Biliary Tract Obstruction Research Articles

Pharmacokinetic study and clinical evaluation of a slow-release 5-fluorouracil implant in pancreatic cancer patients

The aim of this research was to study the pharmacokinetic characteristics of a slow-release 5-fluorouracil implant as well as to evaluate the clinical drug activity of this preparation in pancreatic cancer patients. Pharmacokinetic characteristics of the slow-release 5-fluorouracil implant were evaluated by examining the half-life time (T1/2) and apparent volume of distribution (Vd) in pancreatic cancer patients; the slow-release 5-fluorouracil implant was administered through interstitial chemotherapy (tumor interstitium implantation). In the drug activity study, 36 locally advanced unresectable pancreatic cancer patients were divided randomly into an experimental treatment group (n=18) and a standard treatment group (n=18). The experimental treatment group was treated with interstitial chemotherapy of a slow-release 5-fluorouracil implant combined with systemic chemotherapy of gemcitabine; the standard treatment group was treated with systemic chemotherapy of gemcitabine. An internal drainage procedure was used when biliary and/or gastrointestinal tract obstruction occurred in the two groups. Clinical benefit response, including pain (visual analogue scale), analgesic drug use, general conditions (Karnofsky performance score), weight changes, and survival status, was observed. T1/2 of the slow-release 5-fluorouracil implant was 5475.8±136.4 min, whereas Vd was 45275.0±1028.6 l. Clinical benefit response in the experimental treatment group was better than that in the standard treatment group. The experimental treatment group had longer median survival time compared with the standard treatment group. The slow-release 5-fluorouracil implant could deliver drugs mainly in the regional area of the tumor and prolong the drug action time; interstitial chemotherapy of a 5-fluorouracil implant combined with systemic chemotherapy of gemcitabine could improve the quality of life and survival status of pancreatic cancer patients. The method was promising and worthy of in-depth investigations.

A Case of Malignant Biliary Obstruction with Severe Obesity Successfully Treated by Endoscopic Ultrasonography-Guided Biliary Drainage

Here, we present a case of malignant biliary tract obstruction with severe obesity, which was successfully treated by endoscopic ultrasonography-guided biliary drainage (EUS-BD). A female patient in her sixties who had been undergoing chemotherapy for unresectable pancreatic head cancer was admitted to our institution for obstructive jaundice. She had diabetes mellitus, and her body mass index was 35.1 kg/m2. Initially, endoscopic retrograde cholangiopancreatography (ERCP) was performed, but bile duct cannulation was unsuccessful. Percutaneous transhepatic biliary drainage (PTBD) from the left hepatic biliary tree also failed. Although a second PTBD attempt from the right hepatic lobe was accomplished, biliary tract bleeding followed, and the catheter was dislodged. Consequently, EUS-BD (choledochoduodenostomy), followed by direct metallic stent placement, was performed as a third drainage method. Her postprocedural course was uneventful. Following discharge, she spent the rest of her life at home without recurrent jaundice or readmission. In cases of severe obesity, we consider EUS-BD, rather than PTBD, as the second drainage method of choice for distal malignant biliary obstruction when ERCP fails.

Digital camera image analysis of faeces in detection of cholestatic jaundice in infants.

Stool colour assessment is a screening method for biliary tract obstruction in infants. This study is aimed to be a proof of concept work of digital photograph image analysis of stool colour compared to colour grading by a colour card, and the stool bilirubin level test. The total bilirubin (TB) level contents in stool samples from 17 infants aged less than 1 year, seven with confirmed cholestatic jaundice and ten healthy subjects was measured, and outcome correlated with the physical colour of the stool. The seven infants with cholestasis included 6 cases of biliary atresia and 1 case of pancreatic mass. All pre-operative stool samples in these cases were indicated as grade 1 on the stool card (stool colour in healthy infants ranges from 4 to 6). The average stool TB in the pale stool group was 43.07 μg/g compared to 101.78 μg/g in the non-pale stool group. Of the 3 colour channels assessed in the digital photographs, the blue and green light were best able to discriminate accurately between the pre-operative stool samples from infants with cholestasis and the samples from the healthy controls. With red, green, and blue (RGB) image analysis using wave level as the ANN input, the system predicts the stool TB with a relationship coefficient of 0.96, compared to 0.61 when stool colour card grading was used. Input from digital camera images of stool had a higher predictive capability compared to the standard stool colour card, indicating using digital photographs may be a useful tool for detection of cholestasis in infants.

