Does the intestinal microenvironment have an impact on the choleretic effect of inchinkoto,a hepatoprotective herbal medicine?

Aim

The choleretic effects of inchinkoto (ICKT), a hepatoprotective herbal medicine, are variable among patients. This study sought to investigate the correlation between the choleretic effects of ICKT and the intestinal microenvironment in patients with biliary obstruction.

Methods

Patients with biliary obstruction who underwent external biliary drainage were enrolled. The concentrations of total bilirubin and bile acid in the bile, and genipin, a major active ingredient of ICKT, in the bloodstream before and after ICKT treatment were measured. Feces were collected from the patients to determine bacterial count and organic acid concentrations.

Results

Samples from 37 patients were collected and analyzed. The serum concentration of genipin increased 3 h after ICKT treatment and showed a positive correlation with the percent changes of biliary concentrations of bile acid, total bilirubin, and direct bilirubin. Serum genipin concentration also showed a positive correlation with the fecal concentrations of representative obligate anaerobes such as the Clostridium leptum subgroup, Bacteroides fragilis group, Bifidobacterium, and the Atopobium cluster. In sharp contrast, so‐called harmful bacteria such as Clostridium difficile, Enterobacteriaceae, and Enterococcus showed a negative correlation with the concentration of genipin. Genipin concentration after ICKT administration showed a positive correlation with the fecal concentration of short chain fatty acids such as propionic acid and butyric acid, and a negative correlation with the fecal concentration of lactic acid.

Conclusions

The absorption of genipin was variable among patients. This variability may be associated with the fecal microenvironment profile and partly explain the variable choleretic effects of ICKT among patients.     

Effects of obstructive jaundice on neutrophil production and acquisition of chemotactic activity in the bone marrow

Background and Aims:  Increased numbers and enhanced functions of peripheral neutrophils have been observed in obstructive jaundice. However, the effects of obstructive jaundice on the bone marrow, that is neutrophil production and acquisition of neutrophil chemotactic activity, have been poorly understood. In the present study, differentials of bone marrow cells and chemotactic activity of bone marrow neutrophils were evaluated in bile duct-obstructed rats.
Methods:  Male Wistar rats underwent either bile duct obstruction for 10 days or bile duct obstruction for 4 days followed by 6 days' internal biliary drainage. Differentials of peripheral blood and bone marrow cells were sequentially determined. Chemotactic activity of peripheral and bone marrow neutrophils was evaluated with a modified Boyden method using interleukin-8 (recombinant rat Gro-β) as a chemoattractant.
Results:  Numbers of peripheral neutrophils significantly increased after bile duct obstruction. Significant increases in the myeloid/erythroid (M/E) ratio of bone marrow cells were observed after bile duct obstruction. The neutrophil proliferative pool (promyelocytes and myelocytes) increased initially, followed by an increased neutrophil storage pool (metamyelocytes, bands, and segmented neutrophils). The M/E ratio as well as the neutrophil proliferative and storage pools normalized after internal biliary drainage. Chemotactic activity was enhanced in both peripheral and bone marrow neutrophils after bile duct obstruction, and enhanced chemotaxis was alleviated with internal biliary drainage.
Conclusion:  The present results strongly suggest the principal role of the bone marrow in increasing the number of neutrophils and their chemotactic activity during obstructive jaundice.     

Long-term prognosis of patients with endoscopically treated postoperative bile duct stricture and bile duct stricture due to chronic pancreatitis

