• Advances in the treatment of metastatic or unresectable biliary tract cancer.

      Valle, Juan W; Christie Hospital/The University of Manchester, Manchester, UK. (2010-10)
      The prognosis for advanced/inoperable biliary tract cancer is poor and the management of biliary obstruction and sepsis remains the cornerstone of best supportive care (BSC). Many phase II studies have reported some activity of chemotherapy, usually involving one or more of a fluoropyrimidine, a platinum agent and gemcitabine. No adequately powered study has shown conclusively a benefit for chemotherapy compared with BSC alone although three small randomized studies have suggested an improved survival. Results from the randomized phase III ABC-02 study demonstrated a survival advantage of cisplatin and gemcitabine doublet-chemotherapy over gemcitabine monotherapy {median survival of 11.7 compared with 8.1 months, hazard ratio (HR), 0.64 [95% confidence interval (CI) 0.52 to 0.80]; log rank P < 0.001} as well as a significantly longer progression-free survival [median 8 compared with 5 months; HR 0.63 (95% CI 0.51 to 0.77); log rank P < 0.001]. A similar magnitude of benefit was seen in Japanese patients in a second study using the same treatment regimens (the BT-22 study). Ongoing studies are underway evaluating other chemotherapy regimens in first-line although attention is turning to the addition of targeted therapies; these will be reviewed. Pivotal to success in this process is both the identification of appropriate targets across this heterogeneous group of malignancies (e.g. EGFR, VEGF, MEK inhibition, amongst others) and collaboration between investigators to deliver relevant, timely and adequately powered studies.
    • Gemcitabine alone or in combination with cisplatin in patients with advanced or metastatic cholangiocarcinomas or other biliary tract tumours: a multicentre randomised phase II study - The UK ABC-01 Study.

      Valle, Juan W; Wasan, H; Johnson, P; Jones, Eileen T; Dixon, L; Swindell, Ric; Baka, Sofia; Maraveyas, A; Corrie, P; Falk, S; et al. (2009-08-18)
      BACKGROUND: We assessed the activity of gemcitabine (G) and cisplatin/gemcitabine (C/G) in patients with locally advanced (LA) or metastatic (M) (advanced) biliary cancers (ABC) for whom there is no standard chemotherapy. METHODS: Patients, aged > or =18 years, with pathologically confirmed ABC, Karnofsky performance (KP) > or =60, and adequate haematological, hepatic and renal function were randomised to G 1000 mg m(-2) on D1, 8, 15 q28d (Arm A) or C 25 mg m(-2) followed by G 1000 mg m(-2) D1, 8 q21d (Arm B) for up to 6 months or disease progression. RESULTS: In total, 86 patients (A/B, n=44/42) were randomised between February 2002 and May 2004. Median age (64/62.5 years), KP, primary tumour site, earlier surgery, indwelling biliary stent and disease stage (LA: 25/38%) are comparable between treatment arms. Grade 3-4 toxicity included (A/B, % patients) anaemia (4.5/2.4), leukopenia (6.8/4.8), neutropenia (13.6/14.3), thrombocytopenia (9.1/11.9), lethargy (9.1/28.6), nausea/vomiting (0/7.1) and anorexia (2.3/4.8). Responses (WHO criteria, % of evaluable patients: A n=31 vs B n=36): no CRs; PR 22.6 vs 27.8%; SD 35.5 vs 47.1% for a tumour control rate (CR+PR+SD) of 58.0 vs 75.0%. The median TTP and 6-month progression-free survival (PFS) (the primary end point) were greater in the C/G arm (4.0 vs 8.0 months and 45.5 vs 57.1% in arms A and B, respectively). CONCLUSION: Both regimens seem active in ABC. C/G is associated with an improved tumour control rate, TTP and 6-month PFS. The study has been extended (ABC-02 study) and powered to determine the effect on overall survival and the quality of life.
    • Pneumoperitoneum following percutaneous biliary intervention: not necessarily a cause for alarm.

      Amonkar, Suraj J; Laasch, Hans-Ulrich; Valle, Juan W; Manchester Radiology Training Scheme, University of Manchester, Manchester, M13 9PL, UK. surajamonkar@hotmail.com (2009-04-21)
      Percutaneous transhepatic cholangiography (PTC) is a well-established technique for assessing and treating obstructive jaundice. Plastic and self-expanding metal stents can be deployed as an alternative when ERCP is not feasible or hilar strictures require an antegrade approach. Complication rates of percutaneous procedures are low, and are usually related to bile leakage or hemorrhage; pneumoperitoneum following PTC is rare and is usually taken to indicate bowel perforation. We describe two cases of pneumoperitoneum without peritonitis following PTC and stenting, both of which resolved spontaneously with conservative management. The literature is reviewed and possible causes discussed.