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PubMed1981

Endoscopic papillotomy in the geriatric patient with complicated biliary-tract disease.

Biliary-tract disease is not only more common in the geriatric population but carries an increased surgical risk. Described is a series of 10 middle-aged and elderly patients who had stones in the common bile duct associated with significant underlying medical illness or peri-ampullary pathologic changes. They were successfully treated by endoscopic papillotomy. The 80 percent success rate in such critically ill patients suggests that endoscopic papillotomy might be used as the initial treatment modality in aging patients with amenable biliary-tract disease.

Adult↗
PubMed2005

Capecitabine combined with gemcitabine (CapGem) as first-line treatment in patients with advanced/metastatic biliary tract carcinoma.

BACKGROUND: Biliary tract carcinoma is an aggressive cancer, with median survival rarely exceeding 6 months. There is currently no established palliative standard of care. A Phase II trial was conducted to study a combination of oral capecitabine and gemcitabine (CapGem) as first-line therapy in patients with advanced and/or metastatic biliary carcinoma. METHODS: Patients with unresectable or metastatic intrahepatic or extrahepatic biliary duct carcinoma and gallbladder carcinoma were enrolled. Eligible patients had histologically or cytologically confirmed, measurable adenocarcinoma and had not received prior therapy with capecitabine or gemcitabine. Treatment consisted of intravenous (i.v.) gemcitabine (1000 mg/m(2) on Days 1 and 8) plus oral capecitabine (650 mg/m(2) twice daily on Days 1-14) every 3 weeks for up to 6 cycles. Tumor response, survival, and safety were determined. RESULTS: A total of 44 patients were evaluable. Primary tumor sites were: intrahepatic (n = 14) and extrahepatic biliary duct (n = 16); gallbladder (n = 7); and ampulla (n = 7). Fourteen (32%) patients had a partial response and 15 (34%) patients had stable disease. Median time to disease progression and overall survival were 6.0 (range, 3.8-8.1) and 14 (range, 11.4-16.6) months, respectively. The 1-year survival rate was 58%. No Grade 4 adverse events were seen. Transient Grade 3 neutropenia/thrombocytopenia and manageable (almost invariably Grade 2) nausea, diarrhea, and hand-foot syndrome were the most common adverse events. CONCLUSIONS: CapGem is an active and well tolerated first-line combination chemotherapy regimen for patients with advanced/metastatic biliary tract carcinoma that offers a convenient home-based therapy.

Adult↗
PubMed2005

The efficacy of epirubicin, cisplatin, uracil/tegafur, and leucovorin in patients with advanced biliary tract carcinoma.

BACKGROUND: Advanced biliary tract carcinoma is among the most prevalent fatal diseases in Korea. However, to our knowledge, to date no effective therapeutic modality has been shown to prolong the survival of patients in the inoperable stages of this disease. METHODS: This Phase II study was conducted to determine the efficacy and toxicity of a combined regimen of epirubicin, cisplatin, and uracil/tegafur (UFT) modulated by leucovorin in patients with advanced or recurrent biliary tract carcinoma. RESULTS: Eleven of 40 patients (27.5%) had gallbladder carcinoma, and the remaining patients had tumors arising from other sites in the biliary tract. All patients were treated with intravenous epirubicin (50 mg/m(2) on Day 1), intravenous cisplatin (60 mg/m(2) on Day 1), oral UFT (300 mg/m(2) per day on Days 1-21), and oral leucovorin (75 mg per day on Days 1-21). Nine patients exhibited a partial response, representing 22.5% of the possible response rate (95% confidence interval [95% CI], 12.8-32.2%) based on an intention-to-treat analysis. The median survival was 34 weeks (95% CI, 20-48 weeks), and the median time to disease progression was 16 weeks (95% CI, 7-25 weeks). Neutropenia and thrombocytopenia comprised dose-limiting toxicity conditions. CONCLUSIONS: The combination of epirubicin, cisplatin, and UFT modulated by leucovorin was active marginally in patients with advanced biliary tract carcinoma and was capable of stabilizing the disease effectively. Because it was a safe and convenient treatment modality, it may be used in outpatient care with only minor toxicity in patients with advanced malignancies of the biliary tract.

