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Background: The majority of patients with cholangiocarcinoma present with advanced, irresectable tumours associated with poor prognosis. The incidence and mortality rates associated with cholangiocarcinoma continue to rise, mandating the development of novel strategies for early detection, improved resection and treatment of residual lesions., Aim: To review the current evidence base for surgical, adjuvant and neo-adjuvant techniques in the management of cholangiocarcinoma., Methods: A search strategy incorporating PubMed/Medline search engines and utilising the key words biliary tract carcinoma; cholangiocarcinoma; management; surgery; chemotherapy; radiotherapy; photodynamic therapy; and radiofrequency ablation, in various combinations, was employed., Results: Data on neo-adjuvant and adjuvant techniques remain limited, and much of the literature concerns palliation of inoperable disease. The only opportunity for long-term survival remains surgical resection with negative pathological margins or liver transplantation, both of which remain possible in only a minority of selected patients. Neo-adjuvant and adjuvant techniques currently provide only limited success in improving survival., Conclusions: The development of novel strategies and treatment techniques is crucial. However, the shortage of randomised controlled trials is compounded by the low feasibility of conducting adequately powered trials in liver surgery, due to the large sample sizes that are required., (© 2011 Blackwell Publishing Ltd.)

Background: Porfimer is an intravenous (i.v.) injectable photosensitizing agent used in the photodynamic treatment of tumours and of high-grade dysplasia in Barrett's oesophagus., Aim: To assess the pharmacokinetics as well as the safety profiles of porfimer after a first and a second dose administered 30-45 days apart in patients undergoing photodynamic therapy., Methods: Nineteen patients (16 with cholangiocarcinoma) were enrolled. Porfimer sodium was administered by i.v. injection over 3-5 min. Blood samples were collected prior to starting i.v. drug injection and postdose at different time points after the first and second administrations., Results: Porfimer exposure values after the second administration were statistically higher than those observed after the first administration, suggesting a slight accumulation of porfimer following repeated administration. The apparent mean elimination half-life of porfimer increased from 410 h after the first administration to 725 h after the second administration. The safety profiles of porfimer after a first and a second administration were similar and did not raise additional concern. Eight patients experienced nine serious adverse events. Only photosensitivity was deemed study-drug related., Conclusion: Porfimer appears to display a safe and tolerable profile when used in patients requiring a second photodynamic therapy within 45 days., (2010 Axcan Pharma Inc.)

Background: Invasive measurement of the hepatic venous pressure gradient (HVPG) is regarded as the gold standard for risk stratification and the evaluation of pharmaceutical agents in patients with portal hypertension., Aim: To review the techniques for endoscopic and imaging-based assessment of portal haemodynamics, with particular emphasis on trials where the results were compared with HVPG or direct portal pressure measurement., Methods: Systematic search of the MEDLINE electronic database with keywords: portal hypertension, variceal bleeding, variceal pressure, endoscopic ultrasound, Doppler ultrasonography, magnetic resonance angiography, CT angiography, hepatic venous pressure gradient., Results: Computed tomography angiography and endoscopic ultrasound (EUS) have been both employed for the diagnosis of complications of portal hypertension and for the evaluation of the efficacy of endoscopic therapy. Colour Doppler ultrasonography and magnetic resonance angiography has given discrepant results. Endoscopic variceal pressure measurements either alone or combined with simultaneous EUS, correlate well with HVPG and risk of variceal bleeding and have a low interobserver variability., Conclusions: Endoscopic and imaging-based measurements of portal haemodynamics provide an alternate means for the assessment of complications of portal hypertension. Further studies are required to validate their use in risk stratification and the evaluation of drug therapies in patients with portal hypertension.

Background: Sphincter of Oddi dysfunction is a benign, functional gastrointestinal disorder for which invasive endoscopic therapy with potential complications is often recommended., Aims: To review the available evidence regarding the diagnostic accuracy of non-invasive methods that have been used to establish the diagnosis and to estimate the long-term outcome after endoscopic sphincterotomy., Methods: A systematic review of English language articles and abstracts containing relevant terms was performed., Results: Non-invasive diagnostic methods are limited by their low sensitivity and specificity, especially in patients with Type III sphincter of Oddi dysfunction. Secretin-stimulated magnetic resonance cholangiopancreatography appears to be useful in excluding other potential causes of symptoms, and morphine-provocated hepatobiliary scintigraphy also warrants further study. Approximately 85%, 69% and 37%, of patients with biliary Types I, II and III sphincter of Oddi dysfunction, respectively, experience sustained benefit after endoscopic sphincterotomy. In pancreatic sphincter of Oddi dysfunction, approximately 75% of patients report symptomatic improvement after pancreatic sphincterotomy, but the studies have been non-controlled and heterogeneous., Conclusions: Patients with suspected sphincter of Oddi dysfunction, particularly those with biliary Type III, should be carefully evaluated before considering sphincter of Oddi manometry and endoscopic sphincterotomy. Further controlled trials are needed to justify the invasive management of patients with biliary Type III and pancreatic sphincter of Oddi dysfunction.

Background: In patients with pruritus of cholestasis, response to conventional drug treatment may be unsatisfactory. Activation of 5-hydroxytryptamine receptors on dermal sensory nerve-endings plays a role in the perception of pruritus. The 5-hydroxytryptamine(3) receptor antagonist, ondansetron, has been used in the treatment of pruritus of cholestasis, but there are few controlled data., Aim: To determine whether ondansetron is effective in treating the pruritus of cholestasis., Methods: A total of 19 patients with resistant pruritus were randomized, double blind, to receive either ondansetron 8 mg or placebo as a single intravenous bolus, followed by oral ondansetron 8 mg or placebo twice daily for 5 days. Patients' perception of pruritus was recorded hourly using a visual analogue scale, and scratching activity measured by means of a piezo-electric crystal attached to the fingernail., Results: Mean pruritus score using visual analogue scale and scratching activity were reduced on the first treatment day compared with baseline in both the ondansetron and placebo groups (P < 0.05), but there were no significant differences in mean pruritus perception or scratching activity between the two groups., Conclusion: Ondansetron was of no benefit in this group of pruritic patients during short-term treatment.

