Adjuvant treatment with Capecitabine in patients who received orthotopic liver transplantation with incidental diagnosis of intrahepatic cholangiocarcinoma. Implications on DPYD polymorphisms assessment: report of two cases and review of the literature.

Carolina Liguori, Simona Magi, Alessandra Mandolesi, Andrea Agostini, Gianluca Svegliati-Baroni, Andrea Benedetti Cacciaguerra, Alessandro Parisi, Elisa Tiberi, Marco Vivarelli, Andrea Giovagnoni, Gaia Goteri, Pasqualina Castaldo, Rossana Berardi, Riccardo Giampieri
Author Information
  1. Carolina Liguori: Medical Oncology, Department of Clinical and Molecular Sciences, University Politecnica delle Marche, Ancona, 60126, Italy.
  2. Simona Magi: Department of Biomedical Sciences and Public Health, Section of Pharmacology, University Politecnica delle Marche, Ancona, 60126, Italy.
  3. Alessandra Mandolesi: Anatomic Pathology Unit, University Hospital "Azienda Ospedaliero Universitario delle Marche", Ancona, 60126, Italy.
  4. Andrea Agostini: Department of Radiological Sciences, Division of Clinical Radiology, University Hospital "Azienda Ospedaliero Universitaria delle Marche", Ancona, 60126, Italy.
  5. Gianluca Svegliati-Baroni: Liver Injury and Transplant Unit, University Politecnica delle Marche - University Hospital "Azienda Ospedaliero Universitaria delle Marche", Ancona, 60126, Italy.
  6. Andrea Benedetti Cacciaguerra: Hepatobiliary and Abdominal Transplant Surgery, Department of Experimental and Clinical Medicine, University Politecnica delle Marche - University Hospital "Azienda Ospedaliero Universitaria delle Marche", Ancona, 60126, Italy.
  7. Alessandro Parisi: Medical Oncology, Department of Clinical and Molecular Sciences, University Politecnica delle Marche, Ancona, 60126, Italy.
  8. Elisa Tiberi: Department of Oncology, University Hospital "Azienda Ospedaliero Universitaria delle Marche", Ancona, 60126, Italy.
  9. Marco Vivarelli: Hepatobiliary and Abdominal Transplant Surgery, Department of Experimental and Clinical Medicine, University Politecnica delle Marche - University Hospital "Azienda Ospedaliero Universitaria delle Marche", Ancona, 60126, Italy.
  10. Andrea Giovagnoni: Department of Radiological Sciences, Division of Clinical Radiology, University Hospital "Azienda Ospedaliero Universitaria delle Marche", Ancona, 60126, Italy.
  11. Gaia Goteri: Anatomic Pathology Unit, University Hospital "Azienda Ospedaliero Universitario delle Marche", Ancona, 60126, Italy.
  12. Pasqualina Castaldo: Department of Biomedical Sciences and Public Health, Section of Pharmacology, University Politecnica delle Marche, Ancona, 60126, Italy.
  13. Rossana Berardi: Medical Oncology, Department of Clinical and Molecular Sciences, University Politecnica delle Marche, Ancona, 60126, Italy.
  14. Riccardo Giampieri: Medical Oncology, Department of Clinical and Molecular Sciences, University Politecnica delle Marche, Ancona, 60126, Italy.

Abstract

In recent years, assessing dihydropyrimidine dehydrogenase (DPD) activity has become crucial for cancer patients undergoing 5-fluorouracil (5FU)-based chemotherapy due to the life-threatening toxicity associated with reduced DPD function. The methods for evaluating DPD activity have evolved, with the analysis of DPYD polymorphisms in blood samples becoming the preferred approach. As the indications for liver transplantation are increasing-particularly due to a rise in cases of cholangiocarcinoma (CCA) and non-resectable colorectal liver metastasis-more cancer patients with a history of liver transplantation may experience disease relapse. Furthermore, 5-fluorouracil chemotherapy is a standard treatment for both cancers. This growing need to evaluate DPD activity in transplanted livers arises because standard tests conducted on blood samples reflect the activity of native liver tissue and may produce misleading results. This paper presents two clinical cases from 2022 to 2023 involving patients who underwent successful liver transplants but were later diagnosed with intrahepatic CCA in the explanted liver. Both patients were subsequently prescribed capecitabine as adjuvant chemotherapy, making it essential to assess DPD activity in donor liver tissue to ensure safe treatment protocols. However, there are currently no established guidelines for this specific patient group. If we follow standard clinical practice, this critical analysis will be insufficient, as it only describes the DPD activity of the native liver. It is imperative to determine the DPD activity of the transplanted liver. In summary, this case report highlights the importance of managing this complex situation effectively.

Keywords

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MeSH Term

Humans
Cholangiocarcinoma
Capecitabine
Dihydrouracil Dehydrogenase (NADP)
Liver Transplantation
Bile Duct Neoplasms
Middle Aged
Antimetabolites, Antineoplastic
Male
Chemotherapy, Adjuvant
Polymorphism, Genetic
Female
Incidental Findings
Aged

Chemicals

Capecitabine
Dihydrouracil Dehydrogenase (NADP)
Antimetabolites, Antineoplastic

Word Cloud

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