Adult↗
PubMed1980

Surgery of the liver, biliary tract, and pancreas.

Biliary, hepatic, and pancreatic surgery at the Mayo Clinic during 1973 was retrospectively examined. A total of 1,137 operations were performed in the 12-month period, with an overall hospital mortality of 2.6%. The operative mortality for 586 elective cholecystectomies for chronic cholecystitis with cholelithiasis was 0.3%--for acute cholecystitis 1.5% and for elective common duct exploration 2.9%. The present review is compared with prior reports in which similar methodology permitted comparisons. Improvement in operative mortality was noted in surgery for cholecystitis and pancreatic and hepatic lesions. The figures drawn from this and previous reports represent more than 10,000 operations on the liver, biliary tract, and pancreas performed at the Mayo Clinic.

Biliary Tract Neoplasms↗
PubMed2005

Biliary secretion of moxifloxacin in obstructive cholangitis and the non-obstructed biliary tract.

BACKGROUND: Biliary secretion of antibiotic agents into the bile is considerably compromised by biliary obstruction, a precondition of bacterial cholangitis. Moxifloxacin may be advantageous according to secretion and antimicrobial spectrum. AIM: To establish the secretion of moxifloxacin into obstructed and non-obstructed bile. METHODS: Biliary excretion of moxifloxacin was determined in plasma and bile of 10 patients with biliary obstruction and cholangitis and 10 patients without biliary obstruction 30 min after administration of 400 mg of moxifloxacin intravenously. RESULTS: The plasma concentration of moxifloxacin was similar in both groups (4.45 +/- 1.58 microg/mL; 4.33 +/- 1.23 microg/mL). The concentration of moxifloxacin in the bile was significantly lower in patients with biliary obstruction than without (4.63 +/- 3.94 microg/mL; range 0.71-14.40; vs. 16.90 +/- 13.77 microg/mL; range 1.79-42.50; P = 0.043). Although significantly different, the penetration index was extensively high in those without biliary obstruction (4.41 +/- 4.40; range 0.35-14.45) but still sufficient in those patients with obstructive cholangitis (1.02 +/- 0.74; range 0.29-2.83; P = 0.035). CONCLUSION: These findings are suggestive of an active secretion mechanism for moxifloxacin into the obstructed bile, producing a biliary concentration sufficiently above the minimal inhibitory concentrations for most of the expected bacteria.

Aza Compounds↗
PubMed2006

Bile acid analysis in biliary tract cancer.

The etiology of biliary tract cancer is obscure, but there are evidences that bile acid plays a role in carcinogenesis. To find the association between biliary tract cancer and bile acid, this study compared the bile acid concentration and composition among patients with biliary cancer, biliary tract stones, and no biliary disease. Bile was compared among patients with biliary tract cancer (n = 26), biliary tract stones (n = 29), and disease free controls (n = 9). Samples were obtained by percutaneous transhepatic biliary drainage, endoscopic nasobiliary drainage, or gallbladder puncture, and analyzed for cholic, deoxycholic, chenodeoxycholic, lithocholic, and ursodeoxycholic acid composition. Total bile acid concentration was lower in the cancer group than the biliary stone and control groups; the proportions of deoxycholic (2.2% vs. 10.2% and 23.6%, p < 0.001 and p < 0.001, respectively) and lithocholic acid (0.3% vs. 0.6% and 1.0%, p = 0.065 and p < 0.001, respectively) were also lower. This result was similar when disease site was limited to bile duct or gallbladder. Analysis of cases with bilirubin <or= 2.0 mg/dL also showed lower total bile acid concentration and deoxycholic acid composition in the cancer group compared to controls (5.7% vs. 23.6%, p = 0.003). Although the presence of bile duct obstruction explains some of the difference in total concentration and composition of bile acid, there are other contributing mechanisms. We suspect the alteration of bile acid transport might decrease bile acid excretion and cause the accumulation of carcinogenic bile acid in bile duct epithelium.

