Survey of the association between tooth extraction and development of medication-related osteonecrosis of the jaw in patients undergoing cancer treatment with bone-modifying agents.

OBJECTIVE: This study aimed to verify whether tooth extraction before the administration of bone-modifying agents (BMA) was effective in preventing the onset of medication-related osteonecrosis of the jaw (MRONJ). MATERIALS AND METHODS: This retrospective study included patients with a history of receiving BMA for cancer treatment. The patients were classified into three groups based on the timing of tooth extraction: no tooth extraction before the onset of MRONJ, tooth extraction before the administration of BMA, and tooth extraction after the administration of BMA. The incidence of MRONJ was compared between the groups. Fisher's exact test and Bonferroni correction were used to test for differences in proportions between the three groups. RESULTS: The total number of subjects was 123. Twenty-four patients (19.5%) developed MRONJ. The incidence rates were 12.3% (10/81), 17.9% (5/28), and 64.3% (9/14) in the non-extraction group, the extraction before BMA administration group, and the extraction after BMA administration group, respectively, showing statistically significant differences between the extraction after BMA administration group and the non-extraction groups and between the extraction after BMA administration group and the extraction before BMA administration group (p < 0.001, p = 0.0049). On the other hand, there was no statistically significant difference in incidence between the non-extraction and the extraction before BMA administration group (p = 0.5274). CONCLUSIONS: Tooth extraction before the administration of BMA is effective in preventing the onset of MRONJ in patients receiving BMA for cancer treatment. Prevention of MRONJ development in patients receiving BMA for cancer treatment contributes to the maintenance of patients' quality of life.

The Relationship between the Contouring Time of the Metal Artifacts Area and Metal Artifacts in Head and Neck Radiotherapy.

(1) Background: The impacts of metal artifacts (MAs) on the contouring workload for head and neck radiotherapy have not yet been clarified. Therefore, this study evaluated the relationship between the contouring time of the MAs area and MAs on head and neck radiotherapy treatment planning. (2) Methods: We used treatment planning computed tomography (CT) images for head and neck radiotherapy. MAs were classified into three severities by the percentage of CT images containing MAs: mild (<25%), moderate (25−75%), and severe (>75%). We randomly selected nine patients to evaluate the relationship between MAs and the contouring time of the MAs area. (3) Results: The contouring time of MAs showed moderate positive correlations with the MAs volume and the number of CT images containing MAs. Interobserver reliability of the extracted MAs volume and contouring time were excellent and poor, respectively. (4) Conclusions: Our study suggests that the contouring time of MAs areas is related to individual commitment rather than clinical experience. Therefore, the development of software combining metal artifact reduction methods with automatic contouring methods is necessary to reducing interobserver variability and contouring workload.

Intensive oral care can reduce bloodstream infection with coagulase-negative staphylococci after neutrophil engraftment in allogeneic hematopoietic stem-cell transplantation.

PURPOSE: Bloodstream infection (BSI) is a major complication of allogeneic hematopoietic stem-cell transplantation (allo-SCT). There are several causes of BSI; in particular, severe oral mucositis (OM) can induce BSI due to coagulase-negative staphylococci (CoNS). The OM severity may be reduced with intensive oral care. Thus, we evaluated whether the type of oral care affects the BSI incidence eventually. METHOD: We performed retrospective analysis on 206 recipients who underwent allo-SCT from 2006 to 2017 at our institute. Intensive oral care by a dental specialist was performed for 111 recipients (intensive-care group) and self-oral care was performed by 95 recipients (self-care group). Incidence of BSI was assessed by type of the oral care, before neutrophil engraftment (pre-E-BSI) and after neutrophil engraftment (post-E-BSI) period until 180 days after allo-SCT. RESULT: A total of 112 BSI occurred in 90 of the 206 recipients and 120 bacteria were identified, with CoNS being the most prevalent. There was no significant difference in the incidence of pre-E-BSI between the self-care and intensive-care groups (30.8% and 30.6%, respectively; P = 0.508). Meanwhile, the incidence of post-E-BSI was significantly lower in the intensive-care group than in the self-care group (14.3% and 28.6%; P = 0.008). In addition, the intensive-care group had significantly lower incidence of post-E-BSI with CoNS than the self-care group (8.5% and 21.5%, respectively; P = 0.009). CONCLUSION: Intensive oral care through the period of allo-HCT can significantly reduce the post-E-BSI occurrence, especially due to CoNS.

