Lymph Node Evolution in Eyelid and Orbit Squamous Cell Carcinomas.

OBJECTIVES: To describe a large cohort of eyelid and periorbital SCCs, to compare the location of the tumor and of the pathological lymph nodes, and to analyze the risk factors for lymph node involvement among tumor characteristics. METHODS: All patients managed inside our institution for an eyelid and periorbital SCCs were included. Tumor characteristics, imaging setup, excision margins, lymph node evolution features, local, regional, and distant recurrences rates, and global survival were reported. The risk for lymph node involvement and location of pathological lymph nodes were analyzed through univariate and multivariate analyses. RESULTS: Between January 2012 and August 2022, 115 patients were included, and 18 presented a lymph node evolution (15.7%), involving the parotid gland in 16 cases (88.9%), the submental and submandibular areas in seven cases (38%), and the jugular and carotid areas in four cases (22%). Tumor size above 20 mm, infiltration of the external canthus and periorbital structures, the presence of perineural invasion or vascular embolism, the depth of infiltration, and the presence of a local recurrence were significantly associated with the risk of lymph node evolution. CONCLUSION: Periorbital and eyelid SCCs present a true potential for lymph node evolution especially through the parotid gland. Extension setup including the parotid gland and neck should be mandatory, and lymph node dissection should be associated in case of parotidectomy for lymph node involvement. LEVEL OF EVIDENCE: IV Laryngoscope, 2024.

"Ice cream cone" design of forearm free flap for orbital exenteration reconstruction.

BACKGROUNDS: Reconstruction post-orbital exenteration serves the dual purpose of expediting healing, laying the groundwork for cosmetic restoration, and minimising complications such as orbitosinusal fistulae. The aim of this study was to introduce a modified "Ice cream cone" (ICC) design of the Radial Forearm Free Flap (RFFF) technique used for reconstruction of orbital exenteration cavity, along with the oncological, functional, and aesthetic outcomes. METHODS: The authors conducted a retrospective study between January 2005 and December 2020. Inclusion criteria encompassed patients treated for orbitosinusal malignancies undergoing exenteration with subsequent ICC design of RFFF reconstruction. RESULTS: Twenty-two patients underwent exenteration with the ICC design of RFFF. At the follow-up conclusion, 65% of patients regularly used orbital prosthesis. The average waiting time until the prosthesis was 10 months. Quality of life questionnaires yielded average RFFF POSAS scores of 23.5 (SD 13,6), cervical POSAS scores of 8 (SD 13,2), and orbital cavity rehabilitation scores of 5.9 (SD: 3,32). CONCLUSIONS: ICC design of RFFF is a reliable technique. It can be proposed in cases of extended exenteration with a high risk of cerebrospinal fluid (CSF) but more generally in cases of total exenteration. This technique facilitates optimal postoperative wound healing and accommodates early radiotherapy. Importantly, the bowl-shaped aspect of the orbital socket supports effective prosthetic rehabilitation for patients opting for orbital prosthesis post-surgery.

Upper Aerodigestive Tract Endoscopy Combining Rigid Laryngoscopy and Flexible Endoscopy.

Upper Aerodigestive Tract Endoscopy (UATE) is recommended for initial examination of head and neck squamous cell carcinomas. Reducing delay of initial examination must be a challenge to manage head and neck cancers. We hereby describe the technic combining UATE and flexible endoscopy in a unique general anesthesia with overview of hypopharyngeal, larygeal, tracheal, esophageal, nasopharyngeal sub sites in a unique procedure with system of magnificense and to perform percutaneous gastrostomy during the same time before initiation of therapy.

Is Primary Poorly Differentiated Sarcomatoid Malignancy of the Parotid Gland Sarcomatoid Undifferentiated/Dedifferentiated Melanoma? Report of Three Unusual Cases Diagnosed by Fine-Needle Aspiration Combined with Histological, Immunohistochemical, and Molecular Analyses.

INTRODUCTION: Poorly differentiated primary sarcomatoid parotid malignancies are extremely rare. These tumors have not been consistently studied by morphology, immunohistochemistry, or molecular techniques. CASE PRESENTATION: We report three unusual cases of parotid gland poorly-differentiated sarcomatoid malignancy investigated by fine-needle aspiration and studied histologically, by immunohistochemistry and molecular investigations. Aspirates showed poorly specific polymorphous sarcomatoid malignancy in all cases. Histologically, all cases were polymorphous high-grade malignancies, and additionally, one case showed epithelial structures and was finally classified as salivary carcinosarcoma. Immunohistochemistry showed classical melanocytic markers negativity but positivity for PRAME, CD10, and WT1 in all three tumors and for CD56 in two tumors, which can potentially be supportive of melanocytic origin. Although not entirely specific, molecular characterization also suggested the melanocytic lineage of these tumors. CONCLUSION: Although rare, primary malignant melanoma of salivary gland was already described, but undifferentiated/dedifferentiated amelanotic forms are unknown in this localization up today. Further case reports of similar presentations are required to confirm the unequivocal primary origin of these obscure neoplasms in the parotid gland.

Squamous cell carcinoma of the temporal bone: the impact of local control on survival.

