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Excretion of metroindazole in human bile. Investigations of hepatic bile, common duct bile, and gallbladder bile.

Excretion of metronidazole (MNZ) in the normal and in the diseased biliary tract was investigated in 58 patients after oral or intravenous administration of MNZ. After oral administration MNZ appeared rapidly in hepatic bile, and throughout the period of absorption and elimination almost identical concentrations of MNZ were found in serum and hepatic bile. After intravenous administration no significant differences were found between concentrations of MNZ in common duct bile and serum in the non-obstructed common duct; in common duct obstruction, concentrations of MNZ in common duct bile were 56--99 per cent of corresponding concentrations in serum. MNZ was concentrated in normal gallbladders. In patients with gallbladder stones and preserved function of the gallbladder and in patients with no function of the gallbladder but a patent cystic duct, no significant differences were found between concentrations of MNZ in gallbladder bile, common duct bile, and serum. In most gallbladders with the cystic duct blocked by a stone, no MNZ was found in gallbladder bile.

Administration, Oral↗

[Present status and possibilities of radiotherapy in the interdisciplinary treatment of malignant tumors of the stomach, pancreas and bile ducts. III. Extrahepatic bile ducts and gallbladder].

The malignant tumors of the gall bladder and the extrahepatic bile ducts belong to those having the most unfavorable prognosis. Similarly to the carcinomas of the pancreas, most of these tumors are in a very advanced stage when they are diagnosed. The survival times have not been improved by radical and ultraradical operation techniques, the operation mortality, however, has increased. In the meantime, the efficacy of radiotherapy has been proved for these tumors, too. So an additional application of radiotherapy seems indicated regarding the fact that most of these patients present postoperative locoregional recurrences. As for the carcinomas of the stomach and the pancreas, the best effect of radiotherapy can be expected in case of an intraoperative irradiation; furthermore direct percutaneous intraductal irradiation techniques have been developed for suitable cases. A possible efficacy of additional chemotherapy cannot be assessed yet; a locally adjuvant effect, as in patients with carcinoma of the pancreas, could be imagined. The authors present the surgical, radiotherapeutic, and chemotherapeutic results achieved hitherto in the treatment of the carcinomas of the extrahepatic bile ducts and the gall bladder and propose further possibilities for the future use of radiotherapy. After the failure of surgery alone an improvement of the bad prognosis of these carcinomas by cooperative therapy conceptions is a vital necessity, the more as the role of obstructive jaundice as fatal factor has been eliminated by the non-surgical percutaneous transhepatic drainage of bile ducts.

Bile Duct Neoplasms↗

Main pancreatic duct, common bile duct and sphincter of Oddi structure visualized by optical coherence tomography: An ex vivo study compared with histology.

BACKGROUND: Optical coherence tomography has been proposed to obtain high-resolution imaging of tissue structure of GI tract. Up till now, the optical coherence tomography appearance of the common bile duct, main pancreatic duct and sphincter of Oddi wall structure has not yet been defined. AIMS: To compare, in a prospective study, optical coherence tomography images of pancreato-biliary ductal system with histology and identify the optical coherence tomography pattern of the normal wall structure of the ducts. METHODS: Multiple sections of non-neoplastic segments of five consecutive ex vivo human pancreatic specimens were investigated by optical coherence tomography scanning within 1h of resection. Sixty optical coherence tomography images were compared with the corresponding histological findings. RESULTS: Optical coherence tomography appearance of normal common bile duct, main pancreatic duct and sphincter of Oddi is characterized by a differentiated three-layer architecture with a regular surface and a homogeneous back-scattered signal, corresponding to the single layer of epithelial cells, the connective-muscular layer and the muscular or acinar structure, respectively. Optical coherence tomography and histology findings were concordant in all cases. CONCLUSIONS: Optical coherence tomography was able to provide in real-time images of wall structure of the normal common bile duct, main pancreatic duct and sphincter of Oddi that are similar to those obtained by histology. These results suggest that optical coherence tomography could enable high-resolution images to be obtained from the pancreato-biliary system during an ERCP procedure.

Aged↗

Administration of r-VEGF-A prevents hepatic artery ligation-induced bile duct damage in bile duct ligated rats.

