Chordoma Genetic Aberrations and Targeted Therapies Panorama: A Systematic Literature Review.

Background: Chordomas pose a challenge in treatment due to their local invasiveness, high recurrence, and potential lethality. Despite being slow-growing and rarely metastasizing, these tumors often resist conventional chemotherapies (CTs) and radiotherapies (RTs), making surgical resection a crucial intervention. However, achieving radical resection for chordomas is seldom possible, presenting therapeutic challenges. The accurate diagnosis of these tumors is vital for their distinct prognoses, yet differentiation is hindered by overlapping radiological and histopathological features. Fortunately, recent molecular and genetic studies, including extracranial location analysis, offer valuable insights for precise diagnosis. This literature review delves into the genetic aberrations and molecular biology of chordomas, aiming to provide an overview of more successful therapeutic strategies. Methods: A systematic search was conducted across major medical databases (PubMed, Embase, and Cochrane Library) up to 28 January 2023. The search strategy utilized relevant Medical Subject Heading (MeSH) terms and keywords related to "chordomas", "molecular biology", "gene aberrations", and "target therapies". The studies included in this review consist of preclinical cell studies, case reports, case series, randomized controlled trials, non-randomized controlled trials, and cohort studies reporting on genetic and biological aberrations in chordomas. Results: Of the initial 297 articles identified, 40 articles were included in the article. Two tables highlighted clinical studies and ongoing clinical trials, encompassing 18 and 22 studies, respectively. The clinical studies involved 185 patients diagnosed with chordomas. The tumor sites were predominantly sacral (n = 8, 44.4%), followed by clivus (n = 7, 38.9%) and lumbar spine (n = 3, 16.7%). Primary treatments preceding targeted therapies included surgery (n = 10, 55.6%), RT (n = 9, 50.0%), and systemic treatments (n = 7, 38.9%). Various agents targeting specific molecular pathways were analyzed in the studies, such as imatinib (a tyrosine kinase inhibitor), erlotinib, and bevacizumab, which target EGFR/VEGFR. Common adverse events included fatigue (47.1%), skin reactions (32.4%), hypertension (23.5%), diarrhea (17.6%), and thyroid abnormalities (5.9%). Clinical outcomes were systematically assessed based on progression-free survival (PFS), overall survival (OS), and tumor response evaluated using RECIST or CHOI criteria. Notably, stable disease (SD) occurred in 58.1% of cases, and partial responses (PRs) were observed in 28.2% of patients, while 13.7% experienced disease progression (PD) despite targeted therapy. Among the 22 clinical trials included in the analysis, Phase II trials were the most prevalent (40.9%), followed by I-II trials (31.8%) and Phase I trials (27.3%). PD-1 inhibitors were the most frequently utilized, appearing in 50% of the trials, followed by PD-L1 inhibitors (36.4%), CTLA-4 inhibitors (22.7%), and mTOR inhibitors (13.6%). Conclusions: This systematic review provides an extensive overview of the state of targeted therapy for chordomas, highlighting their potential to stabilize the illness and enhance clinical outcomes.

Impact of Sarcopenia on Survival of Patients With Malignant Salivary Glands Tumors.

OBJECTIVE: Malignant salivary glands tumors (MSGTs) are a quite rare and heterogeneous group of tumors. Management of these lesions remains controversial and challenging. Thus, finding new prognostic factors that can help to guide the decision-making process, appears to be paramount. The aim of this study was to evaluate the prognostic performance of preoperative sarcopenia to stratify MSGTs patients at high risk of disease progression. STUDY DESIGN: Retrospective study. SETTING: A single-institution analysis (Maxillo-facial Surgery Unit, University of Naples Federico II). METHODS: The study consists of a retrospective analysis of 74 patients surgically treated for MSGTs. For all patients, the skeletal muscle index (SMI) was calculated and sarcopenia was defined as SMI < 41 in females and <43 in males. The correlation between sarcopenia and tumor variables was analyzed. The prognostic performance of sarcopenia was evaluated through survival Kaplan-Meier curves. RESULTS: Sarcopenia resulted statistically related to age (P < .001), tumor size (P < .001), lymph node metastases (P < .001), and American Joint Committee on Cancer tumor, node, metastasis stage (P < .001). Kaplan-Meier survival curves show that 47.3% of sarcopenic patients died before their final follow-up. CONCLUSION: Data obtained from our study seem to confirm the correlation between sarcopenia and other high-risk features. The early detection of sarcopenia in patients with negative prognostic factors could be used to implement the support therapeutic strategies aimed at restore the clinical conditions of the patients. Sarcopenia may be routinely investigated before surgery to suggest the implementation of precautionary therapeutic strategies to improve the standard treatment response, reducing possible complications.

