Relocation of inadequate resection margins in the wound bed during oral cavity oncological surgery: A feasibility study

Background: Specimen-driven intraoperative assessment of the resection margins provides immediate feedback if an additional excision is needed. However, relocation of an inadequate margin in the wound bed has shown to be difficult. The objective of this study is to assess a reliable method for accurate relocation of inadequate tumor resection margins in the wound bed after intraoperative assessment of the specimen. Methods: During oral cavity cancer surgery, the surgeon placed numbered tags on both sides of the resection line in a pair-wise manner. After resection, one tag of each pair remained on the specimen and the other tag in the wound bed. Upon detection of an inadequate margin in the specimen, the tags were used to relocate this margin in the wound bed. Results: The method was applied during 80 resections for oral cavity cancer. In 31 resections an inadequate margin was detected, and based on the paired tagging an accurate additional resection was achieved. Conclusion: Paired tagging facilitates a reliable relocation of inadequate margins, enabling an accurate additional resection during the initial surgery

Raman Spectroscopic Analysis of Saliva for the Diagnosis of Oral Cancer: a Systematic Review

Abstract Oral squamous cell carcinoma (OSCC) is one of the most common malignancies worldwide, and new protocols for routine and early detection are required. Raman spectroscopy is an optical based method that can provide sensitive and non-invasive real time detailed information on the biochemical content of a sample like saliva, through the unique vibrations of its constituent molecules and this is sensitive to changes associated with disease. A comprehensive systematic review of the available scientific literature related to Raman spectroscopy of human saliva for diagnosis of OSCC was performed. The 785 nm laser line was most applied wavelength along with principal components analysis associated with linear discriminant analysis. The main salivary components possibly associated with the presence of OSCC were proteins and lipids. Measurement in the liquid physical state, and with no addition of nanoparticles for signal enhancement, seemed to best conserve the salivary integrity. However, in terms of sampling protocols, no differentiation was generally made between stimulated and non-stimulated saliva. Raman spectroscopy of saliva holds a promising future for clinical applications such as early detection of OSCC. However, more systematic analyses are still required for a better elucidation regarding sampling procedure, storage and degradation

The Potential of MET Immunoreactivity for Prediction of Lymph Node Metastasis in Early Oral Tongue Squamous Cell Carcinoma

Objective MET positivity is independently associated with survival in oral squamous cell carcinoma (OSCC). Since MET is a known orchestrator of invasive tumor growth, we investigated its association with LNM in early oral tongue squamous cell carcinoma (OTSCC). As it is recommended by the NCCN to use tumor depth of invasion (DOI) in making decisions on elective neck dissection (END), the results obtained for MET positivity were aligned with those for DOI > 4 mm. The cutoff value used in our institution. Methods Tumor samples from patients who underwent primary tumor resection and neck dissection between 1995 and 2013, were collected from the archives of the Leiden and Erasmus University Medical Center. Immunohistochemistry with D1C2 was performed to identify MET negative (= 10% uniform positivity) cancers. ROC curve analysis and the Chi-squared test were used to investigate the association of MET positivity with LNM (pN+ and occult). Binary logistic regression was used to investigate the association of MET positivity with LNM. Results Forty-five (44.1%) of the 102 cancers were MET positive. Ninety were cN0 of which 20 were pN+ (occult metastasis). The remaining 12 cancers were cN+, of which 10 were proven pN+ and 2 were pN0. MET positivity was associated with LNM with a positive predictive value (PPV) of 44.4% and a negative predictive value (NPV) of 82.5% for pN+. For the occult group, the PPV was 36.8% and the NPV was 88.5%. Regression analysis showed that MET positivity is associated with pN+ and occult LNM (p-value < 0.05). Conclusion MET positivity is significantly associated with LNM in early OTSCC, outperforming DOI. The added value of MET positivity could be in the preoperative setting when END is being considered during the initial surgery. For cases with DO

Raman microspectroscopic study for the detection of oral field cancerisation using brush biopsy samples

Field cancerisation (FC) is potentially an underlying cause of poor treatment outcomes of oral squamous cell carcinoma (OSCC). To explore the phenomenon using Raman microspectroscopy, brush biopsies from the buccal mucosa, tongue, gingiva and alveolus of healthy donors (n = 40) and from potentially malignant lesions (PML) of Dysplasia Clinic patients (n = 40) were examined. Contralateral normal samples (n = 38) were also collected from the patients. Raman spectra were acquired from the nucleus and cytoplasm of each cell, and subjected to partial least squares-discriminant analysis (PLS-DA). High discriminatory accuracy for donor and PML samples was achieved for both cytopalmic and nuclear data sets. Notably, contralateral normal (patient) samples were also accurately discriminated from donor samples and contralateral normal samples from patients with multiple lesions showed a similar spectral profile to PML samples, strongly indicating a FC effect. These findings support the potential of Raman microspectroscopy as a screening tool for PML using oral exfoliated cells

Lentigo maligna - anatomic location as a potential risk factor for recurrences after non-surgical treatment

