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Lymph node metastasis, primarily caused by the migration of oral squamous cell carcinoma (OSCC) cells, stands as a crucial prognostic marker. We have previously demonstrated that EP4, a subtype of the prostaglandin E2 (PGE2) receptor, orchestrates OSCC cell migration via Ca2+ signaling. The exact mechanisms by which EP4 influences cell migration through Ca2+ signaling, however, is unclear. Our study aims to clarify how EP4 controls OSCC cell migration through this pathway. We find that activating EP4 with an agonist (ONO-AE1-473) increased intracellular Ca2+ levels and the migration of human oral cancer cells (HSC-3), but not human gingival fibroblasts (HGnF). Further RNA sequencing linked EP4 to calmodulin-like protein 6 (CALML6), whose role remains undefined in OSCC. Through protein-protein interaction network analysis, a strong connection is identified between CALML6 and calcium/calmodulin-dependent protein kinase kinase 2 (CaMKK2), with EP4 activation also boosting mitochondrial function. Overexpressing EP4 in HSC-3 cells increases experimental lung metastasis in mice, whereas inhibiting CaMKK2 with STO-609 markedly lowers these metastases. This positions CaMKK2 as a potential new target for treating OSCC metastasis. Our findings highlight CALML6 as a pivotal regulator in EP4-driven mitochondrial respiration, affecting cell migration and metastasis via the CaMKK2 pathway. EP4 receptor enhances OSCC cell migration through increased Ca2+ signaling, linking to CALML6 and the CaMKK2 pathway. This process promotes mitochondrial function and metastasis, with CaMKK2 emerging as a potential target for OSCC treatment. [ABSTRACT FROM AUTHOR]

Purpose: Retrograde superselective intra-arterial chemoradiotherapy is a radical treatment for advanced oral cancer. The catheter tip is placed into tumor-feeding arteries—the lingual, facial, or maxillary arteries. The diameter of the tumor-feeding arteries newly bifurcated from the external carotid artery is crucial for determining the requirement of a catheter navigation system. This study aimed to measure the diameter and distribution of the tumor-feeding artery according to an objective protocol using 3D computed tomography angiography images reproducibly. Methods: Angiographic data of 20 noncatheterized carotid arteriesof 10 randomly selected patients were analyzed. We followed the external carotid artery to the entrance of each feeding artery to determine the center point where the artery diameter was measured. The diameter of the optimum circle measured at the adopted center point was taken as the diameter of each tumor-feeding artery. Results: The diameters (mean ± standard deviation) were 3.5 ± 0.45, 2.9 ± 0.56, and 3.5 ± 0.56 mm for the maxillary, lingual, and facial arteries, respectively. The diameters of the maxillary and facial arteries were similar (p = 0.877), whereas the diameter of the lingual artery was smaller than that of the maxillary and facial arteries (p < 0.001). Conclusion: The findings of this study will be beneficial in determining the need of a new catheter navigation system and diameter of catheters to be used in the clinical practice. From the viewpoint of measurement automation and reproducibility, 3DCTA vessel measurement taken according to the proposed protocol was considered to be effective. [ABSTRACT FROM AUTHOR]

In intra-arterial catheterization for head and neck cancer, procedure-related complications such as cerebral infarction and artery perforation may occur. However, guidewire perforation into the oral cavity during intra-arterial catheterization for oral cancer is extremely rare. We hereby report guidewire perforation into the oral cavity from the deep lingual artery during retrograde superselective intra-arterial catheterization for a tongue cancer patient. [ABSTRACT FROM AUTHOR]

Angiosarcomas are aggressive soft tissue sarcomas originating from endothelial cells of lymphatic or vascular origin and associated with a poor prognosis. Angiosarcomas spread hematogenously, most frequently to the lungs, followed by the liver and bones, but metastatic oral angiosarcoma is extremely rare. The early manifestation of gingival angiosarcoma is tender, hemorrhagic, exophytic lesion, and gingival angiomas can be misdiagnosed as hyperplastic or reactive lesions such as pyogenic granuloma, hemangioma, vascular epulis, peripheral giant cell granuloma, or odontogenic lesion. We hereby report metastatic angiosarcoma of the mandibular gingiva. [ABSTRACT FROM AUTHOR]

