Epithelioid sarcoma (ES) is a very rare malignant tumor with few effective treatments other than surgical resection. In this study, the efficacy of BNCT for ES was examined using human ES-derived VA-ES-BJ cell-bearing nude mice. Only tumors in the BNCT group injected with p-borono-L-phenylalanine-fructose complex and irradiated with neutrons were destroyed. This study suggests the potential of BNCT as a new option for the treatment of human ES.

Melanotic neuroectodermal tumor of infancy (MNTI) is a rare pigmented tumor of neural crest origin, commonly occurring in the head and neck region. Despite being a benign tumor, MNTI is characterized by high cell proliferation activity and can sometimes enlarge while destroying surrounding tissues. Herein, we report a case of MNTI in a 3-month-old girl who exhibited rapid tumor growth following a biopsy; we have included a discussion of the case and review of the relevant literature. Upon initial examination, a 20-mm (long axis) elastic hard mass was observed in the left upper alveolar region extending to the oral vestibule. The mucosal surface was smooth, and submucosal blue-gray tissue was visible. A biopsy was performed under general anesthesia, but the lesion rapidly enlarged into a grayish-white, irregular mass within a few days. Subsequently, a diagnosis of MNTI was made, and 14 days after the biopsy, the patient underwent a left maxillary tumor resection and surrounding bone removal under general anesthesia. Following the surgery, a pediatric prosthesis was timely fabricated by the Department of Pediatric Dentistry, resulting in both morphological and functional recovery. Treatment options should carefully consider factors related to quality of life to address potential facial deformities that may become more prominent with the subsequent growth of the child.

Myxofibrosarcoma, a rare malignant tumor, predominantly affects the extremities of the elderly. Because of its invasive nature amputation is sometimes required, resulting in serious deterioration of quality of life. Therefore, cell lines established from amputated surgical specimens of myxofibrosarcoma in the upper limbs of elderly patients were used to create a myxofibrosarcoma-bearing animal model and to investigate the therapeutic effect of BNCT thereon. The results demonstrated selective destruction of tumor cells, suggesting the anti-tumor efficacy of BNCT on myxofibrosarcoma.

Cystadenocarcinoma is an extremely rare lesion with a low incidence rate of 0.18% of all salivary gland tumors in the oral and maxillofacial region. Here, we report two cases of cystadenocarcinoma in the lip. Case 1 was of a 79-year-old woman who presented with discomfort in the right upper lip. On examination, a 16 x 10 mm mass was observed on her right upper lip. The superficial mucosa was smooth but with an irregular margin. The mass was clinically suspected to be a malignant tumor, and tumor resection was performed. Case 2 was of a 51-year-old man who presented with a 20 x 20 mm mass on the left lower lip. The mass was hard, and adhesion to the skin was suspected. On T2-enhanced magnetic resonance imaging, high signal intensity and internal non-uniform features were noted. Before the operation, fine-needle aspiration cytology was performed, and atypical cells were observed; therefore, resection was performed assuming a malignant tumor. The surgeries were performed 3 years ago, and no recurrence or lymph node metastasis has been observed in either case to date.

To theoretically understand the previously reported dry particulate coating process using a mild vibration field with a bead media, a mathematical analysis model of the dry coating system was developed. In this coating process, an ordered mixture with coarse host particles (drug-loaded ion exchange resin, diameter approximately 100 mu m) and fine guest particles (acrylic polymer particle, primary particle size of approximately 100 nm) is formed using a vibrating a vessel. Second, the guest particles on the host particulate surface are firmly fixed using the collision of coated particles zirconia beads (diameter 1.5 mm). Our model assumes that the unfixed guest particles are fixed by particle-to-particle collisions (C-c) provided by the apparatus, thereby increasing the coating ratio. C-c was estimated using the discrete element method and some experimental results. The model includes parameters such as the number of C-c, host particles and unfixed guest particles. The coating time simulated by the established model equation in this study fits well with the experimental results of the dry process. It depends on the ratio of the number of collisions contributing to the increased coating ratio to the number of unfixed guest particles on the surface of host particles. (C) 2022 The Society of Powder Technology Japan. Published by Elsevier B.V. and The Society of Powder Technology Japan. All rights reserved.

Synovial sarcoma is a rare tumor requiring new treatment methods. A 46-year-old woman with primary monophasic synovial sarcoma in the left thigh involving the sciatic nerve, declining surgery because of potential dysfunction of the affected limbs, received two courses of BNCT. The tumor thus reduced was completely resected with no subsequent recurrence. The patient is now able to walk unassisted, and no local recurrence has been observed, demonstrating the applicability of BNCT as adjuvant therapy for synovial sarcoma. Further study and analysis with more experience accumulation are needed to confirm the real impact of BNCT efficacy for its application to synovial sarcoma.

