DUSP1 and SOX2 expression determine squamous cell carcinoma of the salivary gland progression.

Salivary gland squamous cell carcinomas (SG-SCCs) constitute a rare type of head and neck cancer which is linked to poor prognosis. Due to their low frequency, the molecular mechanisms responsible for their aggressiveness are poorly understood. In this work we studied the role of the phosphatase DUSP1, a negative regulator of MAPK activity, in controlling SG-SCC progression. We generated DUSP1 KO clones in A253 human cells. These clones showed a reduced ability to grow in 2D, self-renew in ECM matrices and to form tumors in immunodeficient mice. This was caused by an overactivation of the stress and apoptosis kinase JNK1/2 in DUSP1-/+ clones. Interestingly, RNAseq analysis revealed that the expression of SOX2, a well-known self-renewal gene was decreased at the mRNA and protein levels in DUSP1-/+ cells. Unexpectedly, CRISPR-KO of SOX2 did not recapitulate DUSP1-/+ phenotype, and SOX2-null cells had an enhanced ability to self-renew and to form tumors in mice. Gene expression analysis demonstrated that SOX2-null cells have a decreased squamous differentiation profile -losing TP63 expression- and an increased migratory phenotype, with an enhanced epithelial to mesenchymal transition signature. In summary, our data indicates that DUSP1 and SOX2 have opposite functions in SG-SCC, being DUSP1 necessary for tumor growth and SOX2 dispensable showing a tumor suppressor function. Our data suggest that the combined expression of SOX2 and DUSP1 could be a useful biomarker to predict progression in patients with SG-SCCs.

Clinical and Pathological Features of Osteosarcomas of the Jaws: A Retrospective Study.

INTRODUCTION: Osteosarcomas of the jaw (OSJs) are rare tumors with distinct characteristics from osteosarcomas affecting other bones. This study aims to analyze the clinical, pathological, and therapeutic characteristics of OSJs. METHODS: A retrospective, descriptive cross-sectional study including patients diagnosed with OSJ registered at the "La Paz" University Hospital, Madrid, was performed. RESULTS: Data of eight patients with a diagnosis of OSJ were obtained during the study period of 22 years (2002-2024). The mean age of the patients was 41 years. The distribution was 1:1 between the maxilla and mandible. Painful inflammation was the most frequent clinical manifestation. Conventional osteoblastic osteosarcoma was the most predominant histological type. Survival rate at 5 years was 50%, which decreased to 25% at 10 years. CONCLUSIONS: OSJs differ from conventional osteosarcomas of long tubular bones. Surgery continues to be the mainstay of treatment. However, more studies are needed through which more standardized protocols can be proposed for adjuvant therapeutic management.

Venous malformation differential diagnosis with an odontogenic abscess on a pediatric patient. Case report and review of the literature.

Venous malformations (VMs) are aberrant venous vessel angiogenesis present at birth. However, they can become apparent later in life, debuting in early childhood. This poses a clinical quest for surgeons, dentists, and pediatricians, as they might appear as a compressible mass in the head and neck region, not uncommonly mistaking them for odontogenic abscesses or other soft tissue tumors. The differential diagnosis can be challenging and imaging techniques are often needed. Ultrasounds are extremely useful initially as other diagnostic tools can be potentially harmful in the context of a VM. MRI is key as it provides accurate extension and location information, and allows to plan invasive treatment alternatives if the patient requires it. In this article, we present the case of a 6-year-old girl who was treated by mistake for an infection upon the diagnosis of an incipient odontogenic abscess instead of a venous malformation, and a literature review on VMs. Key words:Venous malformation, odontogenic abscess, differential diagnosis.

Surface scanned 3D designed customized chinstrap for the treatment of intraoral dehiscence in polytraumatized patient. Technical note.