Aim:  To compare the outcome of endoscopic therapy for postoperative benign bile duct stricture and benign bile duct stricture due to chronic pancreatitis, including long-term prognosis.
Methods:  The subjects were 20 patients with postoperative benign bile duct stricture and 13 patients with bile duct stricture due to chronic pancreatitis who were 2 years or more after initial therapy. The patients underwent transpapillary drainage with tube exchange every 3 to 6 months until being free from the tube. Successful therapy was defined as a stent-free condition without hepatic disorder.
Results:  Endoscopic therapy was successful in 90% (18/20) of the patients with postoperative bile duct stricture. The stent was removed (stent free) in 100% (20/20) of the patients, but jaundice resolved in only 10% (2/20) of patients while biliary enzymes kept increasing. Restricture occurred in 5% (1/20) of the patients, but after repeat treatment the stent could be removed. In patients with bile duct stricture due to chronic pancreatitis the therapy was successful in only 7.7% (1/13) of the patients; the stent was retained in 92.3% (12/13) of the patients during a long period. Severe acute pancreatitis occurred in 3.0% (1/33) of the patients as an accidental symptom attributable to endoscopic retrograde cholangiopancreatography (ERCP); however, it remitted after conservative treatment.
Conclusion:  Our results further confirm the usefulness of endoscopic therapy for postoperative benign bile duct strictures and good long-term prognosis of the patients.     

Intraductal chilled saline perfusion to prevent bile duct injury during percutaneous radiofrequency ablation for hepatocellular carcinoma

Background and Aim:  Radiofrequency ablation (RFA) is a promising, minimally invasive treatment for hepatocellular carcinoma (HCC). However, thermal injury sometimes occurs in the bile duct, potentially leading to a critical situation. The aim of the present study was to investigate whether bile duct injury is reduced by an intraductal chilled saline perfusion (ICSP) through a nasobiliary tube during RFA for HCC.
Patients and Methods:  The baseline incidence of bile duct injury at Gifu Municipal Hospital was 3.1% (13 patients) in 424 patients with HCC treated by percutaneous RFA. In all patients, the tumor was within 5 mm of the central bile duct on CT images. The incidence of bile duct injury was 46% among the 28 selected patients whose tumor was close to the central bile duct. To prevent complications in such high-risk patients, we placed a nasobiliary tube endoscopically before RFA, and performed ICSP during RFA. Forty consecutive patients with tumors close to the central bile duct were enrolled in this study.
Results:  Of the 40 enrolled patients, only one had biliary injury, whereas the remaining 39 patients were able to avoid it. The incidence of biliary injury was significantly reduced in the ICSP group (1/40, 2.5%) compared to that in the control group (13/28, 46%) ( P  < 0.0001). Moreover, the liver function 6 months after RFA was also better preserved in the ICSP group according to Child–Pugh grading, thus resulting in a better clinical outcome.
Conclusions:  ICSP through a nasobiliary tube is a potential intervention method to prevent biliary injury by percutaneous RFA.     

Effect of ursodeoxycholic acid on serum liver enzymes and bile acid metabolism in chronic active hepatitis C virus infection

Aim:  Many reports have revealed ursodeoxycholic acid (UDCA) to be effective against chronic hepatitis C virus (HCV). However, some cases resist this therapy and the mechanism of action remains unclear. In this study, UDCA was administered to patients with chronic HCV and the correlation between the bile acids of the biliary bile and serum and the drug efficacy was investigated.
Methods:  Fifteen patients were given 600 mg/day of UDCA for more than 24 weeks. The serum bile acid concentrations and biliary and serum bile acid were collected before and after 24 weeks of UDCA treatment, and composition determined by high-performance liquid chromatography.
Results:  The treatment was effective in nine cases (ALT decreased to less than twice the normal values 80 IU/L) and ineffective in six cases. There was no significant difference in the serum bile acid concentrations before and after UDCA treatment between the values of both cases. After UDCA treatment, the serum percentage of UDCA (effective, 62.5 ± 2.0; ineffective, 53.5 ± 2.5, ( P  = 0.02)) and the percentage of chenodeoxycholic acid (CDCA) showed no remarkable changes. In the biliary bile the percentage of CDCA (effective, 30.9 ± 2.0; ineffective, 20.0 ± 3.0, ( P  = 0.007)) and the percentage of UDCA showed no remarkable changes.
Conclusion:  In the effective cases, the percentage of UDCA in the serum and the percentage of CDCA in biliary bile were significantly higher than in the ineffective cases. This indicates that, when effective, CDCA decreases in hepatocytes and this reduction contributes to hepatoprotection.     

