Bile Stagnation Research Articles

Mucosal cell proliferation activity of the gallbladder in children with anomalous arrangement of the pancreaticobiliary duct.

Anomalous arrangement of the pancreaticobiliary duct (AAPBD) is an anatomical maljunction of the bile duct and the pancreatic duct that is frequently associated with gallbladder carcinoma. In patients with AAPBD, it has been postulated that pancreatic juice regurgitates into the biliary tree, and the mixture of refluxed pancreatic juice and stagnant bile juice acts as an irritant factor to the biliary tract epithelium, leading to chronic inflammation and metaplasia. Eventually these mucosal changes may progress to invasive carcinoma. We reviewed clinicopathologic studies on epithelial changes of the gallbladder in patients with AAPBD to clarify the implications relevant to carcinogenesis. Conventional histological studies have shown that the most characteristic change observed in the gallbladder of children with this anomaly was epithelial hyperplasia. Furthermore, the incidence of mucosal hyperplasia was significantly increased in the gallbladder of children in whom the pancreatic duct joined the common bile duct (P-C type) compared with the incidence in children in whom the common bile duct joined the pancreatic duct (C-P type). In addition, cell kinetic studies have demonstrated increased cellular proliferative activity of the gallbladder in children with AAPBD. Cell proliferative activity was significantly elevated in children with the P-C type of AAPBD compared with that in children with the C-P type of anomaly. In conclusion, AAPBD may yield increased cell proliferation in the gallbladder of patients with this anomaly in early childhood, resulting in epithelial hyperplasia. Although it remains unknown which agents are responsible for promoting the activation of cellular function, it seems that bile acids and refluxed pancreatic proteases are likely play a role in such promotion. Further investigations are needed to elucidate the mechanism of increased cellular function.

EXPERIENCE WITH OPERATION FOR HEPATOLITHIASIS ASSOCIATED WITH ANOMALOUS BILIARY ANATOMY-A CASE REPORT-

A 30-year-old man was admitted to the hospital because of epigastralgia and jaundice. Abdominal ultrasound examination and computed tomography revealed dilated intrahepatic bile ducts in the right posterior and left medial segments. ERCP radiographs showed anomalous biliary anatomy with the right posterior segmental duct inserting into the right anterior segmental duct. In addition, the latter was drained into the left lateral duct. A right posterior segmentectomy and a left medial segmentectomy were conducted. No bilioenteric anastomosis was placed. The patient was discharged on the 21st postoperative day. The general rules for the treatment of hepatolothiasis are to remove calculi completely and to relieve bile stagnation. This case highlights the importance of an awareness of biliary tract anomaly and the necessity of appropriate treatment for hepatolithiasis with anomalous anatomy where a hepatecotmy sholud be employed by making the most use of intraoperative US and cholangioscopy, if it can be a radical operation.

A CASE OF ACCESSORY LIVER CONTAINING HEMATOMA

Accessory liver is a rare congenital abnormality. Only 77 case have been reported in the Japanese literature including or case. A 74-year-old female was admitted to the hospital because of general fatigue. Various imaging methods revealed a tumor in the right subphrenic area. We suspected that this tumor was origniating in the liver or in the right adrenal gland. Preoperative definite diagnosis was not made, but a possibility of co-existence of malignant lesions was not ruled out. So an operation was performed. Entering into the abdominal cavity, found a tumor adherent to the right adrenal gland and compression the right lobe of the liver. Macroscopically, and direct connection between the accessory liver the primary liver was found out. The tumor with the right adrenal gland was excised. The pathological examination of the resected tumor revealed the normal hepatic lubule and no bile stagnation. Furthermore, this tumor contained a hematoma surrounded with lepatic tissue. We considered that the blood vessels, portal vein and bile duct were communicated with the primary liver through a restiform part. However, it is still unclear why the hematoma was occurred.

Cholestasis as a liver protective factor in paracetamol acute overdose

1. 1. The effect of paracetamol overdoses on its disposition was investigated in cholestatic rats. 2. 2. Paracetamol plasma concentration and hepatic accumulation decrease about 70–80% in cholestatic rats. 3. 3. Cholestatic rats intoxicated with paracetamol showed less hepatic damage as concluded from biochemical and histological findings. These data are correlated with liver and plasmatic paracetamol. 4. 4. These results indicate a decrease in paracetamol toxicity related to stagnant bile.