The Use of Artificial Intelligence Algorithms in the Prognosis and Detection of Lymph Node Involvement in Head and Neck Cancer and Possible Impact in the Development of Personalized Therapeutic Strategy: A Systematic Review.

Given the increasingly important role that the use of artificial intelligence algorithms is taking on in the medical field today (especially in oncology), the purpose of this systematic review is to analyze the main reports on such algorithms applied for the prognostic evaluation of patients with head and neck malignancies. The objective of this paper is to examine the currently available literature in the field of artificial intelligence applied to head and neck oncology, particularly in the prognostic evaluation of the patient with this kind of tumor, by means of a systematic review. The paper exposes an overview of the applications of artificial intelligence in deriving prognostic information related to the prediction of survival and recurrence and how these data may have a potential impact on the choice of therapeutic strategy, making it increasingly personalized. This systematic review was written following the PRISMA 2020 guidelines.

Computerized Three-Dimensional Analysis: A Novel Method to Assess the Effect of Open-Door Laminoplasty.

INTRODUCTION: The three-dimensional elaboration of morphological data derived from computed tomography (CT) and magnetic resonance imaging (MRI) scans generates virtual anatomical reconstructions. Here, we propose a novel protocol to analyze the postoperative results of open-door laminoplasty to evaluate differences in the volume of the spinal canal. The protocol uses geometric models in patients with cervical degenerative myelopathy before versus after cervical laminoplasty. MATERIALS AND METHODS: Mimics and 3-Matic software (Materialise, Leuven, BE) programs were used to segment anatomical structures and create polygon meshes of spines. Patients with cervical spondylotic myelopathy were enrolled. The models obtained before and after laminoplasty were superimposed by using a global registration function. The magnitude of divergence was quantified by using the root-mean-square error (RMSE). RESULTS: Using this novel protocol, we were able to map the differences in the volume of the spinal canal before laminoplasty and after laminoplasty and to quantify its magnitude and calculate the volumes. DISCUSSION AND CONCLUSIONS: The development of a procedure to measure the space within the cervical bone walls using geometric parameters represents a new, powerful method to verify the results obtained by cervical laminoplasty. Further research horizons may include the routine use of virtual models in surgical planning for this procedure.

Exploring Deep Cervical Compartments in Head and Neck Surgical Oncology through Augmented Reality Vision: A Proof of Concept.

BACKGROUND: Virtual surgical planning allows surgeons to meticulously define surgical procedures by creating a digital replica of patients' anatomy. This enables precise preoperative assessment, facilitating the selection of optimal surgical approaches and the customization of treatment plans. In neck surgery, virtual planning has been significantly underreported compared to craniofacial surgery, due to a multitude of factors, including the predominance of soft tissues, the unavailability of intraoperative navigation and the complexity of segmenting such areas. Augmented reality represents the most innovative approach to translate virtual planning for real patients, as it merges the digital world with the surgical field in real time. Surgeons can access patient-specific data directly within their field of view, through dedicated visors. In head and neck surgical oncology, augmented reality systems overlay critical anatomical information onto the surgeon's visual field. This aids in locating and preserving vital structures, such as nerves and blood vessels, during complex procedures. In this paper, the authors examine a series of patients undergoing complex neck surgical oncology procedures with prior virtual surgical planning analysis. For each patient, the surgical plan was imported in Hololens headset to allow for intraoperative augmented reality visualization. The authors discuss the results of this preliminary investigation, tracing the conceptual framework for an increasing AR implementation in complex head and neck surgical oncology procedures.

The Role of Temporomandibular Joint Arthroscopy for Diagnosis and Surgical Management of Synovial Chondromatosis.

