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Background The long waiting time for bone uptake after radiopharmaceutical injection in bone scintigraphy is a burden for patients with poor health. Thus, we aimed to investigate the equivalence between maximum standardized uptake values (SUVmax) for imaging with 2- and 3-h uptake times.Methods Thirty patients with jaw osteomyelitis or medication-related osteonecrosis of the jaw who underwent single-photon emission computed tomography (SPECT) twice in the same day were enrolled. The SUVmax for the normal parietal bones and jawbone lesion was calculated using a quantitative analysis software, and values for 2- and 3-h uptake times were compared. Bland–Altman plots were used to determine the limits of agreement (LOAs) for the difference in SUVmax between 2- and 3-h uptake times for the parietal bones and jawbone lesion.Results The LOA ranged from − 0.33 to 0.25 in the parietal bones and %LOA ranged from − 9.8–17.3% in the jawbone lesion, proving high equivalence. The SUVmax showed no clinical differences between 2- and 3-h uptake times for technetium-99m hydroxymethylene diphosphonate SPECT of the jawbone.Conclusions This is the first study to demonstrate that the uptake time in jawbone SPECT can be reduced to only 2 h, justifying a 2–3-h uptake time margin.

Tracing the movements of foreign bodies is challenging after they aberrantly migrate into the soft tissues. Oral soft tissues are extremely mobile and move in a coordinated and highly complex manner during mastication, deglutition, and phonation. This report presents three cases of aberrantly migrated foreign bodies within the soft tissues of the oral cavity. In the first case, a fractured broach used for root canal treatment entered the oral cavity and moved within the soft tissues, making it difficult to identify its position. In the second case, the tip of a chopstick was embedded within the tissues in the palate, and in the third case, a broken needle was embedded in the left maxilla. It was possible to locate and remove the objects in Cases 1 and 2 (broach and chopstick, respectively); however, attempts to remove the object in Case 3 were unsuccessful due to its location behind the maxillary tuberosity. Foreign bodies that enter into the soft tissues migrate in response to the complex and frequent movements of the oral cavity and, ultimately, get embedded at locations away from their original point of entry. Therefore, dentists need to exercise caution while using instruments such as endodontic file and dental needle, and be completely aware of the difficulties involved in removing migrated and embedded foreign bodies.

Effects of long-term bisphosphonate (BP) administration on the metabolism of healthy bone and the concomitant changes in imaging are unclear. Hence, we aimed to retrospectively investigate the effects of long-term BP administration on the intact parietal bone using the standardised uptake value (SUV) derived from single photon emission computed tomography (SPECT). We enrolled 29 patients who had odontogenic infection, osteoporosis, bone metastasis cancer, or rheumatoid arthritis, and classified them into BP-naïve: A (14 patients) and BP-treated: B, P P = 0.0086, respectively). There was a positive correlation between the duration of BP administration and SUVmax of the parietal bone (rs = 0.65, P = 0.0002). The SUVmax was significantly different between A and B (P = 0.02) and between A and C (P = 0.0024) groups. This is the first report on the correlation between long-term BP administration and the SUVmax of the parietal bone using the quantitative bone SPECT analysis.