UW-preservation of cultured human gallbladder epithelial cells: Phenotypic alterations and differential mucin gene expression in the presence of bile

In orthotopic liver transplantation, extended cold ischemia of the graft may induce cell damage, particularly in biliary epithelium. We have investigated the effects of a cold University of Wisconsin (UW) solution on cultured human gallbladder biliary epithelial cells (GBEC) exposed or not exposed to stagnant bile. In UW solution, morphological alterations of cultured GBEC were not prominent under light microscopy after 16 hours at 4°C, being more striking after 24 to 48 hours. Ultrastructural examination of GBEC showed a condensation of chromatin at the periphery of the nuclei after 16 hours in cold UW solution. Both protein and DNA syntheses were strikingly reduced in these cells. After rewarming in standard Williams' medium at 37°C for 24 hours, cultured GBEC exhibited both normal morphology and function. As in both freshly isolated and routinely cultured GBEC, rewarmed cells expressed various mucin genes, namely MUC1, MUC3, MUC4, MUC5AC, and MUC5B genes, whereas MUC2 mRNAs were barely detectable. Adramatic decline in the steady-state mRNA levels of both MUC3 and MUC5B was found in cultured GBEC versus freshly isolated cells. Addition of bile into UW solution at 4°C had no significant effect on GBEC morphology and DNA and protein syntheses. When bile was added during the rewarming period, both protein and DNA syntheses were strongly reduced. Addition of bile during either storage in UW solution or rewarming period induced increased steady-state MUC2, MUC3 and MUC5AC mRNA levels. These results show that UW is a reliable cold storage solution for GBEC and the presence of stagnant bile within the culture medium during the rewarming period leads to deleterious phenotypic alterations of these cells. This suggests changes in the management of liver graft during orthotopic liver transplantation.

Uw-preservation of cultured human gallbladder epithelial cells: Phenotypic alterations and differential mucin gene expression in the presence of bile

In orthotopic liver transplantation, extended cold ischemia of the graft may induce cell damage, particularly in biliary epithelium. We have investigated the effects of a cold University of Wisconsin (UW) solution on cultured human gallbladder biliary epithelial cells (GBEC) exposed or not exposed to stagnant bile. In UW solution, morphological alterations of cultured GBEC were not prominent under light microscopy after 16 hours at 4 degrees C, being more striking after 24 to 48 hours. Ultrastructural examination of GBEC showed a condensation of chromatin at the periphery of the nuclei after 16 hours in cold UW solution. Both protein and DNA syntheses were strikingly reduced in these cells. After rewarming in standard Williams' medium at 37 degrees C for 24 hours, cultured GBEC exhibited both normal morphology and function. As in both freshly isolated and routinely cultured GBEC, rewarmed cells expressed various mucin genes, namely MUC1, MUC3, MUC4, MUC5AC, and MUC5B genes, whereas MUC2 mRNAs were barely detectable. A dramatic decline in the steady-state mRNA levels of both MUC3 and MUC5B was found in cultured GBEC versus freshly isolated cells. Addition of bile into UW solution at 4 degrees C had no significant effect on GBEC morphology and DNA and protein syntheses. When bile was added during the rewarming period, both protein and DNA syntheses were strongly reduced. Addition of bile during either storage in UW solution or rewarming period induced increased steady-state MUC2, MUC3 and MUC5AC mRNA levels.(ABSTRACT TRUNCATED AT 250 WORDS)

The effects on cellular functions of bile acid and trypsin in stagnant bile juice in anomalous arrangement of the pancreaticobiliary duct

To examine the reasons for the high frequency of biliary tract carcinogenesis in individuals with anomalous arrangement of the pancreaticobiliary duct (AAPBD), we investigated the effects on cellular functions of bile acid and trypsin, which are possible risk factors for carcinogenesis found in stagnant bile juice, using a chick embryo fibroblast culture system. Bile acid was found to increase PGE 2 synthesis which has been shown to be increased in premalignant lesions, but to suppress the incorporation of [ 3H]-labelled TdR into DNA. On the other hand, trypsin increased the incorporation of [ 3H]TdR into DNA, but did not increase PGE 2 synthesis. These results suggest that both the bile acid and trypsin present in the stagnant bile juice in AAPBD act to stimulate cell proliferation, but that their mechanisms of action on cell growth differ. Therefore, the combination of these effects of different types of tumor promoters in the stagnant bile juice in AAPBD may account for the high incidence of carcinogenesis.

