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New Challenges in the Management of Cholangiocarcinoma: The Role of Liver Transplantation, Locoregional Therapies, and Systemic Therapy

SIMPLE SUMMARY: Cholangiocarcinoma (CCA) is a highly lethal neoplasia, which incidence has steadily increased in the last years. Although surgical resection remains the cornerstone treatment for CCA, complete resection is only achieved in one third of patients, and the risk of recurrence exceeds 60%...

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Autores principales: Mauro, Ezequiel, Ferrer-Fàbrega, Joana, Sauri, Tamara, Soler, Alexandre, Cobo, Amparo, Burrel, Marta, Iserte, Gemma, Forner, Alejandro
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2023
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9953927/
https://www.ncbi.nlm.nih.gov/pubmed/36831586
http://dx.doi.org/10.3390/cancers15041244
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author Mauro, Ezequiel
Ferrer-Fàbrega, Joana
Sauri, Tamara
Soler, Alexandre
Cobo, Amparo
Burrel, Marta
Iserte, Gemma
Forner, Alejandro
author_facet Mauro, Ezequiel
Ferrer-Fàbrega, Joana
Sauri, Tamara
Soler, Alexandre
Cobo, Amparo
Burrel, Marta
Iserte, Gemma
Forner, Alejandro
author_sort Mauro, Ezequiel
collection PubMed
description SIMPLE SUMMARY: Cholangiocarcinoma (CCA) is a highly lethal neoplasia, which incidence has steadily increased in the last years. Although surgical resection remains the cornerstone treatment for CCA, complete resection is only achieved in one third of patients, and the risk of recurrence exceeds 60%, which impacts the long-term outcome. In this context, the use of other therapeutic strategies such as liver transplantation in selected candidates, locoregional treatments or new chemotherapy schemes based on immunotherapy or targeted therapies may contribute in improving the overall survival of patients with CCA. The development of new treatment strategies forces us to redouble collaborative efforts to conduct prospective, high-quality studies that shed light on their use and applicability. The purpose of this review is discussing the actual controversies and future perspectives in the management of CCA. ABSTRACT: Cholangiocarcinoma (CCA) is a neoplasm with high mortality that represents 15% of all primary liver tumors. Its worldwide incidence is on the rise, and despite important advances in the knowledge of molecular mechanisms, diagnosis, and treatment, overall survival has not substantially improved in the last decade. Surgical resection remains the cornerstone therapy for CCA. Unfortunately, complete resection is only possible in less than 15–35% of cases, with a risk of recurrence greater than 60%. Liver transplantation (LT) has been postulated as an effective therapeutic strategy in those intrahepatic CCA (iCCA) smaller than 3 cm. However, the low rate of early diagnosis in non-resectable patients justifies the low applicability in clinical practice. The evidence regarding LT in locally advanced iCCA is scarce and based on small, retrospective, and, in most cases, single-center case series. In this setting, the response to neoadjuvant chemotherapy could be useful in identifying a subgroup of patients with biologically less aggressive tumors in whom LT may be successful. The results of LT in pCCA are promising, however, we need a very careful selection of patients and adequate experience in the transplant center. Locoregional therapies may be relevant in unresectable, liver-only CCA. In iCCA smaller than 2 cm, particularly those arising in patients with advanced chronic liver disease in whom resection or LT may not be feasible, thermal ablation may become a reliable alternative. The greatest advances in the management of CCA occur in systemic treatment. Immunotherapy associated with chemotherapy has emerged as the gold standard in the first-line treatment. Likewise, the most encouraging results have been obtained with targeted therapies, where the use of personalized treatments has shown high rates of objective and durable tumor response, with clear signs of survival benefit. In conclusion, the future of CCA treatment seems to be marked by the development of new treatment strategies but high-quality, prospective studies that shed light on their use and applicability are mandatory.