Pharmacist involved education program in a multidisciplinary team for oral mucositis: Its impact in head-and-neck cancer patients.

OBJECTIVES: This retrospective study examined how a pharmacist-involved education program in a multidisciplinary team (PEMT) for oral mucositis (OM) affected head-and-neck cancer (HNC) patients receiving concurrent chemoradiotherapy (CCRT). MATERIALS AND METHODS: Total samples data of 53 patients during the stipulated timeframe were retrospectively collected from electronic medical records from February 2017 to January 2019. We compared the presence/absence of OM (OM: yes/no) between patients with and without PEMT (PEMT: yes/no) as the primary endpoint and OM severity as the secondary endpoint. The following information was surveyed: age, gender, weight loss, steroid or immunosuppressant use, hematological values (albumin, white blood cell count, blood platelets, and neutrophils), cancer grade, primary cancer site, type and use of mouthwash and moisturizer, opioid use (yes/no, days until the start of opioid use, and dose, switch to tape), and length of hospital day (LOD). The two groups were compared using Fisher's exact test for qualitative data and the Mann-Whitney U test for quantitative data, and a significance level of p<0.05 was set. RESULTS: The group managed by PEMT had significantly lower weight loss and a significantly lower incidence of local anesthetic and opioid use and switch to tape compared with the group not managed by PEMT (p<0.05). The two groups showed no significant difference in OM (yes/no) or OM severity. The PEMT group had significantly shorter LOD at 57 (53-64) days compared with the non-PEMT group at 63.5 (57-68) days (p<0.05). CONCLUSIONS: Our results showed that PEMT did not improve OM (yes/no) or OM severity in HNC patients undergoing CCRT. However, the PEMT group had a lower incidence of grades 3 and 4 OM than the non-PEMT group, although not significantly. In addition, PEMT contributed to oral pain relief and the lowering of the risk for OM by reduction in weight loss.

A cost-minimization analysis of measures against metallic dental restorations for head and neck radiotherapy.

The aim of this study was to compare the estimated public medical care cost of measures to address metallic dental restorations (MDRs) for head and neck radiotherapy using high-energy mega-voltage X-rays. This was considered a first step to clarify which MDR measure was more cost-effective. We estimated the medical care cost of radiotherapy for two representative MDR measures: (i) with MDR removal or (ii) without MDR removal (non-MDR removal) using magnetic resonance imaging and a spacer. A total of 5520 patients received head and neck radiation therapy in 2018. The mean number of MDRs per person was 4.1 dental crowns and 1.3 dental bridges. The mean cost per person was estimated to be 121 720 yen for MDR removal and 54 940 yen for non-MDR removal. Therefore, the difference in total public medical care cost between MDR removal and non-MDR removal was estimated to be 303 268 800 yen. Our results suggested that non-MDR removal would be more cost-effective than MDR removal for head and neck radiotherapy. In the future, a national survey and cost-effectiveness analysis via a multicenter study are necessary; these investigations should include various outcomes such as the rate of local control, status of oral mucositis, frequency of hospital visits and efforts of the medical professionals.

Radiological imaging features of the salivary glands in xerostomia induced by an immune checkpoint inhibitor.

The clinical features of xerostomia induced by immune checkpoint inhibitors (ICI) are similar to those of Sjögren's syndrome (SS), whereas the immunohistological and serological features are known to differ from those of SS. However, the radiologic imaging features of salivary glands are not yet well known. We report a case of a 56-year-old male patient diagnosed with ICI-induced xerostomia. The patient underwent various imaging examinations to investigate the condition of the salivary glands, which indicated the following: (1) less specific findings on contrast-enhanced computed tomography, (2) mixed with intermediate and low signal intensity on both T1-weighted and fat-suppressed T2-weighted magnetic resonance imaging and poor "salt and pepper" appearance on magnetic resonance sialography, and (3) multiple ovoid hypoechoic areas with hyperechoic bands without acute sialadenitis on ultrasound. These radiologic imaging findings suggested remarkable lymphocyte infiltration, which could be a characteristic of ICI-induced xerostomia.

Multicenter phase I/II study of chemoradiotherapy with high-dose CDDP for head and neck squamous cell carcinoma in Japan.