In the oral and maxillofacial region, most mucoceles arising from minor salivary glands are observed on the lower lip, and less frequently occur at various sites such as the ventral tongue, oral floor, hard and soft palate, buccal mucosa, lingual frenum, uvula, and retromolar and peritonsillar regions. Because mucocele arising from ectopic salivary gland tissue is extremely rare, we report a rare case of mucocele arising from ectopic salivary gland tissue between the bilateral geniohyoid muscles. [ABSTRACT FROM AUTHOR]

Variations of the branches of the external carotid artery are well known. Commonly, the occipital artery arises from the posterior aspect of the external carotid artery, but it is rarely reported for the occipital artery to arise from the internal carotid artery or carotid bifurcation. It is important to know the variations of the carotid arteries and their branches before invasive procedures to avoid complications. We hereby report the occipital artery arising from the superior aspect of the carotid bifurcation as a rare anatomical variant. [ABSTRACT FROM AUTHOR]

Objective: The purpose of this study was to reevaluate preoperative computed tomography lymphography (CTL) and enhanced CT images during follow-up to clarify whether SLNs enhanced by CTL were identified accurately before primary surgery with sentinel lymph node biopsy (SLNB) for clinically N0 early oral cancer. Methods: Thirty two early oral cancer patients without cervical lymph node metastasis were enrolled in this study. To clarify whether SLNs enhanced by CTL were identified accurately before primary surgery with SLNB, we reevaluated preoperative CTL and enhanced CT images during follow-up in all patients. Results: SLNs were detected by CTL in 31 of 32 patients (96.9%). During follow-up after primary surgery with SLNB, 4 of 27 patients without SLN metastasis had occult neck metastasis. Of the 4 patients, only 1 patient with cancer of floor of the mouth had overlooking of SLN, and the overlooking rate of SLN was 3.1%. The overlooked small SLN (2.9 × 3.3 × 3.1 mm) was located at contralateral level IB. The CT numbers before, 2, 5, 10 min after iopamidol injection, were 33 HU, 37 HU, 62 HU, 52 HU, respectively. The CT numbers of overlooked SLN 5 and 10 min after the injection was higher than CT images scanned before the iopamidol injection. Conclusions: The enhancement of SLNs in CTL images after iopamidol injection should be compared sufficiently with CT images before iopamidol injection to avoid overlooking of SLNs in N0 early oral cancer. [ABSTRACT FROM AUTHOR]

Superselective intraarterial infusion chemoradiotherapy is a modality of oral cancer therapy in which the artery feeding the tumor is catheterized. 3D information about the carotid artery is required to enable the surgeon to judge whether to advance, retract, or rotate the catheter. For this purpose, we proposed and conducted a model experiment to assess a new method of catheterization that applies a tracking system using registration with a monocular camera using the maxillary arch as the anatomical landmark. In this method, the preoperative 3D computer tomography angiographic image of the carotid artery that the catheter will be passed through is overlaid on the 2D video image. The mean TRE was 0.96 ± 0.36 mm and 0.88 ± 0.31 mm and 1.12 ± 0.46 mm when images were registered with the anterior and posterior teeth as the landmarks, respectively; the difference was not significant (p = 0.21). This tracking system that enables markerless registration simply by taking images of the maxillary anterior teeth with a single camera was convenient and effective for catheterization. In this study, we propose the new application of this tracking system and a novel method of catheterization for superselective intraarterial infusion chemoradiotherapy for oral cancer. [ABSTRACT FROM AUTHOR]

