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Cancers
Special Issues
Liver Transplantation for Liver Malignancies: Pushing the Limits Further
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Liver Transplantation for Liver Malignancies: Pushing the Limits Further

A special issue of Cancers (ISSN 2072-6694). This special issue belongs to the section "Transplant Oncology".

Deadline for manuscript submissions: 8 September 2024 | Viewed by 1825

Special Issue Editor

Prof. Dr. Long-Bin Jeng

E-Mail Website
Guest Editor
1. Organ Transplantation Center, China Medical University Hospital, Taichung 404, Taiwan
2. Department of Surgery, China Medical University Hospital, Taichung 404, Taiwan
3. Cell Therapy Center, China Medical University Hospital, Taichung 404, Taiwan
Interests: transplant surgery; liver transplantation; gastroenterological surgery; proteomic study of hepatocellular carcinoma

Special Issue Information

Dear Colleagues,

The first human liver transplantation (LT) was performed in 1963 by Professor Starzl. Initially, LT was focused on the treatment of unresectable hepatocellular carcinoma (HCC), which was considered a terminal disease and absolute contraindication for LT and initial experience of LT for HCC-fetched dismal outcomes. Advances in surgery techniques and technology, multidisciplinary approach, improved immunosuppression regimens and better understanding of the disease process have significantly contributed to the improved results of LT. It has now become a definitive therapeutic procedure for many end-stage liver diseases, including both parenchymal and malignant conditions. Among these, HCC with liver cirrhosis from various etiologies has become the most common indication for LT. However, the outcomes for this subgroup of patients were initially not consistent. Following the introduction of Milan’s landmark criteria by Mazzaferro et al. in 1996, it became the gold standard for selecting HCC patients for LT.

The last few decades saw the exponential rise in LT procedures to treat unresectable HCCs with an improved survival. The criteria for HCC requiring LT have been modestly increased over the last two decades, with a plausible outcome. Apart from HCC, treatment option of LT for other primary and metastatic liver malignancies have gained attention over the last decade. Since then, the application of LT to treat colorectal liver metastasis, metastatic neuroendocrine tumors, intrahepatic or perihilar cholangiocarcinoma and other conditions has been reported with variable success rates.

In this Special Issue, we have invited international experts to contribute their updated research and clinical experiences regarding the current status of LT for liver malignancies.

Prof. Dr. Long-Bin Jeng
Guest Editor

Manuscript Submission Information

Manuscripts should be submitted online at www.mdpi.com by registering and logging in to this website. Once you are registered, click here to go to the submission form. Manuscripts can be submitted until the deadline. All submissions that pass pre-check are peer-reviewed. Accepted papers will be published continuously in the journal (as soon as accepted) and will be listed together on the special issue website. Research articles, review articles as well as short communications are invited. For planned papers, a title and short abstract (about 100 words) can be sent to the Editorial Office for announcement on this website.

Submitted manuscripts should not have been published previously, nor be under consideration for publication elsewhere (except conference proceedings papers). All manuscripts are thoroughly refereed through a single-blind peer-review process. A guide for authors and other relevant information for submission of manuscripts is available on the Instructions for Authors page. Cancers is an international peer-reviewed open access semimonthly journal published by MDPI.

Please visit the Instructions for Authors page before submitting a manuscript. The Article Processing Charge (APC) for publication in this open access journal is 2900 CHF (Swiss Francs). Submitted papers should be well formatted and use good English. Authors may use MDPI's English editing service prior to publication or during author revisions.