Recurrence of biliary tract obstructions after primary laparoscopic hepaticojejunostomy in children with choledochal cysts.

The aim of the current study was to investigate the cause and develop a management strategy for recurrent biliary obstructions after primary laparoscopic hepaticojejunostomy in children with choledochal cyst (CDC). Thirty CDC patients (mean age: 7.15years, range 8months-24years, F/M: 22/8) who suffered from recurrent biliary obstructions after primary laparoscopic hepaticojejunostomies were referred to our hospital between January 2006 and June 2014. All patients underwent redo hepaticojejunostomy±ductoplasty±reposition of aberrant right hepatic arteries. All patients developed recurrent cholangitis or persistent abnormal liver function 1month to 7years postoperatively. Liver biopsy pathology verified that 56.7% (17/30) of patients had grades I-IV of liver fibrosis. We identified a previously unreported cause of biliary obstruction, i.e., aberrant right hepatic arteries crossing anteriorly to the proximal common hepatic duct in high percentage of the patients who suffered from postoperative recurrent biliary obstructions (7/30, 23.3%). The hepatic arteries were repositioned behind Roux loop during the redo hepaticojejunostomies. Of remaining patients, nine (30%) patients had associated hepatic duct strictures and underwent ductoplasties and wide hepaticojejunostomies. Fourteen (46.7%) patients had anastomotic strictures and underwent redo hepaticojejunostomies. The median follow-up period was 62months (14-115months). No recurrent biliary obstruction or cholangitis was observed up to date. Liver functions were normalized. Aberrant hepatic artery, unsolved hepatic duct stricture, as well as poor anastomotic technique, can all contribute to recurrent biliary obstructions after the primary laparoscopic hepaticojejunostomies. Early surgical correction is advocated to minimize liver damage.

Divided Laparoscopic Cholecystectomy for Unusual Gall Stones Complication of Mirizzi’s Syndrome

Background: Chronic complications of symptomatic gallstone disease such as Mirizzi’s syndrome are rare. The importance and implications of these conditions are related to their associated surgical complications which are potentially serious such as bile duct injury and to the modern management when encountered during laparoscopic cholecystectomy. Objectives: This research offers a technique to avoid surgical complications in Mirizzi’s syndrome cases during laparoscopic cholecystectomy. Patients and Methods: Between November 2012 and February 2015, 17 patients (12 females and 5 males) with mean age of 51 years (between 29 and 57 years) suffering from Mirizzi’s syndrome underwent the divided cholecystectomy. In this technique the gall bladder was divided into two parts above the gall bladder infundibulum. The distal part was dissected for short distance and used to push liver up. The proximal part of gall bladder was cleared from all its contents and reevaluated from inside. Management was achieved according to the stage of disease. Results: The mean operative time was 70 minutes (between 60 and 90 minutes). No biliary tract obstruction or leakage or stenosis was recorded in this patient group during the period of follow up (18 months). Conclusions: Divided laparoscopic cholecystectomy is a safe and effective technique to face the unusual gallstones complications (Mirizzi’s syndrome).

Biliary duct obstruction treatment with aid of percutaneous transhepatic biliary drainage

