Tophaceous pseudogout of the TMJ

We report a case of tophaceous pseudogout (i.e., calcium pyrophosphate dihydrate [CPPD] crystal deposition disease) in the temporomandibular joint (TMJ) that extended to the base of the skull. A 38-year-old man was referred to our hospital with mild pain in the right chin and tip of the tongue. Panoramic radiography showed a large calcified mass around the right TMJ. Computer tomography (CT) imaging revealed a large, granular, calcified mass surrounding the right condylar head and extending to the base of the skull. The mass was clinically and radiographically suspected to be a pseudogout lesion. A biopsy specimen was collected under general anesthesia to confirm the diagnosis. The mass histologically contained the deposition of numerous rod-shaped and rhomboid crystals, which suggested tophaceous pseudogout. The deposition was identified as CPPD crystal deposition, based on analysis by X-ray diffraction (XRD) and Fourier transform infrared spectroscopy (FT-IR). These two crystallography methods were useful in confirming the diagnosis of CPPD crystal deposition disease in the TMJ

Effectiveness of Newly Developed Water-Equivalent Mouthpiece during External Beam Radiotherapy for Oral Cancer

The objective of this study was to research the effectiveness of newly developed water-equivalent mouthpiece during external beam radiotherapy for oral cancer. In external beam radiotherapy for cancer of the tongue, floor of the mouth, and lower gingiva, it is possible to prescribe a low dose to the upper gingiva and hard palate at an open mouth position using a mouthpiece. However, the inhomogeneity correction resulting from the air cavity and the mobility of the tongue produced by an open mouth position should be considered. Therefore, a new mouthpiece was designed to be fixed by the dental arch, and the air cavity of the mouth can be filled with water-equivalent material. In 30 patients with previously treated oral cancer, the simulated homogeneity index of the calculated water-equivalent mouthpiece by a treatment-planning system was significantly better than that of a conventional mouthpiece (p = 0.004). This new mouthpiece facilitates excellent dose distribution while attaining immobilization of the tongue in patients with oral cancer

Reconstruction of rabbit mandibular bone defects using carbonate apatite honeycomb blocks with an interconnected porous structure

Carbonate apatite (CO3Ap) granules are useful as a bone substitute because they can be remodeled to new natural bone in a manner that conforms to the bone remodeling process. However, reconstructing large bone defects using CO3Ap granules is difficult because of their granular shape. Therefore, we fabricated CO3Ap honeycomb blocks (HCBs) with continuous unidirectional pores. We aimed to elucidate the tissue response and availability of CO3Ap HCBs in the reconstruction of rabbit mandibular bone defects after marginal mandibulectomy. The percentages of the remaining CO3Ap area and calcified bone area (newly formed bone) were estimated from the histological images. CO3Ap area was 49.1 ± 4.9%, 30.3 ± 3.5%, and 25.5 ± 8.8%, whereas newly formed bone area was 3.0 ± 0.6%, 24.3 ± 3.3%, and 34.7 ± 4.8% at 4, 8, and 12 weeks, respectively, after implantation. Thus, CO3Ap HCBs were gradually resorbed and replaced by new bone. The newly formed bone penetrated most of the pores in the CO3Ap HCBs at 12 weeks after implantation. By contrast, the granulation tissue scarcely invaded the CO3Ap HCBs. Some osteoclasts invaded the wall of CO3Ap HCBs, making resorption pits. Furthermore, many osteoblasts were found on the newly formed bone, indicating ongoing bone remodeling. Blood vessels were also formed inside most of the pores in the CO3Ap HCBs. These findings suggest that CO3Ap HCBs have good osteoconductivity and can be used for the reconstruction of large mandibular bone defects

CT imaging of nasopharyngeal and eustachian tube tonsilloliths

Objectives: Nasopharyngeal tonsilloliths (NT) and eustachian tube tonsilloliths (ET) are not as well-known to radiologists as palatine and lingual tonsilloliths. The aim of this investigation was to determine the prevalence and imaging characteristics of NT and ET using CT and panoramic radiographs. Methods: We retrospectively assessed the scans of 2244 patients who underwent consecutive CT and panoramic radiographs of the maxillofacial region. The prevalence, size, number, and position of NT and ET were analysed. Results: NT and ET were detected in 14 (0.6%) and 6 (0.3%) of 2244 patients on CT, respectively, but they were undetectable on panoramic radiographs. No significant difference was found in the prevalence with respect to sex. Although there was also no significant difference in the prevalence among age groups, tonsilloliths were most commonly noted in patients over 40 years old; they appeared as small and round calcified bodies, ranging from 1 to 3 mm in diameter. All NT were found 0 to 3 mm beneath the nasopharyngeal mucosal surface. Conclusions: The prevalence of NT and ET on CT was lower than that of palatine and lingual tonsilloliths. However, since they are encountered more frequently than clinically significant calcifying diseases such as retropharyngeal calcific tendinitis, clinicians should be able to correctly diagnose NT and ET based on their anatomical features