BACKGROUND Taxanes are the current first-line treatment for advanced cutaneous angiosarcoma (CAS) for patients who are considered difficult to treat with doxorubicin owing to advanced age or comorbidity. However, no effective second-line therapy for such patients has been established. METHODS We designed a single-arm prospective observational study of eribulin mesylate (ERB) administered at a dose of 1·4 mg m-2 on days 1 and 8 in a 21-day cycle. Patients with advanced CAS who were previously treated with a taxane and were scheduled to begin ERB treatment were enrolled. The primary endpoint was overall survival (OS) and the secondary endpoints were response rate (RR), progression-free survival (PFS) and toxicity assessment. RESULTS We enrolled a total of 25 patients. The median OS and PFS were 8·6 months and 3·0 months, respectively. The best overall RR was 20% (five of 25). In total, 16 grade 3/4 severe adverse events (SAEs) occurred; however, all patients recovered. Patients who achieved partial response or stable disease as best response had longer OS than those with progressive disease (median OS not reached and 3·3 months, respectively; P < 0·001). Patients who did not experience SAEs showed longer OS than those who did (median OS 18·8 months and 7·5 months, respectively; P < 0·05). Patients with distant metastasis had shorter median OS than those with locoregional disease, but without statistically significant difference. CONCLUSIONS ERB showed a promising RR and is a potential candidate for second-line treatment for patients with CAS, after treatment with taxanes. However, owing to the occurrence of SAEs in over half of the participants, caution should be exercised regarding ERB use in elderly patients. What is already known about this topic? Taxanes are the current first-line treatment for patients with advanced cutaneous angiosarcoma (CAS) who are considered difficult to treat with doxorubicin owing to advanced age or comorbidity. No effective therapy for taxane-resistant CAS has been established thus far. Eribulin suppresses microtubule polymerization and elicits an antitumour effect similar to that of taxanes. What does this study add? In our single-arm prospective observational study to evaluate the efficacy of eribulin for treating patients with advanced CAS who previously received taxanes, the median overall survival and progression-free survival were 8·6 and 3·0 months, respectively. Response rates at weeks 7, 13 and 25 were 20%, 17% and 14%, respectively. Although 16 grade 3/4 severe adverse events occurred, all patients recovered. Eribulin showed a promising response rate and is a potential candidate for second-line treatment in CAS after taxane treatment. Linked Comment: Smrke and Benson. Br J Dermatol 2020; 183:797-798.

Background Zinc is mainly absorbed in the duodenum and proximal jejunum, which are removed during pancreaticoduodenectomy (PD). Little is known about the adverse oral events and skin disorders caused by zinc deficiency after PD. Herein, we reviewed studies on the development of zinc deficiency after PD and reported about a patient with zinc deficiency after PD who required home intravenous zinc replacement. Case presentation A 73-year-old woman with glossitis, taste disorder, and acrodermatitis enteropathica-like eruption on her fingers presented to the Division of Dentistry and Oral Surgery 69 days after PD. Her serum zinc level markedly decreased to 30 μg/dL. Oral zinc administration was inadequate to treat hypozincemia after PD; therefore, multi-trace elements were injected intravenously during readmission. Her serum zinc levels recovered, and her lesions gradually improved. Furthermore, a central venous port was implanted to maintain normal serum zinc levels, and she continued self-injecting zinc at home. Conclusions Zinc deficiency after PD rarely occurs. The clinical oncologist community, including dentists responsible for the oral care of cancer patients, should be aware of the oral adverse events, such as dysgeusia, glossitis, and oral pain, associated with zinc deficiency after cancer surgery and that induced by chemotherapy or head and neck radiation therapy.

Background: Zinc is mainly absorbed in the duodenum and proximal jejunum, which are removed during pancreaticoduodenectomy (PD). Little is known about the adverse oral events and skin disorders caused by zinc deficiency after PD. Herein, we reviewed studies regarding the development of zinc deficiency after PD and presented the case of a patient with zinc deficiency after PD, who required home intravenous zinc replacement.Case presentation: A 73-year-old woman with glossitis, taste disorder, and acrodermatitis enteropathica-like eruption on her fingers presented to the Division of Dentistry and Oral Surgery 69 days after PD. Her serum zinc level markedly decreased to 30 μg/dL. Oral zinc administration was inadequate to treat hypozincemia after PD; therefore, multi-trace elements were injected intravenously under readmission. Her serum zinc levels recovered, and the lesions gradually improved. Furthermore, a central venous port was implanted to maintain normal serum zinc levels, and she continued self-injecting zinc at home.Conclusion: Zinc deficiency after PD rarely occurs. The clinical oncologist community, including dentists responsible for the oral care of cancer patients, should be aware of dysgeusia associated with zinc deficiency after cancer surgery, as well as that induced by chemotherapy or head and neck radiation therapy.