IntroductionPercutaneous Transhepatic Biliary Drainage (PTBD) is a procedure indicated in patients with non-operative lesions, when endoscopic application of prosthesis is impossible due to anatomic reasons, complications or severe general condition of patient. Most often it is a palliative procedure, aiming for live-quality improvement, although not altering prognosis of basic disease. AimThis study presents own experience in biliary drainage with the aid of percutaneous transhepatic method and simultaneous assessment of method effectiveness and safety. The aim was to assess outcomes and complications of PTBD in a large group of patients. Materials and methodIn time period 2007–2014, 167 patients hospitalized in Radiodiagnostics and Radiology Department of Clinical Hospital, were investigated retrospectively. PTBD procedure was applied to patients with biliary tract obstruction. In total 186 procedures of percutaneous drainage were applied. Average age of patients was 63.6years. Bilirubin, alkaline phosphatase and gamma-glutamyl transferase were measured before and after procedure. All data were analyzed statistically. ResultsIn examined group percutaneous drainage was successful in 90.7% interventions. In 8.1% procedures drainage application was ineffective. The most common complication during procedure was hemobilia (3.2%) and the long term complication was drain dislocation (2.7%). The mean bilirubin levels declined from 397.06μmol/l before drainage to 297.88μmol/l after drainage (p<0.05). ConclusionsPTBD is an effective method of biliary tract decompression and it is an important alternative to endoscopic drainage. This method is indicated in patients with neoplastic obstruction of biliary tract with low expected survival rate and thus is a palliative procedure.

Extragonadal yolk sac tumor (endodermal sinus tumor) presenting with biliary tract obstruction in a woman

A 35-year-old woman presented to her primary care physician with early satiety, weight loss, nausea, vomiting, and pruritus. She was eventually found to have a pancreatic mass obstructing the bile duct. The mass was evaluated by endoscopic retrograde cholangiopancreatography (ERCP) and endoscopic ultrasonography (EUS) with biopsy. Histopathology results revealed a high grade malignant neoplasm of uncertain type. The tumor was further characterized by open biopsy, which revealed a yolk sac tumor (endodermal sinus tumor). Her disease was unresectable. Serum alpha-fetoprotein (AFP) levels were markedly elevated (693.3 ng/ml; reference range: 0-8 ng/ml). The patient was treated with bleomycin, etoposide, and cisplatin (BEP) with a partial response and a persistently elevated serum AFP of 139.7 ng/ml. She then received salvage chemotherapy with paclitaxel, ifosfamide, and cisplatin (TIP), with a minimal response (serum AFP, 68 ng/ml). She next received an autologous bone marrow transplant, with a decline in AFP to 19 ng/ml after the first of two tandem transplants. This case report illustrates a rare presentation of an extragonadal endodermal sinus tumor in a woman with biliary tract obstruction as the predominant manifestation.

Cisplatin and gemcitabine in patients with advanced biliary tract cancer (ABC) and persistent jaundice despite optimal stenting: Effective intervention in patients with luminal disease

IntroductionThe advanced biliary tract cancer (ABC)-02 study established cisplatin and gemcitabine (CisGem) as a reference 1st-line regimen for patients with advanced/metastatic biliary tract cancer; patients with bilirubin ⩾1.5 × upper limit of normal (ULN) were excluded and there are few extant data for systemic treatment in the context of elevated bilirubin. MethodsPatients with ABC, receiving CisGem with a baseline bilirubin of ⩾1.5×ULN were eligible for this retrospective analysis; response, toxicity and survival data were collected. ResultsThirty-three patients of 545 screened; median age 59years, range 23–79; 58% male, 58% with metastases (79% in the liver) of performance status (PS) 0 (33%), 1 (64%) or 2 (3%) were eligible. The median baseline bilirubin was 55μmol/L (range 32–286); due to biliary tract obstruction (BTO, 76%) or liver metastases (LM, 24%). Toxicity was comparable to the ABC-02 study; bilirubin normalised in 64% during chemotherapy/follow-up. The median progression-free survival (PFS) was 6.9months (95% confidence interval (CI): 4.4–9.0) and median overall survival (OS) 9.5months (95% CI: 5.7–12.8). Patients with BTO had a longer PFS and OS than those with LM (7.0 versus 2.6months; p=0.1633 and 9.8 versus 4.4months, hazard ratio (HR) 0.74; p=0.465, respectively); not statistically significant (due to small sample size). Normalisation of bilirubin and completion of eight CisGem cycles were associated with longer OS (11.4 versus 2.9months, HR 0.49; p=0.08 and 15.2 versus 5.4months, HR 0.12 p<0.001, respectively). No difference in OS was shown between the bilirubin percentiles (for either PFS or OS). ConclusionFor PS 0-1 patients with ABC and high bilirubin due to luminal disease despite optimal stenting CisGem can be used safely with results similar to those in patients with normal bilirubin.