OBJECTIVE: We report the experience of our maxillo-facial surgery unit into the diagnostic and the therapeutic role of arthroscopy of temporomandibular joint (TMJ) synovial chondromatosis (SC). MATERIALS AND METHODS: A series of sixteen patients with an imaging, arthroscopical, and histological diagnosis of SC treated with arthroscopy was selected. The surgeries were conducted in the Department of Maxillo-facial surgery, Academic hospital of Udine, from January 2016 to December 2022. Medical history, clinical examination, imaging, arthroscopical, and histological characteristics were recorded and then reviewed and discussed. RESULTS: Clinical improvement, both in pain and in maximum incisal opening (MIO), were noticed in whole patients. Histologically, according to Milgram's classification, the sample was fairly homogeneous. Arthroscopic treatment was successful in 87.5% of the patients. Only two cases of SC relapse were registered and were then submitted to open surgery to perform a total sinovectomy. The data collected were used to develop an SC classification proposal based on clinical, radiological (magnetic resonance imaging), arthroscopical, and histopathological characteristics. CONCLUSIONS: TMJ arthroscopy must be considered the first line of treatment for SC, leaving open surgery to relapses cases and those cases with extraarticular extension. A univocal classification is essential to best stage and prognostically characterise this pathology.

Reply to Mattei et al. Jacob Disease, Osteochondroma of the Coronoid Process, Coronoid Process Hyperplasia or Langenbeck Disease: The Big Jumble. Comment on "Raccampo et al. Jacob's Disease: Case Series, Extensive Literature Review and Classification Proposal. J. Clin. Med. 2023, 12, 938".

As authors of the text, we can only thank Mattei et al. [...].

Stem Cells in Facial Regenerative Surgery: Current Clinical Applications. A Multidisciplinary, Systematic Review.

BACKGROUND: Facial reconstruction represents one of the main challenges for surgeons. Stem cells (SC) represent the most studied solution for tissue regeneration. This approach appears particularly promising in combination with bioengineered scaffolds and 3D bioprinting. The purpose of this systematic review is to define the main domains of current application of SC therapy within contemporary clinical workflows, evaluate indications and limitations, report current knowledge in this innovative field of research, and define the landscape of evidence for such approaches. METHODS: A systematic review was performed on the pertinent literature regarding stem cell-based cell therapies currently available in the reconstruction of the face. The review used the main databases for scientific literature based on the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. RESULTS: A total of 15 papers were selected after an independent search was performed. The two major domains for current application of stem cells in clinical practice were bone and skin categories. CONCLUSIONS: Cell therapy in the field of facial reconstruction represents a promising approach. The evidence regarding the current clinical use, however, seems to show this option to be limited. Bioengineering advances and the parallel development of 3D bioprinting technology can potentially enhance the role of stem cells in the future.

Optimizing efficiency in the creation of patient-specific plates through field-driven generative design in maxillofacial surgery.

Field driven design is a novel approach that allows to define through equations geometrical entities known as implicit bodies. This technology does not rely upon conventional geometry subunits, such as polygons or edges, rather it represents spatial shapes through mathematical functions within a geometrical field. The advantages in terms of computational speed and automation are conspicuous, and well acknowledged in engineering, especially for lattice structures. Moreover, field-driven design amplifies the possibilities for generative design, facilitating the creation of shapes generated by the software on the basis of user-defined constraints. Given such potential, this paper suggests the possibility to use the software nTopology, which is currently the only software for field-driven generative design, in the context of patient-specific implant creation for maxillofacial surgery. Clinical scenarios of applicability, including trauma and orthognathic surgery, are discussed, as well as the integration of this new technology with current workflows of virtual surgical planning. This paper represents the first application of field-driven design in maxillofacial surgery and, although its results are very preliminary as it is limited in considering only the distance field elaborated from specific points of reconstructed anatomy, it introduces the importance of this new technology for the future of personalized implant design in surgery.

Outcomes of a Pharmacological Protocol with Pentoxifylline and Tocopherol for the Management of Medication-Related Osteonecrosis of the Jaws (MRONJ): A Randomized Study on 202 Osteoporosis Patients.