Lingual tonsillolith on PR and CT

Objectives: Lingual tonsilloliths are not as well-known to radiologists than palatine tonsilloliths, although they might be common in clinical practice. The aim of this investigation was to clarify the prevalence and imaging characteristics of lingual tonsilloliths using panoramic radiographs and CT images. Methods: This study included 2244 patients without pathology at the base of tongue who had undergone panoramic radiography and CT of the maxillofacial region. The size, number and position of lingual tonsilloliths relative to the mandible and tongue were evaluated. Results: Lingual tonsilloliths were observed in 33 (1.5%) and 108 (4.8%) of all patients on panoramic radiographs and CT images, respectively. The prevalence was higher in patients aged ≥40 years than in those aged < 40 years (χ2, p < 0.01). They appeared as small, round- or rod-shaped calcified bodies, and they always located closely anterior (1–17 mm) to the anterior border of oropharyngeal airway on panoramic radiographs. Lingual tonsilloliths were superimposed over the surrounding soft tissue inferior to the body of the mandible, posteroinferior to the angle of the mandible and posterior to the mandible in 16 (48.5%), 15 (45.5%) and 1 (3.0%) individual, respectively. A significant correlation was observed between the detectability on panoramic radiographs and size (Spearman’s r = 0.961, p < 0.01) of tonsilloliths, as revealed by CT images. Conclusion: Lingual tonsilloliths commonly appear on CT. They also appear on panoramic radiography and may superimpose the surrounding soft tissue of the mandible. Although lingual tonsilloliths may resemble other pathological calcifications including submandibular sialoliths and lingual osseous cholistoma, they can be differentiated by carefully observing panoramic radiographs. When clinicians detect calcified bodies near the base of tongue, lingual tonsilloliths should be included in the differential diagnoses

The Soluble Factor from Oral Cancer Cell Lines Inhibits Interferon-γ Production by OK-432 via the CD40/CD40 Ligand Pathway

OK-432 is a potent immunotherapy agent for several types of cancer, including oral cancer. We previously reported that OK-432 treatment can induce the production of high levels of IFN-γ from peripheral blood mononuclear cells (PBMCs). Moreover, the IFN-γ production from PBMCs by OK-432 is impaired by conditioned media (CM) from oral cancer cells. To determine the inhibitory mechanism of IFN-γ production by CM, the genes involved in IFN-γ production was retrieved by cDNA microarray analysis. We found that CD40 played a key role in IFN-γ production via IL-12 production. Although the expression levels of CD40 were upregulated by OK-432 treatment in PBMCs, CM inhibited OK-432-induced CD40 expression. These findings suggest that uncertain soluble factor(s) in CM may suppress IFN-γ production via the CD40/CD40L–IL-12 axis in PBMCs.(1) Background: OK-432 is a penicillin-killed, lyophilized formulation of a low-toxicity strain (Su) of Streptococcus pyogenes (Group A). It is a potent immunotherapy agent for several types of cancer, including oral cancer. We previously showed that (i) OK-432 treatment induces a high amount of IFN-γ production from peripheral blood mononuclear cells (PBMCs), and (ii) conditioned medium (CM) from oral cancer cells suppresses both the IFN-γ production and cytotoxic activity of PBMCs driven by OK-432. The aim of this study was to determine the inhibitory mechanism of OK-432-induced IFN-γ production from PBMCs by CM. (2) Methods: We performed cDNA microarray analysis, quantitative RT-PCR, and ELISA to reveal the inhibitory mechanism of CM. (3) Results: We found that CD40 plays a key role in IFN-γ production via IL-12 production. Although OK-432 treatment upregulated the expression levels of the IL-12p40, p35, and CD40 genes, CM from oral cancer cells downregulate these genes. The amount of IFN-γ production by OK-432 treatment was decreased by an anti-CD40 neutralizing antibody. (4) Conclusions: Our study suggests that uncertain soluble factor(s) produced from oral cancer cells may inhibit IFN-γ production from PBMCs via suppressing the CD40/CD40L–IL-12 axis