Adolescent↗
PubMed1980

The influence of ischaemia on the biliary tract.

Damage of the biliary tract at the end of a period of hepatic preservation prior to liver transplantation has been observed in man. This damage may be important in the development of early biliary complications. A model of hepatic biliary ischaemia in the pig has been developed which permits comparison between the influences of warm and cold ischaemic damage on the biliary tract. The major damage to the biliary tract in the pig in this model appears to occur after prolonged cold preservation.

Animals↗
PubMed2006

Telomere length variation in biliary tract metaplasia, dysplasia, and carcinoma.

Biliary tract carcinoma, including carcinoma of the gallbladder, intrahepatic bile ducts (cholangiocarcinoma), and extrahepatic bile ducts, affects 7500 people in the United States annually, and has an overall 32% 5-year survival rate for disease limited to the mucosa, and a dismal 10% 5-year survival for more advanced disease. The identification of factors involved in the pathogenesis and progression of biliary tract carcinoma is critical for devising effective methods of screening and treatment. Recent evidence suggests that reduction of the length of telomeres, which normally help maintain chromosomal stability, may promote the development and progression of a variety of carcinomas. Using a novel, recently validated telomere fluorescence in situ hybridization method, we examined telomere length in normal and inflamed gallbladder epithelium, metaplasia and dysplasia of the gallbladder, and biliary tract carcinoma to determine whether telomere shortening is associated with neoplastic progression in the biliary tract. Although normal and inflamed gallbladder epithelium demonstrated uniform normal telomere lengths, over half of all metaplastic lesions demonstrated shortened telomeres, supporting prior evidence that metaplastic lesions of the gallbladder are pre-neoplastic. Dysplastic epithelium and invasive carcinomas demonstrated almost universally abnormally short telomeres, indicating that telomere shortening occurs at an early, preinvasive stage of cancer development. In addition, invasive adenocarcinoma of the biliary tract frequently demonstrated intratumoral heterogeneity of telomere lengths. We conclude that telomere shortening is a consistent and early finding in the development of biliary tract carcinoma.

Biliary Tract Neoplasms↗
PubMed1987

Pancreatitis after biliary tract surgery.

Pancreatitis associated with biliary tract operations continues to be an important clinical problem. The results of biliary tract operations performed on 1256 patients were carefully scrutinized for the presence of postoperative hyperamylasemia and pancreatitis persisting after 48 hours. Patients were evaluated in the context of the presence or absence of preoperative pancreatic dysfunction. Similarly, various operative risk factors were evaluated, including cholangiography, choledocholithiasis, common duct exploration, choledochoscopy, choledochoduodenostomy, and sphincteroplasty. Operative cholangiography did not induce postoperative pancreatitis. The incidence of postoperative pancreatitis following cholecystectomy was 0.6%, which was significantly greater than the incidence following common duct exploration (8.4%). Pancreatitis following biliary tract surgery seemed to be not directly related to the performance of choledochoscopy, sphincteroplasty, or choledochoduodenostomy, as it developed with similar frequency in patients undergoing common duct exploration alone. The timing of operative therapy in patients with biliary tract pancreatitis did not significantly alter the frequency with which pancreatitis persisted in the postoperative period. In 970 patients undergoing cholecystectomy, one patient who had preoperative pancreatitis died of postoperative pancreatitis. Of 286 patients undergoing common duct exploration, seven patients died with pancreatitis. In three of these patients there was no active preoperative pancreatitis, and in one of these patients pancreatitis was the cause of death. Four patients with preoperative pancreatitis eventually died of pancreatitis in the postoperative period. Pancreatitis is an important complication of biliary tract disease and operations, and all efforts should be extended to suppress its occurrence and development.