Long-term outcome of endoscopic therapy in patients with bile duct injury after cholecystectomy

Background and Aim:  Bile duct lesions, including leaks and strictures, are immanent complications of open or laparoscopic cholecystectomy. Endoscopic procedures have gained increasing potential as the treatment of choice in the management of postoperative bile duct injuries.
Methods:  Between January 1996 and December 2006, 44 patients with biliary leakages and 12 patients with biliary strictures after cholecystectomy were identified by analyzing the endoscopic retrograde cholangiopancreatography database, clinical records, and cholangiograms. The long-term follow up of endoscopic treatment in biliary lesions after cholecystectomy was evaluated by this retrospective study.
Results:  In 34 of 35 patients (97%) with peripheral bile duct leakages, endoscopic therapy was successful. Transpapillary endoprothesis and/or nasobiliary drainage were removed after 31 (5–399) days. After stent removal, the median follow-up period was 81 (11–137) months. In patients with central bile duct leakages, the success rate after median 90 (4–145) days of endoscopic therapy was 66.7% (6/9 patients). The median follow up after stent removal in six successfully treated patients was 70 (48–92) months. Eleven of 12 patients (91.6%) with bile duct strictures had successfully completed stent therapy. The follow-up period of this patient group was 99 (53–140) months.
Conclusions:  Endoscopic treatment of bile duct lesions after cholecystectomy is effective, particularly in patients with peripheral bile duct leakages and bile duct strictures. Therefore, it should be the first-line therapy used in these patients. Although endoscopic management is less successful in patients with central bile duct leakages, an attempt is warranted.     

Endoscopic management of bile leaks after blunt abdominal trauma

Background and Study Aims:  Endoscopic retrograde cholangiopancreaticography (ERCP) has been found to be useful for the diagnosis and treatment of post-traumatic bile leaks, but data on outcome after therapeutic ERCP is limited. We performed a prospective study on evaluation of ERCP for diagnosis and treatment of bile leaks following blunt abdominal trauma.
Patients and Methods:  Ten patients of bile leaks following blunt abdominal trauma were evaluated for modes of injury, clinical presentations, investigations, ERCP findings, modes of therapy and outcome. The time interval between trauma and ERCP, ERCP and healing of bile leak and complications of ERCP were also recorded.
Results:  Ten patients (age 21.9 ± 14.5 years, 6 males) presented 24.6 ± 17.1 days following trauma. The modes of injury were motor vehicle accident ( n  = 6), and fall from height ( n  = 4). The ERCP revealed bile leak from the right hepatic duct ( n  = 7), both right and left hepatic ducts ( n  = 1), mid-common bile duct ( n  = 1), and peripheral branches of right hepatic duct ( n  = 1). Procedures for ERCP included endoscopic sphincterotomy (ES) with stenting in nine patients and ES with nasobiliary drainage in one patient. Bile leak resolved in all the patients in 8.5 ± 8.2 days. Biliary stents and the nasobiliary drain were removed after 36.4 ± 16.2 days of their insertion and all the patients remain asymptomatic for follow up of 33 ± 20.8 months.
Conclusions:  Therapeutic ERCP procedures like endoscopic sphincterotomy with stenting or nasobiliary drainage are effective in management of bile leaks following blunt abdominal trauma.     