Clinical Evaluation of a Low Junction of the Cystic Duct

The point of the junction of the cystic duct with the common hepatic duct was studied by means of various preoperative and intraoperative cholangiographic procedures and by gross intraoperative examinations in 468 surgical patients with biliary diseases. The cystic duct entered the hepatic duct at a very low position and was consequently long in 39 patients. The clinical significance of this abnormally low junction of the cystic duct was studied in comparison with 358 patients with gallstones with a normal cystic duct-hepatic duct junction. In the low-junction group with a short common bile duct several complications, including gallstone pancreatitis (7 patients), the Mirizzi syndrome (7), confluence stones (2), gallbladder cancer (3), and congenital dilation of the cystic duct (1), were demonstrated preoperatively. The anomalous junction of the cystic duct with the common bile duct may cause stagnation of bile and/or reflux of pancreatic juice into the bile duct, producing a choledochopancreatic ductal junction and posing difficulties at surgery.

Treatment of postcholedochoduodenostomy symptoms.

Upper abdominal symptoms after side-to-side choledochoduodenostomy (CDDY) may be attributed to stagnant bile, food and calculi pooling in the distal bile duct 'sump' with resultant biliary or pancreatic duct obstruction and sepsis. Endoscopic sphincterotomy (ES) provides a means of draining this sump. The aim of this study was to assess outcome following endoscopic retrograde choledochopancreatography (ERCP) and ES in patients with post-CDDY symptoms. Eight such patients (M: F = 1:7) underwent ERCP between September 1981 and March 1987. Their median age was 60 years (range: 37-72 years) and the median period since CDDY was 11 years (range: 1-28 years). The median follow-up after ERCP was 18 months (range: 14-94 months). Presenting symptoms comprised postprandial (one) or intermittent (seven) abdominal pain, cholangitis (three), pancreatitis (one) and jaundice (one). ERCP revealed bile duct abnormalities in four, consisting of filling defects alone (two), anastomotic narrowing with filling defects (one) and sclerosing cholangitis. ES was performed in seven, of whom three (all with filling defects at ERCP) remain asymptomatic and three are significantly improved. One had recurrent pancreatitis for which a sphincteroplasty and pancreatic duct septectomy was performed. ES was not performed in one because of technical difficulties (there being no subsequent improvement). It is concluded that, in patients with post-CDDY biliary symptoms, endoscopic sphincterotomy relieves the symptoms by either producing drainage of the sump at the distal bile duct, or dividing a dysfunctioning sphincter of Oddi.

Reoperation for Congenital Choledochal Cyst

A reoperation after excisional procedure was carried out in seven cases due to early or late postoperative complications. Of the 12 patients with early complications, four underwent relaparotomy due to anastomotic leakage and bleeding. Late complications were seen in nine patients with recurrent cholangitis caused by an anastomotic stricture, and three patients with intrahepatic involvement required a reoperation several years after the initial surgery. Recurrent cholangitis after biliary reconstruction mainly occurs due to an anastomotic stricture of the hepaticoenterostomy. There was no significant difference in the results between hepaticoduodenostomy and hepaticojejunostomy over a long follow-up period. A wide anastomotic stoma that permits free drainage of bile into the intestine is imperative to the prevention of cholangitis, and can be created by an incision extending along the lateral wall of both the hepatic ducts with a hepaticoenterostomy at the hilum. This procedure is obviously necessary in all patients with or without intrahepatic involvement. Carcinoma of the intrahepatic ducts and the retained distal choledochus have rarely developed in patients undergoing cyst excision followed by biliary reconstruction. Complete excision of the whole extrahepatic bile duct could prevent carcinoma arising in the distal choledochus, although it could not prevent carcinoma arising from the intrahepatic ducts. However, patients with carcinoma of the intrahepatic duct were reported to have had symptoms of biliary stricture for a long time since the cyst excision. Bile stagnation in the intrahepatic ducts is possibly responsible for the development of carcinoma. A wide anastomosis resulting in free drainage of bile appears to be essential to the prevention of carcinoma arising in the intrahepatic ducts after cyst excision.