BACKGROUND: Squamous cell carcinoma (SCC) of the temporal bone (TB) is a rare pathology originating from the external auditory canal (EAC). Surgery remains the gold standard to achieve local control.Aims/Objectives:The aim of this study was to evaluate overall survival (OS) and disease-free survival (DFS) after surgery of the SCC of EAC. MATERIAL AND METHODS: A retrospective chart review in a tertiary referral center included 26 patients: 23 were operated with lateral temporal bone resection (LTBR, n = 10) and extended temporal bone resection (ETBR, n = 13). The outcomes were OS and DFS. RESULTS: Adjuvant radiotherapy was performed in 91.3% (n = 21/23). Mean age was 60.8 and sex ratio was 1. Median follow-up was 43 months; The 5-years OS was 90% (± 9.5%) and 47.7% (± 12.9%) for stage I/II and III/IV respectively (p = .033). DFS was 67.6% (IC 95%, 51.4%-88.9%) without statistical difference between early advanced stage. Incomplete margins (p = .004) and Stage IV(p < .001) were associated with poorer DFS. Free margins significantly correlated with better OS (HR = 9.8, p = .04). CONCLUSION: En bloc surgical resection with free margins, coupled with postoperative radiotherapy, provides optimal local control. For stage IV tumors, where complete margins are achievable, ETBR is recommended to enhance local control.

Safety and reliability of the internal jugular vein for venous anastomoses in head and neck oncological reconstruction: A retrospective study.

This study aimed to assess the efficacy of utilizing the internal jugular vein (IJV) as the primary recipient site for venous anastomoses in head and neck oncological reconstruction. Patients who underwent a free flap reconstruction of the head and neck were retrospectively included. Venous anastomoses were preferentially performed less than 1 cm from the IJV, either end-to-side (EtS) on the IJV, or end-to-end (EtE) on the origin of the thyrolingofacial venous (TLF) trunk. When the pedicle length was insufficient to reach the IJV, anastomoses were performed EtE to a size-matched cervical vein. Of the 246 venous anastomoses, 216 (87.8%) were performed less than 1 cm from the IJV, including 150 EtS on the IJV (61.0%), and 66 EtE on the TLF trunk (26.8%). Thirty veins (12.1%) were anastomosed EtE on other cervical veins more than 1 cm from the IJV. Two venous thromboses occurred (0.9%) and were successfully managed after revision surgery. There was no evidence of an increased thrombosis rate in high-risk or pre-irradiated patients. These findings suggest that the internal jugular vein is safe and reliable as a first-choice recipient vessel for free flap transfers in head and neck oncological reconstruction.

Head and neck INI1-deficient carcinoma without primary: a case report.

BACKGROUND: SMARCB1, also known as INI1, is a member of a large protein complex involved in chromatin remodeling and thus the regulation of gene expression. It is located on chromosome 22q11.2. SMARCB1 tumors have been found in various locations, including the sinonasal region, gastrointestinal tract, central nervous system (in atypical teratoid and rhabdoid tumors), and perirenal region (in malignant rhabdoid tumors) in both adults and children. CASE PRESENTATION: We describe here the first case in the literature of an INI1-deficient neck carcinoma without a primary tumor managed with surgical therapy and neck dissection in a young Caucasian woman of 29 years old, followed by chemotherapy before radiotherapy, with regional control after 18 months of follow-up. Histologic analysis showed an undifferentiated carcinoma without glandular or epidermoid differentiation. Biomolecular analysis of the tumor revealed a homozygous deletion of the SMARCB1 gene on RNA sequencing. CONCLUSION: Research of INI1 deletion should be performed for undifferentiated carcinoma of young patients because of possibilities of molecular therapies such as autophagy inhibitors or proteasome inhibitors could be used in clinical trials.

Fatigue life of 3D-printed porous titanium dental implants predicted by validated finite element simulations.

Introduction: Porous dental implants represent a promising strategy to reduce failure rate by favoring osseointegration or delivering drugs locally. Incorporating porous features weakens the mechanical capacity of an implant, but sufficient fatigue strength must be ensured as regulated in the ISO 14801 standard. Experimental fatigue testing is a costly and time-intensive part of the implant development process that could be accelerated with validated computer simulations. This study aimed at developing, calibrating, and validating a numerical workflow to predict fatigue strength on six porous configurations of a simplified implant geometry. Methods: Mechanical testing was performed on 3D-printed titanium samples to establish a direct link between endurance limit (i.e., infinite fatigue life) and monotonic load to failure, and a finite element model was developed and calibrated to predict the latter. The tool was then validated by predicting the fatigue life of a given porous configuration. Results: The normalized endurance limit (10% of the ultimate load) was the same for all six porous designs, indicating that monotonic testing was a good surrogate for endurance limit. The geometry input of the simulations influenced greatly their accuracy. Utilizing the as-designed model resulted in the highest prediction error (23%) and low correlation between the estimated and experimental loads to failure (R2 = 0.65). The prediction error was smaller when utilizing specimen geometry based on micro computed tomography scans (14%) or design models adjusted to match the printed porosity (8%). Discussion: The validated numerical workflow presented in this study could therefore be used to quantitatively predict the fatigue life of a porous implant, provided that the effect of manufacturing on implant geometry is accounted for.

