ASO Author Reflections: Immediate Fluorescent Tissue Assessment – The ‘Frozen Section’ for Tumor Ablation?

PAST

During the surgical management of hepatic tumors, the resection margins are routinely assessed with pathology. The presence of positive margins allows extension of resection if feasible, or timely administration of adjuvant treatments, either in the form of chemotherapy, repeat resection, or other local treatment. In contrast, tissue is not available for examination after tumor ablation. Therefore, the ablation margins are estimated using imaging, either anatomic and/or metabolic.^1,2 However, a scenario often encountered in clinical practice is tumor recurrence after ablation despite radiographic evidence of adequate margins. To further evaluate this phenomenon and to address the limitation of tissue unavailability, a previous study from our group assessed the ablation zone of colorectal liver metastases with immediate post-procedural biopsies, showing that viable tumor cells can be found in ablation zones radiographically considered adequate. The presence of these cells was an independent predictor of shorter local progression-free survival.³ It is possible that these tumor cells survive the initial insult, remain quiescent for a variable period of time, and lead to local progression. Identification of these patients at risk would allow administration of adjuvant treatments, similar to surgery.

PRESENT

Ideally, the result of ablation zone tissue analysis would be known at the time of the procedure, similar to frozen section during surgery. In the previously mentioned study, the ablation zone biopsy samples underwent routine lengthy pathologic processing and immunohistochemical staining. Thus, the results of tissue sampling were not known at the time of the ablation procedure. The current study evaluated the use of fluorescent stains for the detection of viable tumor cells in ablation zone biopsy specimens. The stained tissues were imaged with confocal microscopy within 30 min from the biopsy.⁴ Interestingly, there was a high concordance rate (94%) in the interpretation of these images with routine pathology. All cases with viable tumor cells were correctly identified using the fluorescent stains. Therefore, fluorescent tissue assessment may provide a real-time biomarker of tumor ablation, an equivalent to frozen section for ablation. Patients at risk could be identified during the ablation, instantly guiding decisions for immediate re-ablation and/or future management.

FUTURE

While ablation zone biopsies may add to the invasiveness of the procedure, no available imaging methods possess the spatial resolution of a microscope. Certainly, future developments in anatomic and molecular imaging may negate the need for a biopsy. In fact, promising results have been reported using diffuse reflectance spectroscopy.⁵ Until then, additional studies are needed to validate the use of fluorescent staining of ablation zone biopsies. Moreover, a clinical trial will have to be designed implementing ablation zone biopsies processed with this novel method into the treatment paradigm. Such developments will allow evolution and optimization of ablation as a treatment for cancer with potential for local cure.