The hepatic artery, through the peribiliary plexus, nourishes the intrahepatic biliary tree. During obstructive cholestasis, the nutritional demands of intrahepatic bile ducts are increased as a consequence of enhanced proliferation; in fact, the peribiliary plexus (PBP) displays adaptive expansion. The effects of hepatic artery ligation (HAL) on cholangiocyte functions during cholestasis are unknown, although ischemic lesions of the biliary tree complicate the course of transplanted livers and are encountered in cholangiopathies. We evaluated the effects of HAL on cholangiocyte functions in experimental cholestasis induced by bile duct ligation (BDL). By using BDL and BDL + HAL rats or BDL + HAL rats treated with recombinant-vascular endothelial growth factor-A (r-VEGF-A) for 1 wk, we evaluated liver morphology, the degree of portal inflammation and periductular fibrosis, microcirculation, cholangiocyte apoptosis, proliferation, and secretion. Microcirculation was evaluated using a scanning electron microscopy vascular corrosion cast technique. HAL induced in BDL rats 1) the disappearance of the PBP, 2) increased apoptosis and impaired cholangiocyte proliferation and secretin-stimulated ductal secretion, and 3) decreased cholangiocyte VEGF secretion. The effects of HAL on the PBP and cholangiocyte functions were prevented by r-VEGF-A, which, by maintaining the integrity of the PBP and cholangiocyte proliferation, prevents damage of bile ducts following ischemic injury.

Animals↗

Role of ERCP in the management of bile duct lesions post bile duct surgery.

INTRODUCTION: Therapeutic Endoscopic Retrograde Cholangio-Pancreatography (ERCP) is an established mode of treatment for bile duct lesions. AIM: This paper reviews the role of ERCP in the management of bile duct lesions developing after biliary surgery. PATIENTS AND METHODS: Of the 894 ERCPs performed in our department between January 1990 and May 1992, 23 (13 female, 10 male) were for patients with post-operative bile duct lesions. The mean age of these 23 patients was 59 years (range 38-91 years). The previous biliary surgical procedures were conventional cholecystectomy (n = 19), laparoscopic cholecystectomy (n = 3) and a cholecystectomy with choledochojejunostomy. Associated medical conditions of ischaemic heart disease, unstable angina, hypertensive heart disease, chronic obstructive airway disease and hepatitis B cirrhosis were present in 7 of these patients. RESULTS: Ten patients had benign biliary strictures. Endoscopic stenting (with one or 2 stents) was successful in 9. The strictures reopened in 2 patients after a total stenting duration of 12 and 18 months respectively. Four patients had biliary leakages that were successfully treated with stenting. Two patients had spontaneous sealing of biliary leak at 3 and 6 months respectively. Nine patients had retained stones (7 with solitary stone, 2 with multiple stones) that were successfully removed with Dormia basket after sphincterotomy. Complications were few and manageable. CONCLUSIONS: Therapeutic ERCP is safe and effective. It is a useful adjunct in the management of patients with post-operative biliary lesions.

Adult↗

Regression of bile duct damage and bile duct proliferation in the non-rearterialized transplanted rat liver is associated with spontaneous graft rearterialization.

The aim of this study was to investigate the long-term consequences of non-rearterialization of the graft in rat liver transplantation. Liver transplantation with (AOLT) and without graft rearterialization (NOLT) was performed in anesthetized male Lewis rats. Quantitative morphometry and semiquantitative histopathology of the liver were performed at various times after operation. Volume fractions of tissue components were determined. The number of arteries and bile ducts per portal tract were measured in histological sections from both groups. Hepatic blood flow was measured using the radioactive microsphere technique in rats after NOLT (6 months). AOLT livers had a preserved lobular architecture at all time points and unaltered volume fractions. In addition, AOLT livers maintained approximately one artery and one bile duct per portal tract after transplantation. NOLT livers showed bile duct damage at 3 days, cellular infiltration and ductular proliferation at 1 week, increased ductular proliferation at 4 weeks, and fibrosis at 6 months. The volume fractions for nonhepatocyte parenchyma (3 days, 19.14 +/- 1.29; 1 week, 20.44 +/- 1.76; 4 weeks, 15.46 +/- 3.14), bile ducts/ductules (1 week, 4.88 +/- 1.07; 4 weeks, 7.20 +/- 2.42), and connective tissue (4 weeks, 4.02 +/- 1.66; 6 months, 14.94 +/- 0.63) were significantly increased. Hepatocyte volume fraction was significantly decreased at all time points. A total of 1.58 +/- 0.08 arteries/portal tract were found in NOLT livers after 4 weeks, rising to 2.44 +/- 0.10 arteries/portal tract after 6 months. At 6 months, hepatic arterial blood flow (0.69 mL/min/g) was significantly higher (P < .02) than control (0.25 mL/min/g).(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

Clinical significance of manometric assessment of both pancreatic duct and bile duct sphincter in the same patient.

