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Study Explores Clinical Applicability of Mass Spec-coupled Surgical Tool to ID Tissues Being Cut

NEW YORK (GenomeWeb News) – The puff of smoke produced as surgeons slice through a patient's tissue with an electrosurgical "knife" may hold molecular clues for identifying the tissue itself, a new study suggests, helping to define where tumor tissue ends and unaffected tissue begins, for instance.

In a study appearing online today in Science Translational Medicine, researchers from the UK and Hungary described an experimental diagnostic tool known as the "intelligent knife" (iKnife, for short) that's being pursued as a means of tracking features of a tissue being cut in almost real-time.

After establish baseline chemical profiles for thousands of tumor and normal tissue samples in the lab, the team took a crack at using iKnife — which brings electrosurgical instruments together with a mass spectrometry method called rapid evaporative ionization mass spec, or REIMS — in an actual surgical setting.

In nearly 100 individuals receiving resection surgery for various forms of cancer, the investigators found that iKnife accurately predicted the histological features of the tissues involved, while also offering hints about the tumor tissue being removed.

"These data provide compelling evidence that the REIMS-iKnife approach can be translated into routine clinical use in a wide range of oncosurgical procedures," Imperial College London researchers Jeremy Nicholson and Zoltán Takáts, the study's co-corresponding authors, and their colleagues wrote.

"It can augment current tumor diagnostics," they noted, "and it has the potential to influence 'on-table' decision-making and ultimately to improve oncological outcomes."

Surgeons tasked with resecting cancerous tissues are forced to toe the line between removing all of the offending tumor material and sparing as much unaffected tissue as possible. But defining the precise boundary between these tissues is no easy task, authors of the new study explained.

At the moment, characteristics of tissues removed during resection are often determined through histological testing on resected tissue samples after surgery. In the case of complicated tumors with difficult-to-discern borders, such histological testing may take place while the patient is being operated on, though that approach is costly and can take up to half an hour — limitations that have prompted researchers to explore alternative means of monitoring tissue features during resection surgery.

For their part, Nicholson, Takáts, and colleagues decided to focus on the evaporating tissue vapor given off during electrosurgery. "We hypothesized that this is a rich source of biological information," they explained, "and therefore used mass spectrometry to measure its metabolomic composition."

To characterize compounds in electrosurgical smoke, the team turned to REIMS, a method previously developed for doing mass spec on tissue samples in situ. Past experiments indicated that pairing REIMS with electrosurgical tools could pick up informative chemical profiles in tissues from animal models.

For the new study, researchers turned their attention to human samples, starting with a collection of tissues that they used to define mass spec profiles associated with various forms of cancer. They also used a range of healthy tissues.

In addition to the 1,624 cancerous and 1,231 healthy samples tested for those experiments, the team also looked at dozens of benign or inflammatory bowel disease tissues.

From there, the group used analytical approaches to narrow in on compounds or mass spec signatures associated with certain tissue types or with the presence of a particular kind of cancer or tumor stage. That information then went into a so-called spectral database that could be tapped during subsequent tests done during resection surgeries.

During electrosurgical tumor resections for 81 individuals with stomach, colon, liver, lung, breast, or brain cancers, for instance, the researchers found that the histological predictions made from iKnife profiles corresponded with more traditional histological testing done on samples after surgery.

The iKnife data distinguished between cancerous and non-cancerous tissues with 96.5 percent specificity, on average, and a sensitivity of nearly 98 percent, though the specificity dipped slightly for certain cancer types such as malignant lung cancers or primary lung tumors.

Still, results of the analysis overall supported the notion that the REIMS-iKnife could be used in clinical settings — for instance, to define and remove tumor margins — at approximately the same time that surgery is done.

"The objectives of this study were to test the REIMS-iKnife method in a surgical environment and to assess its accuracy in the detection of the tumor margin status in patients undergoing resection of brain, liver, lung, breast, or colorectal tumors," the team wrote.

"The results presented here indicate that the envisioned application is feasible," the authors noted, "and that the REIMS-iKnife technique provides a valid alternative to frozen section histology to enhance real-time intra-operative decision-making