In-vivo assessment of acetic acid-cervical tissue interaction using quantitative imaging of backscattered light: its potential use for in-vivo cervical cancer detection grading and mapping

Author(s):  
Constantin J. Balas ◽  
Angelica Dimoca ◽  
Eirini Orfanudaki ◽  
Eugenios Koumantakis
2002 ◽  
Author(s):  
Γεώργιος Θεμελής

Cervical cancer is the commonest form of cancer in females under 35 years of age and the second most common in females of all ages. Limitations of the existing diagnostic methods have led to the development of new diagnostic approaches. Acetic acid is a marker used for more than 70 years in gynecology for the detection of abnormal lesions. Local application of acetic acid causes a temporal whiting to abnormal areas (acetowhite) while normal areas are not affected. Extensive clinical trials have shown that the visual assessment of acetowhitening exhibits similar diagnostic performance to other methods such as Test Pap. The diagnostic method proposed in this project is based on the quantitative and objective assessment of the acetic acid-tissue interaction by means of an Imaging Spectroscopy System. For the purpose of this study a new Imaging Spectroscopy system has been designed and developed. The method was used for the in vivo detection of dysplasias in the cervix and the results, from measurements of 181 women, indicated that there is a strong correlation between the histological condition of the tissue and the kinetics of the acetowhitening development. The best fit of the time course measurements of acetowhitening was achieved by the triple exponential function. Statistical analysis of several parameters that characterize the acetowhitening kinetics, have indicated that the combined evaluation of the parameters that express the duration (t5) and the intensity of acetowhitening (EDRmax) differentiates sufficiently all the examined histological conditions. Estimation of the sensitivity and the specificity of this method indicates that its diagnostic performance is comparable or better than that of the existing methods. In order to explain the experimental results, a model for the acetic acid-tissue interaction is proposed. According to this model the tissue-pH alterations induced by the application of acetic acid can be simulated with a 3-compartment model (the intracellular, the extracellular and the blood sink compartments). The solution of the model has shown that, after the application of acetic acid, the intracellular pH exhibits the same kinetics with the acetowhitening. The alterations of the intracellular pH cause increment in the relative refractive index of the nuclear proteins, and consequently increase the light scattering by the nuclei. Furthermore, this model correlates qualitatively the kinetics of the acetowhitening with some structural, compositional and functional features of the epithelial tissue and successfully interprets the experimental results. In particular, epithelial tissue features such as the nuclear size and inhomogeneity, the epithelium thickness, the cellular energy reserves (e.g. glycogen), the density of cell-packing, the cellular metabolism, and the efficiency of the vascularity determine the acetowhitening kinetics.


2020 ◽  
Vol 117 (13) ◽  
pp. 7338-7346 ◽  
Author(s):  
Menelaos Tzafetas ◽  
Anita Mitra ◽  
Maria Paraskevaidi ◽  
Zsolt Bodai ◽  
Ilkka Kalliala ◽  
...  

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.


2017 ◽  
Vol 27 (2) ◽  
pp. 326-331 ◽  
Author(s):  
Young-Jon Kim ◽  
Byoung-Ryun Kim ◽  
Jae-Suk Ryu ◽  
Gyeong-Ok Lee ◽  
Hak-Ryul Kim ◽  
...  

ObjectiveHeterogeneous nuclear ribonucleoprotein A1 (HNRNPA1), serine/arginine-rich splicing factor 1 (SRSF1), and SRSF3 are splicing regulators associated with oncogenesis. However, the alterations of SF proteins and their diagnostic values in cervical cancer are unclear. To apply SFs clinically, effective marker selection and characterization of the target organ properties are essential.Materials and MethodsWe concurrently analyzed HNRNPA1, SRSF1, SRSF3, and the conventional tumor markers squamous cell carcinoma antigen (SCCA) and carcinoembryonic antigen (CEA) in cervical tissue samples (n = 127) using semiquantitative immunoblotting. In addition, we compared them with p16 (cyclin-dependent kinase inhibitor 2A [CDKN2A]), which has shown high diagnostic efficacy in immunohistochemical staining studies and has been proposed as a candidate protein for point-of-care screening biochemical tests of cervical neoplasia.ResultsHNRNPA1, higher molecular weight forms of SRSF1 (SRSF1-HMws), SRSF3, CEA, and p16 levels were higher (P < 0.05) in cervical carcinoma tissue samples than in nontumoral cervical tissue samples. However, the levels of SRSF1-Total (sum of SRSF1-HMws and a lower molecular weight form of SRSF1) and SCCA, a commonly used cervical tumor marker, were not different between carcinoma and nontumoral tissue samples. In paired sample comparisons, HNRNPA1 (94%) showed the highest incidence of up-regulation (carcinoma/nontumor, >1.5) in cervical carcinoma, followed by p16 (84%), SRSF1-HMws (69%), SRSF3 (66%), CEA (66 %), SCCA (32%), and SRSF1-Total (31%). HNRNPA1 (92%) and p16 (91%) presented the two highest diagnostic accuracies for cervical carcinoma, which were superior to those of SRSF3 (75%), SRSF1-HMws (72%), CEA (72%), SCCA (59%), and SRSF1-Total (55%).ConclusionsOur results identified that HNRNPA1 is the best diagnostic marker among the SFs and conventional markers given its excellent diagnostic efficacy for cervical carcinoma, and it has a p16-comparable diagnostic value. We suggest that HNRNPA1 is an additional effective target protein for developing cervical cancer detection tools.


2005 ◽  
Vol 92 (1) ◽  
pp. 58-63 ◽  
Author(s):  
S. Bomfim-Hyppólito ◽  
E. Santana Franco ◽  
R. Gomes de Matos Meneses Franco ◽  
C. Matos de Albuquerque ◽  
G.C. Nunes

2004 ◽  
Vol 88 (1) ◽  
pp. 65-66 ◽  
Author(s):  
S. Bomfim ◽  
E. Santana-Franco ◽  
L. Bahamondes

1990 ◽  
Vol 15 (7) ◽  
pp. 26???30 ◽  
Author(s):  
Gyula Ficsor ◽  
Susan K. Fuller ◽  
Joy L. Jeromin ◽  
Roger D. Beyer ◽  
Frank C. Janca

1999 ◽  
Vol 53 (1-3) ◽  
pp. 153-157 ◽  
Author(s):  
Costas J Balas ◽  
George C Themelis ◽  
Emmanuel P Prokopakis ◽  
Irene Orfanudaki ◽  
Eugenios Koumantakis ◽  
...  

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