Actinomycotic osteomyelitis is an aggressive and persistent disease capable of invading and destroying bone, and chronic osteomyelitis with proliferative periostitis represents new bone formation with periosteal reaction. We report a rare case of actinomycotic osteomyelitis with proliferative periostitis arising in the mandibular ramus and spontaneous bone regeneration after coronoidectomy. A 14-year-old girl was referred for swelling in the right parotid-masseteric region and severe trismus. Contrast-enhanced CT revealed that heterogenous enhancement of the right masseter muscle, and a reactive bone formation over the lateral cortex of the right mandibular ramus and osteolysis of the condyle were seen in plain CT. MRI showed that the mandibular ramus was a low-signal intensity and the reactive bone on the ramus was signal intensity similar to muscle on T1-weighted images. The lesion was clinically and radiologically diagnosed as chronic osteomyelitis of the mandibular ramus. However, a biopsy was performed intraorally under general anesthesia to rule out a malignant bone tumor, and pathological examination showed fibrous bone and Actinomyces druses. Finally, the lesion was diagnosed as actinomycotic osteomyelitis with proliferative periostitis. She underwent image-guided intraoral removal of impacted right third molar and reactive proliferative bone on the right mandibular ramus under general anesthesia. To improve trismus, coronoidectomy also was performed. After the discharge, AMPC was administrated intraorally for 7.5 months. Postoperative panoramic radiograph and CT showed the right mandibular angle resorption and coronoid process regeneration. There was no recurrence of mandibular osteomyelitis 7 years after surgery. [ABSTRACT FROM AUTHOR]

We report a rare case of schwannoma arising from the sublingual glandular branch of the lingual nerve radiologically masquerading as sublingual gland tumor. A 42-year-old female was referred to our department with a painless swelling in the left submandibular region. Contrast-enhanced computed tomography showed a well-circumscribed, heterogeneous low-density tumor with cystic change in the left sublingual region. Magnetic resonance imaging showed a well-circumscribed, heterogeneous sublingual tumor with low-signal intensity on T1-weighted image and high-signal intensity in T2-weighted image. The lesion was diagnosed radiologically as benign sublingual gland tumor. The patient underwent resection of sublingual gland tumor under general anesthesia. There was no definitive continuity between the tumor and the sublingual gland, and the tumor originated from sublingual glandular branch of the lingual nerve. Pathological examination of the specimen showed schwannoma with highly cellular areas (Antoni A) and hypocellular areas (Antoni B). The postoperative course was uneventful without lingual nerve palsy, and there was no recurrence 4 years after surgery. [ABSTRACT FROM AUTHOR]

Most defects of the mylohyoid muscle are less than 5 mm, but occasionally they may be larger than 2 cm. Therefore, larger herniations may be mistaken both clinically and radiologically for pathologic abnormalities. We report a case of sublingual gland herniation through the defect of the mylohyoid muscle masquerading as submandibular lesion. A 72-year-old female was referred to our department with a painless swelling in the left submandibular region. The elastic hard mass was mobile in the bimanual palpation. The mucosa of the oral floor was normal. Computed tomography showed a well-circumscribed, homogeneous lesion in the left submandibular region. Because the lesion was diagnosed radiologically as a sublingual gland herniation through the defect of the mylohyoid muscle, surgical treatment was not required. Recognition of mylohyoid muscle defect and the typical radiologic appearance of sublingual gland herniation can allow differentiation from other pathologic lesions and prevent unnecessary surgery. [ABSTRACT FROM AUTHOR]

Objective: This study aimed to evaluate swallowing function in advanced tongue cancer patients before and after bilateral neck dissection following superselective intra-arterial chemoradiotherapy (CRT). Methods: A videofluoroscopic swallowing study (VFSS) was used to evaluate swallowing function in 10 patients with advanced tongue cancer before and after bilateral neck dissection. Results: Laryngeal penetration increased in the postoperative VFSS. Temporal analysis comparing two time points revealed that, after surgery, oral transit time increased significantly, but there was no difference in pharyngeal delay time or pharyngeal transit time. Spatial analysis revealed significant decreases after surgery in the maximum distance of upper esophageal sphincter (UES) opening, the maximum distance of hyoid bone movement in both the anterior and superior direction, and the maximum velocity of hyoid bone movement. Conclusions: Laryngeal penetration and aspiration increased as a result of limited hyoid movement and diminished UES opening after bilateral neck dissection following superselective intra-arterial CRT for advanced tongue cancer. [ABSTRACT FROM AUTHOR]