The advent of 3D surgical technology has revolutionized personalized medicine, enabling the development of tailored solutions for individual patients. This technical note presents the application of 3D technology in designing a customized chin guard using flexible 3D resin. The process involves surface scanning the lower facial region of a polytraumatized patient with a structured-light surface 3D scanner, generating a detailed point cloud. The acquired data undergoes meticulous processing within an specific professional software, including erasing unwanted portions, aligning frames, and mesh consolidation. Subsequently, the mesh is exported as an STL file and further refined using a 3D mesh management software. A customized chin support is designed for the specific patient's needs, exported in STL format, and 3D printed using a stereolithography (SLA) printer with Flexible 80A resin. Post-printing procedures involve washing and curing to ensure biocompatibility and optimal mechanical characteristics. The resultant customized chin guard, attached to elastic support straps, offers a precise fit to the patient's anatomy, enhancing comfort and allowing for extended wear. This innovative approach addresses the challenge of surgical intraoral wound dehiscence in a polytraumatized patient, showcasing the potential of 3D technology in personalized medical solutions for complex cases. Key words:Surface scanner, 3D surgery, customized surgery, chinstrap.

Virtual Surgical Planning for Temporomandibular Joint Reconstruction with Stock TMJ Prostheses: Pilot Study.

The temporomandibular joint (TMJ) is one of the most complex joints in the human anatomy. In advanced degenerative stages, conservative or minimally invasive surgical therapies have failed to restore joint function, and joint replacement with prostheses has been required. Stock prostheses, compared to custom-made prostheses, are much less expensive and require less pre-operative preparation time. Four patients followed for years for temporomandibular dysfunction and previously operated on by arthroscopy or open joint surgery that have been reconstructed with stock TMJ prostheses (STMJP) through virtual surgical planning (VSP) and an STL model with surgical and positioning guides were included. The median follow-up was 15 months; the median number of previous TMJ surgeries was 2. The mean preoperative MIO was 24.6 mm and at longest follow-up was 36.4 mm. The median preoperative TMJ pain score was 8, and the median postoperative TMJ pain was 3. All patients have improved their mandibular function with a clear improvement of their initial situation. In conclusion, we believe that stock TMJ prostheses with virtual surgical planning and surgical guides are a good alternative for TMJ reconstruction at the present time. Nonetheless, prospective and randomized trials are required with long-term follow up to assess their performance and safety.

3D designed in-house positioning and cutting guide system for genioplasty surgery. Technical note and case report.

Advances in 3D printing technology have the potential to significantly improve the workflow of maxillofacial surgical planning. In-house fabricated custom positioning and cutting guides allow for intraoperative reproduction of pre-planned osteotomy cuts, which can result in greater surgical accuracy and patient safety while maintaining an acceptable cost-effectiveness ratio. The design and creation of the customized surgical guides is performed in our hospital fab lab, which allows time savings, from an average of 10 days to just 24 hours, and a cost reduction of more than 90%. The process begins with the import of the pre-surgical facial CT scan into 3D software that allows to perform the surgical cuts virtually and the manipulation of the segments. Once the virtual planning of the surgery has been performed, the next step is the creation of the cutting and positioning guides. The final step is the printing of the guides in surgical resin and their sterilization. In addition, post-surgical models can be 3D printed to pre-mold the plates on them, which saves surgical time. The mentoplasty surgery is a simple example of how 3D surgery can be applied to maxillofacial surgery in an efficient way obtaining all the advantages of customized surgery with a limited investment in time and resources. Key words:3Dsurgery, customized, personalized medicine, genioplasty, surgical guides, in house.

Depth of Invasion: Influence of the Latest TNM Classification on the Prognosis of Clinical Early Stages of Oral Tongue Squamous Cell Carcinoma and Its Association with Other Histological Risk Factors.