Background: Retrospective studies have suggested that hormone replacement therapy may reduce the rate of bone loss in primary biliary cirrhosis, but no controlled data are available., Methods: Forty-two post-menopausal women with primary biliary cirrhosis were treated with calcium and vitamin D, either alone (n = 21) or together with transdermal hormone replacement therapy (n = 21). Bone densitometry was performed at baseline and at 1 year, and serum and urinary markers of bone turnover were measured at three-monthly intervals., Results: At entry, 17 patients (40%) had spinal or femoral osteopenia (T score - 1 to - 2.5) and nine (21%) had osteoporosis (T < - 2.5). In those given hormone replacement therapy, there was a significant decrease in the mean urinary deoxypyridinoline :creatinine ratios at 3 months (7.8 vs. 6.1 nm/mm creatinine for no hormone replacement therapy vs. hormone replacement therapy; P = 0.04) and a 48% reduction in urinary calcium excretion at 1 year (0.66 vs. 0.32 mm/mm creatinine; P = 0.01). Repeat bone densitometry at 1 year revealed a 2.25% increase in the hormone replacement therapy group (P = 0.02), compared with a non-significant 0.87% decrease in L2-L4 bone mineral density in those not given hormone replacement therapy. Both treatment regimens were well tolerated, with no increase in cholestasis., Conclusions: Compared with calcium and vitamin D alone, supplemental treatment with transdermal hormone replacement therapy for 1 year improved the vertebral bone density and urinary markers of bone turnover in post-menopausal women with primary biliary cirrhosis.

Background: Inflammatory bowel disease is a risk factor for gall-bladder stones, but there is controversy about the composition of these stones and whether such patients develop lithogenic bile., Methods: In 54 gallstone-free inflammatory bowel disease patients and 13 non-inflammatory bowel disease patients with cholesterol-rich gallstones, we measured the biliary cholesterol saturation indices, nucleation times and bilirubin concentrations, and determined the bile acid composition and molecular species of phosphatidylcholine, in gall-bladder bile., Results: Patients with Crohn's colitis or ulcerative colitis had less saturated bile (mean cholesterol saturation index, 0.9) and longer nucleation times (median, 21 days) than those with ileal Crohn's disease (1.5; 14 days) or those who had undergone colectomy (1.6; 5 days). In patients with ileal Crohn's disease, the mean biliary bilirubin concentration was two- to three-fold higher than that in the other groups, and was associated with a decrease in the percentage of biliary deoxycholate and an increase in the percentage of ursodeoxycholate, compared with disease controls, but phosphatidylcholine species were similar., Conclusions: Patients with small bowel Crohn's disease, or who have undergone colonic resection, have supersaturated bile and an increased risk of cholesterol gallstone formation. In patients with ileal disease, the presence of high biliary bilirubin concentrations and low percentage of deoxycholic acid may also favour the formation of mixed, pigment-rich, gallstones.

Background and Aims: Octreotide treatment of acromegalic patients induces cholesterol gallstone formation, in part by impairing cholecystokinin release and gall-bladder contraction. However, there are few data on the effect of octreotide on biliary arachidonic acid-rich phospholipids or mucin glycoprotein, factors which also influence cholesterol gallstone formation., Methods: In acromegalic patients studied before and during 3 months of octreotide treatment, we measured mucin glycoprotein concentrations and the molecular species of phosphatidylcholine, and related the results to the cholesterol saturation and percentage of deoxycholic acid in gall-bladder bile., Results: The relative proportions of the major arachidonic acid-rich phosphatidylcholine species, PC 16:0-20:4 and PC 18:0-20:4, increased significantly during octreotide treatment. These changes were associated with a rise in the cholesterol saturation index and a non-significant twofold increase in mucin glycoprotein concentration. There were significant correlations between PC 16:0-20:4 and the cholesterol saturation index, percentage of vesicular cholesterol and percentage of deoxycholic acid in gall-bladder bile., Conclusions: In acromegalic patients, octreotide increases the proportions of arachidonic acid-rich phospholipids, with associated rises in: (a) the cholesterol saturation index and percentage of vesicular cholesterol, and (b) the percentage of deoxycholic acid in gall-bladder bile-changes similar to those found in patients with cholesterol-rich gall-bladder stones.

Background: Small bowel bacterial overgrowth secondary to drug-induced hypochlorhydria may be of particular importance in the elderly, in whom anti-ulcer drugs are commonly prescribed and the consequences of malabsorption may be severe., Methods: Duodenal aspirates were obtained from elderly individuals before (n = 24) and during a 2-month treatment course with either omeprazole (20 mg daily; n = 8) or ranitidine (300 mg b.d.; n = 6), and from six patients with small bowel bacterial overgrowth who had diarrhoea and malabsorption., Results: Before treatment, duodenal bacterial counts were normal (< 10(4) colony forming units/mL) in 23 elderly subjects (96%). However, six of 14 patients (43%) treated with omeprazole (5 of 8) or ranitidine (1 of 6) developed bacterial counts > 10(5) cfu/mL. All remained asymptomatic and had normal lactulose breath H2 profiles during treatment., Conclusion: Drug-induced hypochlorhydria causes high duodenal bacterial counts in the elderly but, in the short term, this bacterial overgrowth is not associated with malabsorption.