Depth of invasion (DOI) is the most important predictor for lymph node metastasis (LNM) in early stage (T1-T2) oral cancer. The aim of this study is to validate the cut-off value of 4 mm on which the decision to perform an Elective Neck Dissection (END) is made. We performed a retrospective study in patients with pathologically proven early stage oral cavity squamous cell carcinoma (OCSCC) without clinical or radiological signs of LNM, who were treated between 2013 and 2018. An END was performed when DOI was ≥ 4 mm and a watchful waiting protocol was applied in patients with DOI < 4 mm. Three hundred patients were included. END was performed in 77% of patients with DOI ≥ 4 mm, of which 36% had occult LNM (pN+). Patients in the watchful waiting group (48%) developed a regional recurrence in 5.2% for DOI < 4 mm and 24.1% for DOI ≥ 4 mm. For DOI ≥ 4 mm, regional recurrence free survival was higher for patients who were treated with END compared to watchful waiting (p = 0.002). A Receiver-Operator-Curve -analysis showed that a DOI cut-off value of 4.0 mm was the optimal threshold for the prediction of occult LNM (95.1% sensitivity, 52.9% specificity). A DOI of ≥ 4 mm is an accurate cut-off value for performing an END in early stage OCSCC. END results in higher survival rates and lower regional recurrence rates in patients with DOI ≥ 4 mm.

Rationale: Small airway disease is an important pathophysiological feature of chronic obstructive pulmonary disease (COPD). Recently, “pre-COPD” has been put forward as a potential precursor stage of COPD that is defined by abnormal spirometry findings or significant emphysema on computed tomography (CT) in the absence of airflow obstruction. Objective: To determine the degree and nature of (small) airway disease in pre-COPD using microCT in a cohort of explant lobes/lungs. Methods: We collected whole lungs/lung lobes from patients with emphysematous pre-COPD (n = 10); Global Initiative for Chronic Obstructive Lung Disease (GOLD) stage I (n = 6), II (n = 6), and III/IV (n = 7) COPD; and controls (n = 10), which were analyzed using CT and microCT. The degree of emphysema and the number and morphology of small airways were compared between groups, and further correlations were investigated with physiologic measures. Airway and parenchymal pathology was also validated with histopathology. Measurements and Main Results: The numbers of transitional bronchioles and terminal bronchioles per milliliter of lung were significantly lower in pre-COPD and GOLD stages I, II, and III/IV COPD compared with controls. In addition, the number of alveolar attachments of the transitional bronchioles and terminal bronchioles was also lower in pre-COPD and all COPD groups compared with controls. We did not find any differences between the pre-COPD and COPD groups in CT or microCT measures. The percentage of emphysema on CT showed the strongest correlation with the number of small airways in the COPD groups. Histopathology showed an increase in the mean chord length and a decrease in alveolar surface density in pre-COPD and all GOLD COPD stages compared with controls. Conclusions: Lungs of patients with emphysematous pre-COPD already show fewer small airways and airway remodeling even in the absence of physiologic airway obstruction.

Currently, up to 85% of the oral resection specimens have inadequate resection margins, of which the majority is located in the deeper soft tissue layers. The prognosis of patients with oral cavity squamous cell carcinoma (OCSCC) of the tongue is negatively affected by these inadequate surgical resections. Raman spectroscopy, an optical technique, can potentially be used for intra-operative evaluation of resection margins. To develop in vitro Raman spectroscopy-based tissue classification models that discriminate OCSCC of the tongue from (subepithelial) non-tumorous tissue. Tissue classification models were developed using Principal Components Analysis (PCA) followed by (hierarchical) Linear Discriminant Analysis ((h)LDA). The models were based on a training set of 720 histopathologically annotated Raman spectra, obtained from 25 tongue samples (11 OCSCC and 14 normal) of 10 patients, and were validated by means of an independent validation set of 367 spectra, obtained from 19 tongue samples (6 OCSCC and 13 normal) of 11 patients. A PCA-LDA tissue classification model 'tumor' versus 'non-tumorous tissue' (i.e. surface squamous epithelium, connective tissue, muscle, adipose tissue, gland and nerve) showed an accuracy of 86% (sensitivity: 100%, specificity: 66%). A two-step PCA-hLDA tissue classification model 'tumor' versus 'non-tumorous tissue' showed an accuracy of 91% (sensitivity: 100%, specificity: 78%). An accurate PCA-hLDA Raman spectroscopy-based tissue classification model for discrimination between OCSCC and (especially the subepithelial) non-tumorous tongue tissue was developed and validated. This model with high sensitivity and specificity may prove to be very helpful to detect tumor in the resection margins.

With an incidence of 350.000 new cases per year, cancer of the oral cavity ranks among the 10 most common solid organ cancers. Most of these cancers are squamous cell carcinomas. Five‐year survival is about 50%. It has been shown that clear resection margins (>5 mm healthy tissue surrounding the resected tumor) have a significant positive effect on locoregional control and survival. It is not uncommon that the resection margins of oral tumors are inadequate. However, when providing the surgeon with intraoperative feedback on the resection margin status, it is expected that obtaining adequate resection margins is improved. In this respect, it has been shown that specimen‐driven intraoperative assessment of resection margins is superior to defect‐driven intraoperative assessment of resection margins. In this concise report, it is described how a specimen‐driven approach can increase the rate of adequate resections of oral cavity squamous cell carcinoma as well as that it is discussed how intraoperative assessment can be further improved with regard to the surgical treatment of oral cavity squamous cell carcinoma.