Association of N-acetylcysteine and glucagon during percutaneous cholangiography in the treatment of inspissated bile syndrome

Inspissated bile syndrome (IBS) is a rare neonatal disease. In the majority of cases, it resolves spontaneously and treatment is conservative. Follow-up is recommended with close monitoring of laboratory tests. When IBS does not resolve spontaneously, a catheter can be inserted into the gallbladder for cholangiography, which allows irrigation and drainage. Despite this treatment, some biliary tract obstruction may persist. We report on the case of a 3-month-old infant whose continuous biliary obstruction caused by IBS was successfully managed by interventional radiology with the association of N-acetylcysteine and glucagon. Even as first-line agents, these would allow more rapid clearance of gallstones and prevent infectious complications of indwelling catheters as well as decrease the need for surgery.

The Role of Multidetector Row Computed Tomography in Biliary Tract Malignancy

Early diagnosis of biliary tract tumors is important in accurate staging, to choose the best possible treatment and improve their prognosis. Multidetector row Computed Tomography is an ideal method to evaluate patients with suspected biliary tract obstruction and thereby biliary tract malignancy. Aims and Objective: To evaluate the accuracy of Multidetector row Computed Tomography (MDCT) in evaluation of level of obstruction and to study the imaging features of various causes of biliary tract malignancy. Material and Method: MDCT of 40 patients with clinically suspicion of biliary tract obstruction were prospectively reviewed and only malignant causes were included in the study. Final diagnosis was based on endoscopic retrograde cholangiopancreatography, surgical and histopathological diagnosis. The MDCT diagnosis and final diagnosis was compared for level and imaging features of malignant lesions. Results: The sensitivity, specificity, PPV, NPV and diagnostic accuracy of MDCT in determining the level of malignant obstruction is 100%, 83.33%, 97.77%, 100%, 98%, and cause of malignant obstruction is 97.73%, 83.33%, 97.72%, 83.33%, 96%. MDCT with its high sensitivity and specificity values plays an essential role in the diagnosis of malignant tumors of biliary tract and for the evaluation of therapeutic options. Conclusion: MDCT has a vital role to play in biliary tract malignancy with its high degree of accuracy in establishing the level of obstruction and in defining the imaging features of the malignant lesions.

Endoscopic ultrasound-guided biliary drainage as an alternative to percutaneous drainage and surgical bypass.

Endoscopic retrograde cholangiopancreatography had been a treatment modality of choice for both benign and malignant biliary tract obstruction for more than half century, with a very high clinical success rate and low complications. But in certain circumstances, such as advanced and locally advanced pancreatobiliary malignancies (pancreatic cancer, cholangiocarcinoma, ampullary tumor) and tight benign strictures, endoscopic retrograde cholangiopancreatography (ERCP) fails. Up to this point, the only alternative interventions for these conditions were percutaneous transhepatic biliary drainage or surgery. Endoscopic ultrasound guided interventions was introduced for a couple decades with the better visualization and achievement of the pancreatobiliary tract. And it's still in the process of ongoing development. The inventions of new techniques and accessories lead to more feasibility of high-ended procedures. Endoscopic ultrasound guided biliary drainage was a novel treatment modality for the patient who failed ERCP with the less invasive technique comparing to surgical bypass. The technical and clinical success was high with acceptable complications. Regarded the ability to drain the biliary tract internally without an exploratory laparotomy, this treatment modality became a very interesting procedures for many endosonographers, worldwide, in a short period. We have reviewed the literature and suggest that endoscopic ultrasound-guided biliary drainage is also an option, and one with a high probability of success, for biliary drainage in the patients who failed conventional endoscopic drainage.

