What's behind Margin Status in Oral Cancer?

In the 2nd century AD, Galen argued that the failure to remove any single 'root' of a malignant tumor could result in a local relapse. After nearly 2 millennia, this problem appears to be even more challenging due to our increased understanding of the complexity of tumor formation and spread. Pathological analysis of tumor margins under a microscope remains the primary and only accepted method for confirming the complete tumor removal. However, this method is not an all-or-nothing test, and it can be compromised by various intrinsic and extrinsic limitations. Among the intrinsic limitations of pathological analysis we recall the pathologist handling, tissue shrinkage, the detection of minimal residual disease and the persistence of a precancerous field. Extrinsic limitations relate to surgical tools and their thermal damage, the different kinds of surgical resections and frozen sections collection. Surgeons, as well as oncologists and radiotherapists, should be well aware of and deeply understand these limitations to avoid misinterpretation of margin status, which can have serious consequences. Meanwhile, new technologies such as Narrow band imaging have shown promising results in assisting with the achievement of clear superficial resection margins. More recently, emerging techniques like Raman spectroscopy and near-infrared fluorescence have shown potential as real-time guides for surgical resection. The aim of this narrative review is to provide valuable insights into the complex process of margin analysis and underscore the importance of interdisciplinary collaboration between pathologists, surgeons, oncologists, and radiotherapists to optimize patient outcomes in oral cancer surgery.

Intraoperative Margin Control in Transoral Approach for Oral and Oropharyngeal Cancer.

OBJECTIVES: Piecemeal resection provides an innovative conceptual tool for margins surveillance because it entails the intraoperative evaluation of the whole resection margins and not just sample points, which should result in a better control of deep margins compared to en bloc resection. Although it is recognized that the intraoperative use of narrow band imaging (NBI) results in a better control of superficial margins, in this exploratory study we investigated whether NBI and piecemeal resection could be used in combination to improve margin control at both superficial and deep levels. Because piecemeal resection is based on frozen section analysis, we wanted to verify its reliability compared to definitive histological examination. METHODS: The status of resection margins in a group of patients with oral and oropharyngeal cancers treated with NBI and laser CO2 piecemeal resection (group 1) was compared with that of an historical group of patients (group 2) treated with NBI and conventional en bloc resection. In group 1, sensitivity, specificity, and positive and negative predictive values were used to verify the rate of concordance between frozen section and definitive histology. RESULTS: The difference between deep positive margins in the two groups was statistically significant (P = 0.042). The high sensitivity and specificity (94.6% and 94.7%, respectively) of frozen section analysis also demonstrated its reliability in the examination of larger samples corresponding to the whole margin. CONCLUSION: Even if our findings are limited by the small number of patients, we are confident that the combined use of NBI and piecemeal resection could represent an attractive surgical strategy to improve margin control. LEVEL OF EVIDENCE: 2b Laryngoscope, 129:1810-1815, 2019.

Transoral surgery (TOS) in oropharyngeal cancer: Different tools, a single mini-invasive philosophy.

Surgery with or without adjuvant therapy and radiotherapy with or without chemotherapy have traditionally represented the possible treatment options for oropharyngeal cancer. The adverse effects of non-surgical treatments and recent technical innovations have prompted a new interest in the surgical approach. However, in parallel to the possibility of achieving radical cancer clearance, we should remember the impact that traditional open surgery has on the patient's cosmesis, functionality and quality of life. As a result, transoral surgery is an attractive option for oropharyngeal tumors. The term "transoral surgery" only indicates that the tumor is accessed and resected via the oral cavity, but the surgeon can choose among different resection methods, such as transoral laser microsurgery, transoral robotic surgery, transoral videolaryngoscopic surgery, endoscopic laryngo-pharyngeal surgery, and transoral ultrasound surgery. The aim of this paper is to review the recent literature on the transoral treatment of oropharyngeal cancer, to standardize the terminology of transoral procedures, analyzing the common aspects, main differences and future perspectives of the various forms of transoral surgery.

Tailored resections in oral and oropharyngeal cancer using narrow band imaging.