Changes in IgA following varying degrees of biliary obstruction in the rat

Polymeric IgA is rapidly transported from blood to bile by the rat liver. The effect of varying degrees of biliary obstruction on this transport process was studied. IgA concentrations were measured by radioimmunoassay. Serum IgA concentrations increased progressively, and IgA output in bile declined with increasing bile duct obstruction. The decline in bile IgA output was explained by both diminished bile flow and decreased concentrations of IgA in bile. Very little polymeric IgA was present in normal rat serum. In contrast, using column chromatography on Ultrogel AcA 22, increases in serum IgA associated with cholestasis were shown to be due to increments in polymeric IgA. Serum IgA was a more sensitive indicator of cholestasis than was serum alkaline phosphatase. IgA and secretory component were found, using indirect immunofluorescence, surrounding bile canaliculi and on or adjacent to the hepatocyte plasma membrane lining the sinusoids. With biliary obstruction, staining for IgA and secretory component intensified markedly near the bile canaliculi. We conclude that: (a) polymeric IgA must be efficiently removed from serum by the normal rat liver; (b) even minimal cholestasis impairs IgA output into bile, and (c) impairment of IgA transport during cholestasis appears to occur at or near the canalicular membrane.     

Endoscopic retrograde cholangiopancreatography in hepatic alveolar echinococcosis

Background and Aim:  Hepatic alveolar echinococcosis (HAE) involves both the vascular and biliary structures of the liver. Endoscopic retrograde cholangiopancreatography (ERCP) is said to be an alternative for the diagnosis and treatment of biliary complications of HAE. We present here our experience with ERCP in HAE.
Methods:  We followed 13 patients who underwent ERCP for the treatment of biliary complications of HAE in the endoscopy unit of our clinic at Ataturk University School of Medicine, Erzurum between January 2002 and June 2008.
Results:  Eight men and five women were followed up. Mean age was 43.2 (24–64 years). All patients had non-resectable HAE. Indications for ERCP were biliary fistula in seven patients, obstructive jaundice in five patients and cholangitis in one patient. Endoscopic sphincterotomy (ES) was carried out in 12 patients, and in one patient with biliary leakage, a stent was inserted into the right hepatic branch. ERCP findings were dilated common bile duct, irregular narrowing and distortion of the common bile duct and common hepatic duct, communication with the cystic cavity or biliocutaneous fistula and complete disappearance of the biliary tree above the level of the common hepatic duct or hepatic bifurcation. In patients with biliary leakage, biliary drainage decreased only in two patients after ERCP and in patients with obstructive jaundice, the high bilirubin levels decreased in only one patient.
Conclusion:  ERCP showed structural changes of the external biliary tract and ES has a limited effect on these changes and stents can be used in selected cases.     

Genipin enhances Mrp2 (Abcc2)-mediated bile formation and organic anion transport in rat liver

Inchin-ko-to (ICKT), an herbal medicine, and its ingredients exert potent choleretic effects by a "bile acid-independent" mechanism. The current study was designed to determine whether ICKT or its ingredients potentiate multidrug resistance-associated protein 2 (Mrp2; Abcc2)-mediated choleresis in vivo. Biliary secretion of Mrp2 substrates and the protein mass, subcellular localization, and messenger RNA (mRNA) level of Mrp2 were assessed in rat liver after infusion of genipin, an intestinal bacterial metabolite of geniposide, a major ingredient of ICKT. The function of Mrp2 was also assessed by the adenosine triphosphate (ATP)-dependent uptake of Mrp2-specific substrates using canalicular membrane vesicles (CMVs) from the liver. Infusion of genipin increased bile flow by 230%. It also increased biliary secretion of bilirubin conjugates and reduced glutathione (GSH) by 513% and 336%, respectively, but did not increase bile acid secretion. The ATP-dependent uptake of estradiol 17-beta-D-glucuronide (E(2)17 beta G; by 265%), leukotriene C4 (LTC(4); by 161%), taurolithocholate-3-sulfate (TLC-3S; by 266%), and methotrexate (MTX; by 234%) was significantly stimulated in the CMVs from the liver. These effects were not observed in Mrp2-deficient rats. Under these conditions, genipin treatment increased the protein mass of Mrp2 in the CMVs but not the mRNA level. In immunoelectron microscopic studies, a marked increase in Mrp2 density in the canalicular membrane (CM) and microvilli was observed in the genipin-treated liver tissue sections when compared with the vehicle-treated liver tissue sections. In conclusion, genipin may enhance the bile acid-independent secretory capacity of hepatocytes, mainly by stimulation of exocytosis and insertion of Mrp2 in the bile canaliculi. ICKT may be a potent therapeutic agent for a number of cholestatic liver diseases.     