Extrahepatic Biliary Obstruction Secondary to Traumatic Diaphragmatic Hernia in Dog

A 3-year-old intact mixed hunting dog was referred to Gyeongsang Animal Medical Center with the clinical signs of vomiting, dyspnea, anorexia. The dogs had traumatic history that wounded at abdominal wall during the wild boar hunting 2 week ago. The dogs was diagnosed as extrahepatic biliary tract obstruction (EHBO) secondary to traumatic hernia. Diagnosis was based on radiographic features of a diaphragmatic hernia on survey radiography, dilated bile duct in abdominal ultrasonography and complete recovery due to the return of displaced organs into the peritoneal cavity and repair of the diaphragmatic rent. Diagnostic imaging and surgical intervention may result in a favorable outcome in dog with post hepatic obstruction secondary to diaphragmatic hernia. This case emphasizes the strangulation of bile duct by diaphragmatic rupture could be the cause of EHBO.

Role of CT and MRCP in Evaluation of Biliary Tract Obstruction

Obstructive jaundice which is caused by bile duct obstruction can be clinically and biochemically indistinguishable from cholestatic jaundice caused by hepatocellular disease. The management of both these conditions being radically different, the principle task of the radiologist is to differentiate between hepatocellular and obstructive jaundice, using available imaging modality and help in further management. With the availability of non-invasive modality like computed tomography and magnetic resonance imaging (MRI), it is possible to diagnose obstructive jaundice early and accurately without any patient discomfort. The purpose of this article is to describe the protocol for evaluation of obstructive jaundice with use of MDCT and magnetic resonance cholangio pancreatography sequence of MRI and to describe the imaging features of the most common causes of obstructive jaundice like biliary calculi, bile duct strictures, choledochal cyst, gall bladder carcinoma, cholangiocarcinoma, primary sclerosing cholangitis, and pancreatic head carcinoma.

Comparison of percutaneous transhepatic biliary drainage and endoscopic biliary drainage in the management of malignant biliary tract obstruction: a meta-analysis.

To compare percutaneous transhepatic biliary drainage (PTBD) and endoscopic biliary drainage (EBD) for management of malignant biliary tract obstruction (MBTO). PubMed, Google Scholar, and the Cochrane database were searched to 31 December 2013. Main outcome measurements were therapeutic success rate, 30-day mortality rate, overall complications, cholangitis, and pancreatitis. Eight studies (five retrospective and three randomized controlled trials) were included in the meta-analysis with a total of 692 participants. Combined odds ratio (OR) = 2.18 revealed no significant difference in therapeutic success between PTBD and EBD (95% confidence interval [CI] = 0.73-6.47, P = 0.162). However, after excluding two studies that appeared to be outliers, PTBD exhibited a better therapeutic success rate than EBD (pooled OR = 4.45, 95% CI = 2.68-7.40, P < 0.001). Patients who underwent PTBD were 0.55 times as likely to have cholangitis as those who underwent EBD, whereas the overall complication rate, pancreatitis rate, and 30-day mortality were similar between the two procedures. PTBD may be associated with a better therapeutic success rate and lower incidence of cholangitis than EBD, but the overall complication rate, pancreatitis rate, and 30-day mortality of the two procedures are similar.

Percutaneous transhepatic and endoscopic biliary drainage for malignant biliary tract obstruction: a meta-analysis

BackgroundVarious malignant tumors can obstruct the extrahepatic biliary tract. Two major techniques for restoring bile flow in this circumstance are endoscopic biliary drainage (EBD) and percutaneous transhepatic biliary drainage (PTBD).We conducted a meta-analysis to compare the effectiveness and safety of the two techniques.MethodsMedline, EMBASE and the Cochrane Library database were searched for articles published between January 1980 and December 2013. The outcome measures were therapeutic success rate (primary), 30-day mortality rate and overall complications.ResultsOf 264 screened articles, 3 randomized controlled trials comprising an aggregate total of 183 cancer patients were included in the meta-analysis. Our analysis showed no significant difference in restoration of bile flow between patients treated with EBD and those treated with PTBD (odds ratio (OR) = 2.34, 95% confidence interval (CI) = 0.32 to 17.16, P = 0.401). However, the result of sensitivity analysis indicated that the study conducted by Speer et al. influenced the pooled estimates. After the Speer et al. study was excluded, the therapeutic success rate of patients treated with PTBD was significantly greater than that of those who underwent EBD (OR = 5.48, 95% CI: 2.26 to 13.28, P < 0.001). The 30-day mortality and complication rates were similar in the EBD and PTBD groups.ConclusionsThe results of our meta-analysis indicate that PTBD had a higher therapeutic success rate than EBD in the treatment of malignancy-induced biliary obstruction. The mortality and complication rates of the two techniques were similar.Electronic supplementary materialThe online version of this article (doi:10.1186/1477-7819-12-272) contains supplementary material, which is available to authorized users.