PURPOSE: In a previous pilot study we observed that intra-operative narrow-band imaging (NBI) helps achieve clear superficial resection margins. The aim of this study was to verify if the use of intra-operative NBI can help to obtain tailored resections and if it is influenced by the lesion site, aspects not investigated in our previous study. MATERIALS AND METHODS: The resection margins of 39 oral and 22 oropharyngeal squamous cell carcinomas were first set at 1.5cm from the macroscopic lesion boundary (white light, WL, tattoo). Then, the superficial tumor extension was more precisely defined with NBI, giving rise to three possible situations: NBI tattoo larger than the WL tattoo, NBI tattoo coinciding with the WL tattoo, or NBI tattoo smaller than the WL tattoo. For each of these situations the space comprised between the NBI and WL tattoos was defined "NBI positive", "NBI null", and "NBI negative", respectively. Resections were performed following the outer tattoo. The number of clear superficial resection margins, and the pathological response on the "NBI-positive" and the "NBI-negative" areas were recorded. RESULTS: We obtained 80.3% negative superficial resection margins. NBI provided a more precise definition of superficial tumor extension in 43 patients. Sensitivity, specificity, positive and negative predictive values were 94.4%, 64%, 79.1% and 88.9%, respectively; a test of proportions demonstrated they were not influenced by tumor site. CONCLUSIONS: NBI could allow for real-time definition of superficial tumor extension with possible tailored resections and fewer positive superficial resection margins; it is not influenced by tumor site.

Follow-up of oral and oropharyngeal cancer using narrow-band imaging and high-definition television with rigid endoscope to obtain an early diagnosis of second primary tumors: a prospective study.

Narrow-band imaging (NBI) is an optical technique enhancing mucosal vasculature. The aim of this study is to assess the effectiveness of rigid NBI endoscopy in the early detection of second primaries or local recurrences after treatment for oral (OSCC) and oropharyngeal squamous cell carcinoma (OPSCC), its advantage over standard white-light (WL) endoscopy, and the influence of previous radiotherapy, the learning curve, and lesion site. Between January 2013 and June 2015, 195 patients treated for OSCC or OPSCC with surgery alone (group A) or radiotherapy with or without surgery and/or chemotherapy (group B) underwent additional follow-up assessments using NBI. Sensitivity, specificity, positive/negative predictive values (PPV and NPV), and accuracy for detecting second primaries or local recurrences were calculated for patients with at least two NBI assessments. The effect of previous radiotherapy was determined by test of proportions and that of the learning curve and lesion site with Fisher's exact test. 138/195 patients were included in the analysis. NBI sensitivity, specificity, PPV, NPV, and accuracy for groups A and B were 89.5 vs 100%, 85.2 vs 81.5%, 65.4 vs 69.7%, 96.3 vs 100%, and 86.3 vs 87%, respectively. The diagnostic gain of NBI was 88.2% in group A and 69.6% in group B. The learning curve was the main source of false positives (p = 0.025), whereas radiotherapy and lesion site were uninfluential (p = NS). NBI appears useful for follow-up after treatment for OSCC or OPSCC, its performance being affected only by the learning curve and not by previous treatment or lesion site.

NBI utility in the pre-operative and intra-operative assessment of oral cavity and oropharyngeal carcinoma.

PURPOSE: Despite advances in the surgical management of head and neck squamous cell carcinoma, the identification of synchronous lesions, precancerous lesions around the main tumor, or the unknown primary in the case of neck metastasis remains a problem, as these lesions may be invisible to the naked eye or with standard white light (WL) endoscopy. However, the advent of tools such as narrow-band imaging (NBI) could help the clinician. The purpose of this study was to assess the impact of NBI during the pre-operative and intra-operative stages of management of oral and oropharyngeal cancers. MATERIALS AND METHODS: NBI was used pre-operatively in 47 patients with oral or oropharyngeal squamous cell carcinoma to identify the involvement of adjacent subsites, multifocality, synchronous lesions or an unknown primary. NBI was used intra-operatively in 30 patients to better define the tumor limits and guide the resection. The advantage of NBI versus WL endoscopy was analyzed by calculating the true and false positive rate pre-operatively, and the need for resection enlargements, histology of the enlargement, and the rate of clear margins at definitive histology, intra-operatively. RESULTS: Pre-operatively, the diagnostic gain of NBI was 8.5%, allowing identification of three synchronous tumors and one unknown primary. Intra-operatively, NBI improved the definition of tumor limits in 67.7% of cases, with resection enlargements showing dysplasia and carcinoma in 8 and 12 patients, respectively; we obtained 74.2% negative margins at histology. CONCLUSIONS: NBI could represent an added value in the pre-operative and intra-operative assessment of oral cavity and oropharyngeal carcinoma.