Ursodeoxycholic acid aggravates bile infarcts in bile duct-ligated and Mdr2 knockout mice via disruption of cholangioles

BACKGROUND & AIMS: The effects of ursodeoxycholic acid (UDCA) in biliary obstruction are unclear. We aimed to determine the effects of UDCA in bile duct-ligated and in Mdr2 knockout (Mdr2(-/-)) mice with biliary strictures. METHODS: Mice fed UDCA (0.5% wt/wt) or a control diet were subjected to common bile duct ligation (CBDL), selective bile duct ligation (SBDL), or sham operation. UDCA was also fed to 2-month-old Mdr2(-/-) mice. Serum biochemistry, liver histology, and mortality rates were investigated. The biliary tract was studied by plastination, India ink injection, and electron microscopy. The effects of UDCA on biliary pressure were determined by cholangiomanometry. RESULTS: UDCA feeding in CBDL mice increased biliary pressure, with subsequent rupture of cholangioles and aggravation of hepatocyte necroses, resulting in significantly increased mortality. UDCA feeding in SBDL mice aggravated liver injury exclusively in the ligated lobe. Mdr2(-/-) mice developed liver lesions resembling sclerosing cholangitis characterized by biliary strictures and dilatations. UDCA induced bile infarcts in these animals. CONCLUSIONS: UDCA aggravates bile infarcts and hepatocyte necroses in mice with biliary obstruction via disruption of cholangioles as a result of increased biliary pressure caused by its choleretic action.     

Secretion of lipoprotein-X by perfused livers of rats with cholestasis.

The major abnormal plasma lipoprotein of cholestasis (LP-X) was isolated from blood plasma and from perfusates of isolated livers of rats with biliary obstruction. In both cases LP-X was composed mainly of about equimolar parts of phospholipids and unesterified cholesterol; the small protein component was primarily the arginine-rich apolipoprotein. By electron microscopy, LP-X appeared as a unilamellar liposome (690 A mean diameter, range 400-1000 A) with the trilaminar staining image typical of phospholipid bilayers. Extensive block staining of cholestatic livers for 48 hr with warmed uranyl acetate (37 degrees) permitted the visualization of vesicles indistinguishable from LP-X within hepatic parenchyma. These trilaminar-staining vesicles occurred predominantly within bile canaliculi. They also were seen in nearby cytoplasmic vacuoles or invaginations between hepatocytes and in the space of Disse. Similar vesicles were not seen in the endoplasmic reticulum or Golgi cisternae. These observations raise the possibility that the vesicles are formed within bile canaliculi and are transported from the canaliculi to the space of Disse within pinocytotic vacuoles.     

The utility of liver function test abnormalities concomitant with biliary symptoms in predicting a favorable response to endoscopic sphincterotomy in patients with presumed sphincter of oddi dysfunction

Objectives: We sought to study the utility of liver function test abnormalities concomitant with biliary symptoms in predicting a favorable response to endoscopic sphincterotomy in patients with Geenen class II sphincter of Oddi dysfunction.
Methods: We reviewed the clinical course and liver function test results of 24 Geenen-Hogan class II postcholecystectomy patients with biliary colic secondary to sphincter of Oddi dysfunction who did not undergo sphincter of Oddi manometry before treatment with endoscopic sphincterotomy.
Results: Twenty of the 24 patients had an average of 1.4 episodes of abnormal liver function tests associated with biliary colic; eight patients had dilated common bile duct on cholangiogram. Eighteen of the 20 patients with abnormal liver function tests (90%) were pain-free after sphincterotomy; in contrast, only one of four patients (25%) without liver function test changes responded to sphincterotomy. Fisher exact analysis showed that abnormal liver function tests was a significant predictor for favorable response to sphincterotomy with a two-tail p value of 0.018. Of the eight patients with bile duct dilatation, six (75%) responded favorably to sphincterotomy, whereas 13 of 16 patients (81%) without dilatation also responded to sphincterotomy. Analysis of common bile duct dilatation as a predictive factor showed no significance (   p = 1.00  ).
Conclusions: We conclude that the occurrence of abnormal liver function tests during biliary colic may be used to select patients for endoscopic sphincterotomy. Sphincter of Oddi manometry may not be needed in these cases.     