Medication-related osteonecrosis of the jaws (MRONJ) is a challenging situation in clinics. Previous studies have shown that pentoxifylline combined with tocopherol proved to be beneficial in patients with osteoradionecrosis, due to their antioxidant and antifibrotic properties. The aim of this randomized study was to evaluate the effect of pentoxifylline and tocopherol in patients that had developed MRONJ after tooth extractions. The study population consisted of 202 Stage I MRONJ female patients with an average age of 66.4 ± 8.3 years, who were divided into two groups. The test group (n = 108) received a pharmacological protocol with pentoxifylline and tocopherol (2 months pre-operatively and 6 months post-operatively). The control group (n = 94) had sequestrectomy operations without any pharmacological preparation. The main outcomes were clinical healing of the mucosa after 1 month, and clinical and radiographic healing of the bone lesion at 6 months. In the test group all patients had mucosal healing and there was only one relapse within 6 months. In the control group, in 17% of the patients the mucosa did not heal, 71% of the patients relapsed within two months, and 7% developed infectious complications (such as abscess or phlegmon). After 6 months, the control group patients with persisting issues were prescribed pentoxifylline and tocopherol, as in the test group. At a subsequent follow-up, all those patients healed completely. Patients were monitored for a period of 7.8 ± 0.3 years, during which no relapse or additional problems were reported. As a conclusion, pentoxifylline and tocopherol protocol seems to be beneficial in the management of MRONJ patients.

Extended Complex Temporomandibular Joint Reconstructions Exploiting Virtual Surgical Planning, Navigation Assistance, and Custom-Made Prosthesis: A Comprehensive Protocol and Workflow.

BACKGROUND: Alloplastic temporomandibular joint (TMJ) replacement is a well-established procedure in maxillo-facial surgery. However, the surgical management of large excision in this area requires complex reconstruction beyond the standard TMJ prosthesis. OBJECTIVE: This study aims to describe the design and the consequential application of a protocol which involves the use of computer-assisted surgery tools to best face complex TMJ reconstruction (TMJR). Preoperative accurate study of every single case and intraoperative check of the surgical act are nowadays essential to perform such delicate surgical procedures. MATERIALS AND METHODS: The study is a retrospective and single institution case series. The various processes of the management and planning of extended TMJ reconstruction (eTMJR) are extensively described, from the preoperative clinical evaluation, imaging acquisition protocols and virtual surgical planning (VSP), focusing also on the intraoperative transfer of VSP using navigation and surgical guides. RESULTS: We included nine patients with different pathologies which were candidates for eTMJR. Overall, the application of our protocol and workflow permitted the reduction of complications and pain, and the improvement of the maximum interincisal opening (MIO) of the patients, restoring patients' masticatory function and esthetics. CONCLUSIONS: The eTMJR should be considered as a safe and reliable surgical management modality in selected patients with large temporomandibular joint and skull base (TMJ-SB) lesions. An accurate preoperative protocol and workflow is essential to perform such insidious and complex reconstruction. However, more extensive studies on this type of device have to be conducted in order to validate its real usefulness and indications.

Double osseous flaps for simultaneous midfacial and mandible reconstruction: Automation in surgical complexity within an entirely computerized workflow.

Introduction: Broad maxillofacial surgical resections involving both the midface and the mandible represent a challenge in terms of reconstruction. Although several papers have explored the possibility of simultaneously using two microsurgical flaps, reports on the implementation of a dual osseous flap strategy are limited, and mainly addressed to static anatomical reconstruction, regardless of functional implications. In particular, there is a lack in the literature of a unifying protocol which illustrates how technology including virtual planning, statistical shape modeling, virtual occlusion, 3D-printing and patient-specific implants can address the functional and accuracy needs required for an optimal reconstruction. Materials and methods: In this paper, the Authors present their preliminary experience in a two-center study, showing how broad maxillofacial defects, requiring a simultaneous reconstruction in both the mandible and the midface, can be successfully reconstructed using the combination of two osseous flaps in an automated sequence in which all steps are anticipately defined in a virtual plan, accounting for the optimal alignment of temporomandibular joint, predicting the final occlusion and defining a mandibular shape according to a statistical shape model. Results: Average RMSE for the iliac bone crest flap was of 3.2 ± 0.36 mm; for the fibula flap, RMSE value was of 2.3 ± 0.65 mm, for patient-specific implants, for mandibular prostheses the average RMSE was 2.46 mm with 0.76 mm standard deviation. Temporomandibular joint function increased when a TMJ prosthesis was placed. Conclusions: Double bone free flap is a valuable resource to reconstruct wide defects that simultaneously involve two thirds of the cranio-maxillo-facial skeleton, but a careful virtual planning study should be always performed before approaching this surgical option.

