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PubMed1984

[Chemotherapy of biliary tract infections (XXIV). Biliary excretion and gallbladder tissue levels of mezlocillin].

Mezlocillin (MZPC), a new broad spectrum penicillin, was studied for its biliary excretion and levels in gallbladder tissues. The mean serum concentration immediately after intravenous administration of 2 g of MZPC in 6 cholecystectomized patients was found to be 535.5 +/- 43.5 micrograms/ml, while its concentration in their gallbladder bile was 1,500-6,500 micrograms/ml at 30 minutes-1.5 hours and its concentration in their common duct bile was 6,500 and 4,000 micrograms/ml at 2 hours and 2.5 hours, respectively. Besides, its gallbladder tissue level around 2 hours was 37.5-500 micrograms/g, averaging as high as 215.6 +/- 79.5 micrograms/g. Crossover method was made to compare the biliary excretion of MZPC and PIPC in 4 patients inserted with a T-tube in their common bile duct. Each patient received 2 g each of 2 antibiotics intravenously. In case 1 with normal liver function, both drugs revealed the peak concentration of 3,500 micrograms/ml or more. In case 2, the peak concentration was 3,625 micrograms/ml for MZPC but 2,125 micrograms/ml for PIPC. In case 3 with slight hepatic dysfunction, the peak concentration for MZPC and PIPC was 906.4 micrograms/ml and 375.2 micrograms/ml, respectively. In case 4 with moderate hepatic dysfunction, the peak concentration for MZPC and PIPC was 27.6 micrograms/ml and 14.7 micrograms/ml, respectively. Simultaneous intravenous administration of MZPC and PIPC was made to compare the biliary excretion of these 2 antibiotics in 1 patient with T-tube drain in common bile duct. The bile concentration was measured by HPLC method which was developed by our laboratory.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed2006

Evaluation of the biliary tract in patients with functional biliary symptoms.

The aim of this paper was to describe functional biliary syndromes and methods for evaluation of the biliary tract in these patients. Functional biliary symptoms can be defined as biliary symptoms without demonstrable organic substrate. Two main syndromes exist: Gallbladder dysfunction and sphincter of Oddi dysfunction. The most important investigative tools are cholescintigraphy and endoscopic sphincter of Oddi manometry. In gallbladder dysfunction a scintigraphic gallbladder ejection fraction below 35% can select patients who will benefit from cholecystectomy. Endoscopic sphincter of Oddi manometry is considered the gold standard in sphincter of Oddi dysfunction but recent development in scintigraphic methods is about to change this. Thus, calculation of hilum-to-duodenum transit time and duodenal appearance time on cholescintigraphy have proven useful in these patients. In conclusion, ambient methods can diagnose functional biliary syndromes. However, there are still a number of issues where further knowledge is needed. Probably the next step forward will be in the area of sensory testing and impedance planimetric methods.

Biliary Dyskinesia↗
PubMed1996

[Prospective randomized trial comparing 1/2 FAM (5-fluorouracil (5-FU) + adriamycin + mitomycin C) versus palliative therapy for the treatment of unresectable pancreatic and biliary tract carcinomas (the 2nd trial in non-resectable patients). Japanese Study Group of Surgical Adjuvant Therapy for Carcinomas of the Pancreas and Biliary Tract].

The efficacy of 1/2 FAM, which consists of 5-fluorouracil (5-FU), adriamycin (ADM) and mitomycin C (MMC), was compared with that of palliative treatment in patients with unresectable pancreatic and biliary tract carcinomas in a multicenter randomized trial. The patients assigned to 1/2 FAM group were treated with 5-FU 200 mg/m2/day IV, ADM 15 mg/m2/day IV and MMC 5 mg/m2/day IV. These 3 drugs were given concurrently as the initial dose within a week after palliative operation, and this regimen was repeated for at least 2 whole courses, at 4-week intervals before the next course of therapy. Those randomized to the control group were subjected to palliative treatment alone. Completely eligible for analysis were 42 cases of the 1/2 FAM group and 41 of the control group. There was no significant difference between the groups with respect to the overall and differentiated survival times according to the tumor sites and the clinical efficacy. As for the duration of 50% inhibition of tumor progression, a significantly better outcome was obtained in 1/2 FAM group. Tumor progression was most significantly inhibited in patients with gallbladder carcinoma. In 1/2 FAM group, tumor reduction was achieved in 1 CR and 2 PR patients. The most frequent adverse reaction was gastrointestinal manifestations, along with diarrhea and alopecia. 1/2 FAM did not contribute to the life prolongation, but inhibited the tumor progression for a significantly longer duration and, to a lesser extent, reduced the tumor size in unresectable pancreatic and biliary tract carcinomas. This regimen is suggested to be useful particularly in the treatment of the latter carcinoma.