Here we describe a rare case of mandibular cancer involving almost the entire attached gingiva in a 71-year-old man. First, marginal resection of the entire mandible was performed, followed by one-stage reconstruction comprising application of a split-thickness skin graft onto the wound. This resulted in good alveolar ridge morphology, allowing for a mandibular prosthesis to be installed soon postoperatively. Histopathological analysis revealed a well-differentiated squamous cell carcinoma extending throughout most of the resected attached gingiva, but no malignant features in the stumps. Furthermore, no infiltration into the jawbone was observed, and no vascular or lymphatic invasion or perineural infiltration. At 3 years postoperatively, the patient's clinical course has remained uneventful, with no recurrence or problems arising in the remaining mandible. The patient is also able to eat regularly using the mandibular prosthesis provided.

For binder-free dry particulate coating to prepare controlled-release micron-sized particles, we designed nanocomposite coating agents with the intention to form a core-shell structure composed of two types of acrylic polymers with different glass transition temperatures (Tg) and evaluated their coating performance. A series of nanocomposite acrylic latexes synthesized by emulsion polymerization was freeze-dried after salting-out to create the powder form. An ion-exchange resin loaded with diclofenac sodium (DS, a model drug) (IER-DS) with a median diameter of approximately 100 µm was used as the core particle. Dry coating of the IER-DS with nanocomposite coating agents was carried out using a laboratory-made coating apparatus assisted with mild-intensity vibration and zirconia bead impaction. The coated particles were cured by heating at a temperature 20 °C higher than the Tg for 12 h to complete the film-forming process. It was found that the highest coating efficiency (more than 70%) and a remarkably prolonged release period of the drug (the time required for 50% release reached approximately 12 h) could be achieved when nanocomposite coating agents with a soft polymeric core (Tg = 30 °C) and a hard polymeric shell (Tg = 80 °C) were applied. In contrast, nanocomposite coating agents with a combination of a hard polymeric core and a soft polymeric shell resulted in lower coating efficiency. These results demonstrate that nanocomposite polymeric coating agents composed of a soft core and a hard shell are effective for the production of drug-loaded microparticles with a prolonged release function by a binder-free dry-coating process.

Most patients with cleft lip and palate receive proper and consistent treatment; however, in some cases, patients are not satisfied with the treatment outcomes regardless of improvements in jaw function and morphology after orthognathic surgery, which is considered as one of the final phases of the treatment. Therefore, to improve patients’ satisfaction with the treatment, their psychological conditions were surveyed before and after orthognathic surgery. Thirty-four patients with cleft lip and palate completed a psychological test （MINI-124） before orthognathic surgery, and the findings revealed that the majority showed high scores in each scale designed for measuring lie, hysteria, and association problem. Furthermore, the scores of hypochondriasis, hysteria, and bodily symptoms were significantly higher in patients with cleft lip and palate than in 70 jaw deformity patients without any congenital anomalies measured before surgery. In addition, a questionnaire survey on the orthognathic surgery performed at more than 6 months after the surgery, showed that patients with cleft lip and palate were mostly satisfied with their surgeries. However, some of them showed a slightly lower degree of satisfaction and a strong obsession with their lip scars and nasal deformities.

中性子捕捉療法（NCT）では、ホウ素（10B）を用いる場合に10Bを腫瘍組織内に選択的かつ高濃度でさらには均一に分布させることにより、腫瘍細胞内または近傍で選択的にα線を発生させ、治療を効率的に行うことが可能となる。小型加速器開発の成功と病院施設への導入により、今後のがん治療法としてのNCTの可能性は広がり、適応拡大も図られるものと考えられる。本稿では、NCTの現況を概説し、さらに筆者らの軟部肉腫へのNCTの適応拡大を目指した前臨床研究を基に、臨床で用いられる10B化合物であるp-borono-L-phenylalanine（L-BPA）による腫瘍細胞内10B取り込み、体内動態、抗腫瘍効果の評価と、新たな中性子捕捉用薬剤としてのガドリニウム製剤の可能性について紹介する。

Clear cell sarcoma of tendons and aponeuroses (CCS) is a rare, malignant tumor arising in lower extremities with no effective treatment other than wide surgical resection. Here described is a case of primary CCS in the peroneal tendon of the right foot of a 54-year-old woman enrolled to undergo BNCT. The tumor mass post-BNCT disappeared totally without damage to other normal tissue, demonstrating, for the first time, the potential efficacy of BNCT in complete local control of CCS.