In this study both pancreatic and bile duct sphincter pressures were measured on the same occasion by means of endoscopic manometry in 42 patients with long-standing upper abdominal pain. Nine (53%) of the 17 patients with abnormal sphincter function had a marked difference between the pancreatic duct sphincter pressure (PSOP) and the bile duct sphincter pressure (BSOP): 6 patients with a clinical diagnosis of biliary dyskinesia showed elevated BSOPs, whereas the PSOPs were normal. The reverse, an abnormal PSOP but normal or only a slightly elevated BSOP, was registered in the three patients with chronic pancreatitis. These findings indicate that a motor abnormality may be restricted to only one of the sphincters. Thus, when the sphincter of Oddi is investigated only from the pancreatic duct, manometry may either fail to show an abnormal BSOP in some patients with biliary dyskinesia, or it may falsely suggest this diagnosis in patients with unrecognized pancreatitis.

Adult↗

[Bile duct epithelium and bile duct atresia].

In order to investigate pathogenetic theories about the origins of biliary atresia, a model consisting of cell cultures of bile duct epithelium from the extrahepatic ducts of human and bovine origin is presented. The epithelial nature of the cultivated cells was documented by phase contrast microscopy, by electron microscopy and immunohistochemistry (anti-keratin). Inoculation studies of primary human cell cultures showed a cytopathic effect by light microscopy for all tested viruses (adeno, polio, herpes, rubella) except for reovirus type 3, for which a CPE was not demonstrable. A growth stimulating substrate for bile duct epithelial cells is described; among the purified growth factors epidermal growth factor was without effect (EGF), while cholecystokinin (CCK) led to an increase in cell numbers.

Animals↗

Laparoscopic transcystic duct common bile duct exploration.

The modern era of common bile duct (CBD) surgery started with Mirizzi, who introduced intraoperative cholangiography in 1932. Intraoperative choledoscopy had been developed as an adjunctive to intraoperative cholangiography, which helped to detect CBD stones in an additional 10% to 15% of instances that otherwise would have been missed. Findings have shown choledochoscopy to be an important technique for efficient and effective management of CBD stones. Efforts to treat patients with common duct stones in one session and to avoid the potential complications of endoscopic sphincterotomy resulted in several laparoscopic transcystic CBD (LTCBDE) techniques. The techniques of transcystic stone extraction include lavage, trolling with wire baskets or biliary balloon catheters, cystic duct dilation, biliary endoscopy, and stone retrieval with wire baskets under direct vision and antegrade sphincterotomy, lithotripsy, and catheter techniques. The indications for LTCBDE are filling or equivocal defects at cholangiography, stones smaller than 10 mm, fewer than 9 stones, and possible tumor. The contraindications are stones larger than 1 cm, stones proximal to the cystic duct entrance into the CBD, small friable cystic duct, and 10 or more stones. Experience with LTCBDE shows that the approach is applicable in more than 85% of cases, with a success rate of 85% to 95%. It also is shown to be more cost effective than postoperative endoscopic retrograde cholangiopancreatography. Recent developments in LTCBDE have focused mainly on implementation of robotically assisted surgery and new imaging methods such as magnetic resonance cholangiopancreatography with three-dimensional virtual cholangioscopy and three-dimensional ultrasound. Further technological advances will facilitate the application of laparoscopic approaches to the common duct, which should become the primary strategy for the great majority of patients.

Ampulla of Vater↗

Is drip infusion cholecystocholangiography (DIC) an acceptable modality at cholecystectomy for cholecystolithiasis, considering the frequency of bile duct maljunction and intraoperative bile duct injury?

