Clinical investigation of use of Episil® oral solution in oral mucositis during radiotherapy for head and neck cancer.

Objective: Episil® is a bio adhesive barrier-forming oral liquid gel that has been used in recent years to relieve pain of oral mucositis (OM) with radiotherapy (RT) or chemoradiotherapy (CRT) in head and neck cancer (HNC) patients. We conducted a retrospective analysis of the clinical effects of Episil® on OM in these patients. Study design: Between June 2018 and May 2020, 65 patients with HNC were treated with RT or CRT at our hospital. Results: The median total RT dose was 50 Gy (range, 30-70 Gy) and the completion rate was 63/65 (97%). The median time to OM resolution was 47 (6-90) days and was significantly longer (53 [27-90] days) when the total RT dose was ≥51 Gy (P < 0.001). Episil® was used in 26 patients. Among them, 10 discontinued its use due to ineffective pain relief, usage difficulties, and taste intolerance. The median duration of use was 30 days and was significantly longer (34.5 days) (P < 0.001) when patients experienced pain relief at treatment initiation. Conclusion: Although Episil® has been shown to be effective in improving the pain of OM caused by RT for HNC patients, and medical professionals are required to give careful attention to each patient.

Association between oral health and advisability of oral feeding in advanced cancer patients receiving palliative care: a cross-sectional study.

PURPOSE: Maintenance of oral feeding is important in terms of maintaining and improving the quality of life in terminal cancer patients receiving palliative care. Although adequate oral health status is essential for oral feeding in hospitalized patients, the relationship between oral health and oral feeding in patients receiving palliative care remains unclear. This cross-sectional study aimed to examine how the general condition and oral health status of these patients relate to decisions regarding their nutritional intake methods. METHODS: This retrospective cross-sectional study included 103 terminal cancer patients (59 men and 44 women; mean age, 73.8 ± 10.9 years) who received palliative care between April 2017 and August 2019. The nutritional method was assessed using the Functional Oral Intake Scale (FOIS). We assessed two types of nutritional methods: (1) the method advised by the attending physician until the initial dental examination (FOIS-I) and (2) the recommended method based on consultation with a palliative care doctor and dentist after the initial oral examination (FOIS-R). Furthermore, the participants' basic information and Dysphagia Severity Scale (DSS) and Oral Health Assessment Tool (OHAT) scores were assessed. RESULTS: There was a divergence between FOIS-I and FOIS-R. FOIS-R was significantly higher than FOIS-I (p < 0.001). Multiple regression analysis revealed that the time until death, DSS score, and OHAT score had a significant impact on determining the food form for oral feeding. CONCLUSIONS: Appropriate oral health assessment is important in determining the food form and indication for oral feeding among patients receiving palliative care.

Factors affecting the oral health of inpatients with advanced cancer in palliative care.

PURPOSE: Patients with terminal cancer undergoing multidisciplinary palliative care often have oral health problems, but these details are still unclear. This cross-sectional study aimed to elucidate the oral health of patients with terminal-stage cancer who are inpatient recipients of acute-phase palliative care, and to unveil the factors affecting their oral health. METHODS: Participants were 121 patients with terminal-stage cancer (68 males, 53 females, mean age: 73.6 ± 11.1 years) and oral health complaints. They received palliative care at Tokyo Medical and Dental University Medical Hospital between April 2017 and August 2019. Their demographic and medical details were extracted, retrospectively, from their medical records, and their oral health status, such as the number of natural teeth, removable denture usage, Oral Health Assessment Tool (OHAT), and Dysphagia Severity Scale, were evaluated. All outcomes were assessed by a dentist from the palliative care team. RESULTS: The problems with soft tissue, saliva, and oral cleanliness were observed. The absence of posterior occlusal support was common, and the use of removable dentures was often inadequate. In contrast, swallowing function was relatively well-conserved and 46.3% of the participants were capable of nutrition intake solely by mouth. Multiple regression analysis revealed a significant association between total OHAT score and age, consciousness level, prognostic level, and method of nutritional intake. CONCLUSION: The results revealed that the oral health of terminal cancer patients under palliative care declined despite receiving routine oral care from nurses, and suggest the importance of including dental professionals in multidisciplinary palliative care.

What Factors Affect Changes in Body Composition and Swallowing Function in Patients Hospitalized for Oral Cancer Surgery?