The shark flap: a modified internal mammary artery perforator flap for composite defects in head and neck reconstruction.

This report describes a multi-vector variant of IMAP flap which allows to reconstruct composite head and neck defects. It was named the 'shark flap' because of its shape: a main body (the regular IMAP) and a superior 'fin' based on a randomic vascular pathway.

Jacob's Disease: Case Series, Extensive Literature Review and Classification Proposal.

Jacob's disease is a rare entity consisting of the formation of a pseudojoint between an abnormal coronoid process of the mandible and the inner surface of the zygomatic bone. First described by Jacob in 1899, its diagnosis and definition have never been entirely univocal. In this paper, we present three emblematic cases and an extensive review of the literature on Jacob's disease. Given the variability observed in the presentation of the disease, we have developed a proposal for the classification, here reported.

Computer guided maxillo-malar piezoelectric osteotomies for midface augmentation.

PURPOSE: Despite maxillo-malar osteotomies having been discarded in the most recent literature, in the setting of orthognathic surgery they provide several advantages for middle third augmentation. This paper reintroduces maxillo-malar osteotomies as an effective method to increase volume of midfacial region in combination with contemporary technology, including piezosurgery, virtual surgical planning, and navigation. MATERIAL AND METHODS: Eighteen patients with midface hypoplasia were included in this study and underwent orthognathic surgery with maxillo-malar osteotomies. All patients underwent the same workflow: virtual design of maxillo-malar osteotomies, surgery with navigation-assisted piezoelectric osteotomies, and computerized morphometric analysis. RESULTS: Simulated maxillo-malar osteotomies were successfully replicated in the operating room, as shown by accuracy evaluation performed using three-dimensional analysis. In long-term follow-up period, no permanent complications were assessed. Superimposition between postoperative and preoperative CBCTs revealed that the soft tissue area influenced by the underlying skeletal movement was comparable for all cases. CONCLUSIONS: Virtual surgical planning, navigation, and piezosurgery are today indispensable tools to perform maxillo-malar osteotomies safely and accurately. We suggest incorporating such osteotomies in the surgeon's armamentarium for patients with severe midfacial hypoplasia as they offer an integrated solution to restore functionality and aesthetics.

Contemporary management of complex craniofacial trauma: virtual planning, navigation and the novel thermoformed cage splints in a strategic, sequential, computer-guided protocol.

INTRODUCTION: It was the aim of the study to assess if computerized simulation and the use of thermoformed cage splints are useful to plan cases of complex craniofacial trauma. MATERIALS AND METHODS: patients with fractures in any of the thirds of the craniofacial skeleton and occlusion impairment. Virtual surgical planning with digital reduction of fractures, navigated planning, thermoformed cage splints were used in all cases. Surgical outcomes were evaluated by computing the surface deviation and occlusograms between planned and postoperative models. RESULTS: 13 patients were enrolled in this study. Accuracy of bone repositioning was evaluated compared with the surgical planning. For the mandible, mean Root Mean Square Error (RMSE) was of 1.67 with a standard deviation (SD) of ±0.75 mm (p < 0.001); for the maxilla, average RMSE was of 0.88 with SD of ±0.52 mm (p < 0.001); and for midfacial and upper third bone segments, average RMSE was of 0.59 with SD of ±0.47 mm (p < 0.001) CONCLUSIONS: Within the limitations of the study it seems that thermoformed cage splints might be a promising alternative to other well-established approaches for accurate occlusal restoration and can be fully integrated within the digital workflow.

Oral lichen planus arising after BNT162b2 mRNA COVID-19 vaccine: report of 2 cases.

The ongoing COVID-19 pandemic required a firm and prompt effort in the development of an effective vaccine. Reports of adverse reactions are increasing. Lichen planus, as well as its oral variant, is a condition that has previously been reported to be associated with vaccines. This is one of the first reports of oral lichen planus (OLP) arising after any COVID-19 vaccine. Here the authors present 2 cases of OLP that occurred after BNT162b2 mRNA COVID-19 vaccination (Comirnaty, Pfizer, New York, NY, USA; BioNTech, Mainz, Germany).