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spelling pubmed-99539272023-02-25 New Challenges in the Management of Cholangiocarcinoma: The Role of Liver Transplantation, Locoregional Therapies, and Systemic Therapy Mauro, Ezequiel Ferrer-Fàbrega, Joana Sauri, Tamara Soler, Alexandre Cobo, Amparo Burrel, Marta Iserte, Gemma Forner, Alejandro Cancers (Basel) Review SIMPLE SUMMARY: Cholangiocarcinoma (CCA) is a highly lethal neoplasia, which incidence has steadily increased in the last years. Although surgical resection remains the cornerstone treatment for CCA, complete resection is only achieved in one third of patients, and the risk of recurrence exceeds 60%, which impacts the long-term outcome. In this context, the use of other therapeutic strategies such as liver transplantation in selected candidates, locoregional treatments or new chemotherapy schemes based on immunotherapy or targeted therapies may contribute in improving the overall survival of patients with CCA. The development of new treatment strategies forces us to redouble collaborative efforts to conduct prospective, high-quality studies that shed light on their use and applicability. The purpose of this review is discussing the actual controversies and future perspectives in the management of CCA. ABSTRACT: Cholangiocarcinoma (CCA) is a neoplasm with high mortality that represents 15% of all primary liver tumors. Its worldwide incidence is on the rise, and despite important advances in the knowledge of molecular mechanisms, diagnosis, and treatment, overall survival has not substantially improved in the last decade. Surgical resection remains the cornerstone therapy for CCA. Unfortunately, complete resection is only possible in less than 15–35% of cases, with a risk of recurrence greater than 60%. Liver transplantation (LT) has been postulated as an effective therapeutic strategy in those intrahepatic CCA (iCCA) smaller than 3 cm. However, the low rate of early diagnosis in non-resectable patients justifies the low applicability in clinical practice. The evidence regarding LT in locally advanced iCCA is scarce and based on small, retrospective, and, in most cases, single-center case series. In this setting, the response to neoadjuvant chemotherapy could be useful in identifying a subgroup of patients with biologically less aggressive tumors in whom LT may be successful. The results of LT in pCCA are promising, however, we need a very careful selection of patients and adequate experience in the transplant center. Locoregional therapies may be relevant in unresectable, liver-only CCA. In iCCA smaller than 2 cm, particularly those arising in patients with advanced chronic liver disease in whom resection or LT may not be feasible, thermal ablation may become a reliable alternative. The greatest advances in the management of CCA occur in systemic treatment. Immunotherapy associated with chemotherapy has emerged as the gold standard in the first-line treatment. Likewise, the most encouraging results have been obtained with targeted therapies, where the use of personalized treatments has shown high rates of objective and durable tumor response, with clear signs of survival benefit. In conclusion, the future of CCA treatment seems to be marked by the development of new treatment strategies but high-quality, prospective studies that shed light on their use and applicability are mandatory. MDPI 2023-02-15 /pmc/articles/PMC9953927/ /pubmed/36831586 http://dx.doi.org/10.3390/cancers15041244 Text en © 2023 by the authors. https://creativecommons.org/licenses/by/4.0/Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/).
spellingShingle Review
Mauro, Ezequiel
Ferrer-Fàbrega, Joana
Sauri, Tamara
Soler, Alexandre
Cobo, Amparo
Burrel, Marta
Iserte, Gemma
Forner, Alejandro
New Challenges in the Management of Cholangiocarcinoma: The Role of Liver Transplantation, Locoregional Therapies, and Systemic Therapy
title New Challenges in the Management of Cholangiocarcinoma: The Role of Liver Transplantation, Locoregional Therapies, and Systemic Therapy
title_full New Challenges in the Management of Cholangiocarcinoma: The Role of Liver Transplantation, Locoregional Therapies, and Systemic Therapy
title_fullStr New Challenges in the Management of Cholangiocarcinoma: The Role of Liver Transplantation, Locoregional Therapies, and Systemic Therapy
title_full_unstemmed New Challenges in the Management of Cholangiocarcinoma: The Role of Liver Transplantation, Locoregional Therapies, and Systemic Therapy
title_short New Challenges in the Management of Cholangiocarcinoma: The Role of Liver Transplantation, Locoregional Therapies, and Systemic Therapy
title_sort new challenges in the management of cholangiocarcinoma: the role of liver transplantation, locoregional therapies, and systemic therapy
topic Review
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9953927/
https://www.ncbi.nlm.nih.gov/pubmed/36831586
http://dx.doi.org/10.3390/cancers15041244
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