Neutron capture therapy using 157Gd (Gd-NCT) is currently under development as a cancer radiotherapy. Melanoma cells were treated with gadolinium-loaded chitosan nanoparticles (Gd-nanoCPs) for Gd-NCT. Smaller Gd-nanoCPs had higher Gd content and better cellular association of Gd and thereby made the tumor-killing effect more efficient in comparison to larger Gd-nanoCPs. This indicates that Gd-nanoCP size reduction is an efficient method for improving the cellular affinity of Gd-nanoCPs and for enhancing the tumor-killing effect of Gd-NCT.

Bone metastasis has a major impact on the quality of life that general therapy cannot control. We established a bone metastasis model with a human breast cancer cell line and investigated the therapeutic effect of boron neutron capture therapy (BNCT). BNCT suppressed tumor growth in cases of intramedullary small tumors without damaging normal tissues, providing preliminary evidence that it is a potentially new therapeutic option for controlling tumor growth from bone metastasis. Further research is warranted for its clinical application.

We employed a new dry coating process with mild-intensity vibration to prepare a 100-µm-sized microparticle capable of prolonged release of a drug. To accomplish this without using a binder, a series of laboratory-made acrylic latexes with different glass transition temperatures (Tg) ranging from 30 °C to 80 °C were employed as coating agents, and the effects of Tg and powdering method of the coating agents on coating performance were investigated. The laboratory-made acrylic latexes were powdered by spray-drying (SD) or freeze-drying (FD). Diclofenac sodium (DS)-loaded ion-exchange-resin with particle size ∼100 µm was used as a core particle. The process utilized vibrations with amplitude of 0.5 mm and frequency of 90 Hz to form an ordered mixture composed of the core particles with the loosely-layered coating agents. Subsequently, the coating agents were fixed mechanically on the core particle by impaction of zirconia beads. The coating agents powdered by FD showed higher coating efficiencies than those powdered by SD, irrespective of the differences in Tg values. Among the coating agents powdered by FD, the particles coated at Tg = 60 °C exhibited the most prolonged drug-release, although the coating efficiency was not the highest. In our proposed process utilizing mild vibration, we demonstrated that adjusting the Tg of the coating agents is crucial to the formation of binder-free multiple coating layers for prolonged drug release.

"Composite particles" can be defined idiomatically as the particles fabricated with two or more components. The composite particles in a narrow sense are referred to as the particles that are fabricated to have a well-designed, established structure and more specifically, sophisticated functions. The composite particles can be conventionally classified into two types: monolithic structure and layered-structure. The major purpose of forming composite particles may be to compensate some disadvantages of one component with another component(s) and/or to give new or specific functionalities to the resulting particles through the composite formation of the components. Most of the currently available processes for particle production can be potentially applicable for the production of composite particles. Fluidized beds equipped with a spraying system are often used for this process, especially in the pharmaceutical field. Selection of materials is crucial in design and preparation of composite particles since the possible combinations of the components are almost infinite.

The method to improve the properties of dry granules was investigated by introducing pre-coating process with an active pharmaceutical ingredient (API) and a submicron-sized binder prior to conventional roller compaction. Hydroxypropylcellulose (HPC) and acetaminophen (APAP) were used as models of a binder and a low-compactible API, respectively. The submicron-sized HPC (HPC-subMP) was obtained by a lab-scale spray dryer. The APAP particles were pre-coated with 5–10% of the HPC-subMP by a high shear mixer, formed into granules using a lab-scale roller compactor, mixed with other excipients and then compressed to make them tablets containing 50% APAP. The tablets prepared with the HPC-subMP showed a high tensile strength without significant retardation of the disintegration time in comparison to those with a raw HPC particle, indicating that the use of API particles pre-coated with submicron-sized binder particles in roller compaction was effective to prepare granules suitable for tableting without any fundamental changes of materials and manufacturing processes.

Orthognathic surgery has recently become a significant element in the field of oral surgery. Owing to factors such as advancements in surgical techniques and the development and improvement of surgical equipment, orthognathic surgery is becoming increasingly safe ; however, intraoperative blood loss can still pose a difficult problem in some cases. Therefore, we examined whether tranexamic acid (TXA) can reduce intraoperative blood loss during orthognathic surgery. The initial group of subjects in this prospective, randomized controlled trial comprised 377 individuals who underwent orthognathic surgery at the Department of Stomatology, Tokyo Metropolitan Ohtsuka Hospital between April 2006 and March 2017. After excluding patients with congenital anomalies (e.g., cleft lip and palate), combined surgery patients, patients with intraoperative complications, reoperation patients, and patients with incomplete intraoperative records, 270 patients were ultimately included in the analysis. Of these 270 patients, 171 underwent sagittal split ramus osteotomy (SSRO) and 99 underwent Le Fort I osteotomy and SSRO (LFI+ SSRO). The subjects were randomly assigned to a TXA group or a control group. The optimal dose of TXA was set at 20mg/kg. Patients who underwent SSRO were classified into two groups : a TXA20 group, which received TXA 20mg/kg immediately prior to surgery, and a control group. Patients who underwent LF I+ SSRO were classified into three groups : a TXA20 group, which received a single administration of TXA 20mg/ kg immediately prior to maxillary osteotomy; a TXA10+10 group, which received two separate administrations of TXA 10mg/kg immediately prior to maxillary and mandibular osteotomy ; and a control group. Groups were compared in terms of age, male/female ratio, body mass index, body surface area, surgical time, total intraoperative blood loss, and intraoperative blood loss per hour of surgery. Of the patients who underwent SSRO, there was no significant difference in any variable between the two groups. Of the patients who underwent LF I+SSRO, there was no significant difference in total intraoperative blood loss between the TXA20 group and the control group. However, when patients who underwent LF I+SSRO were reclassified based on surgical time, a significant difference was observed in the total intraoperative blood loss in the long surgical time group. In addition, a significant difference was observed in intraoperative blood loss per hour of surgery between the TXA10+10 group and the control group. These results suggest that TXA may be able to reduce intraoperative blood loss during orthognathic surgery.

