Cureus. 2026 Feb 20;18(2):e103966. doi: 10.7759/cureus.103966. eCollection 2026 Feb.

ABSTRACT

Recurrence after curative-intent resection remains common in intrahepatic cholangiocarcinoma (ICC) and continues to limit long-term survival. Although repeat liver resection may benefit carefully selected patients, this opportunity is often lost because recurrence is detected only after radiographic progression. Postoperative surveillance relies primarily on cross-sectional imaging, which performs well for macroscopic disease but lacks sensitivity for microscopic residual tumor. Consequently, relapse is frequently recognized only after structural visibility, when tumor biology may already be unfavorable. Minimal residual disease (MRD) represents the persistence of viable malignant cells below the threshold of radiographic detection and is increasingly implicated in early relapse. Circulating tumor DNA (ctDNA) analysis enables the detection of tumor-specific genomic alterations in peripheral blood and reflects active tumor biology rather than delayed anatomical change. Across solid tumors, ctDNA positivity has been associated with recurrence lead times of approximately 2-6 months before radiographic detection; however, ICC-specific prospective performance metrics, including sensitivity, specificity, and predictive values, remain limited and incompletely defined. Important practical challenges include assay variability, tumor shedding heterogeneity in biliary tract cancers, clonal hematopoiesis-related false positives, and uncertainty in managing isolated low-level molecular positivity. Accordingly, ctDNA should be considered a complementary rather than a replacement modality. This narrative review synthesizes current imaging and molecular evidence and proposes a hypothesis-generating hybrid imaging-molecular surveillance framework intended to guide future prospective validation rather than serve as an evidence-validated clinical algorithm.

PMID:41873318 | PMC:PMC13005992 | DOI:10.7759/cureus.103966

Biotechniques. 2026 Jan-Dec;78(1-12):123-136. doi: 10.1080/07366205.2026.2645352. Epub 2026 Mar 24.

ABSTRACT

Minimal residual disease (MRD) is a key prognostic marker for progression-free and overall survival in multiple myeloma (MM). Existing high sensitivity assays primarily focus on tumor burden assessment, rely on bone marrow sampling, and are limited in their ability to support frequent longitudinal disease monitoring. Here, we describe a proof-of-principle workflow for isolating morphologically preserved circulating tumor cells (CTCs) from peripheral blood (PB) using size-based filtration. Based on controlled spiking experiments with RPMI 8226 myeloma cells, we demonstrate an analytical limit of detection of approximately 1 tumor cell per 10⁷ white blood cells. Isolated cells retain nuclear integrity and cytomorphology, allowing for downstream immuno-phenotyping, three-dimensional (3D) telomere fluorescence in situ hybridization (FISH), and single-cell telomere profiling, a known marker of genomic instability and disease progression in multiple myeloma. The proposed workflow demonstrated its feasibility for isolating, profiling, and analyzing plasma cells from PB of MM patients at different disease stages. It revealed distinct nuclear and telomeric features in MM CTCs compared with normal lymphocytes. The established technically robust liquid biopsy workflow enables 3D telomere profiling of MM CTCs that can be adopted for noninvasive MRD monitoring based on genomic instability rather than on the enumeration of MM plasma cells alone.Article HighlightsCurrent high-sensitivity assays for assessing minimal residual disease (MRD) in multiple myeloma (MM) patients rely on invasive bone marrow sampling and are limited by sampling bias and poor suitability for frequent longitudinal monitoring.This study presents a proof-of-principle liquid biopsy workflow that enables isolation of morphologically intact circulating tumor cells (CTCs) from peripheral blood (PB) using size-based filtration with the ScreenCell^® device.Controlled spiking experiments with RPMI 8226 myeloma cells established an analytical limit of detection of approximately 1 tumor cell per 10⁷ white blood cells.Technical feasibility of the new workflow for isolating intact CTCs from liquid biopsy was confirmed in a cohort of 20 newly diagnosed MM patients at diagnosis, during induction therapy, and after relapse, supporting its potential utility for longitudinal disease monitoring.Isolated CTCs were successfully immunophenotyped and subjected to quantitative three-dimensional telomere fluorescence in situ hybridization (FISH), allowing single-cell analysis of telomere length, number, aggregation, nuclear volume, and spatial distribution.Quantitative telomere profiling revealed statistically significant differences in nuclear and telomeric parameters between MM CTCs and normal lymphocytes, consistent with known markers of genomic instability and disease aggressiveness in MM.By combining enumeration with risk assessment based on telomere profiling, the current workflow can provide clinicians with much-needed biological insight beyond mere tumor burden assessment. Incorporating minimally invasive telomere profile-based risk assessment into MRD guidelines may guide treatment decisions in cases of sustained MRD and inform the need for new treatment regimens when residual disease is detected.

PMID:41873241 | DOI:10.1080/07366205.2026.2645352