Mylohyoid Muscle: Current Understanding for Clinical Management-Part I: Anatomy and Embryology.

The mylohyoid is one of the suprahyoid muscles, along with the geniohyoid, digastric, and stylohyoid muscles. It lies between the anterior belly of the digastric muscle inferiorly and the geniohyoid superiorly. In Part I, the anatomy and embryology of the mylohyoid muscle will be reviewed in preparation for the clinical discussion in Part II.

Mylohyoid Muscle: Current Understanding for Clinical Management Part II: Clinical Anatomy, Radiology, and Surgical/Clinical Relevance.

The mylohyoid is one of the suprahyoid muscles along with the geniohyoid, digastric, and stylohyoid muscles that lies between the anterior belly of the digastric muscle inferiorly and the geniohyoid superiorly. In Part II, the radiology and clinical/surgical importance of the mylohyoid muscle will be discussed.

Preservation of the Nerve to the Mylohyoid Muscle During Submental Island Flaps: An Anatomic Feasibility Study for Facial Nerve Reanimation Procedures.

The submental island flap is an axial pattern pedicle flap widely used in head and neck surgery because of its ease and success. Indications of the submental island flap range from reconstruction for the malignant tumor resection to loss of temporal bone and facial skin due to trauma. Whereas, intraoperative facial nerve injury is not uncommon. We verified whether it was possible to localize the nerve to the mylohyoid muscle and reanimate the facial nerve during submental island flap procedures by preserving the mylohyoid muscle using human fresh cadaveric specimens. Six cadaveric heads were dissected and the position of the nerve to the mylohyoid muscle identified to the mylohyoid triangle documented. We identified the nerve to the mylohyoid muscle on all sides within the mylohyoid triangle and were able to separate the nerve from the submental island flap completely. Our results suggest that facial nerve reanimation using the nerve to the mylohyoid muscle can be used while reconstructing with a submental island flap in cases of intraoperative facial nerve injury.

What is a superior labial frenulum? An anatomical and histological study.

Anatomy of the superior labial frenulum (SLF), at first glance, seems to be well established. However, existing studies on the SLF lack description of the incisivus labii superioris (ILS), which cannot be ignored when discussing the SLF. We believe that thorough understanding of the SLF necessitates the anatomical knowledge of the ILS. This study aimed to elucidate the anatomical relationship between the orbicularis oris (OO), ILS, and SLF. A total of 20 formalin fixed human cadaveric specimens were used for gross anatomical and/or histological observation. For histological observation, all specimens were stained with Masson-trichrome. The SLF was a mucosal fold between the gingival mucosa and alveolar mucosa with connective tissue deep to it. The connective tissue attached to the alveolar bone in the junction between the right and left ILS. Skeletal muscle fibers other than orbicularis oris was found in one specimen, which were considered the ILS. During a frenulectomy, removal of the connective tissue bundle is required to prevent recurrence of the high SLF insertion.

Ligneous periodontitis exacerbated by Behçet's disease in a patient with plasminogen deficiency and a stop-gained variant PLG c.1468C > T: a case report.