BACKGROUND: Dysphagia is a prominent symptom after esophagectomy and may cause aspiration pneumonia. Swallowing evaluation after esophagectomy can predict and help control the incidence of postoperative pneumonia. The aim of this study was to clarify whether the change in tongue pressure was associated with any related factor and postoperative dysphagia/pneumonia in patients with esophageal cancer after esophagectomy. METHODS: Fifty-nine inpatients (41 males and 18 females; 33-77 years old) who underwent esophagectomy participated in this study. Measurement of tongue pressure and the repetitive saliva swallowing test (RSST) was performed before esophagectomy (baseline) and at 2 weeks postoperatively. The general data were collected from patients' medical records, including sex, age, type of cancer, cancer stage, location of cancer, operative approach, history of previous chemotherapy, surgical duration, amount of bleeding during surgery, incidences of postoperative complications, intubation period, period between surgery and initiation of oral alimentation, and intensive care unit (ICU) stay, blood chemical analysis, and lifestyle. RESULTS: Tongue pressure decreased significantly after esophagectomy (p = 0.011). The decrease of tongue pressure was significantly associated with length of ICU stay and preoperative tongue pressure on multiple regression analysis (p CONCLUSIONS: The decrease in tongue pressure was significantly associated with the length of ICU stay, preoperative tongue pressure, and the incidence of dysphagia and pneumonia among inpatient after esophagectomy.

Purpose Survival time after bisphosphonate use has been increasingly recognized to be associated with the incidence of medication-related osteonecrosis of the jaw (MRONJ); however, this has not been elucidated sufficiently in the literature. This study aimed to clarify the incidence of MRONJ and the corresponding survival rate of patients treated with zoledronic acid (ZA) for each type of cancer and obtain useful information for the oral management of cancer. Methods We evaluated 988 patients who were administered ZA at our hospital; among them, 862 patients with metastatic bone tumors or myeloma were included. Results The median survival time (MST) after ZA initiation was 35, 34, 8, 41, 12, and 6 months for patients with breast, prostrate, lung, myeloma, renal, and other cancers, respectively. Patients with cancers that had a short survival time (lung and other cancers [MST = 8 and 6 months, respectively] and cancers with MST

Aims: Symptomatic treatment is insufficient for chemotherapy- or targeted therapy-induced oral mucositis (OM) pain, and benzydamine mouthwash is not commercially available in Japan. We evaluated the analgesic effects of an in-hospital preparation of 0.25% indomethacin spray (IMS) on anticancer drug-induced OM pain. Methods: This single-arm prospective trial enrolled 20 patients (median age 62.0 years) with OM and numerical rating scale scores of >= 5 who were undergoing chemotherapy or targeted therapy in our hospital. Pain scores were recorded using a visual analog scale (VAS) before and 30 min after IMS administration. Pain relief (PR) scores were recorded at 15, 30, and 60 min after IMS administration; total PR after 60 min (TOTPAR(60)) was calculated, and the mean PR score after 3 days (PR3days) was determined. Results: The median (interquartile range) OM grade of the participants was 2.0 (2.0-2.3). The VAS score decreased significantly at 30 min after IMS administration (p = .001). The median (interquartile range) TOTPAR(60) and PR3days were 6.0 (3.8-7.3) and 2.0 (2.0-3.0), respectively. Conclusions: IMS helped improve patients' quality of life. The risk of systemic adverse effects was low because of the low dose administered. IMS effectively relieved anticancer drug-induced OM pain and may be useful for immediate self-medication.

Lower third molar extraction is the most common surgical treatment among routine dental and oral surgical procedures. while the surgical procedures for lower third molar extraction are well established, the difficulty of tooth extraction and the frequency of postoperative complications differ depending on the patient’s background. To establish a management protocol for the lower third molars, the prevalence of and risk factors for postoperative complications after lower third molar extraction were investigated in a large number of Japanese patients in a multicenter prospective study. During 6 consecutive months in 2020, 1826 lower third molar extractions were performed at the 20 participating institutions. The medical records of the patients were reviewed, and relevant data were extracted. The prevalence of and risk factors for postoperative complications were analyzed. The prevalence of postoperative complications after lower third molar extraction was 10.0%. Multivariate analysis indicated that age (≤32 vs >32, odds ratio [OR]: 1.428, 95% confidence interval [95% CI]: 1.040–1.962, P < .05), the radiographic anatomical relationship between the tooth roots and mandibular canal (overlapping of the roots and canal vs no close anatomical relationship between the roots and the superior border of the canal, OR: 2.078, 95% CI: 1.333–3.238, P < .01; overlapping of the roots and canal vs roots impinging on the superior border of the canal, OR: 1.599, 95% CI: 1.050–2.435, P < .05), and impaction depth according to the Pell and Gregory classification (position C vs position A, OR: 3.7622, 95% CI: 2.079–6.310, P < .001; position C vs position B, OR: 2.574, 95% CI: 1.574–4.210, P < .001) are significant independent risk factors for postoperative complications after lower third molar extraction. These results suggested that higher age and a deeply impacted tooth might be significant independent risk factors for postoperative complications after lower third molar extraction.