PURPOSE: There are few studies about sarcopenia before and after surgery for oral cancer. Therefore, we examined body composition during hospitalization and factors affecting weight loss, skeletal muscle mass index (SMI) reduction, and swallowing function at discharge in this patient group. PATIENTS AND METHODS: A prospective survey was conducted at Tokyo Medical and Dental University Dental Hospital for patients who underwent primary surgery for oral cancer and reconstruction using free flaps. We compared body weight, SMI, grip strength, and walking speed at admission and discharge. We also examined factors affecting weight loss and SMI reduction and the functional oral intake scale (FOIS) score at discharge. RESULTS: There were 26 patients that we could survey during the period. As a result of Wilcoxon's signed-rank test, body weight, SMI, and grip strength were significantly reduced during hospitalization, but no reduction was noted for sarcopenia. As a result of multiple regression analysis, postoperative chemoradiotherapy was a risk factor for weight loss, reduced SMI, and low FOIS score at discharge. CONCLUSION: Postoperative chemoradiotherapy is a risk factor for weight loss, muscle mass loss, and dysphagia at discharge, and chemoradiotherapy may affect rather than an invasion of surgery. After surgery, besides follow-ups for cancer, oral cancer patients should be followed up to assess dysphagia, undernutrition, and sarcopenia.

Imaging findings of intraosseous traumatic neuroma of the mandible.

A traumatic neuroma is an uncommon pseudotumor associated with peripheral nerves and occurs following surgery or trauma. It mostly occurs in the extraosseous soft tissue; traumatic neuromas of intraosseous origin are extremely rare. We herein report an unusual case of an intraosseous traumatic neuroma associated with the inferior alveolar nerve that was incidentally found on a panoramic image. In this report, we place special emphasis on the imaging features of traumatic neuroma, including the computed tomography and magnetic resonance imaging findings.

Association of Temporomandibular Joint Pain According to Magnetic Resonance Imaging Findings in Temporomandibular Disorder Patients.

PURPOSE: This study investigated the associations between magnetic resonance imaging (MRI) findings and pain in the temporomandibular joint (TMJ). MATERIALS AND METHODS: The study included 646 TMJs of 323 consecutive patients with temporomandibular disorders; of these, 222 (34.4%) had TMJ pain whereas 424 (65.6%) had no TMJ pain. MRIs were used to evaluate disc position, osteoarthritis, joint fluid, and bone marrow edema. Internal derangement was classified as normal, anterior disc displacement with reduction, and anterior disc displacement without reduction (ADDWOR); condylar morphology was classified as normal, moderate bony change, and severe bony change. The odds ratio (OR) for each MRI variable for nonpainful versus painful TMJs was computed using logistic regression analysis. RESULTS: Compared with joints with normal disc position, the OR of those with ADDWOR was 2.74 (P < .001) for TMJ pain. Similarly, compared with joints with normal condylar morphology, the OR of those with severe bony change was 4.62 (P = .02) for TMJ pain. In addition, the risk of TMJ pain increased by 2.37 in joints with joint fluid (P < .001) and by 2.34 in joints with bone marrow edema (P = .006). The risk of TMJ pain increased significantly with ADDWOR in combination with severe bony change, joint fluid, and bone marrow edema. CONCLUSIONS: These results suggest an association between TMJ pain and ADDWOR, severe bony change, joint fluid, and bone marrow edema. Thus, combining various MRI variables may improve the diagnostic accuracy of TMJ pain.

MRI changes in the temporomandibular joint following mandibular setback surgery using sagittal split ramus osteotomy with rigid fixation.

OBJECTIVES: This study examined the changes in temporomandibular joint dysfunction (TMD) symptoms and investigated the variations in the disc position, disc and condylar morphology following sagittal split ramus osteotomy (SSRO) with rigid fixation in patients with mandibular prognathism. Furthermore, the authors examined the correlation between mandibular setback and TMD symptoms. METHODS: The study included 24 Japanese patients with jaw deformities who were treated using bilateral SSRO and Le Fort I osteotomy. The clinical and magnetic resonance imaging findings in the temporomandibular joint were evaluated preoperatively and at three and six months postoperatively. RESULTS: The preoperative TMD symptoms were significantly associated with the prevalence of TMD symptoms at six months postoperatively. Anterior disc displacement improved in four joints with slight displacement and with no morphological change. There were no postoperative changes in condylar morphology. There was no significant correlation between mandibular setback and the postoperative TMD symptoms. CONCLUSION: Postoperative TMD symptoms may be influenced mainly by preoperative TMD symptoms rather than mandibular setback using SSRO with rigid fixation. Therefore, patients with TMD symptoms require physical examination and MRI for appropriate diagnosis preoperatively.

Bilateral nasolabial cysts: a case report.