A 60-Year-Old Man With Chronic Cough and Green Sputum

Question: A 60-year-old man with a past medical history of pancreatic neuroendocrine tumor with metastasis to the liver, chronic cholangitis, and liver abscess presented with a 2-month history of productive cough with green sputum and right upper quadrant pain. Past surgical history includes partial liver resection, liver chemoembolization and Y-90 microsphere radiation, cholecystectomy, and multiple intraabdominal surgeries. On examination, the patient was a cachectic-appearing white male. Oral cavity examination shows a greenish coating on tongue but no jaundice. Significant laboratory results included an alkaline phosphatase level of 523 U/L (normal, 55-135), aspartate aminotransferase of 57 U/L (normal, 10-40), and normal bilirubin level. Computed tomography was nondiagnostic. Magnetic resonance cholangiopancreatography without contrast revealed several nonspecific areas of abnormal increased T2 signal adjacent to the liver at the hepatic dome and within the right lower lobe of the lung, numerous poorly defined hepatic lesions. As part of his evaluation, a HIDA scan was performed (Figure A, results at 5 minutes; Figure B, at 40 minutes). Endoscopic retrograde cholangiopancreatography (ERCP) was then performed for diagnosis and therapeutic intervention (Figure C). What is the diagnosis? What is the appropriate management? Look on page 576 for the answer and see the Gastroenterology web site (www.gastrojournal.org) for more information on submitting your favorite image to Clinical Challenges and Images in GI.

Bile deficiency induces changes in intestinal Cl(-) and HCO3 (-) secretions in mice.

Biliary tract obstruction is a common clinical lesion. However, the effect of biliary tract obstruction on intestinal secretion is poorly understood. In this study, we made an investigation on intestinal HCO3 (-) and Cl(-) secretions in an experimental model of murine biliary duct ligation. Murine intestinal mucosal HCO3 (-) and Cl(-) secretions were examined in vitro in Ussing chambers by pH-stat and short-circuit current (Isc ) techniques. The mRNA and protein expressions of the cystic fibrosis transmembrane conductance regulator (CFTR) and the Na(+) -K(+) -2Cl(-) cotransporter (NKCC1) were analysed by real-time PCR, western blot and immunohistochemistry. Basal Cl(-) secretion and forskolin-stimulated duodenal and jejunal mucosal HCO3 (-) and Cl(-) secretions in mice with common biliary duct ligation were markedly elevated, compared with controls (P < 0.05 and P < 0.01). Further experiments showed that basal Cl(-) secretion and forskolin-stimulated duodenal and jejunal mucosal HCO3 (-) and Cl(-) secretions in mice with external bile drainage were also markedly elevated. CFTRinh -172 inhibited forskolin-stimulated HCO3 (-) and Cl(-) secretions. The mRNA and protein expression levels of CFTR and NKCC1 in the intestinal mucosa with both biliary duct ligation and external bile drainage were markedly higher than those in controls (P < 0.001). Bile acid administration restored the changes in function and expression of CFTR and NKCC1 in the intestinal mucosa. Bile deficiency in the intestine up-regulates the expressions of intestinal mucosal CFTR and NKCC1 and enhances intestinal mucosal HCO3 (-) and Cl(-) secretion capacity, which contributes to the understanding of intestinal physiological function for patients with biliary duct obstruction.