Background: The Oral Care BC-trial reported that professional oral care (POC) reduces the incidence and severity of oral mucositis in patients receiving everolimus (EVE) and exemestane (EXE). However, the effect of POC on clinical response among patients receiving EVE and EXE was not established. We compared outcomes for estrogen receptor-positive metastatic breast cancer patients who received POC to those who had not, and evaluated clinical prognostic factors. All patients simultaneously received EVE and EXE. Methods: Between May 2015 and Dec 2017, 174 eligible patients were enrolled in the Oral Care-BC trial. The primary endpoint was the comparative incidence of grade 1 or worse oral mucositis, as evaluated for both the groups over 8 weeks by an oncologist. The secondary endpoints were progression-free survival (PFS) and overall survival (OS). Data were collected after a follow-up period of 13.9 months. Results: There were no significant differences in PFS between the POC and Control Groups (P = 0.801). A BMI < 25 mg/m2 and non-visceral metastasis were associated with longer PFS (P = 0.018 and P = 0.003, respectively) and the use of bone modifying agents (BMA) was associated with shorter PFS (P = 0.028). The PFS and OS between the POC and control groups were not significantly different in the Oral-Care BC trial. Conclusions: POC did not influence the prognosis of estrogen receptor-positive metastatic breast cancer patients. Patients with non-visceral metastasis, a BMI < 25 mg/m2, and who did not receive BMA while receiving EVE and EXE may have better prognoses.Trial registration: The study protocol was registered online at the University Hospital Medical Information Network (UMIN), Japan (protocol ID 000016109), on January 5, 2015 and at ClinicalTrials.gov (NCT02376985).

Development of quantitative analysis software has enabled application of several standardised uptake values (SUV) for bone analysis in single photon emission computed tomography (SPECT). The present retrospective study aimed to develop a reliable method of monitoring bone inflammatory activity in antiresorptive agent-related osteonecrosis of the jaw (ARONJ) using SPECT quantitative analysis software. Fifteen ARONJ patients underwent SPECT before and after anti-inflammatory therapy. We calculated the mean maximum SUV (SUVmax) of the bilateral cranial bones using quantitative analysis software and used this as the control [C]. We attempted to adjust the SUVmax of the lesion [L] as follows: adjusted SUVmax (aSUVmax) = [L] − [C]. The optimum threshold to calculate the metabolic bone volume (MBV) (cm3) was [C] + 3. The threshold values obtained for each case were input to calculate MBV at each osteomyelitis site. Retrospectively, we compared aSUVmax and MBV of each patient’s ARONJ before and after anti-inflammatory therapy. The patients’ high aSUVmax or large MBV of the ARONJ reduced rapidly, reflecting individual clinical findings after treatment. Application of SPECT quantitative analysis software to monitor bone inflammatory activity in ARONJ could improve the prognosis-deciding abilities of clinicians and enable them to treat ARONJ effectively.

Background: The Oral Care BC-trial reported that professional oral care (POC) reduces the incidence and severity of oral mucositis in patients receiving everolimus (EVE) and exemestane (EXE). However, the effect of POC on clinical response among patients receiving EVE and EXE was not established. We compared outcomes for estrogen receptor-positive metastatic breast cancer patients that received POC to those that had not and evaluated clinical prognostic factors. All patients simultaneously received EVE and EXE. Methods: Between May 2015 and Dec 2017, 174 eligible patients were enrolled in the Oral Care-BC trial. The primary endpoint was the comparative incidence of grade 1 or worse oral mucositis, as evaluated by an oncologist over 8 weeks between groups. The secondary endpoints were progression-free survival (PFS) and overall survival (OS). Data were collected after a follow-up period of 13.9 months. Results: There were no significant differences in PFS between the POC and Control Groups ( P = 0.801). A BMI < 25 mg/m 2 and non-visceral metastasis were associated with longer PFS ( P = 0.018 and P = 0.003, respectively) and the use of bone modifying agents (BMA) was associated with shorter PFS ( P = 0.028). The PFS and OS between the POC and control groups were not significantly different in the Oral-Care BC trial. Conclusions: POC did not influence the prognosis of estrogen receptor-positive metastatic breast cancer patients. Patients with non-visceral metastasis, a BMI < 25 mg/m 2 , and who did not receive BMA while receiving EVE and EXE may have better prognoses. Trial registration: The study protocol was registered online at the University Hospital Medical Information Network (UMIN), Japan (protocol ID 000016109), on January 5, 2015 and at ClinicalTrials.gov (NCT02376985).