近年,高齢社会の進行に伴って,水なしで服 用可能な口腔内崩壊錠(OD錠)が盛んに上市 されている.OD 錠は口腔内で錠剤を構成する 個々の微粒子へ崩壊する際に粒子径が 200 μm を超えると砂を噛んだような不快な服用感を与 えることが知られている.コーティングが必要 な原薬を OD錠とする場合,コーティング剤の 溶液や分散液を微粒子にスプレーする微粒子 コーティング技術が利用されるが,微粒子は付 着性が高く,粒子同士の凝集防止にスプレー速 度を低下させるために長時間プロセスとなり, 製造コストの高騰が課題の一つとなっている. 従って,溶媒を使用せずに固体粒子を被覆する ドライプロセスが求められている.ドライプロ セスは,医薬品含有母粒子周囲にコーティング 剤子粒子を配向させた後に機械的な負荷をかけ て母粒子表面に子粒子をコーティングする方法 として古くから提案されているが,固体粒子の 付着力の制御が困難であるため,医薬品の放出 制御に必要な子粒子の多層構造の形成が実現の 障壁となっている.先行研究では,低融点物質 を溶融させて結合剤とすることで多層構造を実 現しているが(Fukumori Y. et al., 1998),保存 安定性や精密な放出制御に難がある.装置につ いても回転パドルとの衝突を利用したものが多 く,高速回転では母粒子の粉砕が生じるリスク があり,低速では装置内のパドルの届かない領 域に微粒子が滞留するなど実用化のための材料 と装置の最適化がなされていない.

In order to control the interaction between the artificial mucin layer and pH-responsive shells of the core-shell drug delivery vehicles, two types of cross-linking agents with different molecular weights were added to the shells. The surface interaction between each vehicle and mucin was measured by colloid probe atomic force microscopy under different pH conditions. By adding 0.08 mol% cross-linking agents, the shell swelling phenomena at pH > 6 were maintained. Addition of a low molecular weight cross-linking agent (TEGDMA) reduces the interaction distance of repulsive force during approaching process. Addition of a high molecular weight cross-linking agent (PEGDMA) increased the interaction distance of repulsive force. A long interaction distance of attractive force during the separating process disappeared at pH = 6 after the addition of PEGDMA. However, TEGDMA addition maintained the long interaction distance of attractive force at pH = 8, which suggested that the vehicle might remain for an extended duration in the small intestine.

We aimed to investigate the feasibility of our previously proposed method for improving the properties of dry granules by pre-coating of active pharmaceutical ingredients (API) with a submicron-sized binder before conventional roller compaction in bench-scale production. Hydroxypropylcellulose (HPC) and acetaminophen (APAP) were used as the binder and API with low compactibility, respectively. The submicron-sized HPC (HPC-subMP) was obtained using a bench-scale spray dryer; the weight fraction for particle size less than 1 mm was a maximum of approximately 50 wt%. Co-mixing APAP with 5-20 wt% HPC-subMP in the high shear mixer resulted in the APAP particles being pre-coated with HPC-subMP (HPC-coated APAP). The HPC-coated APAP particles were converted into granules following ribbons using roller compactors, mixed with other excipients and compressed as a formulation containing 50% APAP using a single-punch tableting machine. The tablets obtained showed a high tensile strength without significantly prolonged disintegration time; thus, the compactibility of the dry granules could be improved using the HPC-coated APAP. Raman imaging study suggested that the distributional homogeneity of HPC-subMP in the ribbons was an important factor in producing roller-compacted granules suitable for tableting of API with low compactibility without any fundamental changes in materials and manufacturing processes. (c) 2017 Elsevier B.V. All rights reserved.