BACKGROUND/PURPOSE: Knowledge of the configuration of the extrahepatic bile duct is indispensable to avoid bile duct injury during cholecystectomy. Various methods of examining the biliary tract have been developed; however, the most appropriate preoperative diagnostic modality at cholecystectomy for cholecystolithiasis has not yet been reported. Considering the frequency of bile duct maljunction (BDM) and operative bile duct injury, in addition to the cost and invasiveness of the various examination methods, we evaluated the usefulness of drip infusion cholecystocholangiography (DIC) as the optimal method of examination at cholecystectomy for cholecystolithiasis. METHODS: Preoperative diagnostic accuracy of BDM was analyzed in relation to operative bile duct injury using 469 patients with benign biliary diseases who was diagnosed with DIC and endoscopic retrograde cholecystography and underwent cholecystectomy. BDM was classified according to Hisatsugu criteria. RESULTS: Out of 469 consecutive patients who underwent a cholecystectomy for biliary stones between January 1, 1995, and September 30, 1998, at Ohta Nishinouchi General Hospital, 21 (4.48%) had a cystic duct maljunction (CDM) and 12 (2.56%) had an aberrant bile duct (ABD). The most common variants were types C and D for CDM, and types II and III for ABD, according to Hisatsugu's classification. Fourteen patients (42.4%) were diagnosed before the surgery; 13 of them received preoperative endoscopic retrograde cholangiography (ERC), and the remaining patient underwent preoperative drip infusion cholecystocholangiography (DIC). Nineteen patients could not be correctly diagnosed based on their preoperative examinations, but were diagnosed during surgery. Operative bile duct injury occurred in 1 patient (0.2%) whose maljunction could not be diagnosed before the operation. CONCLUSIONS: Taking into account the medical cost and invasiveness, and the frequency of BDM and related bile duct injuries, we conclude that DIC is an acceptable preoperative diagnostic modality to employ at cholecystectomy for cholecystolithiasis. Knowledge of the configuration of the extrahepatic bile duct is indispensable to avoid bile duct injury during cholecystectomy. Various methods of examining the biliary tract have been developed; however, the most appropriate preoperative diagnostic modality at cholecystectomy for cholecystolithiasis has not yet been reported. Considering the frequency of bile duct maljunction (BDM) and operative bile duct injury, in addition to the cost and invasiveness of the various examination methods, we evaluated the usefulness of drip infusion cholecystocholangiography (DIC) as the optimal method of examination at cholecystectomy for cholecystolithiasis.

Bile Ducts, Extrahepatic↗

Differential expression of cyclooxygenase-2 (COX-2) in human bile duct epithelial cells and bile duct neoplasm.

It is well known that chronic inflammatory conditions involving the bile ducts predispose to the development of bile duct carcinoma, although the relationship between chronic inflammation and malignant transformation is unclear. In this study, by combining immunohistochemistry and computer imaging techniques, we quantified and compared the cyclooxygenase-2 (COX-2) protein expression levels of epithelial cells according with their histopathological backgrounds. This technique revealed that the highest levels of COX-2 were expressed in bile duct carcinoma cells, mainly in cytoplasm, and the expression pattern was homogenous and abundant. Moderate levels of COX-2 protein expression were also observed in noncancerous epithelial cells with inflammatory reaction, but the staining intensity was heterogeneous among the positive cells exhibiting inflammation. In contrast, only scattered weak reactivity of COX-2 protein was observed in the noncancerous bile duct epithelial cells without inflammatory reaction. Moreover, bile duct epithelial cells in primary sclerosing cholangitis (PSC) showed very strong expression of COX-2 protein, that was comparable with carcinoma cells. On the other hand, primary biliary cirrhosis (PBC) epithelial cells showed moderate levels of COX-2 expression. In addition, specific COX-2 inhibitors, JTE-522 and NS-398, directly inhibited the growth of 4 bile duct carcinoma and 1 gall bladder carcinoma cell lines that expressed COX-2 protein, in vitro. These data suggest that COX-2 expression might regulate carcinogenesis of bile duct epithelial cells in inflammatory regions and tumor progression in this cancer. The data also suggest that COX-2 selective inhibitors might have therapeutic effects not only on bile duct carcinoma, but other hepatobiliary carcinomas.

Animals↗

D-glucaric acid in common duct bile and relation to choledocholithiasis.

BACKGROUND: The aim was to investigate a possible association between D-glucaric acid (DGA), biliary bilirubin glucuronidation and brown pigment stones in the common bile duct. METHODS: A high performance liquid chromatography method with a strong cation resin (HPX-87H) was developed for measuring biliary DGA. Bile was obtained during ERCP by deep cannulation of the common bile duct in 100 patients with suspected biliary disease. RESULTS: The concentration of DGA in common bile duct bile was 60 (1.1-633) micromol l(-1) (median, range). The values were lower than previously reported. There were no differences in DGA concentrations in patients with common bile duct stones compared to patients without common bile duct stones, irrespective of stone type, cholesterol or brown pigment stones. Bilirubin conjugates in common duct bile did not vary with DGA concentrations. CONCLUSION: DGA is probably insignificant in the pathogenesis of common bile duct stones.

Bile↗

The infiltration of bile duct carcinoma along the bile duct wall.

The infiltration of extrahepatic bile duct carcinoma along the bile duct wall was studied in 29 resection cases. Histologically, spreading took place by mucosal infiltration in one case, mucosal and transmural in three, and transmural in 25. The average microscopic infiltrating distance from the gross margin of the tumor (ID) was 16.8 mm towards the liver, 6.5 mm towards the duodenum. The ID of the infiltrating type in the gross appearance of the tumor and the ID of the tubular adenocarcinoma in the histological cellular type tended to be long. The severer the invasion of the carcinoma to the lymphatic vessels, the longer the ID. The result indicated that most bile duct carcinomas have a tendency for long infiltration along the wall. An exceedingly wide resection involving hepatectomy is advisable for treatment.