Acetaldehyde, associated with consumption of alcoholic beverages, is known to be a carcinogen and to be related to the tongue dorsum. Objective The aim of this study was to investigate the relationship between acetaldehyde concentration in mouth air and bacterial characteristics on the tongue dorsum. Methodology Thirty-nine healthy volunteers participated in the study. Acetaldehyde concentrations in mouth air were evaluated by a high-sensitivity semiconductor gas sensor. A 16S rRNA gene sequencing technique was used to compare microbiomes between two groups, focusing on the six samples with the highest acetaldehyde concentrations (HG) and the six samples with lowest acetaldehyde concentrations (LG). Results Acetaldehyde concentration increased in correlation with the increase in bacterial count (p=0.048). The number of species observed in the oral microbiome of the HG was higher than that in the oral microbiome of the LG (p=0.011). The relative abundances of Gemella sanguinis, Veillonella parvula and Neisseria flavescens in the oral microbiome of the HG were higher than those in the oral microbiome of the LG (p

Background The incidence of oral mucositis (any grade) after everolimus treatment is 58% in the general population and 81% in Asian patients. This study hypothesized that professional oral care (POC) before everolimus treatment could reduce the incidence of everolimus‐induced oral mucositis. Materials and Methods This randomized, multicenter, open‐label, phase III study evaluated the efficacy of POC in preventing everolimus‐induced mucositis. Patients were randomized into POC and control groups (1:1 ratio) and received everolimus with exemestane. Patients in the POC group underwent teeth surface cleaning, scaling, and tongue cleaning before everolimus initiation and continued to receive weekly POC throughout the 8‐week treatment period. Patients in the control group brushed their own teeth and gargled with 0.9% sodium chloride solution or water. The primary endpoint was the incidence of all grades of oral mucositis. We targeted acquisition of 200 patients with a 2‐sided type I error rate of 5% and 80% power to detect 25% risk reduction. Results Between March 2015 and December 2017, we enrolled 175 women from 31 institutions, of which five did not receive the protocol treatment and were excluded. Over the 8 weeks, the incidence of grade 1 oral mucositis was significantly different between the POC group (76.5%, 62 of 82 patients) and control group (89.7%, 78 of 87 patients; p = .034). The incidence of grade 2 (severe) oral mucositis was also significantly different between the POC group (34.6%, 28 of 82 patients) and control group (54%, 47 of 87 patients; p = .015). As a result of oral mucositis, 18 (22.0%) patients in the POC group and 28 (32.2%) in the control group had to undergo everolimus dose reduction. Conclusion POC reduced the incidence and severity of oral mucositis in patients receiving everolimus and exemestane. This might be considered as a treatment option of oral care for patients undergoing this treatment. Clinical trial identification number: NCT 02069093. Implications for Practice The Oral Care‐BC trial that prophylactically used professional oral care (POC), available worldwide, did not show a greater than 25% difference in mucositis. The 12% difference in grade 1 or higher mucositis and especially the ∼20% difference in grade 2 mucositis are likely clinically meaningful to patients. POC before treatment should be considered as a treatment option of oral care for postmenopausal patients who are receiving everolimus and exemestane for treatment of hormone receptor‐positive, HER2‐negative advanced breast cancer and metastatic breast cancer. However, POC was not adequate for prophylactic oral mucositis in these patients, and dexamethasone mouthwash prophylaxis is standard treatment before everolimus., Oral mucositis is a clinically significant complication of mucotoxic cancer therapy. This article focuses on the effect of dental intervention, before everolimus treatment, on oral mucositis.