BACKGROUND: The American Joint Committee on Cancer (AJCC), in its 8th edition, introduces modifications to the previous TNM classification, incorporating tumour depth of invasion (DOI). The aim of this research is to analyse the prognosis (in terms of disease-free survival and overall survival) of clinical early stage (I and II) squamous cell carcinomas of the oral tongue according to the DOI levels established by the AJCC in its latest TNM classification to assess changes to the T category and global staging system and to evaluate the association between DOI and other histological risk factors. METHODS: A retrospective longitudinal observational study of a series of cases was designed. All patients were treated with upfront surgery at our institution between 2010 and 2019. The variables of interest were defined and classified into four groups: demographic, clinical, histological and evolutive control. Univariate and multivariate analyses were carried out and survival functions were calculated using the Kaplan-Meier method. Statistical significance was established for p values below 0.05. RESULTS: Sixty-one patients were included. The average follow-up time was 47.42 months. Fifteen patients presented a loco-regional relapse (24.59%) and five developed distant disease (8.19%). Twelve patients died (19.67%). Statistically significant differences were observed, with respect to disease-free survival (p = 0.043), but not with respect to overall survival (p = 0.139). A total of 49.1% of the sample upstaged their T category and 29.5% underwent modifications of their global stage. The analysis of the relationship between DOI with other histological variables showed a significant association with the presence of pathological cervical nodes (p = 0.012), perineural invasion (p = 0.004) and tumour differentiation grade (p = 0.034). Multivariate analysis showed association between depth of invasion and perineural invasion. CONCLUSIONS: Depth of invasion is a histological risk factor in early clinical stages of oral tongue squamous cell carcinoma. Depth of invasion impacts negatively on patient prognosis, is capable per se of modifying the T category and the global tumour staging, and is associated with the presence of cervical metastatic disease, perineural invasion and tumoural differentiation grade.

HPV infection in oral cancer, our experience: prevalence, clinical implications, and current vaccination program in Spain.

Background: Oral cancer is the 11th most common type of cancer in the world, with established major risk factors as tobacco and alcohol, and recently included high-risk human papillomavirus types 16 and 18. HPV types 16 and 18 are the etiologic agents of cervical cancers and a proportion of oropharyngeal cancers. However, the picture of HPV and the clinical implications of oral cancers are not clear with most reports combining oral cancer data with head and neck cancers. It has been confirmed as a favorable prognostic factor in oropharyngeal cancer. However, the prognostic value of HPV in oral squamous cell carcinoma is still unclear. Material and Methods: The main objective of this article is to present the evidence encountered following a bibliographical review of recent publications specifically related to oral cancer and its differences from oropharyngeal cancer. The secondary goals are to present the findings of a five-year retrospective observational study of the prevalence of HPV infection in oral cancer patients treated by the Oral and Maxillofacial Surgery Department at La Paz University Hospital (Madrid, Spain), and finally, we to evaluate and compare our country's HPV prevention program in comparison to other European countries. Results: According to the review of the literature, HPV positive oral squamous cell carcinoma is associated with significantly decreased overall survival and distant control. Bibliographic review suggest HPV infection can be used as a negative prognostic factor in oral squamous cell carcinoma. Conclusions: As regards diagnostic testing for HPV, it should be extended to as many cases of oral cavity squamous cell carcinoma as possible, especially in those with risk factors. The current vaccination program in Spain does not have adequate coverage and is significantly under the level of other European Union countries; it should be expanded and catch-up strategies should be included. Key words:HPV, OSSC, Papillomavirus, oral carcinoma, prevention.

Use of surgical bone cement to increase the projection of the nasomaxillary buttress in a case of orthognathic surgery. Technical note.

The soft tissue outcome of the projection at the level of the nasomaxillary buttress is difficult to manage in cases of severe hypoprojection, being orthognathic surgery resolutive at the occlusal level but sometimes insufficient at the level of esthetic outcome. The literature describes the use of alloplastic prostheses and autologous bone grafts, but there are few documented cases of the use of premolded surgical cement for this purpose. The main advantage of the use of bone cement over the alternatives described is its ability to be premolded for customization, low cost, easy availability, speed of preparation and minimal comorbidity. This technical note describes the surgical steps and outcome of the use of surgical bone cement for projection augmentation at this level, including notes on preparation, premolding and fixation. Key words:Orthognathic surgery, maxillary surgery, surgical bone cement, nasomaxillary buttress.

Peripheral odontogenic keratocyst. A Case report.

Odontogenic keratocysts (OKCs) are benign cysts arising from the dental lamina and its remnants. They are most commonly located in the posterior body and the ramus of the mandible. The diagnosis of peripheral OKCs (other than intraosseous) are extremely rare and the current literature is limited. The most common location is the gingiva, but mucosal, epidermal, and even intramuscular sites have also been described. Currently 15 cases have been described. The origin and nature of peripheral OKC still remains controversial. The differential diagnosis includes gingival cyst, mucoceles and epidermoid cyst. Soft tissue OKCs have a lower rate of recurrences; 12,5% vs. 62% in intraosseus OKCs. We report a case of a 58-year-old woman with a peripheral OKC, located in the left masticatory space. We performed a review of the existing literature on peripheral odontogenic keratocysts. Key words:Odontogenic keratocysts (OKCs), peripheral keratocyst, mandibular cyst.