BACKGROUND: Plasminogen serves as the precursor to plasmin, an essential element in the fibrinolytic process, and is synthesized primarily in the liver. Plasminogen activation occurs through the action of plasminogen activator, converting it into plasmin. This conversion greatly enhances the fibrinolytic system within tissues and blood vessels, facilitating the dissolution of fibrin clots. Consequently, congenital deficiency of plasminogen results in impaired fibrin degradation. Patients with plasminogen deficiency typically exhibit fibrin deposits in various mucosal sites throughout the body, including the oral cavity, eyes, vagina, and digestive organs. Behcet's disease is a chronic recurrent systemic inflammatory disease with four main symptoms: aphthous ulcers of the oral mucosa, vulvar ulcers, skin symptoms, and eye symptoms, and has been reported worldwide. This disease is highly prevalent around the Silk Road from the Mediterranean to East Asia. We report a case of periodontitis in a patient with these two rare diseases that worsened quickly, leading to alveolar bone destruction. Genetic testing revealed a novel variant characterized by a stop-gain mutation, which may be a previously unidentified etiologic gene associated with decreased plasminogen activity. CASE PRESENTATION: This case report depicts a patient diagnosed with ligneous gingivitis during childhood, originating from plasminogen deficiency and progressing to periodontitis. Genetic testing revealed a suspected association with the PLG c.1468C > T (p.Arg490*) stop-gain mutation. The patient's periodontal condition remained stable with brief intervals of supportive periodontal therapy. However, the emergence of Behçet's disease induced acute systemic inflammation, necessitating hospitalization and treatment with steroids. During hospitalization, the dental approach focused on maintaining oral hygiene and alleviating contact-related pain. The patient's overall health improved with inpatient care and the periodontal tissues deteriorated. CONCLUSIONS: Collaborative efforts between medical and dental professionals are paramount in comprehensively evaluating and treating patients with intricate complications from rare diseases. Furthermore, the PLG c.1468C > T (p.Arg490*) stop-gain mutation could contribute to the association between plasminogen deficiency and related conditions.

Angiogenin and plexin-B2 axis promotes glioblastoma progression by enhancing invasion, vascular association, proliferation and survival.

BACKGROUND: Angiogenin is a multifunctional secreted ribonuclease that is upregulated in human cancers and downregulated or mutationally inactivated in neurodegenerative diseases. A role for angiogenin in glioblastoma was inferred from the inverse correlation of angiogenin expression with patient survival but had not been experimentally investigated. METHODS: Angiogenin knockout mice were generated and the effect of angiogenin deficiency on glioblastoma progression was examined. Angiogenin and plexin-B2 genes were knocked down in glioblastoma cells and the changes in cell proliferation, invasion and vascular association were examined. Monoclonal antibodies of angiogenin and small molecules were used to assess the therapeutic activity of the angiogenin-plexin-B2 pathway in both genetic and xenograft animal models. RESULTS: Deletion of Ang1 gene prolonged survival of PDGF-induced glioblastoma in mice in the Ink4a/Arf-/-:Pten-/- background, accompanied by decreased invasion, vascular association and proliferation. Angiogenin upregulated MMP9 and CD24 leading to enhanced invasion and vascular association. Inhibition of angiogenin or plexin-B2, either by shRNA, monoclonal antibody or small molecule inhibitor, decreases sphere formation of patient-derived glioma stem cells, reduces glioblastoma proliferation and invasion and inhibits glioblastoma growth in both genetic and xenograft animal models. CONCLUSIONS: Angiogenin and its receptor, plexin-B2, are a pair of novel regulators that mediate invasion, vascular association and proliferation of glioblastoma cells. Inhibitors of the angiogenin-plexin-B2 axis have therapeutic potential against glioblastoma.

Reproduction of the Antitumor Effect of Cisplatin and Cetuximab Using a Three-dimensional Spheroid Model in Oral Cancer.

Background/Aim: Cancer research has been conducted using cultured cells as part of drug discovery testing, but conventional two-dimensional culture methods are unable to reflect the complex tumor microenvironment. On the other hand, three-dimensional cultures have recently been attracting attention as in vitro models that more closely resemble the in vivo physiological environment. The purpose of this study was to establish a 3D culture method for oral cancer and to verify its practicality. Materials and Methods: Three-dimensional cultures were performed using several oral cancer cell lines. Western blotting was used for protein expression analysis of the collected cell masses (spheroids), and H-E staining was used for structural observation. The cultures were exposed to cisplatin and cetuximab and the morphological changes of spheroids over time and the expression changes of target proteins were compared. Results: Each cell line formed spheroidal cell aggregates and showed enhancement of cell adhesion molecules over time. H-E staining showed tumor tissue-like structures specific to each cell line. Cisplatin showed concentration-dependent antitumor effects due to loss of cell adhesion and spheroid disruption in each cell line, while cetuximab exhibited antitumor effects that correlated with EGFR expression in each cell line. Conclusion: Spheroids made from oral cancer cell lines appeared to have tumor-like characteristics that may reflect their clinical significance. In the future, it may become possible to produce tumor spheroids from tissue samples of oral cancer patients, and then apply them to drug screening and to develop individualized diagnostic and treatment methods.

