the experimental period.

Alanine Transaminase

Susceptibility of the liver and biliary tract to anaerobic infection in extrahepatic biliary tract obstruction. Bacteriological investigations - an experimental study in rabbits.

The influence of common duct occlusion on susceptibility to infection with anaerobic gram-negative rods was investigated in rabbits. Intravenous inoculation was performed with three B. fragilis strains isolated from human infections and with a stock culture of Fusobacterium mortiferum. Liver tissue, gallbladder, bile, and blood were investigated. Anaerobic culture procedures were based on the use of a 'glove-box' with an oxygen-free atmosphere and pre-reduced, anaerobically sterilized media. Anaerobic transport was based on flushing of samples with oxygen-free carbon dioxide and transport-time less than 30 minutes. In regard to two B. fragilis strains (ss. fragilis) and in regard to Fusobacterium mortiferum, common duct occlusion significantly increased the number of infected animals compared to a control group of inoculated animals without common duct occlusion. Spontaneous infection did not arise in a control group of animals with common duct ligation. It is concluded that: 1) in biliary tract occlusion, anaerobic bacteria are able to invade the biliary tract from the blood stream, and 2) biliary tract occlusion produces sufficient anaerobic conditions for obligate anaerobic bacteria to multiply in the bile.

Animals

Biliary tract excretion of cefazolin, cephalothin, and cephaloridine in the presence of biliary tract disease.

The biliary tract excretion of three cephalosporins, cefazolin, cephaloridine, and cephalothin, was compared in patients with biliary tract disease. In the absence of obstruction, mean antibiotic levels in bile from gall bladder and common duct in patients undergoing cholecystectomy were highest for cefazolin (17 and 31 mug/ml, respectively) than either cephaloridine (7 and 9 mug/ml) or cephalothin (1 and 4 mug/ml). Biliary tract levels generally paralleled serum levels. In no patient with cystic duct obstruction were any of the cephalosporins detectable in appreciable amounts in gall bladder bile. In patients with T-tube drainage given each of the three different cephalosporins on separate days, concentrations of cefazolin in bile were many-fold higher than either cephaloridine or cephalothin. Peak levels of cefazolin in T-tube bile averaged 51 mug/ml after intravenous and 26 mug/ml after intramuscular administration, whereas mean peak levels of cephalothin and cephaloridine were only 6 and 16 mug/ml, respectively. Here, too, T-tube levels reflected serum concentrations and obstruction to biliary flow impaired excretion of each of the drugs.

Biliary Tract

Demonstration of transient bacterobilia by foreign body implantation in feline biliary tract.

The biliary tract of cats is known to be free of autochthonous bacteria above the sphincter of Oddi. In this experiment we investigated whether transient bacterobilia occurs in the biliary system under normal conditions. Polyethylene tubes and human cholesterol stones were implanted surgically into the gallbladder of cats. Sham cholecystostomy was performed as control operation. These cats were euthanized at two, six, and 12 weeks, and the implants were removed, cultured, and studied by scanning electron microscopy (SEM). Cultures and SEM also were undertaken for material scraped from the mucosal surface of the biliary tract from these animals. Colonization of bacteria on the polyethylene tubes and the gallstones was found six and 12 weeks after implantation. Adherent bacterial biofilms were demonstrated on the surfaces of these implants. This experiment showed that transient bacterobilia exists in the feline biliary tract. The foreign body implants have facilitated the adhesion of planktonic bacteria in the bile onto their surfaces and have initiated the formation of adherent biofilms within which these bacteria persisted until the system was sampled.

Acinetobacter

[Cultured biliary tract epithelial cells/alkaline and neutral elution as a model for the detection of carcinogens to the biliary tract epithelium].

Alkaline and neutral elution techniques were applied to detect chemical carcinogens in biliary tract cancer using biliary tract epithelial cells in culture. Since biliary tract epithelial cells actively grow in culture, DNA breaks induced by carcinogens in the [14C] thymidine-prelabeled DNA could be detected as radioactivities in the eluted fractions. Our study demonstrated that aflatoxin B1, 20-methylcholanthrene and dimethylnitrosamine induced DNA single-strand breaks in the biliary tract epithelial cells by the use of this system. Cultured biliary tract epithelial cells/alkaline and neutral elution offers a sensitive and organ-specific model for the detection of chemical carcinogens to the biliary tract epithelium.