Genetic Profile of Arteriovenous Anomalies of the Head and Neck: Implications in Progression and Therapeutic Approaches.

BACKGROUND: Arteriovenous Malformations (AVMs) are complex vascular anomalies that are usually sporadic and can have a variable clinical course. Treatment of AVMs can lead to severe sequeale and require thorough decision-making. There is a lack of standardized treatment protocols showing a growing need for pharmacological targeted therapies, specially in the most severe cases where surgery may not be feasible. Current knowledge in molecular pathways and genetic diagnosis have shed light in the pathophysiology of AVMs, opening possibilities for personalized treatment strategies. METHODS: We performed a retrospective review of patients with head and neck AVMs treated in our department between 2003 and 2021 and performed a complete physical examination and imaging with ultrasound and angio-CT or MRI. Patients underwent genetic testing on AVMs' tissue samples and/or peripheral blood samples. Patients were grouped according to the genetic variant and a correlation between phenotype and genotype was studied. RESULTS: 22 patients with head and neck AVMs were included. We found eight patients with varians in MAP2K1, four patients with pathogenic variants in KRAS, six patients with pathogenic variants in RASA1, one patient with a pathogenic variant in BRAF, one patient with a pathogenic variant in NF1, another patient with a pathogenic variant in CELSR1 and one patient with pathogenic variants in PIK3CA and GNA14. Patients with MAP2K1 variants were the biggest group, with a moderate clinical course. Patients with KRAS mutations showed the most aggressive clinical course and a high rate of recurrence and osteolysis. Patients with RASA1 variants showed a characteristic phenotype with an ipsilateral capillary malformation in the neck. CONCLUSION: We found a correlation between genotype and phenotype in this group of patients. The genetic diagnosis of AVMs is recommended in order to stablish a personalized treatment strategy. Targeted therapies are currently being investigated with promising results and may be recommended in addition to conventional surgical or embolization procedures, specially in the most complex cases. LEVEL OF EVIDENCE: Level IV.

Buccal cheek mucosa solitary fibrous tumor. Case report.

Solitary fibrous tumor (STF) is a mesenchymal tumor that mainly appears in the pleura. Its presence in the oral cavity is very uncommon, being the buccal mucosa the most frequent location. Imaging cannot distinguish this entity between other types of tumors, being histological and immunohistochemical studies essential for its diagnosis. Immunohistochemical stains typically show positive results for CD34, Bcl2, and CD99. Surgical removal with wide margins is the gold standard treatment, requiring a close follow up due to recurrence risk. We present a case report of a solitary fibrous tumor located in the buccal cheek mucosa and the surgical approach. Key words:Solitary fibrous tumor, Buccal mucosa, Intraoral, Immunohistochemical markers.

A Quantitative and Qualitative Clinical Validation of Soft Tissue Simulation for Orthognathic Surgery Planning.

The purpose of this study was to perform a quantitative and qualitative validation of a soft tissue simulation pipeline for orthognathic surgery planning, necessary for clinical use. Simulation results were retrospectively obtained in 10 patients who underwent orthognathic surgery. Quantitatively, error was measured at 9 anatomical landmarks for each patient and different types of comparative analysis were performed considering two mesh resolutions, clinically accepted error, simulation time and error measured by means of percentage of the whole surface. Qualitatively, evaluation and binary questions were asked to two surgeons, both before and after seeing the actual surgical outcome, and their answers were compared. Finally, the quantitative and qualitative results were compared to check if these two types of validation are correlated. The quantitative results were accurate, with greater errors corresponding to gonions and lower lip. Qualitatively, surgeons answered similarly mostly and their evaluations improved when seeing the actual outcome of the surgery. The quantitative validation was not correlated to the qualitative validation. In this study, quantitative and qualitative validations were performed and compared, and the need to carry out both types of analysis in validation studies of soft tissue simulation software for orthognathic surgery planning was proved.

