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.

Liver transplantation for hepatic malignancies has emerged as a well-documented and proven treatment modality. However, early unsatisfactory results emphasized that only a highly selected patient population would benefit from transplantation. Currently, 15% of all liver transplants performed are for hepatocellular carcinoma (HCC). There is no controversy about the fact that liver transplantation for HCC in the adult population yields good results for patients whose tumour masses do not exceed the Milan criteria. It remains to be determined whether patients with more extensive tumours can be reliably selected to benefit from the procedure. In patients with small HCC at an early stage and preserved liver function, liver resection provides an alternative to transplant. Liver resection may offer similar survival results to orthotopic liver transplantation (OLT) in the short term, and does not carry the long-term effects of immunosuppression; however, long-term and disease-free survival favours liver transplantation. Very promising results have been obtained for cholangiocarcinoma treated by aggressive combination therapies, including chemo- and radiotherapy followed by OLT. Survival rate in these selected patients can approach that of patients with cholestatic liver disease, and the role of transplantation now requires re-evaluation. Similarly, hepatoblastoma is an excellent indication in paediatric patients with unresectable or recurrent tumours. Epithelioid hemangioendothelioma is also an appropriate indication for liver transplantation, even in the presence of extrahepatic metastases, unlike angiosarcoma which is associated with a very poor survival and considered as a contraindication. And finally for metastatic liver disease from neuroendocrine tumours, liver transplantation can result in long-term survival and even cure in well selected patients. Conversely, the value of transplantation for colorectal liver metastases (currently a contraindication) requires further evaluation by well-designed trials.

https://onlinelibrary.wiley.com/doi/pdf/10.1111/j.1432-2277.2008.00735.x

Liver transplantation for primary and metastatic liver cancers

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.

Purpose of reviewThe purpose of this review is to present recent data demonstrating the success of neoadjuvant therapy followed by liver transplantation for hilar cholangiocarcinomaRecent findingsThe most recent outcomes of a protocol involving neoadjuvant therapy followed by liver transplant for h

Successful liver transplantation for hilar cholangiocarcinoma.

Primary sclerosing cholangitis (PSC) is a chronic inflammatory cholangiopathy that results in fibrotic strictures and dilations of the intra- and extrahepatic bile ducts. PSC is uncommon, occurs predominantly in males and has a strong association with inflammatory bowel disease. While the pathogenesis of PSC has not been fully elucidated, emerging evidence supports roles for the innate and adaptive immune systems, and genome-wide analyses have identified several genetic associations. Using the best available evidence, the present review summarizes the current understanding of the diagnosis, pathogenesis and management of PSC. Despite its rarity, there is an urgent need for collaborative research efforts to advance therapeutic options for PSC beyond liver transplantation.

/pdf/management-of-primary-sclerosing-cholangitis-conventions-and-re8h8vknvc.pdf

Management of primary sclerosing cholangitis: conventions and controversies.

Introduction. Palliative treatment for nondisseminated irresectable hilar cholangiocarcinoma (HCC) 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 that for 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 HCC and identify prognostic factors for survival. Methods. We retrospectively reviewed 36 patients undergoing OLT for HCC over 13 years. Results. The actuarial survival rate at 1, 3, and 5 years was 82%, 53%, and 30%, respectively. The main cause of death was tumor recurrence (53%). In the univariate analysis, the factors for a poor prognosis were vascular invasion (P .001) namely 0% survival at 3 years when present versus 63% and 35% at 3 and 5 years, respectively, when it was not; and stages III to IVA (P .05), namely 15% survival at 5 years versus 47% for stages I to II. Lymph node and perineural invasion also reduce survival. In the multivariate analysis, the factors for poor prognosis included vascular invasion (P .01) and stages III to IVA (P .01). Conclusions. OLT for nondisseminated irresectable HCC has higher survival rates at 3 and 5 years than palliative treatments, especially with initial stage tumors, which means that more information is needed to better select cholangiocarcinoma patients for transplantation.

Liver transplantation for hilar cholangiocarcinoma: Spanish experience.

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

Liver transplantation for peripheral cholangiocarcinoma: Spanish experience

Improvement in correlation between oral dose of cyclosporine and cyclosporinemia after substitution of conventional cyclosporine by neoral cyclosporine in 296 liver transplant patients

E de Vicente

Papers

Liver transplantation for hilar cholangiocarcinoma: Spanish experience.

Liver transplantation for peripheral cholangiocarcinoma: Spanish experience

Improvement in correlation between oral dose of cyclosporine and cyclosporinemia after substitution of conventional cyclosporine by neoral cyclosporine in 296 liver transplant patients