Human papilloma virus integration sites and genomic signatures in head and neck squamous cell carcinoma.

A prevalence of around 26% of human papillomavirus (HPV) in head and neck squamous cell carcinoma (HNSCC) has been previously reported. HPV induced oncogenesis mainly involving E6 and E7 viral oncoproteins. In some cases, HPV viral DNA has been detected to integrate with the host genome and possibly contributes to carcinogenesis by affecting the gene expression. We retrospectively assessed HPV integration sites and signatures in 80 HPV positive patients with HNSCC, by using a double capture-HPV method followed by next-generation Sequencing. We detected HPV16 in 90% of the analyzed cohort and confirmed five previously described mechanistic signatures of HPV integration [episomal (EPI), integrated in a truncated form revealing two HPV-chromosomal junctions colinear (2J-COL) or nonlinear (2J-NL), multiple hybrid junctions clustering in a single chromosomal region (MJ-CL) or scattered over different chromosomal regions (MJ-SC) of the human genome]. Our results suggested that HPV remained episomal in 38.8% of the cases or was integrated/mixed in the remaining 61.2% of patients with HNSCC. We showed a lack of association of HPV genomic signatures to tumour and patient characteristics, as well as patient survival. Similar to other HPV associated cancers, low HPV copy number was associated with worse prognosis. We identified 267 HPV-human junctions scattered on most chromosomes. Remarkably, we observed four recurrent integration regions: PDL1/PDL2/PLGRKT (8.2%), MYC/PVT1 (6.1%), MACROD2 (4.1%) and KLF5/KLF12 regions (4.1%). We detected the overexpression of PDL1 and MYC upon integration by gene expression analysis. In conclusion, we identified recurrent targeting of several cancer genes such as PDL1 and MYC upon HPV integration, suggesting a role of altered gene expression by HPV integration during HNSCC carcinogenesis.

Time-dependent in silico modelling of orthognathic surgery to support the design of biodegradable bone plates.

Orthognathic surgery is performed to realign the jaws of a patient through several osteotomies. The state-of-the-art bone plates used to maintain the bone fragments in place are made of titanium. The presence of these non-degradable plates can have unwanted side effects on the long term (e.g. higher infection risk) if they are not removed. Using a biodegradable material such as magnesium may be a possible solution to this problem. However, biodegradation leads to a decrease of mechanical strength, therefore a time-dependent computational approach can help to evaluate the performance of such plates. In the present work, a computational framework has been developed to include biodegradation and bone healing algorithms in a finite element model. It includes bone plates and the mandible, which are submitted to masticatory loads during the early healing period (two months following the surgery). Two different bone plate designs with different stiffnesses have been tested. The stiff design exhibited good mechanical stability, with maximum Von Mises stress being less than 40% of the yield strength throughout the simulation. The flexible design shows high stresses when the bone healing has not started in the fracture gaps, indicating possible failure of the plate. However, this design leads to a higher bone healing quality after two months, as more cartilage is formed due to higher strains exerted in fracture gaps. We therefore conclude that in silico modelling can support tuning of the design parameters to ensure mechanical stability and while promoting bone healing.

Mechano-driven regeneration predicts response variations in large animal model based on scaffold implantation site and individual mechano-sensitivity.

It is well founded that the mechanical environment may regulate bone regeneration in orthopedic applications. The purpose of this study is to investigate the mechanical contributions of the scaffold and the host to bone regeneration, in terms of subject specificity, implantation site and sensitivity to the mechanical environment. Using a computational approach to model mechano-driven regeneration, bone ingrowth in porous titanium scaffolds was simulated in the distal femur and proximal tibia of three goats and compared to experimental results. The results showed that bone ingrowth shifted from a homogeneous distribution pattern, when scaffolds were in contact with trabecular bone (max local ingrowth 12.47%), to a localized bone ingrowth when scaffolds were implanted in a diaphyseal location (max local ingrowth 20.64%). The bone formation dynamics revealed an apposition rate of 0.37±0.28%/day in the first three weeks after implantation, followed by limited increase in bone ingrowth until the end of the experiment (12 weeks). According to in vivo data, we identified one animal whose sensitivity to mechanical stimulation was higher than the other two. Moreover, we found that the stimulus initiating bone formation was consistently higher in the femur than in the tibia for all the individuals. Overall, the dependence of the osteogenic response on the host biomechanics means that, from a mechanical perspective, the regenerative potential depends on both the scaffold and the host environment. Therefore, this work provides insights on how the mechanical conditions of both the recipient and the scaffold contribute to meet patient and location-specific characteristics.

[Epidemiology, diagnosis and treatment of head and neck cancers]. / Épidémiologie, diagnostic et traitement des cancers ORL.

Cancers of the upper aerodigestive tracts are the fourth most common cancer in France. The main risk factors are smoking and alcohol. They do not necessarily present specific signs, making their early diagnosis difficult. A change in the patient's general condition is a late sign leading to a poor prognosis of the disease.