OBJECTIVE: Recent data indicated that concurrent chemoradiotherapy (CCRT) using high dose cisplatin (CDDP) is the most useful treatment for advanced head and neck squamous cell carcinoma (SCC). Regarding the dose of CDDP, 100mg/m2 is most recommended in Western countries. However, in terms of a balance of efficacy and adverse events, appropriate dose of cytotoxic drugs such as CDDP may be different among the different ethnic groups. In this multicenter phase I/II study, we aimed to identify the optimal dose of CDDP in CCRT for patients with advanced head and neck SCC in the Japanese. METHODS: Patients were eligible for inclusion if they had head and neck SCC that was treated with radical CCRT comprising whole-neck irradiation of the primary lesion and level II-IV lymph nodes on both sides. For the phase I study, a CDDP dose was 70mg/m2 for level 0, 80mg/m2 for level 1, and 100mg/m2 for level 2. Maximum tolerated dose (MTD) and dose-limiting toxicity (DLT) were examined by phase I trial, by which CDDP dose for phase II was determined. The primary endpoint for the phase II was CCRT completion rate, and the secondary endpoint was full-dose-CCRT completion rate, the percentage of patients receiving a total CDDP dose of ≥200mg/m2, response rate, and incidences of adverse events. RESULTS: A CDDP dose of 100mg/m2 was the MTD for phase I, and the recommended dose for phase II was 80 mg/m2. Forty-seven patients were evaluated in the phase II trial. CCRT completion rate, full-dose-CCRT rate, and the percentage of patients receiving a total CDDP dose of ≥200mg/m2, were 93.6%, 78.7%, and 93.6%, respectively. One patient (2.1%) developed grade 2 renal dysfunction, and no patient developed febrile neutropenia or a grade 4 adverse event. CONCLUSION: The present phase I study indicated that a CDDP dose of 80mg/m2 is the optimal dose in terms of safety. The phase II study revealed that CCRT completion rate, response rate, and rates of adverse events were not inferior for a CDDP dose of 80mg/m2 as compared with a dose of 100mg/m2, and a dose of 80mg/m2 is therefore recommended in CCRT for the Japanese. This study was registered with the University Hospital Medical Information Network Clinical Trials Registry (UMIN-CTR; identification No. UMIN000010369).

Nondestructive Microcomputed Tomography Evaluation of Mineral Density in Exfoliated Teeth with Hypophosphatasia.

Most cases of hypophosphatasia (HPP) exhibit early loss of primary teeth. Results of microcomputed tomography (micro-CT) analysis of teeth with HPP have rarely been reported. The purpose of the present study was to describe the mineral density distribution and mapping of exfoliated teeth from an HPP patient using micro-CT. Four exfoliated teeth were obtained from a patient with HPP. Enamel and dentin mineral densities of exfoliated teeth were measured on micro-CT. The mean values of enamel and dentin mineral densities in mandibular primary central incisors with HPP were 1.61 and 0.98 g/cm3, respectively. The corresponding values in the mandibular primary lateral incisors were 1.60 and 0.98 g/cm3, respectively. Enamel hypoplasia was seen in the remaining teeth, both maxillary and mandibular primary canines and first and second molars. Micro-CT enables nondestructive, noninvasive evaluation and is useful for studying human hard tissues obtained from patients.

Two-step consumption of yolk granules during the development of quail embryos.

The mechanism of yolk consumption was studied morphologically and biochemically in Japanese quail Coturnix japonica. The amount of yolk granules in the yolk (or 'yolk cell') decreased in two steps during embryonic development. In the first step, during days 0-4 of incubation, the yolk-granule weight decreased at a rate of 13 mg/day. This decrease was due to segregation by endodermal cells that were newly formed in the developing yolk sac. In the second step after day 6, the decrease was drastic at a rate of 29.8 mg/day during days 6-12 and very slow thereafter. The decrease at the second step was due to the enzymatic digestion of yolk granules by cathepsin D that coexisted in yolk spheres. This digesting reaction was triggered by the solubilization of the granules with high concentrations of salts that were supplied after disruption of the limiting membrane of yolk spheres. The 'yolk cell' seemed to die around day 5 of incubation. Thus the digestion products might be taken up together with yolk lipids by endocytosis into the endodermal cells and transported to blood vessels.