Impact of the COVID-19 Pandemic on Head and Neck Cancer Management: The Experience of the Maxillo-Facial Surgery Department of a French Regional Referral Center in a High-Incidence Area.

Background: Cancer patients are at a high risk of complications in cases of infection, and head and neck cancers (HNC) are no exception. Since late 2019, SARS-CoV-2 has caused a global health crisis, with high rates and severe forms of the disease in cancer patients. Hospitalization, surgery and radiotherapy were rapidly described as increasing the risk of infection. Since March 2020, the Amiens University Hospital (France) has been taking care of COVID-19 patients while its maxillofacial surgery department managed HNC patients without interruption, even during lockdown periods. However, many questions concerning the impact on patient care were still pending. The aim of this study is to describe HNC management in our center during the first epidemic peak and to evaluate the impact of containment measures on patient treatment. Methods: We retrospectively included 44 HNC patients treated in our department between 1 March and 31 August 2020. Two groups were defined according to the period of care: lockdown (March to May) and lighter restrictions (June to August). Results: The results show typical epidemiological characteristics, maintained management times and non-downgraded procedures. Conclusions: Thus, during the first epidemic peak, continuity of care and patients' safety could be ensured thanks to adequate means, adapted procedures and an experienced surgical team.

Evaluation of a Granular Bone Substitute for Bone Regeneration Using an Optimized In Vivo Alveolar Cleft Model.

Alveolar cleft is a common congenital deformity that requires surgical intervention, notably using autologous bone grafts in young children. Bone substitutes, in combination with mesenchymal stem cells (MSCs), have shown promise in the repair of these defects. This study aimed to evaluate the regenerative capabilities of a granular bone substitute using an optimized alveolar cleft model. Thirty-six rats underwent a surgical procedure for the creation of a defect filled with a fragment of silicone. After 5 weeks, the silicone was removed and the biomaterial, with or without Wharton's jelly MSCs, was put into the defect, except for the control group. The rats underwent µCT scans immediately and after 4 and 8 weeks. Analyses showed a statistically significant improvement in bone regeneration in the two treatment groups compared with control at weeks 4 and 8, both for bone volume (94.64% ± 10.71% and 91.33% ± 13.30%, vs. 76.09% ± 7.99%) and mineral density (96.13% ± 24.19% and 93.01% ± 27.04%, vs. 51.64% ± 16.51%), but without having fully healed. This study validates our optimized alveolar cleft model in rats, but further work is needed to allow for the use of this granular bone substitute in the treatment of bone defects.

Use of intraoperative 3D imaging in the maxillofacial operating room: A French national survey.

PURPOSE: To gain a comprehensive understanding of the utilization of intraoperative 3D imaging among maxillofacial surgeons practicing in France through a web-based questionnaire. METHODS: An 18-point multiple-choice questionnaire was developed and distributed to participants. The questionnaire was divided into two sections, with the first section gathering general information about the respondents and the second section providing an overview of the utilization of 3D imaging techniques, such as cone-beam computed tomography (CBCT), computed tomography (CT) scan, and magnetic resonance imaging (MRI), including the conditions, frequencies, and indications for use, with a particular focus on the number of acquisitions per procedure and the other departments with whom the equipment is shared. RESULTS: A total of 75 participants completed the survey, with 30% of university hospital departments and 0% of private clinics currently utilizing intraoperative 3D imaging systems. The main indications for 50% of the users were for temporomandibular joint surgery and orbital fractures. CONCLUSION: The results of this survey indicate that the utilization of intraoperative 3D imaging in French maxillofacial surgery is limited to university centers, with poor utilization and a lack of standardization in indications for use.

Surgical treatment outcomes of solitary fibrous tumors in the head and neck: A retrospective study.

The aim of this study was to better characterize head and neck solitary fibrous tumors (SFTs) and to evaluate surgical treatment. This retrospective study included patients who presented with head and neck SFTs. Clinical, radiological, and histological information and data regarding the treatments performed were collected. The risk of locoregional and distant metastases was calculated, and for orbital SFTs a specific classification was used. Overall, 34 patients were included. The majority of the SFTs were found in the oral cavity (n = 10), followed by the neck region (n = 8). The mean time to recurrence was 67.4 months. All patients underwent primary surgical resection. Recurrence was observed in five patients with a low risk of locoregional recurrence and distant metastasis. The treatment of choice is complete resection. Recurrence seems to be highly correlated with positive surgical margins. The safety margin should be increased when removing the lesion, and long-term follow-up should be performed.