Amylases↗
PubMed1990

[Diagnosis and treatment of biliary tract obstruction in children with biliary atresia].

Fifty children from one month to 14 years of age were examined and subjected to surgical treatment. Atresia of the bile ducts was diagnosed in 34 of them, hypoplasia of the bile ducts in 5, and a cyst of the choledochus in 11. Biliary atresia was managed by different variants of portoenterostomy, mostly after Kasai I, and two operations of cholecystojejunostomy were conducted in the so-called correctable type of atresia. 5 patients with biliary hypoplasia were treated by cholecystectomy, lavage of the bile ducts, and denervation of the hepatic artery. The following operations were carried out on 11 patients with a cyst of the choledochus: extirpation of the cyst with subsequent hepaticojejunostomy in 4, cystojejunostomy in 5, and cystoduodenostomy in 2 patients. Ultrasonic examination of the liver was undertaken in all 50 patients with impaired patency of the biliary tract as a screening test. Nine patients died in the postoperative period.

Adolescent↗
PubMed2003

Imatinib mesylate (STI571; Glivec)--a new approach in the treatment of biliary tract cancer?

Non-resectable biliary tract cancer is associated with poor prognosis due to widespread resistance to chemotherapeutic agents and radiotherapy. It is therefore essential to explore new therapeutic approaches like the inhibition of tyrosine kinases. The aim of this study was to determine the expression of c-kit and platelet-derived growth factor (PDGF) receptors (PDGFRs) and the effects of the tyrosine kinase inhibitor imatinib +/- 5-fluorouracil (5-FU) on proliferation and apoptosis in biliary tract cancer cell lines. The expression of c-kit and PDGFR mRNA was examined in 12 biliary tract cancer cell lines using RT-PCR. Cells were treated with imatinib (1, 10, 20 and 50 micromol/l) +/- 5-FU (0.1 microg/ml) for 6 days and inhibition of cell growth was assessed by manual cell counting. Cell proliferation and apoptosis were analyzed by flow cytometry of BrdU and Annexin-V/propidium iodide-stained cells. c-kit and PDGF mRNA expression was detected in 50 and 75%, respectively. Imatinib (10 and 20 micromol/l) alone inhibited cell growth significantly higher in c-kit+ cell lines (p<0.02) and inhibition was independent of PDGFR status. The combination with 5-FU increased the effect of imatinib mesylate in all cell lines. Treatment of cells with imatinib +/- 5-FU was associated with a significant induction of apoptosis, but no inhibition of proliferation. We conclude that imatinib alone exerts marked effects on c-kit+ biliary tract cancer cell lines only at intermediate and high concentrations, but there is a potential role of low-dose imatinib in combination with 5-FU for the treatment of biliary tract cancers.

Antineoplastic Agents↗
PubMed2006

A phase II study of LFP therapy (5-FU (5-fluorourasil) continuous infusion (CVI) and Low-dose consecutive (Cisplatin) CDDP) in advanced biliary tract carcinoma.