Clinical Anatomy Research Association in Oral and Maxillofacial Surgery.

ABSTRACT: Sufficient knowledge of anatomy is critical for oral and maxillofacial surgeons to provide the best treatment to their patients. The authors have recently established the "Clinical Anatomy Research Association in Oral and Maxillofacial Surgery." There is no doubt as to the benefits of collaboration between oral and maxillofacial surgeons/radiologists and anatomists. In this article, we share what was accomplished at the first annual online conference and discuss our mission for the future.

A narrative review and clinical anatomy of herpes zoster infection following COVID-19 vaccination.

INTRODUCTION: In this review, cases of herpes zoster (HZ) infection following receipt of COVID-19 vaccines will be analyzed. We also present two cases of oral HZ following the COVID-19 vaccine and discuss this clinical anatomy. MATERIALS AND METHODS: A database search using PubMed was conducted in August 2021 and 20 articles were found to be eligible for review. Patient data and vaccine information were analyzed. In addition, two cases of oral HZ infection following the receipt of COVID-19 vaccines are presented. RESULTS: A total of 399 cases were identified. The affected dermatomes mimicked the regular distribution of HZ. For the dermatomes of the face, the various reports used different ways to describe the areas involved; CNV, CNV1, CNV2, CNV3, lower jaw, forehead, and under the eyebrow (CNV, 2 cases; CNV1, 4 cases; CNV2, 3 cases; and CNV3, 3 cases). Some patients who had a history of varicella zoster virus vaccination had HZ following the COVID-19 vaccination. Two patients with oral HZ following vaccination were found to have involvement of the greater palatine nerve. CONCLUSIONS: Vaccine-related HZ cases have been reported worldwide. Although many studies with a larger number of cases are ongoing, detailed information can be obtained from case reviews as reported herein.

What are the retromolar and bifid/trifid mandibular canals as seen on cone-beam computed tomography? Revisiting classic gross anatomy of the inferior alveolar nerve and correcting terminology.

PURPOSE: Since cone-beam computed tomography was developed, a number of radiological studies on the bifid mandibular canals (BMCs) and trifid mandibular canals (TMCs) have been reported. However, many of the suggested subtypes of the BMC described in the literature seem to be normal branches of the inferior alveolar nerve. This might be due to a lack of revisiting classic anatomical studies in the field of radiology. Therefore, such studies are revisited here. METHODS: A database search using PubMed and Google Scholar was conducted on BMC and TMC. Eighty-nine articles underwent full-text assessment. The reported three classifications of BMC and the six modified classifications were reviewed and compared to the intramandibular inferior alveolar nerve branches. RESULTS: Some subtypes of BMC and TMC simply represent normal inferior alveolar nerve branches, i.e., retromolar branch, molar branch (alveolar branch/dental branch), large mental branch, or communicating branch. Others such as Naitoh's type III BMC and forward canal might be a true BMC. CONCLUSION: We found that the bifid mandibular canal is an additional intramandibular canal running parallel to the mandibular canal with/without confluence with the main canal through comparison of classifications of BMC/TMC between the radiology and anatomy fields.

Expression of SARS-CoV-2 entry factors in human oral tissue.