We herein report a case of squamous cell carcinoma of the buccal mucosa with N3 cervical lymph node metastasis in a 63-year-old man. The patient was treated with combination therapy comprising radiotherapy (2 Gy/day, total of 70 Gy), superselective intra-arterial chemotherapy via a superficial temporal artery (docetaxel, total of 70 mg/m2 and cisplatin, total of 175 mg/m2), cetuximab (initial dose of 400 mg/m2 with subsequent weekly doses of 250 mg/m2 intravenously), and four sessions of hyperthermia for cervical lymph node metastases. The patient responded well to the therapy, with a complete response of the primary tumor. Radical neck dissection was performed with reconstructive surgery, including resection of the overlying skin. A pathologic complete response was achieved for the N3 and all other cervical lymph node metastases. The patient showed no evidence of recurrence in the 3 years following treatment. Based on the findings in the present case, the use of retrograde superselective intra-arterial chemoradiotherapy combined with hyperthermia and cetuximab seems to be a promising modality for patients with N3 cervical lymph node metastasis of oral cancer. [ABSTRACT FROM AUTHOR]

Aneurysms of the external carotid artery and its branches are rare, and usually occur in the more superficial branches. Lingual artery (LA) aneurysms are particularly rare, and pseudoaneurysms are associated with trauma, infection, and surgical intervention. Only a few cases of idiopathic LA aneurysms have been reported in the English literature. LA aneurysms can be fatal if they are not recognized and treated. Here, we report a case of bilateral idiopathic aneurysms of the LA identified by three-dimensional (3D) computed tomography angiography (CTA). An 80-year-old man with right tongue cancer (T2N0M0) and left tongue leukoplakia was referred to our department for treatment. He had no previous history of trauma, infection, surgery, or aneurysm in the oral and maxillofacial region. CTA with 3D reconstruction showed right and left aneurysms of the LA, with sizes of 2.4 × 2.3 × 2.1 mm and 3.4 × 3.2 × 2.5 mm, respectively. The patient underwent bilateral partial glossectomy under general anesthesia without intervention for the aneurysms, and the post-operative course was uneventful. A radiological follow-up has been performed regularly for the small unruptured aneurysms. [ABSTRACT FROM AUTHOR]

Squamous cell carcinoma (SCC) of the tongue is the most common oral cancer. Most cases occur on the lateral border of the tongue and only very rarely on the dorsum. We retrospectively investigated the incidence of SCC of the tongue dorsum in our department between April 2006 and March 2015. Of the 368 patients with tongue cancer, only 3 had SCC of the tongue dorsum (incidence, 0.8 %). All patients with advanced cancer of the tongue dorsum underwent superselective intra-arterial chemoradiotherapy for organ preservation. We discuss the present findings in relation to past case reports and series in the English language literature as well as discuss treatments for SCC of the tongue dorsum. [ABSTRACT FROM AUTHOR]

Purpose: Proton beam therapy (PBT), compared with conventional radiotherapy, can deliver high-dose radiation to a tumor, while minimizing doses delivered to surrounding normal tissues. The better dose distribution of PBT may contribute to the improvement in local control rate and reduction in late adverse events. We evaluated therapeutic results and toxicities of PBT combined with selective intra-arterial infusion chemotherapy (PBT-IACT) in patients with stage III-IVB squamous cell carcinoma of the tongue. Materials and methods: After 2 systemic chemotherapy courses and whole-neck irradiation (36 Gy in 20 fractions), we administered concurrent chemoradiotherapy comprising PBT for the primary tumor [28.6-33 Gy(RBE) in 13-15 fractions] and for the metastatic neck lymph node [33-39.6 Gy(RBE) in 15-18 fractions] with weekly retrograde intra-arterial chemotherapy by continuous infusion of cisplatin with sodium thiosulfate. Results: Between February 2009 and September 2012, 33 patients were enrolled. The median follow-up duration was 43 months. The 3-year overall survival, progression-free survival, local control rate, and regional control rate for the neck were 87.0, 74.1, 86.6, and 83.9 %, respectively. Major acute toxicities >grade 3 included mucositis in 26 cases (79 %), neutropenia in 17 cases (51 %), and dermatitis in 11 cases (33 %). Late grade 2 osteoradionecrosis was observed in 1 case (3 %). Conclusions: PBT-IACT for stage III-IVB tongue cancer has an acceptable toxicity profile and showed good treatment results. This protocol should be considered as a treatment option for locally advanced tongue cancer. [ABSTRACT FROM AUTHOR]