Surgical navigation in maxillofacial surgery: A French national survey.

PURPOSE: to gain a national understanding of the utilization of surgical navigation among maxillofacial surgeons in France through a web-based questionnaire. METHODS: A 14-point multiple-choice questionnaire was created and distributed to the participants, divided into two sections. The first section gathered general information about the respondents, and the second section provided an overview of the use of surgical navigation. RESULT: A total of 75 participants completed the survey. The results showed that a majority of university hospital departments (65%) utilize an intra-operative 3D imaging system, while very few private clinics and general hospitals use this technology. CONCLUSION: The survey suggests that surgical navigation is primarily used in university centers in French maxillofacial surgery, with limited utilization and non-standardized indications for use.

Survival outcomes, prognostic factors, and effect of adjuvant radiotherapy and prophylactic neck dissection in salivary acinic cell carcinoma: A prospective multicenter REFCOR study of 187 patients.

BACKGROUND: Acinic cell carcinomas (AciCCs) are malignant tumours of the salivary glands. The aim of this work was to analyse data from the national REFCOR multicenter cohort (i) to investigate the prognostic factors influencing survival outcomes in AciCC, (ii) to assess the impact on survival of postoperative radiotherapy (RT) in patients treated for AciCC without high-grade transformation and (iii) to explore the prognostic impact of prophylactic neck dissection (ND) in patients treated for AciCC of the major salivary glands. PATIENTS AND METHODS: Data from all the patients treated for salivary AciCC between 2009 and 2020 were extracted from the REFCOR database. Survival outcomes and prognostic factors influencing Disease-Free Survival (DFS) and Overall Survival (OS) were investigated using univariate and multivariate analyses. Propensity score matching was used to assess the impact of postoperative RT and prophylactic ND on DFS. RESULTS: A total of 187 patients were included. After a median follow-up of 53 months, their 5-year OS and DFS rates were 92.8% and 76.2%, respectively. In multivariate analysis, male sex, older age, higher T and N status, and high grade were independently associated with a worse DFS. In the subpopulation analysed after propensity score matching, patients with cN0 AciCC without high-grade transformation who were treated by surgery and RT did not have an improved DFS compared to patients who were treated by surgery alone (hazard ratio (HR) = 0.87, p = 0.8). Factors associated with nodal invasion were T3-T4 status and intermediate/high histological grade. After propensity score matching, prophylactic ND was associated with a trend toward a better DFS (HR = 0.46, p = 0.16). CONCLUSIONS: These results suggest that (i) long-term follow-up (>5 years) should be considered in patients with AciCC, (ii) treatment by surgery alone could be an option in selected cN0 patients with AciCC without high-grade transformation and (iii) prophylactic ND may be considered preferentially in patients with T3-T4 status and/or intermediate/high histological grade.

The Facial Graft: A Graft of Emotions? (About the Reanimation of the Facial Allotransplantation).

Although there have been numerous scientific papers reporting on composite allotransplantation of the face, few have been about assessment and evolution of the functional benefit for patients in terms of soft tissue mobility, movement coordination, and face expressions, even fewer on the choice of the surgical procedures to restore motricity. On some videos and interviews, it is possible to analyze significative motricity. Of course that has been voluntary motricity, not emotional motricity. The data confirmed that the result on the complexity of the expression of the face is not great, providing opportunity to reflect on the question of nerve regeneration.

Quantified analysis of facial movement: A reference for clinical applications.

Most techniques for evaluating unilateral impairments in facial movement yield subjective measurements. The objective of the present study was to define a reference dataset and develop a visualization tool for clinical assessments. In this prospective study, a motion capture system was used to quantify facial movements in 30 healthy adults and 2 patients. We analyzed the displacements of 105 reflective markers placed on the participant's face during five movements (M1-M5). For each marker, the primary endpoint was the maximum amplitude of displacement from the static position (M0) in an analysis of variance. The measurement precision was 0.1 mm. Significant displacements of markers were identified for M1-M5, and displacement patterns were defined. The patients and age-matched healthy participants were compared with regard to the amplitude of displacement. We created a new type of radar plot to visually represent the diagnosis and facilitate effective communication between medical professionals. In proof-of-concept experiments, we collected quantitative data on patients with facial palsy and created a patient-specific radar plot. Our new protocol for clinical facial motion capture ("quantified analysis of facial movement," QAFM) was accurate and should thus facilitate the long-term clinical follow-up of patients with facial palsy. To take account of the limitations affecting the comparison with the healthy side, we created a dataset of healthy facial movements; our method might therefore be applicable to other conditions in which movements on one or both sides of the face are impaired. The patient-specific radar plot enables clinicians to read and understand the results rapidly.