The distribution of cells expressing SARS-CoV-2 entry factor angiotensin-converting enzyme 2 (ACE2) and transmembrane serine protease 2 (TMPRSS2) in human oral tissues were tested. The investigation was conducted with normal flesh tissue and paraffin-embedded specimens. The ACE2 and TMPRSS2 expression was detected with all subjects in the normal mucosa of the keratinized stratified squamous epithelia of the tongue and non-keratinized stratified squamous epithelia of the lip and cheek. It was found that ACE2 is expressed in the cytoplasm and on the cell membrane mainly in the stratum granulosum of the epithelia while the TMPRSS2 is strongly expressed on the cell membrane mainly in the stratum granulosum and stratum spinosum, but not in the stratum basale. Antibodies' reactions for ACE2 and TMPRSS2 were not observed in the nuclei or keratin layer. The expression of ACE2 and TMPRSS2 in the oral epithelia appears to be general, and the expression was also observed in the mucous and serous acini of the labial glands. The SARS-CoV-2 may transiently attach to the oral mucosa and the minor salivary glands which are present under all of the oral mucosa. The oral cavity can be considered an important organ for SARS-CoV-2 attachment and may provide a preventive medical avenue to guard against COVID-19 by preventing saliva from scattering.

Mandibular canal vs. inferior alveolar canal: Evidence-based terminology analysis.

INTRODUCTION: The mandibular canal, as it was formerly named in Terminologia Anatomica (TA), has also been called the inferior alveolar (nerve) canal in many scientific publications. This study was conducted to investigate how these terms have been understood in different regions and different areas of expertise and to discuss the appropriate future application of the term "mandibular canal." METHODS: A literature search was conducted using PubMed, and articles using different terms for this structure were classified into two groups, inferior alveolar canal/inferior alveolar nerve canal (IAC/IANC) and the mandibular canal (MC). The 50 most recent articles in each group were included. Publication year, journal title, country of the first author, and affiliation of all authors were recorded in both groups for all 100 articles. RESULTS: There was a significant difference between the IAC/IANC and MC groups in the numbers of anatomy journals, other journals, and anatomy affiliations. Turkey published most frequently with a total of 15 articles, followed by Iran with 10 articles, and China/India/United States with seven each. When the six countries of the first author that had three or more publications in each group were compared, only Turkey appeared in both groups; otherwise, different countries were in the two groups. CONCLUSIONS: Based on the results of this analysis, and considering that the tentative new term "inferior alveolar foramen" is used in the latest TA, we suggest that the mandibular canal should be renamed the "inferior alveolar canal."

Mandibular canal versus inferior alveolar canal: A Delphi study.

The general principles of anatomical terminology indicate that the "mandibular canal" should be named the "inferior alveolar canal" as it accommodates the inferior alveolar neurovascular bundles. Therefore, we performed a Delphi study to evaluate the current understanding and use of the terminology in different geographical regions and areas of expertise and to determine the appropriate terminology for this bony canal. A Delphi panel was formed and questions sent and answered via email about: field of expertise (anatomy, oral surgery/oral and maxillofacial (OMF) surgery, oral radiology/OMF radiology, plastic surgery, ENT surgery, or dentistry with the exception of oral/OMF surgery and oral/OMF radiology), years of experience in the field of expertise, country currently working in, "what is the name of the bony canal that contains the inferior alveolar neurovascular bundle," and "what should the structure above be called, in general?" A total of 52 participants responded to the questionnaire. Half or more of the experts in anatomy, oral/OMF surgery, and ENT/plastic surgery considered "mandibular canal" to be the most appropriate name for this bony canal. In contrast, more than half of all experts in oral/OMF radiology and dentistry, that is, most fields of dentistry, considered "either mandibular canal or inferior alveolar canal" to be the appropriate name. The results of the Delphi study and general principles suggest that an alternative term for the "mandibular canal" should be "inferior alveolar canal."

The potential for facial artery injury during mandibular third molar extraction. An anatomical study using contrast-enhanced computed tomography.