Adult↗
PubMed2005

[Prevention, diagnosis and surgical treatment of injuries of the biliary tract during laparoscopic cholecystectomy. Treatment of papilla injuries caused by invasive endoscopy. Part 2. Surgical treatment of biliary tract injuries].

INTRODUCTION: Introduction of endoscopic invasive procedures in the 70th and 80th years leaded to decrease reoperations on biliary tree. latrogenic injury of the biliary tract have increased in incidence in the first decade with the introduction of laparoscopic cholecystectomy. Athough a number of factors have been identified with a high risk of injury (and number of technical steps have been emphasized to avoid these injury, the incidence of the bile duct injury has reached at least double the rate observed with open cholecystectomy. Most patients that sustained a bile duct injury are recognized in the weeks following laparoscopic cholecystectomy. Careful preoperative preparation should include control of sepsis by draining any bile collections or fistulas and complete cholangiography. Long-term results are best achieved in specialized hepatobiliary centers performing biliary reconstruction with a Roux-Y hepaticojejunostomy. Success rates over 90% have been reported from several centres to date with intermediate follow-up. Introduction of an invasive endoscopy. Very dangerous is injury after endoscopic papilotomy. OWN EXPERIENCES: In an article of a review of experiences of the Ist Department of Surgery of General hospital in Prague since 1971 in 1 017 reoperations on biliary tree has been carried out. There were in 311 patients 164 hepato-hepatostomies and 147 hepaticojejunostomies used (Tab. 1). By laparoscopic injuries in the last decade were hilary injuries (Bismuth IV) and hepaticojejunostomy was done in all cases. Died 6%, long-term results are acceptable by injured patients with hepatico-hepaticostomies in 70%, by hepaticojejunostomies in 90%. Reoperated were 10% patients. Remnant patients were dilated endoscopically. Postoperatively morbidity was high, above 26%. In years 1995-2003 were 8 patients with papila injury and inflammation in retroperitoneum operated as a injured duodenum (Tab. 2). CONCLUSIONS: Better experiences with treatment of injured biliary tree and papila are in centres interested in hepatobiliary surgery which know anatomy of hilus of the liver and can see wide hepaticojejunostomy. Transfer of drained injured patient to centre is possible.

Ampulla of Vater↗
PubMed1995

Three-dimensional reconstruction of the biliary tract from two-dimensional biliary images.

To make conventional two-dimensional cholangiography easier and more precise to read, we used techniques in computer vision to reconstruct the images in three dimensions. A 72-year-old man and a 70-year-old woman suffering from acute cholangitis were treated using endoscopic nasobiliary drainage. Their cholangiograms, from two orthogonal views, were used for three-dimensional reconstruction. We used video image-grabber and film scanner methods to digitize the original conventional biliary radiographs, and applied two different image processing methods to show the biliary structure. Both methods of three-dimensional reconstruction of the biliary tract were highly useful in evaluating the biliary tracts in these two patients, especially when a semitranslucence overlapping display technique was applied in the second patient. With this technique, the biliary tree itself and the stones inside the common bile duct can be clearly delineated. The technique of three-dimensional reconstruction of biliary images can make the conventional cholangiographs more lifelike and has great potential in surgical simulation in the near future.

Aged↗
PubMed2000

Disrupted transforming growth factor-beta signaling and deregulated growth in human biliary tract cancer cells.

Biliary tract carcinoma is a common neoplasm in Japan, and its treatment is difficult because it tends to promote fibrosis and easily invades surrounding tissues. To better characterize the biological features of this carcinoma, we investigated abnormalities in the transforming growth factor-beta (TGF-beta) signaling pathway in five human biliary tract cancer cell lines: RBE, KMBC, SK-ChA-1, Mz-ChA-1, and Mz-ChA-2. We stably transfected into these cells the luciferase reporter plasmid carrying promoter of the plasminogen activator inhibitor-1 gene, the expression of which is stimulated by TGF-beta1. Treating the KMBC and Mz-ChA-1 cells with TGF-beta1 neither inhibited cell growth nor stimulated luciferase activity. In contrast, the RBE and Mz-ChA-2 cells responded well to TGF-beta1 treatment. TGF-beta1-treated SK-ChA-1 cells exhibited attenuated luciferase activity and their growth was not inhibited. Smad4 mRNA was not detected in SK-ChA-1 and Mz-ChA-1 cells by Northern blot analysis. Genetic analysis disclosed a nonsense mutation in the Mad homologue 2a domain of the Smad4 gene in the SK-ChA-1 cells and a heterozygous deletion in the TGF-beta type II receptor gene in the KMBC cells. Expression of the exogenous Smad4 gene in the Mz-ChA-1 cells by transient transfection restored their luciferase activity. When these TGF-beta1-insensitive and less-TGF-beta1-sensitive cell lines were xenografted into nude mice, they developed tumors that had more prominent, intervening fibrosis (desmoplasia) than the tumors caused by TGF-beta1-sensitive cells. Thus, a tight correlation between disruption of the TGF-beta signaling pathway and deregulated growth of cancer cells has been demonstrated in biliary tract carcinoma. This seems to be a critical event in this carcinoma and may also be correlated with stromal cell reaction in cancer invasion.