Evaluation of Proton MR Spectroscopy for the Study of the Tongue Tissue in Healthy Subjects and Patients With Tongue Squamous Cell Carcinoma: Preliminary Findings.

Purpose: To noninvasively assess spectroscopic and metabolic profiles of healthy tongue tissue and in an exploratory objective in nontreated and treated patients with tongue squamous cell carcinoma (SCC). Methods: Fourteen healthy subjects (HSs), one patient with nontreated tongue SCC (NT-SCC), and two patients with treated tongue SCC (T-SCC) underwent MRI and single-voxel proton magnetic resonance spectroscopy (1H-MRS) evaluations (3 and 1.5T). Multi-echo-times 1H-MRS was performed at the medial superior part (MSP) and the anterior inferior part (AIP) of the tongue in HS, while 1H-MRS voxel was placed at the most aggressive part of the tumor for patients with tongue SCC. 1H-MRS data analysis yielded spectroscopic metabolite ratios quantified to total creatine. Results: In HS, compared to MSP and AIP, 1H-MRS spectra revealed higher levels of creatine, a more prominent and well-identified trimethylamine-choline (TMA-Cho) peak. However, larger prominent lipid peaks were better differentiated in the tongue MSP. Compared to HS, patients with NT-SCC exhibited very high levels of lipids and relatively higher values of TMA-Cho peak. Interestingly, patients with T-SCC showed almost nonproliferation activity. However, high lipids levels were measured, although they were relatively lower than lipids levels measured in patients with NT-SCC. Conclusion: The present study demonstrated the potential use of in-vivo 1H-MRS to noninvasively assess spectroscopic and metabolic profiles of the healthy tongue tissue in a spatial location-dependent manner. Preliminary results revealed differences between HS and patients with tongue NT-SCC as well as tongue T-SCC, which should be confirmed with more patients. 1H-MRS could be included, in the future, in the arsenal of tools for treatment response evaluation and noninvasive monitoring of patients with tongue SCC.

[Toward precision surgery for Head and Neck tumors]. / Principe et applicabilité de la chirurgie de précision aux cancers de la tête et du cou.

Surgical resection is the most frequent curative treatment proposed to patients with head and neck cancers. It is currently integrated into specific therapeutic schemes and therapeutic stratification, but the surgical procedure itself as well as its evaluation do not rely on tumor biology. Here, we present a number of recent studies, mostly based on system analyses and genomics, that show how tumor analyses could help to: i) define the indications and the extent of surgical resections; ii) personalize the perioperative management; iii) facilitate the detection of post-surgical tumor recurrence. Overall, these studies provide a proof of principle that precision surgery, i.e. based on tumor biology, similarly to precision medicine, is applicable to head and neck cancers.

Title: Principe et applicabilité de la chirurgie de précision aux cancers de la tête et du cou. Abstract: La chirurgie est la modalité de traitement curatif la plus fréquemment utilisée dans les cancers de la tête et du cou. Elle est intégrée dans des schémas de stratification thérapeutique précis, mais la conduite de l'acte chirurgical et son évaluation ne tiennent, la plupart du temps, pas compte de la biologie tumorale. Nous présentons dans cette revue plusieurs études qui montrent comment les analyses de la biologie tumorale pourraient préciser les indications et le contour d'une résection chirurgicale, personnaliser la prise en charge péri-opératoire du patient, et faciliter la détection des récurrences tumorales. Ces études apportent ainsi une preuve de principe qu'une chirurgie de précision, c'est-à-dire adossée à la biologie tumorale, à la façon de la médecine de précision pour d'autres cancers, est applicable aux cancers de la tête et du cou.

Masseteric nerve position on the "temporomandibular joint-chin tip" artificial axis: an anatomical study.