Severe cholestatic jaundice after a single administration of ajmaline; a case report and review of the literature

BackgroundAjmaline is a pharmaceutical agent now administered globally for a variety of indications, particularly investigation of suspected Brugada syndrome. There have been previous reports suggesting that repetitive use of this agent may cause severe liver injury, but little evidence exists demonstrating the same effect after only a single administration.Case presentationA 33-year-old man of Libyan origin with no significant past medical history underwent an ajmaline provocation test for investigation of suspected Brugada syndrome. Three weeks later, he presented with painless cholestatic jaundice which peaked in severity at eleven weeks after the test. Blood tests confirmed no evidence of autoimmune or viral liver disease, whilst imaging confirmed the absence of biliary tract obstruction. A liver biopsy demonstrated centrilobular cholestasis and focal rosetting of hepatocytes, consistent with a cholestatic drug reaction. Over the course of the next few months, he began to improve clinically and biochemically, with complete resolution by one year post-exposure.ConclusionWhilst ajmaline-related hepatotoxicity was well-recognised in the era in which the drug was administered as a regular medication, clinicians should be aware that ajmaline may induce severe cholestatic jaundice even after a single dose administration.

Cholestatic Hepatitis with Pancreatitis as Presenting Features of Epstein-Barr Virus Infection

In children with Epstein-Barr virus (EBV) infection biochemical evidence of liver involvement is frequent. However cholestasis and pancreatitis are rare. We report a child where this association, usually suggestive of biliary tract obstruction, was instead secondary to EBV infection without the typical clinical and hematological features of infectious mononucleosis (IM).

Efficacy and safety of cisplatin and gemcitabine (CG) chemotherapy for advanced biliary tract cancer (ABC) in jaundiced patients (pts).

294 Background: The ABC-02 study established cisplatin/gemcitabine (CG) as a 1st-line regimen for pts with advanced/metastatic biliary tract cancer (ABC). Biliary tract obstruction (BTO) is common in ABC and pts with bilirubin (bili) ≥1.5xULN were excluded from ABC-02. We assessed retrospectively the safety/efficacy of CG in ABC pts with high bili despite optimal stenting. Methods: Eligible pts had biopsy-proven ABC; received 1st-line CG; baseline bili levels ≥1.5xULN and had follow-up, response and toxicity data available. Survival analysis (Kaplan-Meier), long-rank test, Cox regression and multiple linear regression analyses were performed. Results: Thirty-three pts (of 545 pts screened) met inclusion criteria: median age 58.8 years (range 23-79); male 58%; cholangiocarcinoma 76%; gallbladder 18% or ampullary cancer 6%; locally advanced 42%; metastatic 58% (79% in liver); 68% had a biliary stent; and 97% of pts had good baseline performance status (PS) 0/1/2: 33%/64%/3%. Median baseline bili was 55umol/l (range 32-286); due to BTO in 76% or liver metastases (LM) in 24%. A median of 6 (range 1-8) cycles were given, 70% of pts started full dose CG; 40% completed 8 planned cycles; 40% needed a dose reduction. Early discontinuation (61% of all pts) was due to toxicity (25%), clinical (60%) or radiological progression (15%). Bili normalised in 64% of pts after CG; no unexpected side effects occurred. Most pts achieved stable disease (61%); with one partial response (3%); the median PFS was 6.9 mo (95%-CI: 4.4-9.0) and median OS 9.5 mo (95%-CI: 5.7-12.8). BTO pts had a trend for longer PFS than LM (7.0 vs. 2.6 mo; p=0.1633). Normalisation of bili and completion of CG were associated with longer OS (11.4 vs. 2.9 mo, HR 0.49; p=0.08 and 15.2 vs. 5.4 mo, HR 0.12 p&lt;0.001, respectively). Completion of CG was an independent prognostic factor for OS (multivariate analysis, p=0.001); no difference in OS was shown between the percentiles of baseline bili (p=0.57). Conclusions: For fit ABC patients with high bili, CG can be employed safely with encouraging results. Cause of jaundice (BTO, rather than bilirubin level), completion of chemotherapy and normalisation of bili are associated with improved OS.