Hyperthermia is a promising anti-cancer treatment in which the tissue temperature is increased to 42-45 °C, and which is often used in combination with chemotherapy or radiation therapy. Our aim in the present work was to examine the feasibility of combination therapy for oral cancer with cisplatin and hyperthermia generated with ferucarbotran (Resovist; superparamagnetic iron oxide) in an alternating magnetic field (AMF). First, we established that administration of ferucarbotran at the approved dosage for magnetic resonance imaging provides an iron concentration sufficient to increase the temperature to 42.5 °C upon exposure to AMF. Then, we examined the effect of cisplatin combined with ferucarbotran/AMF-induced hyperthermia on cultured human oral cancer cells (HSC-3 and OSC-19). Cisplatin alone induced apoptosis of cancer cells in a dose-dependent manner, as is well known. However, the combination of cisplatin with ferucarbotran/AMF was significantly more effective than cisplatin alone. This result suggests that it might be possible to reduce the clinically effective dosage of cisplatin by administering it in combination with ferucarbotran/AMF-induced hyperthermia, thereby potentially reducing the incidence of serious cisplatin-related side effects. Further work seems justified to evaluate simultaneous thermo-chemotherapy as a new approach to anticancer therapy. [ABSTRACT FROM AUTHOR]

It is recognized that the branches of the external carotid artery (ECA) can show variation, but the presence of a thyrolinguofacial trunk is extremely rare and always originates from the ECA. We report a case of the thyrolinguofacial trunk arising from the carotid bifurcation (CB) on the left side in a 76-year-old man with advanced tongue cancer, as revealed by three-dimensional computed tomography angiography for vascular mapping of the carotid vessels prior to superselective intra-arterial catheterization. The thyrolinguofacial trunk arose 1.6 mm below the CB from the anterior surface of the left CB. The inner diameter of the thyrolinguofacial trunk at origin was 4.4 mm and the angle between the thyrolinguofacial trunk and CB was 128°. After a 1.7-mm course, the trunk divided into the superior thyroid artery and a linguofacial trunk, the inner diameters of which were 1.5 and 3.4 mm, respectively, at origin. The angle between the two arteries was 88°. After a 9.8-mm course from the bifurcation, the linguofacial trunk divided into the lingual artery and facial artery, the inner diameters of which were 1.8 and 1.9 mm, respectively, at origin. The angle between the two arteries was 61°. It is important to recognize such an anatomic variation of the branches of the ECA prior to superselective intra-arterial catheterization or microsurgical reconstruction for head and neck cancer. [ABSTRACT FROM AUTHOR]

It is well-known that the branches of the external carotid artery (ECA) can show anatomical variation, but it is extremely rare that thyrolingual trunk originates from common carotid artery (CCA). Here we report a case of the thyrolingual trunk arising from the CCA on the right side in a 73-year-old female as revealed by three-dimensional computed tomography angiography for vascular mapping of the carotid vessels before head and neck microsurgical reconstruction. The thyrolingual trunk arose from the anterior surface of the right CCA, with an origin 14.5 mm (difference between the carotid bifurcation and upper border of the origin 12.7 mm) below the carotid bifurcation. The inner diameter of origin of the thyrolingual trunk was 3.5 mm, and the angle between the thyrolingual trunk and the CCA was 130°. After a 10.2-mm course, the thyrolingual trunk divided into the superior thyroid artery (STA) and lingual artery (LA). The inner diameters of the origins of the STA and LA were 1.7 and 1.9 mm, respectively, and the angle between the branches was 94°. It is important to recognize this anatomic variation of the branches of the ECA before the microsurgical reconstruction or super-selective intra-arterial chemotherapy for head and neck cancer. [ABSTRACT FROM AUTHOR]