The purpose of this study was to evaluate the risk of injury to the facial (FA) and related arteries during mandibular third molar (MTM) extraction using contrast-enhanced computed tomography (CE-CT). CE-CT images of the MTM region were retrospectively reviewed. The area of the MTM was equally divided into three zones in the coronal images from mesial to distal, that is, zone 1, zone 2, and zone 3. The FA, submental artery (SMA), and sublingual artery (SLA) were identified. The distance from the mandible to FA, SMA, and SLA and the diameter of the FA, SMA, and SLA was measured in three zones, respectively. The thickness of the facial soft tissues and width of the mandible were measured at their maximum. The mean distance from the FA to the buccal cortical bone in zone 1, zone 2 and zone 3 was 2.24 mm, 2.39 mm and 1.67 mm, respectively. The SMA and SLA were found to be distal to the mandible. The mean diameter of the FA was 1.26 mm in males and 1.04 mm in females, respectively (p < 0.0001). The distance between the FA and buccal cortical bone of the mandible, and the patients' weight showed moderate correlation in zones 1 and 2. Based on our findings, the FA can be damaged if the surgical invasion reaches the facial soft tissues during MTM surgery. The patients' weight might be a good predictor for FA injury when CE-CT is not available.

Comprehensive review of lower third molar management: A guide for improved informed consent.

Lower third molar removal is the most commonly performed dental surgical procedure. Nevertheless, it is difficult to ensure that all the informed consent forms given to patients are based on the best evidence as many newer publications could change the conclusions of previous research. Therefore, the goal of this review article is to cover existing meta-analyses, randomized control trials, and related articles in order to collect data for improved and more current informed consent.

A rare anatomical variation of the submental artery.

The submental artery usually runs anteriorly on the inferior surface of the mylohyoid muscle, giving branches to that muscle and to the anterior belly of the digastric muscle, finally supplying the submental skin. Branches of it often perforate the mylohyoid muscle and enter the sublingual space. During a routine anatomy dissection, we encountered a case in which the main trunk of the submental artery perforated the mylohyoid muscle, where the sublingual artery usually runs. No branches coursed anteriorly to supply the submental skin. To our knowledge, this submental artery variation has not been reported in the English literature. Any surgical procedure in the submandibular area, such as the axial pattern submental local flap, requires knowledge of such arterial variations.

Duplication of the external jugular vein: a language barrier of database search in classic anatomical studies.

OBJECTIVE: Many anatomical variations of the superficial veins of the head and neck have been reported throughout the literature. Accordingly, anatomists and surgeons must have a comprehensive understanding of these variations to avoid confusion. Duplication of the external jugular vein (EJV) is occasionally observed during routine cadaveric dissections; however, this variation seems to be reported less often than actual experience suggests. Therefore, to gain a better understanding of its anatomical and clinical implications, an analysis of the available data should be available. Thus, in this article, we reviewed the current available literature for studies reporting duplication of the EJV. METHODS: We conducted a search using PubMed and Google Scholar with the following keywords: "duplication of the external jugular vein," "division of the external jugular vein," and "fenestration of the external jugular vein," "double external jugular vein," and "doubled external jugular vein." As a case illustration, we also describe a case of a duplicated EJV found during a right neck dissection of a female cadaver. RESULTS: Twenty sides across sixteen different studies were analyzed including the present case. All studies were published between 2009 and 2020. EJV division patterns were classified as either duplication, fenestration, fenestration followed by duplication, or double fenestrations. CONCLUSIONS: We have reviewed the literature regarding cases documenting duplication/fenestration of the EJV. As it is often difficult to find recent studies that report on classic anatomical variations, therefore, revisiting older articles and textbooks is necessary for achieving a "comprehensive" review, especially across different languages.

High-mobility group box 1 induces bone destruction associated with advanced oral squamous cancer via RAGE and TLR4.

Bone destruction of maxillary and mandibular bone by invasive oral squamous cell cancer (OSCC) raises various problems in the management of patients, resulting in poor outcomes and survival. However, the mechanism behind bone destruction by OSCC remains unclear. High-mobility group box 1 (HMGB1), a highly conserved ubiquitous nuclear non-histone DNA-binding protein, has been demonstrated to be secreted by aggressive cancers and regulate osteoclastogenesis, a central player during bone destruction. We therefore reasoned that HMGB1 secreted by OSCCs contributes to bone destruction. Our results showed that HMGB1 is produced by human cell lines of OSCC and promotes osteoclastogenesis via up-regulation of the expression of receptor activator of nuclear factor kappa-Β ligand in osteoblasts and osteocytes, and consequently osteoclastic bone destruction in mice. Further, we found that these actions of HMGB1 are mediated via the receptor for advanced glycation end products and toll-like receptors. These findings suggest that HMGB1 of OSCC and its down-stream signal pathways are potential targets for the treatment of bone destruction associated with advanced OSCC.

