The intelligent knife (iKnife) and its intraoperative diagnostic advantage for the treatment of cervical disease

Abstract

Clearance of surgical margins in cervical cancer prevents the need for adjuvant chemoradiation and allows fertility preservation. In this study, we determined the capacity of the rapid evaporative ionization mass spectrometry (REIMS), also known as intelligent knife (iKnife), to discriminate between healthy, preinvasive, and invasive cervical tissue. Cervical tissue samples were collected from women with healthy, human papilloma virus (HPV) ± cervical intraepithelial neoplasia (CIN), or cervical cancer. A handheld diathermy device generated surgical aerosol, which was transferred into a mass spectrometer for subsequent chemical analysis. Combination of principal component and linear discriminant analysis and least absolute shrinkage and selection operator was employed to study the spectral differences between groups. Significance of discriminatory m/z features was tested using univariate statistics and tandem MS performed to elucidate the structure of the significant peaks allowing separation of the two classes. We analyzed 87 samples (normal = 16, HPV ± CIN = 50, cancer = 21 patients). The iKnife discriminated with 100% accuracy normal (100%) vs. HPV ± CIN (100%) vs. cancer (100%) when compared to histology as the gold standard. When comparing normal vs. cancer samples, the accuracy was 100% with a sensitivity of 100% (95% CI 83.9 to 100) and specificity 100% (79.4 to 100). Univariate analysis revealed significant MS peaks in the cancer-to-normal separation belonging to various classes of complex lipids. The iKnife discriminates healthy from premalignant and invasive cervical lesions with high accuracy and can improve oncological outcomes and fertility preservation of women treated surgically for cervical cancer. Larger in vivo research cohorts are required to validate these findings.REIMS | cervical cancer | mass spectrometry | iKnife | fertility preservation

Laser-assisted rapid evaporative ionisation mass spectrometry (LA-REIMS) as a metabolomics platform in cervical cancer screening

“…A number of mass spectrometry studies have previously reported satisfactory diagnostic accuracy of cervical cancer or pre-cancer, however these were performed either on cervical tissue samples 27 , rendering it unsuitable as a screening approach, or using more laborious and time-consuming approaches 9 , [11] , [12] , [13] . Different studies employing vibrational spectroscopic approaches, including Raman and infrared spectroscopy, have demonstrated the ability of detecting biological differences between normal, precancerous and cancerous cervical pathologies using cytology samples 66 , 67 .…”

“…The tissue-derived smoke that is created from the rapid heating contains information about the phospholipid signature of the tissue which can be used for accurate discrimination of tissue types as well as real-time, intraoperative detection of cancer or evaluation of surgical margins [24] , [25] , [26] . We have also recently shown that REIMS coupled to electrosurgery via a handheld device (also known as the intelligent knife – iKnife) permits detection of precancerous lesions and cervical cancer with high diagnostic accuracy 27 .…”

Mass Spectrometry-Based Omics for the Characterization of Triple-Negative Breast Cancer Bio-Signature

“…In cancer research, proteome profiling is the most promising approach, but for now high-resolution mass spectrometry still lacks in many aspects, such as high costs, the required expertise (to run the instruments and analyze the data) and standardization [ 54 , 55 ]. To overcome some of these aspects, some revolutionary MS-based instruments are under development, such as the iKnife [ 56 ] and the MasSpec Pen [ 57 ], both used for intra-operatory diagnosis. The implementation of these kinds of device could also have a tremendous impact in the diagnosis of breast cancer and, therefore, a better classification and characterization of each type of cancerous tissue is mandatory.…”

Electrocautery, Diathermy, and Surgical Energy Devices

“… 44 – 46 It is also able to discriminate HPV infected cervical samples from those without HPV. 47 It is therefore highly likely that if present in tissue or biofluids subjected to diathermy, remnants of the SARS-CoV2 are likely to be detectable.…”