Cholangiocarcinoma (CCA) is the most common biliary tract malignancy. CCA is classified as intrahepatic, perihilar or distal extrahepatic; the individual subtypes differ in their biologic behavior, clinical presentation, and management. Throughout the last decades, CCA incidence rates had significantly increased. In addition to known established risk factors, novel possible risk factors (i.e. obesity, hepatitis C virus) have been identified that are of high importance in developed countries where CCA prevalence rates have been low. CCA tends to develop on the background of inflammation and cholestasis. In recent years, our understanding of the molecular mechanisms of cholangiocarcinogenesis has increased, thereby, providing the basis for molecularly targeted therapies. In its diagnostic evaluation, imaging techniques have improved, and the role of complementary techniques has been defined. There is a need for improved CCA biomarkers as currently used ones are suboptimal. Multiple staging systems have been developed, but none of these is optimal. The prognosis of CCA is considered dismal. However, treatment options have improved throughout the last two decades for carefully selected subgroups of CCA patients. Perihilar CCA can now be treated with orthotopic liver transplantation with neoadjuvant chemoradiation achieving 5-year survival rates of 68%. Classically considered chemotherapy-resistant, the ABC-02 trial has shown the therapeutic benefit of combination therapy with gemcitabine and cisplatin. The benefits of adjuvant treatments for resectable CCA, local ablative therapies and molecularly targeted therapies still need to be defined. In this article, we will provide the reader with an overview over CCA, and discuss the latest developments and controversies.

Cancer review: Cholangiocarcinoma.

Purpose of review Surgical resection is the primary modality of treatment for hilar and intrahepatic cholangiocarcinoma (HCCA-ICCA). For unresectable early-stage HCCA, excellent long-term tumor recurrence-free patient survival has been achieved using a strict regimen of preoperative staging and neoadjuvant chemoradiation treatment followed by orthotopic liver transplantation (OLT). However, in the case of unresectable ICCA, data on outcomes after OLT are limited. The present article reviews the current literature on the surgical treatment of ICCA focusing on the role of OLT in combination with neoadjuvant therapy and risk stratification of patients being considered for transplantation for unresectable ICCA. Recent findings Numerous studies reported poor survival outcomes after OLT for ICCA. Recent data using a combination of neoadjuvant therapy followed by OLT in appropriately selected patients with unresectable ICCA demonstrated promising disease recurrence-free survival. Summary Risk stratification for patient selection is crucial to optimize survival outcomes. Excellent long-term disease recurrence-free survival can be achieved in selected patients with unresectable ICCA using a combination of OLT and neoadjuvant therapy. Current data support the expansion of liver transplant criteria for treatment of unresectable ICCA.

Orthotopic liver transplantation in combination with neoadjuvant therapy: a new paradigm in the treatment of unresectable intrahepatic cholangiocarcinoma.

Background
Our purpose was to assess the clinicopathological features and surgical outcomes of combined hepatocellular-cholangiocarcinoma (HCC-CC) in an Asian center.

Clinical and pathological analysis of 27 patients with combined hepatocellular-cholangiocarcinoma in an Asian center

/pdf/cholangiocarcinoma-a-review-of-the-literature-and-future-4t5xtocej7.pdf

Cholangiocarcinoma: a review of the literature and future directions in therapy

Cholangiocarcinomas (CCA) are a group of rare cancers with an incidence of about 1.26 per 100,000 people. The disease reflects one of three different subtypes: intrahepatic, perihilar or hilar and distal cholangiocarcinoma. The preferred modality of definitive therapy is surgical resection with or without adjuvant therapy, however the majority of patients with this disease do not present at an early stage. Some efforts to improve survival rates have come in the form of offering neoadjuvant therapy prior to surgical resection or liver transplantation. Some new protocols are in the process of development for neoadjuvant therapy. Despite advancements in locally advanced or borderline resectable lesions, most patient present at an advanced stage. The mainstay of treatment for advanced stage disease is chemotherapy regardless of location. The mainstay of treatment in fit patients is the combination of gemcitabine and cisplatin. The addition of nab-paclitaxel to this backbone is currently being evaluated in phase III trial. In addition, the role of targeted therapy is currently being studied extensively through multiple different mutational pathways including isocitrate dehydrogenase-1 (IDH1), fibroblast growth factor receptor (FGFR), epidermal growth factor receptor (EGFR) and ERBB2 (HER2/neu). CCA remains a significant challenge in medicine, however recent studies have shown that there is significant interest in advancing therapy in the form of neoadjuvant, adjuvant and palliative intent treatment. 

/pdf/cholangiocarcinoma-a-review-of-the-literature-and-future-1cw391sy.pdf

Introduction Palliative treatment for nondisseminated unresectable peripheral cholangiocarcinoma (PCC) carries a 0% 5-year survival rate. The role of orthotopic liver transplantation (OLT) in these patients is controversial because the survival rate is lower than with other indications for transplantation and the lack of available donor organs. The aim of this paper was to review the Spanish experience in OLT for PCC to identify prognostic factors for survival. Methods We retrospectively reviewed 23 patients undergoing OLT in Spain for PCC over a period of 13 years. Results The actuarial survival rates were 77%, 65%, and 42% at 1, 3, and 5 years, respectively. The main cause of death was tumor recurrence (35%). Prognotic factors for an adverse outcome were pTNM classification (P Conclusions OLT for nondisseminated irresectable PCC displays higher survival rates at 3 and 5 years than palliative treatments, especially for tumors in the initial stages, which means that more information is needed to help better select PCC patients for transplantation.

http://www.biblioteca.uma.es/bbldoc/articulos/1664198x.pdf

M Fleiras

Papers

Liver transplantation for peripheral cholangiocarcinoma: Spanish experience