@article{SievertMantsopoulosMuelleretal.2022, author = {Sievert, Matti and Mantsopoulos, Konstantinos and M{\"u}ller, Sarina K. and Eckstein, Markus and Rupp, Robin and Aubreville, Marc and Stelzle, Florian and Oetter, Nicolai and Maier, Andreas and Iro, Heinrich and Goncalves, Miguel}, title = {Systematic interpretation of confocal laser endomicroscopy: larynx and pharynx confocal imaging score}, volume = {42}, journal = {Acta otorhinolaryngologica italica}, number = {1}, publisher = {Pacini}, address = {Pisa}, issn = {1827-675X}, doi = {https://doi.org/10.14639/0392-100X-N1643}, pages = {26 -- 33}, year = {2022}, abstract = {Objective. Development and validation of a confocal laser endomicroscopy (CLE) classification score for the larynx and pharynx. Methods. Thirteen patients (154 video sequences, 9240 images) with laryngeal or pharyngeal SCC were included in this prospective study between October 2020 and February 2021. Each CLE sequence was correlated with the gold standard of histopathological examination. Based on a dataset of 94 video sequences (5640 images), a scoring system was developed. In the remaining 60 sequences (3600 images), the score was validated by four CLE experts and four head and neck surgeons who were not familiar with CLE. Results. Tissue homogeneity, cell size, borders and clusters, capillary loops and the nucleus/ cytoplasm ratio were defined as the scoring criteria. Using this score, the CLE experts obtained an accuracy, sensitivity, and specificity of 90.8\%, 95.1\%, and 86.4\%, respectively, and the CLE non-experts of 86.2\%, 86.4\%, and 86.1\%. Interobserver agreement Fleiss' kappa was 0.8 and 0.6, respectively. Conclusions. CLE can be reliably evaluated based on defined and reproducible imaging features, which demonstrate a high diagnostic value. CLE can be easily integrated into the intraoperative setting and generate real-time, in-vivo microscopic images to demarcate malignant changes.}, language = {en} } @article{SievertAubrevilleGostianetal.2022, author = {Sievert, Matti and Aubreville, Marc and Gostian, Antoniu-Oreste and Mantsopoulos, Konstantinos and Koch, Michael and M{\"u}ller, Sarina K. and Eckstein, Markus and Rupp, Robin and Stelzle, Florian and Oetter, Nicolai and Maier, Andreas and Iro, Heinrich and Goncalves, Miguel}, title = {Validity of tissue homogeneity in confocal laser endomicroscopy on the diagnosis of laryngeal and hypopharyngeal squamous cell carcinoma}, volume = {279}, journal = {European Archives of Oto-Rhino-Laryngology and Head \& Neck}, number = {8}, publisher = {Springer Nature}, address = {Cham}, issn = {1434-4726}, doi = {https://doi.org/10.1007/s00405-022-07304-y}, pages = {4147 -- 4156}, year = {2022}, abstract = {Purpose Confocal laser endomicroscopy (CLE) allows imaging of the laryngeal mucosa in a thousand-fold magnification. This study analyzes differences in tissue homogeneity between healthy mucosa and squamous cell carcinoma (SCC) via CLE. Materials and methods We included five SCC patients with planned total laryngectomy in this study between October 2020 and February 2021. We captured CLE scans of the tumor and healthy mucosa. Analysis of image homogeneity to diagnose SCC was performed by measuring the signal intensity in four regions of interest (ROI) in each frame in a total of 60 sequences. Each sequence was assigned to the corresponding histological pattern, derived from hematoxylin and eosin staining. In addition, we recorded the subjective evaluation of seven investigators regarding tissue homogeneity. Results Out of 3600 images, 1620 (45\%) correlated with benign mucosa and 1980 (55\%) with SCC. ROIs of benign mucosa and SCC had a mean and standard deviation (SD) of signal intensity of, respectively, 232.1 ± 3.34 and 467.3 ± 9.72 (P < 0.001). The mean SD between the four different ROIs was 39.1 ± 1.03 for benign and 101.5 ± 2.6 for SCC frames (P < 0.001). In addition, homogeneity yielded a sensitivity and specificity of 81.8\% and 86.2\%, respectively, regarding the investigator-dependent analysis. Conclusions SCC shows a significant tissue inhomogeneity in comparison to the healthy epithelium. The results support this feature's importance in identifying malignant mucosa areas during CLE examination. However, the examiner-dependent evaluation emphasizes that homogeneity is a sub-criterion that must be considered in a broad context.}, language = {en} } @article{SievertMantsopoulosMuelleretal.2021, author = {Sievert, Matti and Mantsopoulos, Konstantinos and M{\"u}ller, Sarina K. and Rupp, Robin and Eckstein, Markus and Stelzle, Florian and Oetter, Nicolai and Maier, Andreas and Aubreville, Marc and Iro, Heinrich and Goncalves, Miguel}, title = {Validation of a classification and scoring system for the diagnosis of laryngeal and pharyngeal squamous cell carcinomas by confocal laser endomicroscopy}, volume = {2022}, journal = {Brazilian Journal of Otorhinolaryngology}, number = {88, S4}, publisher = {Elsevier}, address = {Amsterdam}, issn = {1808-8694}, doi = {https://doi.org/10.1016/j.bjorl.2021.06.002}, pages = {26 -- 32}, year = {2021}, abstract = {Introduction Confocal laser endomicroscopy is an optical imaging technique that allows in vivo, real-time, microscope-like images of the upper aerodigestive tract's mucosa. The assessment of morphological tissue characteristics for the correct differentiation between healthy and malignant suspected mucosa requires strict evaluation criteria. Objective This study aims to validate an eight-point score for the correct assessment of malignancy. Methods We performed confocal laser endomicroscopy between March and October 2020 in 13 patients. 197 sequences (11.820 images) originated from the marginal area of pharyngeal and laryngeal carcinomas. Specimens were taken at corresponding locations and analyzed in H\&E staining as a standard of reference. A total of six examiners evaluated the sequences based on a scoring system; they were blinded to the histopathological examination. The primary endpoints are sensitivity, specificity, and accuracy. Secondary endpoints are interrater reliability and receiver operator characteristics. Results Healthy mucosa showed epithelium with uniform size and shape with distinct cytoplasmic membranes and regular vessel architecture. Confocal laser endomicroscopy of malignant cells demonstrated a disorganized arrangement of variable cellular morphology. We calculated an accuracy, sensitivity, specificity, positive predictive value, and negative predictive value of 83.2\%, 81.3\%, 85.5\%, 86.7\%, and 79.7\%, respectively, with a κ-value of 0.64, and an area under the curve of 0.86. Conclusion The results confirm that this scoring system is applicable in the laryngeal and pharyngeal mucosa to classify benign and malignant tissue. A scoring system based on defined and reproducible characteristics can help translate this experimental method to broad clinical practice in head and neck diagnosis.}, language = {en} }