Magnetic resonance cholangiography using half-Fourier acquisition for diagnosing choledocholithiasis

Objective: Magnetic resonance cholangiography (MRC), using a half-Fourier acquisition single-shot turbo spin-echo (HASTE) sequence, noninvasively provides very rapid (1–2 s) and high-quality images of the biliary tract. We assessed the diagnostic usefulness of HASTE-MRC for choledocholithiasis.
Methods: A total of 101 patients with suspected choledocholithiasis underwent MRC, ultrasonography, and endoscopic retrograde cholangiopancreatography (ERCP). In 97 patients in whom ERCP fully depicted the common bile duct, we retrospectively analyzed the capability of MRC to image the common bile duct and to diagnose choledocholithiasis, in comparison with that of ultrasonography.
Results: In 34 patients, ERCP demonstrated bile duct stones, which were confirmed at endoscopic or surgical treatment. The common bile duct was fully delineated in 98% by MRC and in 70% by ultrasonography. MRC (91%) was more sensitive than ultrasonography (71%) for detecting choledocholithiasis (   p < 0.05  ). MRC demonstrated bile duct stones in all patients with stones ≥11 mm but missed calculi in the 29% of patients with small (3–5 mm) stones. MRC was capable of detecting choledocholithiasis regardless of bile duct caliber. The specificity of MRC (100%) was higher than that of ultrasonography (95%).
Conclusion: HASTE-MRC, a fast and noninvasive procedure, can accurately diagnose choledocholithiasis although the detectability for small stones is limited.     

Intermediate filaments of hepatocytes and biliary epithelial cells in bile duct obstruction: transmission and scanning electron microscopy study

The cytoskeletons of hepatocytes and biliary epithelial cells in bile duct ligated rate livers were investigated by transmission and scanning electron microscopy. The three dimensional organization of the intermediate filaments (IFs) of hepatocytes and biliary epithelial cells was clearly demonstrated by scanning electron microscopy. Cell borders and dilated bile canaliculi were well preserved after perfusion with detergent solution. A very dense filamentous network of IFs was seen throughout the cytoplasm, especially around the dilated bile canaliculi and at the cell borders. IFs in biliary epithelial cells were more numerous compared with hepatocytes. Morphometric analysis showed that the IFs of hepatocytes significantly (p greater than 0.001) increased in amount in bile duct ligated rats. The IFs of biliary epithelial cells showed no significant changes in bile duct ligated rats compared to controls. These results suggest that the increase in IFs in hepatocytes results from the adaptation of the hepatocytes to the stress imposed by bile duct ligation. It may be that the resulting intracanalicular pressure and back diffusion of bile induces a metaplastic change in hepatocytes so that they acquire more IFs to function like the bile duct epithelium to conduct bile flow.     

Developmental expression of canalicular transporter genes in human liver

BACKGROUND/AIMS: BSEP, MRP2, and MDR3 are major hepatic canalicular transporters mediating bile secretion. Their expression in human liver during development has not been reported. METHODS: Human liver samples from fetus at gestational age 14-20 weeks, adult livers and liver samples of infants with biliary atresia were tested for mRNA expression of BSEP, MDR3, MRP2, NTCP, FIC1, and FXR genes by using real-time RT-PCR. Immunohistochemical staining of BSEP, MDR3, and MRP2 were performed on fetal and adult livers. RESULTS: All the genes tested were expressed at mid-gestational age. MDR3 and NTCP showed significant lower levels in fetal livers compared to adults. In patients with biliary atresia, all the genes tested showed higher mean expression levels than adults except for NTCP, but not statistically significant. The immunohistochemical staining of MRP2 in fetal liver was canalicular, BSEP showed both intracellular and canalicular staining, and MDR3 staining was faint, only occasional canalicular pattern could be seen. CONCLUSIONS: The major canalicular transporter genes are expressed at mid-gestational stage during human fetal development, but are different in expression level and targeting pattern, indicating differential regulation and maturation.     