Aflatoxin B1

[Biliary excretion and clinical evaluation of cefoperazone in the biliary tract infections].

Biliary excretion Cefoperazone (CPZ) in a dose of 1 g was intravenously injected to each of 13 cases with obstructive jaundice. Entire bile was collected through percutaneous transhepatic cholangiodrainage (PTCD) catheter in every 1 hour for 6 hours. The mean concentration of CPZ in serum was 112.1 +/- 17.8 micrograms/ml (mean +/- S.E.) at 1 hour and 55.1 +/- 19.2 micrograms/ml at 6 hours after injection. The mean recovery of CPZ in bile within 6 hours was 1.13 +/- 0.60%. Average CPZ concentrations in bile were 64.0 +/- 45.8 micrograms/ml in the 1 hour fraction, 142.7 +/- 78.4 micrograms/ml in the 2 hours fraction and 72.2 +/- 34.0 micrograms/ml in the 6 hours fraction. Biliary excretion of CPZ was low in cases where the serum concentration of total bilirubin was high, but maximum CPZ level in bile in patients with higher serum bilirubin concentrations than 30 mg/dl was still more than 3 micrograms/ml. Clinical evaluation. CPZ was administered to 43 patients with biliary tract infections. The efficacy ratio was 88.4% (excellent and good cases) in all cases, and especially high in cases with cholecystolithiasis. But no difference in efficacy ratio was observed among cases with cholecystolithiasis, choledocholithiasis without gallstone and cases subjected to PTCD. In 10 patients examined by ultrasonography, 8 cases showed reduced diameters of gallbladder. No adverse effect of CPZ was noted in any cases. These results suggest that a fairly large portion of CPZ was excreted through bile and that CPZ is a very useful drug for the treatment of biliary tract infections.

Adult

[Chemotherapy of biliary tract infections (XXXVII). Excretion into bile and gallbladder tissue levels of levofloxacin and its clinical effect in biliary tract infections].

Evaluations were made on biliary excretion and penetration into the gallbladder tissue of levofloxacin (LVFX, DR-3355), a new quinolone antibacterial agent, and its clinical efficacy in biliary tract infections. 1. Gallbladder tissue concentrations and biliary concentrations of LVFX at 2-6 hours at oral administration of 100 mg were 0.58-1.99 micrograms/g and 0.49-5.63 micrograms/ml, respectively. These tissue and biliary levels are almost equal or somewhat higher than the serum levels (0.55-1.63 micrograms/ml) of the compound. 2. The concentrations of LVFX and optical isomer DR-3354 in the serum, gallbladder tissue, and bile were determined after a single or a concomitant administration of LVFX 100 mg and/or ofloxacin (OFLX) 100 to 200 mg. The concentration ratio of LVFX to DR-3354 paralleled with the ratio of the 2 compounds administrated. 3. At a dose of 100 mg, the glucuronide of LVFX in the common duct bile was detected at proportions between 0.9 and 36.0%. 4. A total of 11 patients with biliary tract infections, including 6 cholecystitis 3 cholangitis, and 1 each of cholecystocholangitis and liver abscess was treated with LVFX at 100-200 mg t.i.d. for 3-14 days. Clinical results were excellent or good in 8 cases and fair in 3 cases, resulting in an efficacy rate of 72.7%. 5. A side effect and an abnormal change in laboratory findings were observed in both 1 case each and they were both mild. It was concluded that LVFX showed good penetration to the biliary tract as does OFLX, and that it would be a useful oral agent for the treatment of biliary tract infections.

Adult

Route of infection in extrahepatic biliary tract disease. II: Bacterial recovery from gallbladder bile and gallbladder wall in human biliary tract disease.

Bacterial recovery from gallbladder wall and gallbladder bile was investigated in 73 patients with extrahepatic biliary tract diseases. The technique of anaerobic culture was based on the use of a 'glove-box' and prereduced anaerobically sterilized media. Transport of samples was based on evacuation of atmospheric air with oxygen-free carbon dioxide and a transport time less than 30 minutes. When samples of bile and tissue were obtained simultaneously before operations on the biliary tract were begun and handled by one of the authors to avoid contamination, no significant difference in bacterial recovery between bile and tissue was observed. If samples were handled routinely by the staff or if biopsy from the gallbladder wall was not obtained until after operation on the biliary tract was finished, bacterial recovery from gallbladder tissue was significantly more frequent compared to bile. Under these last mentioned circumstances, the difference in bacterial recovery was due to bacterial species like Staph. aureus, Staph. albus, P. acnes and Difteroids.