Adenoma, Bile Duct↗

Pancreatic enzymes in the epithelium of intrahepatic large bile ducts and in hepatic bile in patients with extrahepatic bile duct obstruction.

AIM: To determine whether pancreatic enzymes are present in hepatic bile and in intrahepatic bile duct epithelium. METHODS: The activity and proteins of pancreatic enzymes (pancreatic alpha-amylase, lipase, trypsin/trypsinogen) in hepatic bile were investigated using biochemical and western blot analyses in 25 patients with extrahepatic bile duct obstruction. Immunolocalization of enzyme proteins was evaluated by immunohistochemistry in 20 necropsy livers with extrahepatic bile duct obstruction. RESULTS: Western blot analysis showed proteins of pancreatic alpha-amylase, lipase, and trypsin in 19 of 25 (76%), 10 of 25 (40%), and 14 of 25 (56%) patients, respectively. Pancreatic alpha-amylase and lipase activities was present in every bile specimen. Radioimmunoassay showed that trypsin was present in every bile sample. Immunohistochemically, the immunoreactivity of the three enzymes was present in epithelia and in the lumina of intrahepatic large bile ducts, septal bile ducts, and peribiliary glands in all cases. CONCLUSIONS: These results strongly suggest that biliary epithelia of larger intrahepatic ducts produce pancreatic alpha-amylase, lipase, and trypsin, and that these enzymes are secreted into the lumina of intrahepatic bile ducts.

Aged↗

Resection of intrahepatic bile duct carcinoma with hilar bile duct and portal vein invasion--a case report.

A case of resected intrahepatic bile duct cancer with hilar bile duct and portal vein invasion is presented. Percutaneous transhepatic biliary drainage was performed to alleviate jaundice and evaluate the biliary system. Intraductal tumor extension was determined, and an accurate histological diagnosis was made in biopsy material obtained under percutaneous transhepatic cholangioscopy. Preoperative surgical planning was carried out on the basis of an evaluation of the findings of ultrasonography, computed tomography, arteriography, portography and percutaneous transhepatic cholangioscopy. Curative surgery, which included right hepatic lobectomy with total caudate lobectomy and combined resection and reconstruction of the portal vein, was performed. Bilioenteric continuity was re-established by a Roux-en-Y jejunal loop. The histological diagnosis was moderately differentiated tubular adenocarcinoma originated in the right posterior branch of the intrahepatic bile duct. Postoperative recovery was very good, and the patient has now been enjoying a good active social life for the past three years with no signs of tumor recurrence. This case report discusses the accurate diagnosis and rational surgical treatment for intrahepatic bile duct carcinoma with hilar invasion.

Adenoma, Bile Duct↗

Low conjunction of the cystic duct with the common bile duct: does it correlate with the formation of common bile duct stones?

BACKGROUND: This study aimed to evaluate the accuracy of magnetic resonance cholangiography (MRC) in detecting variants of low cystic duct conjunction, which can be a source of confusion during surgery when unrecognized. METHODS: All cases with both MRC and endoscopic retrograde cholangiography (ERC) indicating suspected common bile duct stones between January 1999 and January 2004 were retrospectively reviewed by investigators blinded to the final diagnosis. Assessment with ERC was regarded as the gold standard. The aim was to find a low conjunction of the cystic duct with the bile duct. The sensitivity and specificity of MRC were calculated in comparison with those for ERC. The cystic junction radial orientation was defined as lateral (insertion diagonally from the right), medial (insertion into the left side of the common hepatic duct), or posteroanterior (overlap of the junction with the bile duct in the posteroanterior view). A spiral cystic duct and a long parallel course were evaluated separately. RESULTS: Low insertion of the cystic duct was found on ERC in 66 of 622 patients (11%; 28 men and 38 women; mean age, 64.5 years). The sensitivity and specificity of MRC for detecting low cystic entrance were 100% (90.4% on an intention-to-diagnose basis and 100%, respectively). In 11 patients (16.6%), the radial orientation of the cysticohepatic junction could not be defined with MRC. The rate of correct MRC delineation was 95% for lateral (n = 21), 77% for medial (n = 26), and 74% for posteroanterior (n = 19) insertion of the cystic duct. CONCLUSION: The findings showed that MRC has good correlation with ERC with regard to the location and anatomic details of cystic duct insertion. Although this does not generate a separate indication for MRC before laparoscopic cholecystectomy, the anatomic information can be of additional use when MRC is clinically indicated in this setting.

Aged↗