Animals↗
PubMed2003

The tumor-selective viral protein apoptin effectively kills human biliary tract cancer cells.

Biliary tract cancer, or cholangiocarcinoma, has a poor prognosis. Resection is the only curative treatment, but only a minority of patients are eligible. Chemotherapy and gamma-irradiation are merely palliative, as they are unable to remove the malignancy completely. The chicken anemia virus-derived protein apoptin induces apoptosis in a wide range of human tumor cells and is not hindered by mutations inactivating p53 or by overexpression of Bcl-2, changes known to frustrate chemotherapy and radiation therapy. We examined whether apoptin kills human biliary tract cancer cells. Expression of apoptin by means of plasmids caused extensive cell death in three independent cholangiocarcinoma cell lines, CC-LP, CC-SW, and Mz-ChA-1, regardless of their oncogenic mutations, which included inactivated p16 and p53 and the disruption of the transforming growth factor beta signaling pathway. In vitro delivery of apoptin by an adenoviral vector completely eradicated cholangiocarcinoma cells. Moreover, coexpression of the broad-spectrum caspase inhibitor p35 with apoptin only delayed the induced cell death. Changes in nuclear morphology still occurred early after transfection, and nuclei eventually disintegrated, suggesting that apoptin-induced cell death in these cells is not blocked by mutations in either the initiation or execution phase of apoptosis. The efficient induction of cell death by apoptin in cholangiocarcinoma cell lines makes apoptin an attractive candidate for molecular therapy of biliary tract cancer.

Adenoviridae↗
PubMed1984

Biliary excretion of aztreonam in patients with biliary tract disease.

The biliary excretion of aztreonam was studied in 10 post-cholecystectomy patients with T-tube biliary drainage (group A) and four other subjects with obstructive biliary tract disease who had recent placement of external biliary drainage (group B). Maximum biliary levels ranged from 9.7 to 88.2 micrograms/ml (mean, 42.9 +/- 7.9 micrograms/ml) and occurred 2.4 h after injection of a single 1-g dose intravenously. Peak biliary levels observed in group B patients were approximately one-third those in group A. Cumulative 12-h biliary excretion (group B) accounted for 0.18 +/- 0.06% of the total dose. In the same period, urinary excretion accounted for 65 to 72% of the total dose. The lower biliary levels of aztreonam observed in group B patients relative to those in group A suggest that in patients with total biliary tract obstruction the liver may not recover full secretory capacity, at least within 3 to 7 days after biliary decompression.

Adult↗
PubMed1999

Experience with percutaneous transhepatic cholangioscopy (PTCS) in the management of biliary tract disease.

BACKGROUND: Biliary tract disorders often present significant management difficulties, particularly in patients who are poor surgical candidates. Percutaneous transhepatic cholangioscopy (PTCS) is an infrequently utilized alternative that might offer significant therapeutic benefit. We reviewed our experience with the use of this modality as a definitive therapy for biliary tract disorders. METHODS: Patient records at the Atlanta VAMC and Emory University hospitals were reviewed. We identified 17 patients who had undergone 25 PTCS interventions between August 1994 and December 1998. The indications for PTCS included dilatation of biliary-enteric anastomoses in four patients, biliary stone removal (with or without lithotripsy) in eight patients, stricturoplasty in four patients, biopsy of suspected biliary neoplasms in seven patients, and removal of obstructing clot in one patient. Most procedures (n = 17) were performed through percutaneous transhepatic tracts (12-18 Fr) that were <1 week old. All tracts were dilated to operating size on the day of the procedure. All patients received periprocedural antibiotics. RESULTS: The interventions were successful in seven of eight stone removals, four of five stricturoplasties, three of four anastomotic dilatations, seven of seven biopsies, and the single clot removal. The only complication involved one episode of hemobilia, requiring angio-embolization of a small branch of the right hepatic artery. CONCLUSIONS: PTCS is a safe, useful, and well-tolerated adjunct to the more common endoscopic and surgical techniques for managing complicated biliary tract disorders. Our experience suggests that PTCS can be performed early, without prolonged sequential dilatation of the percutaneous transhepatic tract, and may allow avoidance of operation in high-risk surgical candidates.