Adult

Mouse strain differences in susceptibility to sporidesmin-induced biliary tract injury.

Biliary tract injury was examined in four inbred strains of mice orally dosed with 500 micrograms of the fungal toxin sporidesmin. Semiquantitative histological analysis was used to assess the grade of necroinflammatory changes in the gall bladder, intra- and extrahepatic biliary tree and lobular parenchyma. Injury was greatest in the C57BL/6 and C3H strain mice and was least in SJL/J mice. In these strains injury was greatest at 4 days and had regressed by 10 days. In BALB/c mice the damage, although similar to that in SJL/J mice at 4 days, persisted at the same severity at day 10 and was accompanied by periductal fibrosis and occasionally by obliteration of ducts typical of sclerosing cholangitis. Analysis of the time-course of development of the lesions in C57BL/6 mice showed that the primary target for the toxin is the biliary epithelium. The severity of the lesions within the liver increased centripetally and the worst affected ducts were found at the confluence of the lobar ducts with the common bile duct. The variation in the degree of damage and rate of healing between strains may be due to differences in sporidesmin excretion in bile or interactions with biliary epithelial cells and/or efficacy of protective cellular repair mechanisms.

Animals

Percutaneous biliary drainage as an initial therapy in sepsis of the biliary tract.

Percutaneous biliary drainage offers a rapid, low-risk, effective method of decompressing the biliary tract in the patient with cholangitis and sepsis. A definite surgical procedure can be delayed until the patient is stabilized. The procedure provides anatomic detail that can be used to plan surgical treatment. In some patients who do not have surgically correctable lesions, operation can be avoided altogether.

Adult

Pathology of anomalous junction of the pancreaticobiliary ductal system: mutagenicity of the contents of the biliary tract and nuclear atypia of the biliary epithelium.

Congenital biliary dilatation is frequently complicated by biliary tract cancer, and anomalous junction of the pancreaticobiliary ductal system, a major factor constituting the pathology of this disease, is considered to be important as a background for carcinogenesis in the biliary tract. To clarify the mechanism of carcinogenesis in the biliary tract under the circumstance of anomalous junction, we evaluated the mutagenicity of the contents of the biliary tract in patients with congenital biliary dilatation and analyzed the nuclear atypia of the biliary epithelium by fluorocytometry. A mutagenicity test using Bacillus subtilis showed positive results in 6 of 12 patients. Since mutagenicity correlates well with carcinogenicity, these results suggest the necessity of separation surgery between the bile and pancreatic ducts in patients with anomalous junction regardless of the presence or absence of biliary dilatation. On the other hand, DNA histograms of the nuclei of gallbladder epithelial cells produced by fluorocytometry in 4 patients revealed a high incidence of polyploid DNA in 2 patients with marked hypertrophic changes. These patients were also positive for mutagenicity of the contents of the biliary tract, suggesting that mutagens are involved in the atypia at the cellular and nuclear levels.

Adolescent

Three-dimensional fine structure of the biliary tract: scanning electron microscopy of biliary casts.

The three-dimensional structure of the biliary tract was studied by scanning electron microscopy (SEM) of biliary casts. The replica of the biliary tract was successfully prepared by retrograde injection of low viscosity resin into the common bile duct. Bile canaliculi are intricate networks in which hexagonal and pentagonal meshworks are interconnected. Each hexagonal or pentagonal meshwork is on a plane, but adjoining meshworks are on different planes. Bile canalicular networks connect with bile ductules at the periphery of the portal tract. The intrahepatic bile duct showed considerable interspecies variation. The human bile duct has plexiform side branches and periductal sacculi, which are most numerous near the liver hilum and fewest in the smaller portal tracts. The hilar plexus and sacculi are present on opposite sides of the bile duct. The plexus formed at the bifurcation of the bile ducts exhibits a plane. Periductal sacculi were also observed in the monkey and pig bile ducts, particularly the latter, while rat bile ducts possess a peculiar portal bile ductular plexus situated between the portal tract and the surrounding liver parenchyma. No such structures were observed in either the dog or rabbit bile ducts. SEM of the biliary casts showed that the biliary tract was not a simple draining tube but had additional structures, such as periductal sacculi and plexiform side branches. These structures, together with the peribiliary vascular plexus, may be implicated in the modification of bile.

Biliary Tract