Biliary drainage by endoscopic choledochoduodenal fistulotomy in patients with papillary carcinoma

BACKGROUND: There are few reports of endoscopic choledochoduodenal fistulotomy (endoscopic fistulotomy) in patients with papillary carcinoma by using a needle-knife. METHODS: Among 35 patients with papillary carcinoma requiring biliary drainage, 14 with a suprapapillary bulge underwent endoscopic fistulotomy alone or with widening of the fistula by using a standard sphincterotome or dilation balloon catheter. OBSERVATIONS: Transfistula bile duct cannulation was successful on the first attempt in 13 of 14 patients (93%) and temporary biliary drainage through the fistula was successfully established in all 13 patients. The single complication was minor bleeding (7%) in 1 patient. In 6 patients with biliary obstruction who were not operative candidates, endoscopic fistulotomy was used for palliation, and all remained asymptomatic for a mean period of 3.2 months. CONCLUSIONS: Endoscopic fistulotomy is an effective, relatively safe biliary drainage procedure. It should be considered in selected patients with bile duct obstruction caused by papillary carcinoma and a suprapapillary bulge caused by the dilated bile duct.     

Intermediate filaments of hepatocytes and biliary epithelial cells in bile duct obstruction: Transmission and scanning electron microscopy study

The cytoskeletons of hepatocytes and biliary epithelial cells in bile duct ligated rate livers were investigated by transmission and scanning electron microscopy. The three dimensional organization of the intermediate filaments (IFs) of hepatocytes and biliary epithelial cells was clearly demonstrated by scanning electron microscopy. Cell borders and dilated bile canaliculi were well preserved after perfusion with detergent solution. A very dense filamentous network of IFs was seen throughout the cytoplasm, especially around the dilated bile canaliculi and at the cell borders. IFs in biliary epithelial cells were more numerous compared with hepatocytes. Morphometric analysis showed that the IFs of hepatocytes significantly (p>.001) increased in amount in bile duct ligated rats. The IFs of biliary epithelial cells showed no significant changes in bile duct ligated rats compared to controls. These results suggest that the increase in IFs in hepatocytes results from the adaptation of the hepatocytes to the stress imposed by bile duct ligation. It may be that the resulting intracanalicular pressure and back diffusion of bile induces a metaplastic change in hepatocytes so that they acquire more IFs to function like the bile duct epithelium to conduct bile flow. This study was supported in part by a grant no. 62480198 from the Ministry of Education, Japan. We are thanksful to Miss Noriko Iwanami and Miss Atsuko Fujimoto for their secretarial help.     

Intraoperative fiberoptic choledochoscopy for malignant biliary tract obstruction

A prospective study to determine the safety and effectiveness of intraoperative fiberoptic choledochoscopy in the management of malignant obstruction of the biliary tree was conducted in 44 patients. There were 12 patients with cancer of the pancreatic head, 9 with adenocarcinoma of the distal common bile duct, 4 with adenocarcinoma of the ampulla of Vater, 8 with cholangiocarcinoma of the common hepatic duct, 9 with intrahepatic bile duct carcinoma, and 2 with hepatocellular carcinoma. Five patients with intrahepatic bile duct carcinoma and two with hepatocellular carcinoma were found during a search for intrahepatic duct stones in patients with recurrent cholangitis. In nine patients with bile duct carcinoma (seven extrahepatic and two intrahepatic), histopathological diagnosis was made at operative endoscopy. Treatment strategy was altered in seven patients based on findings at operative choledochoscopy. Complications were few with no mortality. Intraoperative fiberoptic choledochoscopy was safe and useful in the management of malignant obstruction of the biliary tree.