Adult↗
PubMed2006

Gemcitabine and oxaliplatin combination chemotherapy in advanced biliary tract cancers.

BACKGROUND: Biliary tract cancers are uncommon tumors with a poor prognosis and most patients present with invasive and inoperable disease at diagnosis. Chemotherapy represents a palliative treatment, with poor response rates and a median survival of less than 6 months. Oxaliplatin and gemcitabine have shown an interesting activity as single agents in this group of patients. PATIENTS AND METHODS: We carried out a multicenter phase II study to evaluate the efficacy and safety of combined oxaliplatin and gemcitabine in locally advanced and metastatic biliary tract carcinoma. The schedule of chemotherapy included oxaliplatin 100 mg/m(2) on day 1 and gemcitabine 1000 mg/m(2) on days 1 and 8, every 21 days. RESULTS: All the 24 patients were evaluable for response and toxicity. According to RECIST criteria we observed one complete response and 11 partial responses for an overall response rate of 50%. Overall survival for all the patients on study was 12 months (range 2-30). According to WHO criteria, three patients (12.5%) suffered grade 3 neutropenia and three patients (12.5%) grade 3 thrombocytopenia. Only two patients (8%) suffered grade 3 neuropathy. CONCLUSIONS: Oxaliplatin and gemcitabine chemotherapy seems to be effective with a favorable safety profile in first-line chemotherapy of advanced biliary tract cancers.

Adenocarcinoma↗
PubMed1979

Damage to the biliary tract during preservation.

Biliary complications following liver transplantation continue to present major difficulties. Damage to the biliary tract has been reported after preservation of the liver before transplantation. Studies in the rabbit are reported that confirm the extensive biliary autolysis during preservation. This damage is directly related to the presence of bile in the biliary tract and can be reduced by the washout of bile and biliary perfusion.

Animals↗
PubMed1992

[Prospective randomized trial comparing modified FAM (5-fluorouracil (5-FU) + adriamycin + mitomycin C) versus 5-FU alone for the treatment of non-resectable pancreatic and biliary tract carcinomas (the 1st trial in non-resectable patients). Study Group of Surgical Adjuvant Therapy for Carcinomas of the Pancreas and Biliary Tract].

The modified FAM (5-fluorouracil (5-FU) + adriamycin (ADR) + mitomycin C (MMC)) therapy (FAM group) was compared with 5-FU mono-therapy (F group) by multi-institutional randomized trial in the patients with cancer of the pancreas or the biliary tract who underwent non-resection. The patients in FAM group received 6 mg/m2 of i.v. MMC during operation, 310 mg/m2 of i.v. 5-FU for 5 days in the 1st and 3rd postoperative weeks and 12 mg/m2 of i.v. ADR in the 2nd postoperative week. Those in F group received only 5-FU course in the administration schedule of FAM group. Among the cases which completed respective whole administration schedules. 35 cases in FAM group and 36 in F group, better effect than partial response (PR) was observed in neither groups, and there was no significant difference between groups with respect to overall/each disease survival duration, progression-suppressed duration and clinical effect. Primary adverse effects were alimentary symptoms and hepatic dysfunction, neither of which was serious, and there was no difference between groups except that hair loss was observed in more cases in FAM group (p less than 0.05). Results in FAM group did not statistically surpass those in F group, but a tendency was observed that FAM group was better than F group in terms of survival duration and clinical effect for cancer of the gall-bladder.

Adult↗
PubMed1981

Clinical experience with cefoperazone in biliary tract infections.

The biliary excretion of cefoperazone in experimental animals, and humans, was investigated. Biliary excretion of cefoperazone in rats, rabbits, dogs, and monkeys was always higher than that of cephazolin. Biliary excretion was markedly reduced in experimentally-produced liver cirrhosis in rats. Comparing the biliary excretion of cefoperazone and cephazolin in a crossover study in patients, the excretion of cefoperazone was shown to be much higher than that of cephazolin. In clinical studies in 116 patients with biliary tract infections such as cholecystitis, cholangitis, and liver abscess, cefoperazone was effective in 90 (78%). The incidence of side effects was low. In conclusion, cefoperazone was considered to be effective in treating biliary tract infections because of its broad antibacterial spectrum and high penetration into bile.

Adult↗