PURPOSE: The use of the masseteric nerve develops in the surgery of facial paralysis rehabilitation. The objective of this study was to determine the topography of the masseteric nerve and to deduce and predict a precise and reproducible anatomical cluster to facilitate its clinical identification during V-VII neurotization surgery. METHOD: For the purpose of this work, a cadaveric study was performed on 31 hemi-faces. All dissections were performed bilaterally and comparatively, following steps aiming at simulating, as close as possible, the clinical conditions of a facial palsy rehabilitation by V-VII anastomosis. RESULT: For the identification of the masseteric nerve, bony reference points were used, i.e., the temporomandibular joint (TMJ) and the chin point (CT). A virtual axis was drawn between the TMJ and the CT, and the distance [TMJ-MN] determining the smallest length h was then plotted against the distance [TMJ-CT] determining the largest length H, thus allowing the calculation of an h/H proportion ratio (PR) indicating the proximal part of the masseteric nerve from the TMJ. The average length h between the TMJ and the NM was 3.5 cm (± 0.1 cm) from the TMJ, i.e., an average ratio h/H [TMJ-MN]/[TMJ-CT] of 28.1% 4.0 and a median ratio of 28.6% of the distance [TMJ-CT]. CONCLUSION: Our study opens new perspectives for facilitating its identification and use, offering practitioners a tool to make V-VII the neurotization procedure less complex, with the eventual prospect of a minimally invasive procedure combining imaging, surgery, and augmented reality.

Mass Spectrometry-Based Differentiation of Oral Tongue Squamous Cell Carcinoma and Nontumor Regions With the SpiderMass Technology.

Oral cavity cancers are the 15th most common cancer with more than 350,000 new cases and ~178,000 deaths each year. Among them, squamous cell carcinoma (SCC) accounts for more than 90% of tumors located in the oral cavity and on oropharynx. For the oral cavity SCC, the surgical resection remains the primary course of treatment. Generally, surgical margins are defined intraoperatively using visual and tactile elements. However, in 15-30% of cases, positive margins are found after histopathological examination several days postsurgery. Technologies based on mass spectrometry (MS) were recently developed to help guide surgical resection. The SpiderMass technology is designed for in-vivo real-time analysis under minimally invasive conditions. This instrument achieves tissue microsampling and real-time molecular analysis with the combination of a laser microprobe and a mass spectrometer. It ultimately acts as a tool to support histopathological decision-making and diagnosis. This pilot study included 14 patients treated for tongue SCC (T1 to T4) with the surgical resection as the first line of treatment. Samples were first analyzed by a pathologist to macroscopically delineate the tumor, dysplasia, and peritumoral areas. The retrospective and prospective samples were sectioned into three consecutive sections and thaw-mounted on slides for H&E staining (7 µm), SpiderMass analysis (20 µm), and matrix-assisted laser desorption ionization (MALDI) MS imaging (12 µm). The SpiderMass microprobe collected lipidometabolic profiles of the dysplasia, tumor, and peritumoral regions annotated by the pathologist. The MS spectra were then subjected to the multivariate statistical analysis. The preliminary data demonstrate that the lipidometabolic molecular profiles collected with the SpiderMass are significantly different between the tumor and peritumoral regions enabling molecular classification to be established by linear discriminant analysis (LDA). MALDI images of the different samples were submitted to segmentation for cross instrument validation and revealed additional molecular discrimination within the tumor and nontumor regions. These very promising preliminary results show the applicability of the SpiderMass to SCC of the tongue and demonstrate its interest in the surgical treatment of head and neck cancers.

Donor variability alters differentiation and mechanical cohesion of tissue-engineered constructs with human endothelial/MSC co-culture.

To move towards clinical applications, tissue engineering (TE) should be validated with human primary cells and offer easy connection to the native vascularisation. Based on a sheet-like bone substitute developed previously, we investigated a mesenchymal stem cells/endothelial cells (MSCs/ECs) coculture to enhance pre-vascularisation. Using MSCs from six independent donors whose differentiation potential was assessed towards two lineages, we focused on donor variability and cell crosstalk regarding bone differentiation. Coculture was performed on calcium phosphate granules in a specific chamber during 1 month. MSCs were seeded first then ECs were added after 2 weeks, with respective monocultures as control groups. Cell viability and organisation (fluorescence, electronic microscopy), differentiation (ALP staining/activity, RT-qPCR) and mechanical cohesion were analysed. Adaptation of the protocol to coculture was validated (high cell viability and proliferation). Activity and differentiation showed strong trends towards synergistic effects between cell types. MSCs reached early mineralisation stage of maturation. The delayed addition of ECs allowed for their attachment on developed MSCs' matrix. The main impact of donor variability could be here the lack of cell proliferation potential with some donors, leading to low differentiation and mechanical cohesion and therefore absence of sheet-like shape successfully obtained with others. We suggest therefore adapting protocols to cell proliferation potentials from one batch of cells to the other in a patient-specific approach.

Efficiency of advanced-PRF usage in the treatment of alveolar cleft with iliac bone graft: A retrospective study.