BACKGROUND: A higher incidence of lentigo maligna (LM) recurrences on the nose was previously observed in our cohort after non‐surgical treatment. OBJECTIVES: To determine histological parameters that might be related to the previously observed higher incidence of LM recurrences on the nose after non‐surgical treatment. METHODS: We randomly selected 22 surgical specimens of LM on the nose and 22 on the cheek. Histopathological analysis was performed on haematoxylin and eosin stained and microphthalmia transcription factor immunohistochemically stained slides. The number of pilosebaceous units (PSU) per mm, maximum depth of atypical melanocytes along the skin appendages and maximum depth of the PSU itself were determined. RESULTS: The nose had a significantly higher density of PSU than the cheek. The atypical melanocytes extended deeper along the PSU on the nose with a mean (SD) depth of 1.29 mm (0.48) vs. a mean depth of 0.72 mm (0.30) on the cheek (P < 0.001). The maximum depth of the PSU on the nose was greater than on the cheek, mean (SD) depth of 2.28 mm (0.41) vs. 1.65 mm (0.82) (P = 0.003). CONCLUSIONS: The higher recurrence risk of LM on the nose after non‐surgical treatment that we previously observed in our cohort is most likely based on a higher density of atypical melanocytes and also their deeper extension into the follicles. These results shed more light on our previous findings and learn that anatomical location is relevant for the risk of recurrence of LM after non‐surgical treatment

Utilization of Raman spectroscopy to identify breast cancer from the water content in surgical samples containing blue dye

This is the final version. Available on open access from Wiley via the DOI in this record. Data availability: The data that support the findings of this study are available from the corresponding author upon reasonable request.Breast conserving surgery (BCS) for breast cancer aims for optimal oncological results with minimal tissue excision. Positive margins due to insufficient resection results in significant numbers of patients requiring re‐excision, which could be resolved with intra‐operative margin analysis (IMA). High wavenumber (HWN) Raman Spectroscopy (RS) examines the difference in protein/lipid environment and water content in tissues. Fluorescence from haemoglobin and blue dye surgical pigments (commonly present in excised breast tissue) can confound HWN RS. We present a Raman system with 785 nm excitation laser and indium gallium arsenide camera capable of quantifying changes in water content in different environments (protein‐rich and lipid‐rich) by measuring the water/total area ratio (W/TAR) of the HWN spectrum. We demonstrate that haemoglobin and blue dye do not adversely affect water content analysis by the W/TAR calculation. Measurement of paired tumour/non‐tumour human breast tissue specimens showed the biochemical differences between tissues, and spectral analysis with W/TAR demonstrated large differences in water content and that our Raman system can accurately differentiate between tumour and non‐tumour tissue, even in the presence of surgical pigments. This provides proof of principle that this Raman system is suitable for further investigation with a view to providing IMA in the clinical environment.National Institute for Health Research (NIHR)Engineering and Physical Sciences Research Council (EPSRC

Lentigo maligna - anatomic location as a potential risk factor for recurrences after non-surgical treatment

BACKGROUND: A higher incidence of lentigo maligna (LM) recurrences on the nose was previously observed in our cohort after non‐surgical treatment. OBJECTIVES: To determine histological parameters that might be related to the previously observed higher incidence of LM recurrences on the nose after non‐surgical treatment. METHODS: We randomly selected 22 surgical specimens of LM on the nose and 22 on the cheek. Histopathological analysis was performed on haematoxylin and eosin stained and microphthalmia transcription factor immunohistochemically stained slides. The number of pilosebaceous units (PSU) per mm, maximum depth of atypical melanocytes along the skin appendages and maximum depth of the PSU itself were determined. RESULTS: The nose had a significantly higher density of PSU than the cheek. The atypical melanocytes extended deeper along the PSU on the nose with a mean (SD) depth of 1.29 mm (0.48) vs. a mean depth of 0.72 mm (0.30) on the cheek (P < 0.001). The maximum depth of the PSU on the nose was greater than on the cheek, mean (SD) depth of 2.28 mm (0.41) vs. 1.65 mm (0.82) (P = 0.003). CONCLUSIONS: The higher recurrence risk of LM on the nose after non‐surgical treatment that we previously observed in our cohort is most likely based on a higher density of atypical melanocytes and also their deeper extension into the follicles. These results shed more light on our previous findings and learn that anatomical location is relevant for the risk of recurrence of LM after non‐surgical treatment

Feasibility of integrated high‐wavenumber Raman imaging and fingerprint Raman spectroscopy for fast margin assessment in breast cancer surgery

Intraoperative assessment of surgical margins remains one of the main challenges in cancer surgery. Raman spectroscopy can detect cancer cells with high accuracy, but it is time‐consuming. In this paper, we investigated a selective‐sampling Raman spectroscopy approach, based on high wavenumber (HW) Raman imaging (spectral range 2,500–3,500 cm−1) and fingerprint Raman spectroscopy (spectral range 600–1,800 cm−1), to reduce the overall tissue analysis time while maintaining high diagnostic accuracy. HW Raman mapping was used as a first step to identify the adipose tissue regions based on the C–H stretching bands at 2,700–2,950 cm−1. As residual tumors are typically found in nonadipose tissue, an algorithm was developed to allocate sampling points for fingerprint Raman spectroscopy at locations corresponding to low intensity in the HW‐Raman maps. Preliminary results show that HW‐Raman imaging based on a 671 nm laser is effective and fast for mapping of adipose tissue in breast resections, with typical imaging times of 2 min for tissue areas as large as 2 × 2 cm2 areas. Albeit the remaining high fluorescence background in the fingerprint region prevents the use of single 671‐nm laser, the HW Raman imaging can be still exploited in combination with 785‐nm excitation Raman spectroscopy for identifying residual tumor. Although this study demonstrates the feasibility of this approach, further improvements, such as using single element detectors for HW Raman imaging, are required to increase the analysis speed further towards intraoperative use in the routine clinical setting