Virtual Surgical Planning and Customized Subperiosteal Titanium Maxillary Implant (CSTMI) for Three Dimensional Reconstruction and Dental Implants of Maxillary Defects after Oncological Resection: Case Series.

Maxillectomies cause malocclusion, masticatory disorders, swallowing disorders and poor nasolabial projection, with consequent esthetic and functional sequelae. Reconstruction can be achieved with conventional approaches, such as closure of the maxillary defect by microvascular free flap surgery or prosthetic obturation. Four patients with segmental maxillary defects that had been reconstructed with customized subperiosteal titanium maxillary implants (CSTMI) through virtual surgical planning (VSP), STL models and CAD/CAM titanium mesh were included. The smallest maxillary defect was 4.1 cm and the largest defect was 9.6 cm, with an average of 7.1 cm. The reconstructed maxillary vertical dimension ranged from 9.3 mm to 17.4 mm, with a mean of 13.17 mm. The transverse dimension of the maxilla at the crestal level was attempted to be reconstructed based on the pre-excision CT scan, and these measurements ranged from 6.5 mm in the premaxilla area to 14.6 mm at the posterior level. All patients were rehabilitated with a fixed prosthesis on subperiosteal implants with good esthetic and functional results. In conclusion, we believe that customized subperiosteal titanium maxillary implants (CSTMI) are a safe alternative for maxillary defects reconstruction, allowing for simultaneous dental rehabilitation while restoring midface projection. Nonetheless, prospective and randomized trials are required with long-term follow-up, to assess its long-term performance and safety.

New Technologies for Personalized Medicine in Head and Neck Oncologic and Reconstructive Surgery.

The search for standardized protocols has been a constant concern in Head and Neck Reconstructive Surgery [...].

Maxillary reconstruction with subperiosteal implants in a cancer patient: A one-year follow-up.

Introduction: To describe a clinical case on cancer patient with ablative tumor surgery, from treatment planning, surgical resection and subsequent implantological rehabilitation. Case Report: A 61-year-old male, diagnosed with a squamous cell carcinoma in the maxilla, requires the removal of the lesion and corresponding oral rehabilitation. However, two surgeries were necessary to rehabilitate the upper jaw. A custom-made prosthesis was fabricated. It was made from sintered titanium using machined subperiosteal implants with a universal external connection. Finally, a milled cobalt- chrome structure was produced and a feldspar ceramic covering was subsequently applied. Conclusions: Rehabilitation using subperiosteal implants may be an alternative tool for complex surgery involving large atrophies or cancer patients who have undergone highly ablative surgery. Key words:Oral rehabilitation, oral cancer, subperiostal implants.

Prognosis Value of Immunoregulatory Molecules in Oral Cancer Microenvironment: An Immunohistochemical Study.

OBJECTIVES: To evaluate the relationship of the immune-checkpoint PD-1/PD-L1 with the clinical evolution of OSCC; to assess survival in OSCC based on the characteristics of TME and histologic risk score; to evaluate the clinical and histopathological relationship of OSCC with immunological TME. MATERIAL AND METHODS: A retrospective study was carried out on 65 samples from patients with OSCC on the floor of the mouth or tongue. Clinicopathological variables and the expression of the biomarkers PD-1, PD-L1, FoxP3, CD4, CD8, CSF1R, and p16 were recorded. The relationship of the clinical and histological variables with the expression of the biomarkers and survival was studied. RESULTS: The univariate and multivariate analysis indicated that positive PD-1 expression was an independent protective factor for survival (overall, disease-free, disease-specific survival) and that high PD-L1 also improved survival. Poorly differentiated histological grades and metastasis were associated with a worse prognosis. CONCLUSIONS: PD-1 is a protective survival factor that is maintained independently of PD-L1 expression. High values of PD-L1 expression also improve survival. Higher expression of PD-1 is observed in smaller tumors, and higher expression of PD-L1 is more likely in women. No relationship between the tumor microenvironment and histologic risk score was found to influence the survival patterns studied in the OSCC. There is no evidence of a relationship between the histopathological features and the studied markers, although the positive PD-1 and PD-L1 cases have a lower risk of a high WPOI score, and positive PD-1 expression was associated with a lower DOI.