Keywords

  • liver cancer
  • hepatocellular carcinoma
  • liver transplantation
  • liver malignancies
  • Milan criteria

Published Papers (1 paper)

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Research

21 pages, 767 KiB  
Article
Circulating Tumor DNA Profiling in Liver Transplant for Hepatocellular Carcinoma, Cholangiocarcinoma, and Colorectal Liver Metastases: A Programmatic Proof of Concept
by Hanna Hong, Chase J. Wehrle, Mingyi Zhang, Sami Fares, Henry Stitzel, David Garib, Bassam Estfan, Suneel Kamath, Smitha Krishnamurthi, Wen Wee Ma, Teodora Kuzmanovic, Elizabeth Azzato, Emrullah Yilmaz, Jamak Modaresi Esfeh, Maureen Whitsett Linganna, Mazhar Khalil, Alejandro Pita, Andrea Schlegel, Jaekeun Kim, R. Matthew Walsh, Charles Miller, Koji Hashimoto, David Choon Hyuck Kwon and Federico Aucejoadd Show full author list remove Hide full author list
Cancers 2024, 16(5), 927; https://doi.org/10.3390/cancers16050927 - 25 Feb 2024
Viewed by 1212
Abstract
Introduction: Circulating tumor DNA (ctDNA) is emerging as a promising, non-invasive diagnostic and surveillance biomarker in solid organ malignancy. However, its utility before and after liver transplant (LT) for patients with primary and secondary liver cancers is still underexplored. Methods: Patients undergoing LT [...] Read more.
Introduction: Circulating tumor DNA (ctDNA) is emerging as a promising, non-invasive diagnostic and surveillance biomarker in solid organ malignancy. However, its utility before and after liver transplant (LT) for patients with primary and secondary liver cancers is still underexplored. Methods: Patients undergoing LT for hepatocellular carcinoma (HCC), cholangiocarcinoma (CCA), and colorectal liver metastases (CRLM) with ctDNA testing were included. CtDNA testing was conducted pre-transplant, post-transplant, or both (sequential) from 11/2019 to 09/2023 using Guardant360, Guardant Reveal, and Guardant360 CDx. Results: 21 patients with HCC (n = 9, 43%), CRLM (n = 8, 38%), CCA (n = 3, 14%), and mixed HCC/CCA (n = 1, 5%) were included in the study. The median follow-up time was 15 months (range: 1–124). The median time from pre-operative testing to surgery was 3 months (IQR: 1–4; range: 0–5), and from surgery to post-operative testing, it was 9 months (IQR: 2–22; range: 0.4–112). A total of 13 (62%) patients had pre-transplant testing, with 8 (62%) having ctDNA detected (ctDNA+) and 5 (32%) not having ctDNA detected (ctDNA-). A total of 18 (86%) patients had post-transplant testing, 11 (61%) of whom were ctDNA+ and 7 (33%) of whom were ctDNA-. The absolute recurrence rates were 50% (n = 5) in those who were ctDNA+ vs. 25% (n = 1) in those who were ctDNA- in the post-transplant setting, though this difference was not statistically significant (p = 0.367). Six (29%) patients (HCC = 3, CCA = 1, CRLM = 2) experienced recurrence with a median recurrence-free survival of 14 (IQR: 6–40) months. Four of these patients had positive post-transplant ctDNA collected following diagnosis of recurrence, while one patient had positive post-transplant ctDNA collected preceding recurrence. A total of 10 (48%) patients had sequential ctDNA testing, of whom n = 5 (50%) achieved ctDNA clearance (+/−). The remainder were ctDNA+/+ (n = 3, 30%), ctDNA−/− (n = 1, 10%), and ctDNA−/+ (n = 1, 11%). Three (30%) patients showed the acquisition of new genomic alterations following transplant, all without recurrence. Overall, the median tumor mutation burden (TMB) decreased from 1.23 mut/Mb pre-transplant to 0.00 mut/Mb post-transplant. Conclusions: Patients with ctDNA positivity experienced recurrence at a higher rate than the ctDNA- patients, indicating the potential role of ctDNA in predicting recurrence after curative-intent transplant. Based on sequential testing, LT has the potential to clear ctDNA, demonstrating the capability of LT in the treatment of systemic disease. Transplant providers should be aware of the potential of donor-derived cell-free DNA and improved approaches are necessary to address such concerns. Full article
(This article belongs to the Special Issue Liver Transplantation for Liver Malignancies: Pushing the Limits Further)
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