Evaluation of overall and disease-free survival in patients with free flaps for oral cancer resection.

PURPOSE: Sarcopenia is characterized by depletion of skeletal muscle mass (SMM) and can cause increased postoperative complication in free flap procedure. One of the most important considerations while deciding the indication of the procedure is patients' survival. This study aimed to verify the relationship between low SMM and survival in patients who undergo oral cancer resection using free flap. METHODS: SMM was evaluated using the skeletal muscle index (SMI cm2 /m2 ), which was defined using cross-sectional areas of skeletal muscles on computed tomography at the level of the third lumbar vertebrae normalized for height. Overall, 111 patients who underwent primary oral cancer resection and free flaps were included. Multivariate Cox regression analyses were used to evaluate the prognostic factors for survival. RESULTS: A total of 25 patients (22.5%) were diagnosed with low SMM. The mean SMI was 42.2 cm2 /m2 . Multivariable analyses showed that increased age (hazard ratio [HR]; 4.98, p = .004), infiltrative growth pattern INF-c (HR; 3.83, p = .037), and low SMM (HR; 2.59, p = .034) were significant negative prognostic factors for overall survival. Increased age (HR; 3.18, p = .005), extra-nodal extension (HR; 3.30, p = .001), and low SMM (HR; 2.42, p = .017) were significant negative prognostic factors for disease-free survival. CONCLUSIONS: Low SMM is a significant negative prognostic factor for overall and disease-free survival in oral cancer patients undergoing free flap. Future prospective studies are warranted to identify effective preoperative exercise and nutrition programs to improve low skeletal muscle and survival rate in patients undergoing free flap procedures.

Microsurgical Anatomy of the Superior Wall of the Mandibular Canal and Surrounding Structures: Suggestion for New Classifications for Dental Implantology.

Our goal was to clarify the relationship between the superior wall of the mandibular canal and the presence of teeth. We also sought to study the structural changes of the mandibular canal after tooth loss. Twenty sides from 10 dry mandibles derived from six males and four females were used for this study. The age of the specimens at the time of death ranged from 57 to 91 years. The mandibles were cut in the midline resulting in 20 hemi-mandibles. The presence of teeth (from the second premolar to the third molar) was recorded for each hemi-mandible. The mandibular canal in the body of the mandible was divided into four areas, that is, Areas 1-4. The superior wall of the mandibular canal and a cancellous bone pattern above the mandibular canal were observed. Next, the mandibular canal was horizontally cut at its center and the superior wall of the mandibular canal observed inferiorly. A total of 75 areas (20 dentulous areas and 55 edentulous areas) were produced. The distal view was classified into three groups, Type I (trabecular pattern), Type II (osteoporotic pattern), and Type III (dense/irregular pattern). The Type I pattern was found in 60.0% (12/20) of the dentulous areas and 32.7% of the edentulous areas. While the Type II pattern was found in 15.0% (23/55) of the dentulous areas and 41.8% of the edentulous areas. The inferior view was classified into four groups depending on the surface of the superior wall of the mandibular canal, that is, Class I (trabecular pattern), Class II (osteoporotic pattern), Class III (dense/irregular pattern), and Class IV (smooth).The Class I pattern was seen most frequently (55.0%) in dentulous areas and the Class IV pattern (45.5%) most frequently in edentulous areas. Based on these results, we conclude that the superior wall of the mandibular canal could change following tooth loss. Clin. Anat. 33:223-231, 2020. © 2019 Wiley Periodicals, Inc.