Is NBI-Guided Resection a Breakthrough for Achieving Adequate Resection Margins in Oral and Oropharyngeal Squamous Cell Carcinoma?

OBJECTIVES: Obtaining free resection margins is the main goal of oncological surgeons. Narrow-band imaging (NBI) has been recently used to help define resection margins in transoral laser microsurgery for laryngeal carcinoma. The aim of this study was to evaluate the effect of intraoperative NBI in defining the surgical resection margins of oral and oropharyngeal cancers. METHODS: Between January 2014 and March 2015, NBI was used intraoperatively after an initial definition of resection margins with white light in 26 patients (group A). The rate of superficial positive margins at definitive histology was compared with that of a historical cohort of 44 patients (group B) previously managed without the use of intraoperative NBI. RESULTS: A statistically significant reduction in the rate of positive superficial margins was observed at definitive histology in group A (P = .028). NBI helped to identify the presence of dysplasia and cancer around the visible tumor not otherwise detectable with visual examination alone. CONCLUSIONS: NBI could be a useful tool for obtaining free resection margins in oral and oropharyngeal carcinoma.

Open questions and novel concepts in oral cancer surgery.

The persistence of cancerous cells after surgery in oral squamous cell carcinoma (OSCC) represents a major challenge, as it often leads to local recurrences and secondary primary tumors, which are eventually responsible for a large proportion of deaths. This persistence is currently evaluated by histological analyses. In this review we discuss some important pitfalls of the histopathological analysis, such as margin evaluation, specimen shrinkage and T staging. In addition, we critically analyze the appropriateness of current surgical techniques in relation to the concept of field cancerization. Finally, we describe some novel imaging and molecular approaches, which might be useful in tailoring surgical resections and encourage the use of OSCC animal models to explore and provide proof of concept of the feasibility and potential clinical utility of innovative surgical protocols.

Narrow band imaging in the intra-operative definition of resection margins in oral cavity and oropharyngeal cancer.

OBJECTIVES: In oncological surgery, a three-dimensional resection 1.5-2 cm from the gross tumour edge is currently considered appropriate, and the status of resection margins is the most reliable indicator of radicality. Awareness of "field cancerization" calls for a re-evaluation of the benchmarks of tumour resection; however, its identification is not simple because the dysplastic areas may be far from the main lesion and difficult to recognize macroscopically. New technologies such as narrow band imaging (NBI) could improve the detection of neoplastic and pre-neoplastic areas, ensuring more precise resections. The main purpose of this study was to investigate the value of NBI in detecting pre-cancerous areas and/or cancer around the tumour bulk intra-operatively, to achieve adequate resection of the tumour. MATERIALS AND METHODS: The resection margins of 8 oral cavity and 8 oropharyngeal cancers were first drawn by macroscopic evaluation and then re-defined using NBI. Resections were performed following the NBI-drawing if extemporaneous histological examinations of the NBI-defined enlargements were positive for dysplasia or cancer. The number of clear margins was evaluated. RESULTS: Resections margins were free of tumour or dysplasia at extemporaneous examination; on definitive histology, two patients had a margin positive for cancer and dysplasia, respectively. Among the NBI-defined enlargements, 25% were positive for dysplasia and 75% for cancer. The sensitivity, specificity, positive and negative predictive values were 100%, 88.9%, 100% and 87.5%, respectively. CONCLUSION: The method we propose could be useful for obtaining free surgical margins and reducing the potential development of tumour foci resulting from incomplete resection.