Letters to the editor. Vol. 68, No. 2 (1987)

Nowadays, to prevent exacerbation of chronic cholecystitis it is recommended to follow a strict diet, in particular to limit consumption of fats. But it is known that fats and some other foodstuffs cause shrinkage of gallbladder, free it from bile and possible presence of gallstones and bacteria. Any violation of the outflow of bile from the gallbladder, stagnation of bile in it contributes to the formation of gallstones and the development of infection in the bladder, and therefore exacerbation or appearance of cholecystitis.

IgA-associated glomerular deposits in liver disease

IgA-associated immunopathologic renal injury has been reported in patients with cirrhosis. In an effort to elucidate the pathogenesis of this phenomenon, the livers and kidneys obtained at autopsy from a group of patients with cystic fibrosis were studied; these patients were selected because of their broad spectrum of liver abnormalities. On the basis of histologic examination of sections of liver, the patients were divided into two groups: Group I (20 patients) included patients with focal biliary cirrhosis and multilobular biliary cirrhosis; all had anatomic distortion of the biliary system, and many had cholestasis. Group II (28 patients) showed no bile duct anomalies. Immunofluorescence studies of the corresponding kidneys for immunoglobulin, complement, and free secretory component (FSC) revealed significantly more numerous IgA-containing glomerular deposits in group I (P less than 0.02). Although FSC was virtually absent in these deposits, significant in vitro binding of this protein revealed the polymeric nature of the glomerular IgA. This is consistent with previous observations of elevated serum levels of polymeric IgA, which forms the dominant component of glomerular deposits in cirrhotic patients. Since IgA glomerular deposition occurred in patients with focal biliary and no hepatocellular dysfunction, it seems that the source of this polymeric IgA is related to its impaired serum clearance by a distorted and stagnant bile duct system. However, the mechanism that leads to the deposition of this immunoglobulin in the glomeruli and other tissues remains conjectural.

Liver microsomal bilirubin UDP-Glucuronyltransferase disturbances in bile duct ligated rats

The activity of bilirubin UDP-Glucuronyltransferase was determined in microsomes from normal and bile duct ligated rats. It was measured after 2 and 8 days following bile duct ligation and compared with normal rats. A decrease of 33% in the total enzyme activity was observed on day 2; a fall of 70% was founded on day 8. Bilirubin diglucuronide represented approximately 20% of total conjugates in both groups of cholestatic rats, as compared with 65% found in normals. It was concluded that bilirubin microsomal conjugating capacity is markedly altered during cholestasis. This can be attributed to microsomal membrane damage produced by stagnant bile.

A CASE OF CHOLANGIOCARCINOMA ASSOCIATED WITH HEPATOLITHIASIS

The diagnosis of hepatolithiasis, a condition which had previously been difficult to diagnose and treat, has become easier because of ultrasonic examination and puncture under ultrasonographic imaging. The results of treatment have also improved with the development of lithotomy under percutaneous cholangiographic observation by ultrasound, i.e., the application of ultrasonic examination and puncture. However, cholangiocarcinoma occurring as a complication of hepatolithiasis remains an important problem. The clinical course of a 28-year-old male patient who suffered cholangiocarcinoma associated with hepatolithiasis for 12 years is reported with references to the Japanese literature. Since cases of cholangiocarcinoma associated with hepatolithiasis are considered to result from repetition of chronic intrahepatic cholangitis and bile stagnation, it is necessary for the treatment of hepatolithiasis to perform ultrasonic examination together with biopsy of the bile duct in the liver by selective arteriography, biliary cytodiagnosis or cholangioscopy, even after lithotomy, and to continue careful postoperative observation.

Peripapillary duodenal diverticulum and biliary tract diseases.

The relationship between peripapillary duodenal diverticulum and benign biliary tract disease was studied. Peripapillary duodenal diverticulum could be classified pathophysiologically into three types. Type I represents the disease not directly affecting the biliary tract. Type II shows the elevation of bile duct pressure directly caused by intraduodenal pressure loading. Type III includes patients in whom the diverticulum is small and is prone to cause papillitis or mechanical stimulation. This, then, may lead to organic changes in Oddi's sphincter and possibly to biliary tract disorders. In our patients, many cases of peripapillary duodenal diverticulum were associated with calcium bilirubinate stones, indicating that a peripapillary duodenal diverticulum is likely to lead to bile stagnation and ascending infection of the biliary tract and thus cause formation of calcium bilirubinate stones. Based on findings in this study, we want to emphasize that Type II peripapillary duodenal diverticulum should be surgically treated.

