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Work-up
Early diagnosis of gallbladder or cholangiocellular carcinoma is nearly impossible or can only be realized in exceptional cases
In a patient with specific clinical symptoms or ultrasound suspicion of biliary tract cancer, a spiral CT and chest x-ray should be performed
Medically fit, nonjaundiced patients whose disease appears potentially resectable may proceed directly to surgical exploration without needle biopsy to avoid tumor spread. Consider a laparoscopic evaluation before open surgery owing to the common occurrence of otherwise nonvisible metastatic spread to the peritoneum
If the potential to perform a resection remains uncertain and for those with jaundice, a more precise assessment of tumor extent and lymph node involvement should be obtained with MRCP ± MRA, which may help to rule out vascular invasion and anomalous anatomic findings for surgical planning
If it is obvious that a resection will not be possible or if distant metastases are present, fine-needle biopsy for tissue confirmation should be obtained
In nonresectable jaundiced patients, depending on the location of the biliary obstruction, a percutaneous transhepatic cholangiography (PTC) or an endoscopic retrograde cholangiography (ERC) should be considered to guide placement of a stent
Fong Y et al. Cancer of the liver and biliary tree. In: Principles and Practice of Oncology, 6th ed. Baltimore, MD: Lippincott Williams & Wilkins 2001:1162–1203
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Pathology
Lazcano-Ponce EC et al. CA Cancer J Clin 2001;51:349–364
Nakeeb A et al. Ann Surg 1996;224:463–475
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Five-Year Survival (Cholangiocarcinoma and Gallbladder Cancer)✫
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Staging
Edge SB, Byrd DR, Compton CC, Fritz AG, Greene FL, Trotti A, editors. AJCC Cancer Staging Manual. 7th ed. New York: Springer; 2010
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Biliary tract malignancies include carcinoma of the gallbladder as well as of the intrahepatic, perihilar, and distal bile ducts. Complete surgical resection remains the only curative modality for gallbladder cancer (cholecystectomy, en bloc hepatic resection, and lymphadenectomy with or without bile duct excision). Postoperative therapy for patients who undergo an operative resection might be considered with adjuvant chemotherapy and/or fluoropyrimidine-based radiochemotherapy, in selected cases. Patients with unresectable tumor without obvious metastatic disease and without jaundice may benefit from a regimen of fluorouracil- or capecitabine-based chemotherapy ± radiation. Metastatic disease is typically treated with systemic chemotherapy. Interventional procedures including brachytherapy and photodynamic therapy represent a therapeutic option for selected patients. However, overall survival of such patients remains poor (Razumilava and Gores, 2013)
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Less than 20% of all patients have disease that is deemed resectable, and even after having undergone potential curative resection, recurrence rates are high. Thus for the majority of patients, systemic chemotherapy is the mainstay of treatment. The problem concerning chemotherapy is the fact that most studies conducted in the past have been single-center, nonrandomized, phase II studies with relatively small patient numbers (Hezel and Zhu, 2008). Heterogeneous inclusion criteria, inherent difficulties in measuring tumor response, and the lack of studies having applied RECIST (Response Evaluation Criteria in Solid Tumors) methodology for confirmation of treatment effects further contribute to our limited knowledge how to best treat patients with advanced tumors (Eckel and Schmid, 2007)
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In the absence of validated data from prospective randomized studies, patients with biliary cancer were usually treated with gemcitabine or fluoropyrimidines ± platinum compounds. This, however, changed with the publication of the results from the ABC-01 trial that evaluated patients with locally advanced or metastatic cholangiocarcinoma, gallbladder cancer, or ampullary cancer (Valle et al, 2010). After a median follow-up of 8.2 months, the median overall survival was 11.7 months in the cisplatin plus gemcitabine group and 8.1 months in the gemcitabine group (HR, 0.64; 95% CI, 0.52 to 0.80; P <0.001). The median progression-free survival was 8 months in the cisplatin plus gemcitabine group and 5 months in the gemcitabine-only group (P <0.001). Adverse events were similar in both groups, with the exception of neutropenia—higher in the cisplatin plus gemcitabine group—although the number of neutropenia-associated infections was similar in the 2 groups. Consequently, a cisplatin + gemcitabine regimen has become the standard of care on this indication
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Novel agents, such as epidermal growth factor receptor blockers, MEK inhibitors and angiogenesis inhibitors, may hold promise for improving the therapeutic results obtained with conventional chemotherapy alone, but clinical study results are pending (Sasaki et al, 2013)
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Intrahepatic cholangiocarcinoma
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Patients who have undergone a tumor resection with or without ablation with negative margins may be followed up with observation, because there is no definitive adjuvant regimen to improve their overall survival. For individuals whose disease is resectable but who are left with positive margins after resection: (a) consider additional resection, (b) ablative therapy, or (c) combined radiation with or without chemotherapy using either fluorouracil- or capecitabine-based regimens or gemcitabine (Horgan et al, 2012). For patients with unresectable disease, therapeutic options include, depending on tumor location, extent of disease, and performance status: (a) chemotherapy with cisplatin plus gemcitabine or a fluorouracil- or capecitabine-based regimen, (b) combined radiochemotherapy, or (c) best supportive care
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Extrahepatic cholangiocarcinoma
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Patients with positive margins after resection should be considered candidates for either cisplatin plus gemcitabine or fluorouracil- or capecitabine-based chemotherapy with radiation (external beam therapy or brachytherapy) (Valero et al, 2012). The addition of adjuvant therapy in patients after potential curative surgical resection remains a subject of clinical investigation. Patients whose disease is deemed unresectable at the time of surgery should undergo biliary drainage if required, ideally nonsurgically; that is, by using a stent. Photodynamic therapy has demonstrated to be even more effective than stenting alone (Ortner et al, 2003). Given their overall poor prognosis, further options for patients with unresectable disease, include: (a) chemotherapy with cisplatin plus gemcitabine, (b) a clinical trial, (c) chemoradiation (fluorouracil- or capecitabine-based chemotherapy/RT), and (d) best supportive care
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Eckel F et al. Br J Cancer 2007;96:896–902
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Hezel AF et al. Oncologist 2008;13:415–423
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Horgan AM et al. J Clin Oncol 2012; 30:1934–1940
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Ortner ME et al. Gastroenterology 2003;125:1355–1363
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Razumilava N, Gores GJ. Clin Gastroenterol Hepatol 2013;11:13–21
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Sasaki T et al. Korean J Intern Med 2013;28:515–524
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Valero V et al. Expert Rev Gastroenterol Hepatol 2012;6:481–495
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Valle J et al. N Engl J Med 2010;362:1273–1281
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