BACKGROUND: Nasoalveolar cysts are rare non-odontogenic cysts that occur beneath the nasal alar region. Few cases of bilateral nasoalveolar cysts have been described. CASE PRESENTATION: We report a rare case of a 67-year-old Japanese woman with bilateral nasoalveolar cysts who presented to our department with the chief complaint of a swollen left nasal alar base. Panoramic radiography revealed no abnormalities. Computed tomography and magnetic resonance imaging revealed a well-circumscribed oval lesion at both alar bases. Therefore, bilateral nasoalveolar cysts were clinically diagnosed. Furthermore, these cysts were extirpated under general anesthesia; the aforementioned diagnosis was histopathologically confirmed. No recurrence has been observed 1 year after surgery. CONCLUSIONS: Nasoalveolar cysts are rare. It is necessary to be careful because nasoalveolar cysts can show bilateral occurrence.

Gelatin hydrogel as a carrier of recombinant human fibroblast growth factor-2 during rat mandibular distraction.

PURPOSE: The aim of the present study was to evaluate the feasibility of a gelatin hydrogel system to enhance recombinant human fibroblast growth factor-2 (rhFGF-2)-induced osteogenic effects during rat mandibular distraction. MATERIALS AND METHODS: Mandibular distraction was performed in 28 male Wistar rats. Then, the rats were divided into 5 groups in which the designated gel mix was inserted into the distracted area: group 1, rhFGF-2 alone (n = 5); group 2, collagen alone (n = 6); group 3, collagen incorporating rhFGF-2 (n = 6); group 4, gelatin hydrogel alone (n = 5); and group 5, gelatin hydrogel incorporating rhFGF-2 (n = 6). The mandibles were excised 29 days after surgery and the newly formed bone was analyzed radiologically and histologically. The experimental groups were compared using the Fisher post hoc test (95% statistical significance threshold; P < .05). RESULTS: Peripheral quantitative computed tomographic analysis, von Kossa staining, and calcein staining showed that using gelatin hydrogel with rhFGF-2 (group 5) significantly increased cortical bone mineral density, the domain area of hard tissue, the domain area of cortical bone area, total bone mineral content, cortical bone mineral content, the von Kossa-stained area, and the calcein-stained area compared with the collagen carrier (group 3). Group 5 also had a significantly larger number of cells positive for tartrate-resistant acid phosphatase compared with group 3 and radiopaque areas were observed more frequently. CONCLUSIONS: The present findings suggest that gelatin hydrogel is a feasible delivery system for rhFGF-2, and when used together perform better in regard to hard tissue healing and treatment time after surgery.

Integrated genotypic analysis of hedgehog-related genes identifies subgroups of keratocystic odontogenic tumor with distinct clinicopathological features.

Keratocystic odontogenic tumor (KCOT) arises as part of Gorlin syndrome (GS) or as a sporadic lesion. Gene mutations and loss of heterozygosity (LOH) of the hedgehog receptor PTCH1 plays an essential role in the pathogenesis of KCOT. However, some KCOT cases lack evidence for gene alteration of PTCH1, suggesting that other genes in the hedgehog pathway may be affected. PTCH2 and SUFU participate in the occurrence of GS-associated tumors, but their roles in KCOT development are unknown. To elucidate the roles of these genes, we enrolled 36 KCOT patients in a study to sequence their entire coding regions of PTCH1, PTCH2 and SUFU. LOH and immunohistochemical expression of these genes, as well as the downstream targets of hedgehog signaling, were examined using surgically-excised KCOT tissues. PTCH1 mutations, including four novel ones, were found in 9 hereditary KCOT patients, but not in sporadic KCOT patients. A pathogenic mutation of PTCH2 or SUFU was not found in any patients. LOH at PTCH1 and SUFU loci correlated with the presence of epithelial budding. KCOT harboring a germline mutation (Type 1) showed nuclear localization of GLI2 and frequent histological findings such as budding and epithelial islands, as well as the highest recurrence rate. KCOT with LOH but without a germline mutation (Type 2) less frequently showed these histological features, and the recurrence rate was lower. KCOT with neither germline mutation nor LOH (Type 3) consisted of two subgroups, Type 3A and 3B, which were characterized by nuclear and cytoplasmic GLI2 localization, respectively. Type 3B rarely exhibited budding and recurrence, behaving as the most amicable entity. The expression patterns of CCND1 and BCL2 tended to correlate with these subgroups. Our data indicates a significant role of PTCH1 and SUFU in the pathogenesis of KCOT, and the genotype-oriented subgroups constitute entities with different potential aggressiveness.

Clinical manifestations and treatment for keratocystic odontogenic tumors associated with nevoid basal cell carcinoma syndrome: a study in 25 Japanese patients.