The aim of this study was to evaluate the efficiency of a new alveolar bone grafting protocol using advanced-PRF (a-PRF) by comparing the volumes of newly formed bone after a bone graft combining autogenous iliac crest bone with either PRF or a-PRF. Patients presenting with unilateral or a bilateral alveolar cleft were included retrospectively in two groups: one group was grafted using cancellous iliac crest bone with PRF (PRF group), whereas for the other group the same procedure was followed using a-PRF (a-PRF group). CBCT scans were performed 3 months preoperatively and 6 months postoperatively. The volume of newly formed bone was measured by subtracting the postoperative cleft volume from the preoperative cleft volume. The mean volume of newly formed bone was compared between the two groups using Student's t-test. Twenty-four patients were included, with 12 allocated to each group. Forty-eight CBCT scans were analyzed. The mean volume of newly formed bone was 0.29 (±0.09) cm3 in the a-PRF group, versus 0.20 (±0.08) cm3 in the PRF group (Student's t-test, p = 0.024). The percentage of newly formed bone was 60.4 (±10.4) % in the a-PRF group versus 51.4 (±18.4) % in the PRF group (Student's t-test, p = 0.165). Our study demonstrated improved bone regeneration in the a-PRF group. While bearing in mind the limitations of this study, the a-PRF procedure should be adopted in cleft bone grafting whenever possible.

Contribution of Genomics to the Surgical Management and Study of Oral Cancer.

BACKGROUND: Oral squamous cell carcinoma (OSCC) is the most frequent type of tumor arising from the oral cavity. Surgery is the cornerstone of the treatment of these cancers. Tumor biology has long been overlooked as an important contributor to the outcome of surgical procedures, but recent studies are challenging this concept. Molecular analyses of tumor DNA or RNA provide a rich source of information about the biology of OSCC. METHODS: We searched for relevant articles using PubMed. We examined in particular the prospect of applying molecular methods for minimally invasive exploration of OSCC biology. RESULTS: We examined five potential applications of genomics to the surgical management and study of OSCC: i) assessing oral potentially malignant lesions; ii) tumor staging prior to surgery; iii) predicting postoperative risk in locally advanced tumors; iv) measuring minimal residual disease and optimizing the longitudinal monitoring of OSCC; and v) predicting the efficacy of medical treatment. CONCLUSIONS: Genomic information can be harnessed in order to identify new biomarkers that could improve the staging, choice of therapy and management of OSCC. The identification of new biomarkers is awaited for better personalization of the surgical treatment of OSCC.

Donor site sequelae and patient satisfaction after head and neck reconstruction with a radial forearm free flap.

PURPOSE: Radial forearm free flap (RFFF) being a workhorse flap in head and neck reconstruction, we investigated its donor site delayed consequences. METHODS: Multicentric case series evaluating 189 patients who underwent RFFF for carcinologic reasons at least 6 months before. Patients and surgeon's appreciation regarding the aesthetic and functional consequences of the flap harvest on their daily life were evaluated by questionnaires using likert scales. Medical data were collected from patients' charts retrospectively. RESULTS: Thirty percent of patients had at least one sequelae. Experiencing a graft necrosis did not worsen long-term results. Cosmetic satisfaction was significantly worst for women, according to patients' and surgeons' opinion. For 81% and 92% patients, respectively, the flap harvest had no impact on daily life nor sport practice. Ratio between the benefits of reconstruction and the sequelae at the donor site was judged "excellent" for 77% patients. CONCLUSIONS: Although objectively important, RFFF morbidity has little impact in head and neck cancer patient's life.

Therapeutic Perspectives for the Perioperative Period in Oral Squamous Cell Carcinoma (OSCC).

The perioperative period is the relatively short window of time, usually measured in days or weeks, around the surgical procedure. Despite its short duration, this time period is of great importance for cancer patients. From a biological point of view, the perioperative period is complex. Synchronous with primary tumor removal, surgery has local and distant consequences, including systemic and local inflammation, coagulation and sympathetic activation. Furthermore, the patients often present comorbidities and receive several medical prescriptions (hypnotics, pain killers, anti-emetics, hemostatics, inotropes, antibiotics). Because of the complex nature of the perioperative period, it is often difficult to predict the oncological outcome of tumor resection. Here, we review the biological consequences of surgery of Oral Squamous Cell Carcinoma (OSCC), the most frequent form of primary head and neck tumors. We briefly address the specificities and the challenges of the surgical care of these tumors and highlight the biological and clinical studies that offer insight into the perioperative period. The recent trials examining neoadjuvant immunotherapy for OSCC illustrate the therapeutic opportunities offered by the perioperative period.