Background: The branching patterns of the external carotid artery vary among individuals, and consideration of the proximity of nerves is important during catheter insertion in superselective intra-arterial infusion via the superficial temporal artery. We aimed to evaluate the anatomy of the external carotid artery and its surrounding nerves for safe and accurate administration of superselective intra-arterial chemotherapy via the superficial temporal artery. Methods: We analyzed the external carotid artery and its branches morphometrically in 28 Japanese cadavers (56 sides). Results: Vascular tortuosity in the preauricular region of the catheter insertion site was observed in 42.9% of the sides; the main trunk of the external carotid artery was excessively tortuous in 25.0% of the sides, primarily in the preparotid region. Faciolingual and superior thyrolingual trunks were observed in 28.6 and 1.8% of the sides, respectively. The superior thyroid, lingual, facial, occipital, and maxillary arteries branched from the external carotid artery above the carotid bifurcation in 41.1% of the sides. The mean distance between the insertion site and maxillary artery was 39.5 mm, indicating the extent of catheter insertion. The auriculotemporal nerve was observed near the superficial temporal artery in the preauricular region in 44.6% of the sides; however, the clearly identifiable nerves in the exposed area were difficult to avoid. Conclusion: Because of the branching variations observed in individuals and sides, preoperative angiography is extremely important for avoiding complications. [ABSTRACT FROM AUTHOR]

Sebaceous carcinoma is the rarest type of oral malignancies. We report a case of primary sebaceous carcinoma of the tongue. Systemic imaging studies revealed that the patient had a T2N2cM0 (International Union Against Cancer guidelines) primary lingual tumor. Histopathological examination revealed neoplastic sebocytic and basaloid cells, and Sudan III staining and electron microscopy revealed intracytoplasmic lipid droplets. The neoplastic cells stained positive for adipophilin; epithelial membrane antigen; epithelial antigen; and cytokeratins 7, 8, and 15, but negative for cytokeratins 5/6, 18, 19, and 20; the androgen receptor; and carcinoembryonic antigen. Superselective intraarterial chemotherapy was administered via the superficial temporal artery concurrent with daily radiotherapy. Multiple biopsies confirmed a complete response of the primary lesion. The patient then underwent neck dissection followed by pathological examination, which revealed lymph nodes metastases. After postoperative radiotherapy to the neck, distant metastases were identified in the mediastinal lymph nodes and the lung. The patient died 17 months after completing the initial course of chemoradiotherapy. Our case demonstrates that superselective intraarterial chemotherapy combined with concurrent radiotherapy can be effective in treating the primary lesion of patients with a sebaceous carcinoma of the tongue. However, an effective strategy to eradicate metastases has yet to be established. [ABSTRACT FROM AUTHOR]

We describe secure surgical method for catheter placement using ultrasonic scalpel via the occipital artery to achieve retrograde superselective intra-arterial chemotherapy for advanced oral cancer, as alternative to approach via the superficial temporal artery. [ABSTRACT FROM AUTHOR]

We describe use of a variable oral device for efficient measurement of oral lesions. [ABSTRACT FROM AUTHOR]

Background: The objectives of this retrospective study were to evaluate the usefulness of computed tomography lymphography (CTL) and to clarify the optimal timing of CTL in sentinel lymph node (SLN) mapping of clinically N0 early oral cancer., Methods: Twenty patients with clinically N0 early oral cancer underwent CTL with a 128 multi-detector row CT scanner to detect SLN the day before resection of primary tumor and SLN biopsy with indocyanine green (ICG) fluorescence guidance. CT scanning was performed in the first 10 patients at 2, 5, and 10 min after submucosal injection of iopamidol and in the remaining 10 patients at 2, 3.5, 5, and 10 min after the injection of contrast medium. We evaluated the SLN detection rate at each scan timing and the number and location of SLNs. We evaluated whether CTL-enhanced SLNs could be identified intraoperatively as ICG fluorescent lymph nodes., Results: SLNs were detected by CTL in 19 of the 20 patients (95.0%), and the mean number of SLNs was 2 (range, 1-4). All SLNs were located on the ipsilateral side; 35 of 37 SLNs were located at level I and II, and 2 SLNs were lingual lymph nodes. All SLNs could be detected 2 min and 3.5-5 min after contrast medium injection, and CTL-enhanced SLNs could be identified intraoperatively as fluorescent lymph nodes., Conclusions: CTL could facilitate the detection of SLNs in early oral cancer, and the optimal timing of CT scanning was at 2 and 5 min after injection of contrast medium.