BACKGROUND: Nevoid basal cell carcinoma syndrome (NBCCS) is an autosomal dominant disorder and is characterized by tumorigenesis and physical deformity. Keratocystic odontogenic tumors (KCOTs) of the jaws are a common manifestation of this syndrome. This study involved a pooled analysis of Japanese individuals with NBCCS and was performed with the aim of analyzing the clinical features of NBCCS and the patterns of occurrence and recurrence of KCOTs in Japanese individuals. METHODS: This study included 25 patients. The relative frequencies of the major symptoms in these patients were compared with those reported in the literature. We also investigated 11 patients with KCOTs (40 lesions) initially treated at Tokyo Medical and Dental University. RESULTS: KCOTs (100%) and palmar and/or plantar pits (n = 19; 76.0%) were the most frequently observed manifestations. Eleven patients (44.0%) had a radiologically confirmed rib anomaly. Nineteen patients (76.0%) had a family history of the syndrome within first-degree relatives. Japanese patients had a relatively low frequency of basal cell carcinoma (n = 7; 28.0%) and falx calcification (n = 7; 28.0%) compared with that reported in other populations. Twelve of the total 40 KCOTs (30.0%) that were followed up for 6 months or more recurred. All recurrent cases had undergone conservative treatment, whereas no recurrences occurred in cases that had undergone radical treatment. CONCLUSIONS: Recurrence of KCOTs associated with NBCCS is frequently encountered, and further investigations are required to confirm the optimal treatment that will ensure a complete cure improving the patient's quality of life.

Selective haploinsufficiency of longer isoforms of PTCH1 protein can cause nevoid basal cell carcinoma syndrome.

Nevoid basal cell carcinoma syndrome (NBCCS) is an autosomal dominant disorder characterized by developmental defects and tumorigenesis. The gene responsible for NBCCS is PTCH1. The PTCH1 gene has five alternatively used first exons resulting in the translation of three isoforms of the PTCH1 protein; that is, PTCHL, PTCHM and PTCHS. However, the biological significance of each isoform is unclear. Here we show an individual with NBCCS carrying a nonsense mutation in PTCH1 exon2, c.387G>A (p.W129X). As the mutation lay upstream of the ATG codon used for PTCHS translation, the mutant allele still expressed RNA isoforms that encode PTCHS. These results clearly demonstrate that a selective haploinsufficiency of longer isoforms of the PTCH1 protein, PTCHL and PTCHM, but not PTCHS is sufficient to cause NBCCS. Although mice selectively deficient in PTCHS isoforms are currently unavailable, this study sheds light on the complex in vivo roles of PTCH1 isoforms.

Morphological and immunohistochemical changes in muscle tissue in association with mandibular distraction osteogenesis.

PURPOSE: Studies of changes in the surrounding soft tissue in association with distraction osteogenesis in the maxillofacial region, where various different kinds of tissue are tightly packed, are rare. In this study, we performed morphological and immunohistochemical investigations of muscle tissue during mandibular distraction osteogenesis. MATERIALS AND METHODS: Japanese white rabbits were divided into 2 groups. In 1 group, the mandibular bone was distracted at a rate of 1 mm/day (DO group), whereas in the other group it was advanced by 10 mm all at once (O group). The cross-section of the anterior belly of the digastric muscle was examined using hematoxylin and eosin, periodic acid-Schiff (PAS), and proliferating cell nuclear antigen (PCNA) staining methods, as well as scanning electronmicroscopy (SEM). RESULTS: In the DO group, the cross-section of muscle bundle revealed no remarkable changes. In PAS staining, type II fibers gradually disappeared with distraction, but eventually reappeared after a period of consolidation. In the SEM photographs, striation-like laminated structures were evident in the control and the 3-mm distraction, ambiguous in the 6-mm distraction, and not evident in the 10-mm distraction. In contrast, the structure appeared to be restored in the consolidation for 1 week thereafter. In the PCNA immunostaining, the numbers of PCNA-positive nuclei increased during periods of distraction, but subsequently tended to decrease gradually. CONCLUSIONS: Although minute injuries were induced in muscle fibers in association with distraction osteogenesis, it is suggested that muscle fibers regenerate starting in the distraction period and thus can adapt to the environment.

The nephroblastoma overexpressed gene (NOV/ccn3) protein associates with Notch1 extracellular domain and inhibits myoblast differentiation via Notch signaling pathway.

We demonstrate a novel interaction of the nephroblastoma overexpressed gene (NOV), a member of the CCN gene family, with the Notch signaling pathway. NOV associates with the epidermal growth factor-like repeats of Notch1 by the CT (C-terminal cysteine knot) domain. The promoters of HES1 and HES5, which are the downstream transducers of Notch signaling, were activated by NOV. Expressions of NOV and Notch1 were concomitant in the presomitic mesoderm and later in the myocytes and chondrocytes, suggesting their synergistic effects in mesenchymal cell differentiation. In C2/4 myogenic cells, elevated expression of NOV led to down-regulation of MyoD and myogenin, resulting in inhibition of myotube formation. These results indicate that NOV-Notch1 association exerts a positive effect on Notch signaling and consequently suppresses myogenesis.