マイクロファイバーを用いた多孔質炭酸アパタイト顆粒の開発とウサギ頭蓋骨における組織学的評価

Carbonate apatite (CO3Ap) granules are known to show good osteoconductivity and replaced to new bone. On the other hand, it is well known that a porous structure allows bone tissue to penetrate its pores, and the optimal pore size for bone ingrowth is dependent on the composition and structure of the scaffold material. Therefore, the aim of this study was to fabricate various porous CO3Ap granules through a two-step dissolution-precipitation reaction using CaSO4 as a precursor and 30-, 50-, 120-, and 205-μm diameter microfibers as porogen and to find the optimal pore size of CO3Ap. Porous CO3Ap granules were successfully fabricated with pore size 8.2-18.7% smaller than the size of the original fiber porogen. Two weeks after the reconstruction of rabbit calvarial bone defects using porous CO3Ap granules, the largest amount of mature bone was seen to be formed inside the pores of CO3Ap (120) [porous CO3Ap granules made using 120-μm microfiber] followed by CO3Ap (50) and CO3Ap (30). At 4 and 8 weeks, no statistically significant difference was observed based on the pore size, even though largest amount of mature bone was formed in case of CO3Ap (120). It is concluded, therefore, that the optimal pore size of the CO3Ap is that of CO3Ap (120), which is 85 μm

Current status and future development of carbonate apatite as a bone substitute

A main inorganic component of human bone is not hydroxyapatite but carbonate apatite (CQ3Ap). Hydroxyapatite is not resorbed in the body but C03Ap can be resorbed and replaced with bone. We have succeeded in fabricating low crystalline CQ3Ap without sintering by dissolution-precipitation reaction using calcium hydroxide as a precursor. C03Ap showed excellent biocompatibility and faster bone formation compared to other bone substitutes (anorganic bovine bone and hydroxyapatite) in rabbit femur and dog mandible. Clinical study on effectiveness and safety of C03Ap granules in sinus floor augmentation was successfully concluded in 2016. CQ3Ap granules were approved by Japanese government in 2017, and marketed in 2018 as Cytrans® Granules. This comprehensive review explains the clinical cases of sinus lift and alveolar ridge augmentation of Cytrans® and its recommended clinical usage. Furthermore, we have succeeded in developing porous C03Ap and showed it was useful for reconstruction of mandibular bone defect in rabbit model and also aim to use it as a scaffold for bone regenerative medicine.ヒトの骨の無機主成分はハイドロキシアパタイトではなく，炭酸アパタイト (CO3Ap) である．ハイドロキシアパタイトは体内で吸収されないが，CO3Apは吸収されて骨と置換する．われわれは水酸化カルシウムを前駆物質として，焼結操作を用いずに溶解析出反応によって低結晶性の炭酸アパタイトを人工合成することに成功した．炭酸アパタイ卜顆粒は，ウサギ大腿骨とイヌ顎骨における実験で，他の骨補填材よりも骨が速く形成すること，優れた生体親和性を示すことを明らかにした．2016年に上顎洞底挙上術での臨床治験を成功裏に終え，2017年に炭酸アパタイト顆粒は薬事承認され，2018年からサイトランス® グラニュールとして市販された本総説では，サイトランス® による上顎洞底挙上症例と歯槽堤造成術症例を紹介すると共に，その臨床的推奨使用法を説明した．さらに，著者らは多孔質の炭酸アパタイトの作製に成功し，炭酸アパタイト多孔体がウサギの下顎骨欠損モデルにおいて骨再建に有用であることを示した．現在，炭酸アパタイト多孔体の骨再生医療用スキャフォールドヘの応用を目指している

Staged Sinus Floor Elevation Using Novel Low-Crystalline Carbonate Apatite Granules : Prospective Results after 3-Year Functional Loading

The aim of this study was to evaluate clinical outcomes of staged sinus floor elevation (SFE) using novel low-crystalline carbonate apatite (CO3Ap) granules. Patients who needed SFE for implant placement were recruited into this clinical trial. A staged procedure (lateral window technique using CO3Ap granules, followed by implant placement after 7 ± 2 months) was employed in 13 patients. Bone-height increase and insertion torque values (ITVs) were assessed along with histological evaluation. The survival and success rates of 3-year functioning implants were also evaluated. Mean of bone-height increase after SFE using CO3Ap granules was 7.2 ± 2.5 mm and this increase allowed implant placement in all cases (17 implants). Mean of ITV was 25.1 ± 13.2 Ncm and primary stability was achieved successfully in all cases. Histological analyses revealed mature new bone formation (36.8 ± 17.3%) and residual CO3Ap granules (16.2 ± 10.1%) in the compartment after SFE. The survival and success rates after 3-year functional loading were 100% and no complications were found. These results clearly indicate the clinical usefulness of CO3Ap granules for SFE