血清γ‐ＧＴＰアイソザイムのアガロース等電点電気泳動分析

Analysis of serum γ-GTP isoenzymes was attempted with isoelectric focusing using agarose gel as a supporting medium. After testing various conditions to obtain electrophoretic patterns with good reproducibility, suspension of Ampholine in Agarose IEF was finally chosen as a supporting medium, and electrolysis at 6.25W/plate (length 12.5cm×width 11cm) for 1hr under cooling with circulating water was found to be most appropriate. A serum sample, 20μl, absorbed to a small piece of filter paper was applied onto the medium 1cm away from the cathode. Under these conditions, the pH gradient was linear in the range from pH 3.5 to 9.5, and serum proteins were clearly separated.This method was applied to the separation of γ-GTP isoenzymes. γ-GTP was stained with γ-L-glutamyl-p-diethylaminoanilide. After electrophoresis, the gel was fixed with 50% saturated ammonium sulfate solution followed by removal of the ammonium sulfate, and then submitted to staining procedures. This pretreatment was found to give very clear and permanently preservable electrophoretic patterns. Serum γ-GTP was separeted into 7 isoenzyme bands by this method. The bands which consistently appeared were in pI range of 4.5-5.0, while a band at pI 5.5 was noted in the cases of bile stagnation, and a band at pI 6.5 was observed in cases with malignant tumors.

Refinements in Chiba needle trans hepatic cholangiography

The recent wide acceptance of Chiba needle transhepatic cholangiography prompted this elaboration of present techniques, intraprocedure observations, and special interpretive considerations based on a series of 100 consecutive examinations. The established safety margin of this technique now permits up to 15 needle passes to obtain a cholangiogram; thus success rates of duct opacification presently approach 100%. Special phenomena related to the small caliber of the needle include duct filling from "invisible" radicles, perivenous or periductal dissection of contrast, and pseudolesions in an incompletely decompressed stagnant bile column. The role of fine needle cholangiography in light of other present day technology for evaluating obstructive jaundice (ultrasonography, computed tomography, and endoscopic retrograde cholangiography) is discussed.

Intrahepatic biliary obstruction in congenital bile duct atresia.

The three-dimensional structure of small intrahepatic bile ducts in congenital biliary atresia was examined by graphical reconstruction of serial histological sections. In the disease, intrahepatic bile duct system was constituted by an extremely complex network of proliferating bile ductules. Bile duct proliferation was interpreted as a reaction of the bile system to bile stagnation and bile leakage in the portal area. The restoration of a patent intrahepatic bile system seemed to depend upon the preservation of `main routes' of bile passage, which probably belonged to the pre-existing bile duct system. The maintenance of anatomically recognizable main routes could be correlated with the clinical effect of extrahepatic bile duct plasty.

Carcinoma in Choledochal Cyst

Choledochal cysts are congenital malformations and can be classified into four types. The type 1 lesion is the usual form; the others are extremely uncommon. The treatment in most cases should be surgical drainage into the gastrointestinal tract, preferably using the jejunum in Roux-en-Y fashion. The presence of a carcinoma within the cyst requires excision of the cyst if technically feasible as this offers the best hope for cure. The role of prolonged exposure of the cyst epithelium to stagnant bile in the etiology of the carcinoma has not yet been settled. Two patients with carcinoma in a choledochal cyst were treated at the New York Hospital—Cornell Medical Center.

Biliobiliary Fistulae

Biliobiliary fistulae constitute one of the nonmalignant complications of gallstone disease. Never diagnosed before the operation—either clinically or roentgenologically—they are exclusively an operating-table finding. They always occur in connection with long-standing lithiasis. In our practice we have been able to observe several patients with this type of complication. Etiologically this condition is directly related to the impaction of stones at some level of the biliary tract, where they originate decubitus lesions. The calculus obstructs the bile flow and its pressure on the wall impairs the local circulation at the site of impaction. There is venous congestion, followed later by arterial ischemia, leading to the infarction of the decubitus plaque, with or without contamination of the stagnant bile. At the affected zone, the normal elements of the wall are replaced by scar tissue, leaving a locus minoris resistentiae. The process can more frequently be observed at the neck of