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Peer-reviewedCC BY 4.0Cancers

Liquid Biopsy in Hepatobiliary and Pancreatic Malignancies: Current Evidence and Implications for Surgical Practice

4 affiliations
  1. 1Unit of Hepato-Biliary and Pancreatic Surgery, “F. Miulli” General Hospital, 70021 Acquaviva Delle Fonti, Italy
  2. 2Department of Medicine and Surgery, LUM University, 70010 Casamassima, Italy
  3. 3Transplant and HPB Unit, Department of Surgery Sciences, University of Rome Tor Vergata, 00133 Rome, Italy
  4. 4Unit of Interventional Radiology, F. Miulli Hospital, 70021 Acquaviva Delle Fonti, Italy

Abstract

Liquid biopsy is an emerging approach for the molecular characterization of hepatopancreatobiliary (HPB) malignancies through the analysis of circulating tumor DNA (ctDNA), circulating tumor cells (CTCs), and extracellular vesicles (EVs). These biomarkers may complement conventional imaging and serum markers by providing additional information on tumor biology and disease evolution. This narrative review examines the available evidence concerning the potential applications of liquid biopsy in HPB surgical practice, with particular emphasis on preoperative prognostic assessment, postoperative molecular residual disease detection, recurrence monitoring, and treatment adaptation. Among the different circulating biomarkers, ctDNA currently has the most developed perioperative evidence base. Studies involving pancreatic ductal adenocarcinoma, hepatocellular carcinoma, and biliary tract cancers have demonstrated associations between ctDNA detection and unfavorable oncological outcomes, particularly postoperative recurrence. Nevertheless, the available evidence remains predominantly observational, with considerable heterogeneity in patient populations, sampling protocols, analytical platforms, and outcome definitions. Although the integration of circulating biomarkers with conventional anatomical criteria has generated interest in the concept of “biological resectability”, this framework remains hypothetical and has not been prospectively validated for surgical treatment selection. Similarly, ctDNA-guided modifications of neoadjuvant therapy, adjuvant treatment, or postoperative surveillance have not yet demonstrated clinical benefit in HPB malignancies. Liquid biopsy should therefore currently be regarded as a promising investigational prognostic tool rather than an established determinant of surgical or oncological management. Standardized methodologies and prospective interventional trials are required before its routine clinical implementation.

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BibTeX
@article{caringi2026liquid,
  title = {{Liquid Biopsy in Hepatobiliary and Pancreatic Malignancies: Current Evidence and Implications for Surgical Practice}},
  author = {Silvio Caringi and Antonella Delvecchio and Annachiara Casella and Valentina Ferraro and Matteo Stasi and Nunzio Tralli and Tommaso Maria Manzia and Riccardo Inchingolo and Michele Tedeschi and Riccardo Memeo},
  journal = {Cancers},
  year = {2026},
  month = oct,
  doi = {10.3390/cancers18203349},
  url = {https://www.mdpi.com/2072-6694/18/20/3349},
  note = {CC BY 4.0},
}
RIS
TY  - JOUR
TI  - Liquid Biopsy in Hepatobiliary and Pancreatic Malignancies: Current Evidence and Implications for Surgical Practice
AU  - Silvio Caringi
AU  - Antonella Delvecchio
AU  - Annachiara Casella
AU  - Valentina Ferraro
AU  - Matteo Stasi
AU  - Nunzio Tralli
AU  - Tommaso Maria Manzia
AU  - Riccardo Inchingolo
AU  - Michele Tedeschi
AU  - Riccardo Memeo
PY  - 2026
DA  - 2026/10/01
JO  - Cancers
DO  - 10.3390/cancers18203349
UR  - https://www.mdpi.com/2072-6694/18/20/3349
AB  - Liquid biopsy is an emerging approach for the molecular characterization of hepatopancreatobiliary (HPB) malignancies through the analysis of circulating tumor DNA (ctDNA), circulating tumor cells (CTCs), and extracellular vesicles (EVs). These biomarkers may complement conventional imaging and serum markers by providing additional information on tumor biology and disease evolution. This narrative review examines the available evidence concerning the potential applications of liquid biopsy in HPB surgical practice, with particular emphasis on preoperative prognostic assessment, postoperative molecular residual disease detection, recurrence monitoring, and treatment adaptation. Among the different circulating biomarkers, ctDNA currently has the most developed perioperative evidence base. Studies involving pancreatic ductal adenocarcinoma, hepatocellular carcinoma, and biliary tract cancers have demonstrated associations between ctDNA detection and unfavorable oncological outcomes, particularly postoperative recurrence. Nevertheless, the available evidence remains predominantly observational, with considerable heterogeneity in patient populations, sampling protocols, analytical platforms, and outcome definitions. Although the integration of circulating biomarkers with conventional anatomical criteria has generated interest in the concept of “biological resectability”, this framework remains hypothetical and has not been prospectively validated for surgical treatment selection. Similarly, ctDNA-guided modifications of neoadjuvant therapy, adjuvant treatment, or postoperative surveillance have not yet demonstrated clinical benefit in HPB malignancies. Liquid biopsy should therefore currently be regarded as a promising investigational prognostic tool rather than an established determinant of surgical or oncological management. Standardized methodologies and prospective interventional trials are required before its routine clinical implementation.
SN  - 2072-6694
ER  -