BACKGROUND: Unresectable biliary tract carcinoma is known to demonstrate a poor prognosis. We conducted a single arm phase II study of LFP therapy (5-FU (5-fluorourasil) continuous infusion (CVI) and Low-dose consecutive (Cisplatin) CDDP) for advanced biliary tract malignancies basically on an outpatient basis. METHODS: Between February 1996 and September 2003, 42 patients were enrolled in this trial. LFP THERAPY: By using a total implanted CV-catheter system, 5-FU (160 mg/m2/day) was continuously infused over 24 hours for 7 consecutive days and CDDP (6 mg/m2/day) was infused for 30 minutes twice a week as one cycle. The administration schedule consisted of 4 cycles as one course. RESIST criteria (Response evaluation criteria for solid tumors) and NCI-CTC (National Cancer Institute-Common Toxicity Criteria) (ver.3.0) were used for evaluation of this therapy. The median survival time (MST) and median time to treatment failure (TTF) were calculated by the Kaplan-Meier method. RESULTS: Patients characteristics were: mean age 66.5(47-79): male 24 (54%): BDca (bile duct carcinoma) 27 GBca (Gallbladder carcinoma) 15: locally advanced 26, postoperative recurrence 16. The most common toxicity was anemia (26.2%). Neither any treatment related death nor grade 4 toxicity occurred. The median number of courses of LFP Therapy which patients could receive was two (1-14). All the patients are evaluable for effects with an over all response rates of 42.9% (95% confidence interval C.I.: 27.7-59.0) (0 CR, 18 PR, 13 NC, 11 PD). There was no significant difference regarding the anti tumor effects against both malignant neoplasms. Figure 2 Shows the BDca a longer MST and TTF than did GBca (234 vs 150, 117 vs 85, respectively), but neither difference was statistically significant.The estimated MST and median TTF were 225 and 107 days, respectively. The BDca had a longer MST and TTF than GBca (234 vs 150, 117 vs 85, respectively), but neither difference was statistically significant. CONCLUSION: LFP therapy appears to be useful modality for the clinical management of advanced biliary tract malignancy.

Aged↗
PubMed1996

In vivo gene transfer to the human biliary tract.

The human biliary tract offers an excellent model for gene transfer studies for a variety of diseases localized to the liver. The aim of this study was to determine if a viable liver might be employed to study viral transfection of the human biliary system in order to mimic in vivo human experiments. Using a normal human liver initially procured for transplantation, but subsequently found unsuitable, and with an intact biliary tree, the hepatic vascular supply was accessed for continuous perfusion. The common and left hepatic biliary system was isolated by balloon catheterization. A replication defective adenoviral vector containing the Escherichia coli beta-galactosidase (lac Z) reporter gene (AdCMVLacZ) was injected into the catheter-isolated left and common bile duct lumen. Viral exposure to the right duct system was prevented by ligation. The bile duct segments were excised and prepared for enzymatic (X-gal) staining. Intense staining was observed in the biliary epithelium exposed to the adenoviral vector. No evidence of beta-galactosidase staining was noted in the unexposed biliary mucosa. We report direct transfection of biliary epithelial cells from normal human liver with a recombinant adenovirus. Our data suggest potential therapeutic applications for gene therapy of hepatobiliary disorders.

Adenoviridae↗
PubMed1995

The utility of the CCK DISIDA scan in the treatment of occult biliary tract disease.

The vast majority of biliary tract disease is correlated with calculi, and the diagnosis of biliary disease is made simpler when calculi are detected. There are good screening studies for the detection of calculi; however, a reproducible objective test for biliary tract disease in the absence of gallstones has been lacking. Occult biliary tract disease should be considered when symptoms typical of biliary tract disease are present, gallstones cannot be demonstrated, and other diseases have been ruled out. This is characteristically a diagnosis of exclusion, with only the subjective criteria of pain relief to validate surgical intervention. Recently, we have used a nuclear medicine test that simulates the gallbladder response to normal postprandial physiologic stress, to study in an objective fashion the gallbladder function of a group of patients who have symptoms typical of biliary tract disease, but no demonstrable calculi. We have found that the CCK DISIDA study has correlated well with occult pathology. The experience at Easton Hospital has confirmed that the CCK augmented DISIDA scan with calculation of ejection fraction is a reasonably accurate study, with a sensitivity of 88% in detecting previously suspected but undemonstrable pathology in this selected population. This corresponds closely to the observed finding that the pathology reports of 77% of the resected gallbladders noted some abnormality. Of further interest is the long term symptomatic relief achieved in 85% of the patients available for follow up interviews, including a symptomatic benefit in eight of the 11 patients with a normal pathology report.(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