BackgroundThis randomized, controlled, multicenter, open-label, phase III study was conducted to determine whether professional oral care (POC) reduces oral mucositis in estrogen receptor-positive metastatic breast cancer patients treated with everolimus and exemestane.MethodsOne hundred seventy-four patients were randomized into the POC group (n = 86) or the control group (n = 88). Four patients in the POC group and one patient in the control group were excluded from the study because they did not receive the protocol treatment. Thus, 169 patients (POC group: 82 patients; control group: 87 patients) were evaluated for efficacy and safety. The POC group received oral health instruction (OHI), professional mechanical tooth and tongue cleaning, gargling with a benzethonium chloride mouthwash, and dexamethasone ointment when grade 1 mucositis manifested. The control group received OHI and gargling. Eight weeks after everolimus and exemestane were administered, the patients were evaluated for oral status (based on the Oral Assessment Guide [OAG] criteria) and oral mucositis status (assessed with Common Terminology Criteria for Adverse Events [CTCAE] functional and clinical examinations).ResultsThe incidences of oral mucositis of any grade and severe mucositis of grade 2 were significantly lower in the POC group (p = 0.034 and p = 0.013, respectively), based on the CTCAE functional and CTCAE clinical examinations (p = 0.034 and p # These authors contributed equally to this work.

Candida infections are frequently encountered fungal infections in the oral mucosa. This study aimed to evaluate the effect of eliminating Candida spp. on stimulated whole salivary flow rate (SWS) in patients with oral candidiasis.This study involved 66 patients with oral candidiasis. Fifty-two consecutive patients, successfully treated by antifungal therapy, were available to examine the effect of elimination of oral Candida spp. on SWS (success group); the 14 patients who tested positive for Candida after therapy were retrospectively included (control group). SWS were used to measure saliva production. Moreover, tongue pain and xerostomia were evaluated using visual analog score (VAS).By eliminating oral Candida spp., SWS significantly increased in the success group after antifungal therapy [SWS: mean value 0.89±0.51ml/min (median 0.82ml/min: 0.15-2.14) to mean value 1.16±0.58ml/min (median 1.05ml/min: 0.2-2.93), P0.001]. Furthermore, VAS scores for subjective tongue pain and xerostomia were significantly decreased compared with those before therapy in the success group [xerostomia: mean value 52.5±28.8 (median 53: 9-100) to 24.2±1.6 (median 17: 0-70), tongue pain: mean value 52.6±27.2 (median 56: 1-93) to 15.3±18.0 (median 9: 0-62). P0.001]. There was no significant difference in SWS, subjective tongue pain, or xerostomia in the control group after antifungal therapy. [SWS: mean value 1.08±0.83ml/min (median 0.69ml/min: 0.2-2.7) to 0.98±0.59ml/min (median 0.8ml/min: 0.45-2.5), P=0.65], [xerostomia: mean value 62.8±5.3 (median 62: 28-70) to 64.0±8.8 (median 64: 56-73), P=0.58, tongue pain: mean value 64.3±18.6 (median 67: 31-87) to 58.4±20.0 (median 8: 20-78), respectively; P=0.24] CONCLUSION: Our study demonstrated that SWS may increase by eliminating oral Candida spp. in patients with oral candidiasis.

Intravascular fasciitis (IF), a variant of nodular fasciitis (NF), is a reactive intravascular proliferation of myofibroblasts. IF is an indolent subcutaneous or intramuscular nodule that is most commonly found on the extremities, head and neck.1, 2 This article is protected by copyright. All rights reserved.

Summary: Medication-related osteonecrosis of jaws (MRONJ) is one of the most complicated inflammatory conditions in oral and maxillofacial region. It is very difficult to correctly evaluate the degree and extent of necrosis and infection. This refractory osteonecrosis often needs extended surgery, leading to impaired quality-of-life. We have performed hyperbaric oxygen therapy (HBO) combined with conservative surgery for advanced cases. We have appraised the value of FDG-PET and 3-phase bone scintigraphy in the diagnosis and management of this condition. MRONJ showed significantly higher SUVmax on FDG-PET than the others. Although the 3 phase pool bone images did not change significantly, perfusion and static bone image as well as PET showed remarkable response to HBO for MRONJ. SUVmax after HBO was significantly lower than those of before HBO. These preliminary results indicate that FDG-PET is useful for monitoring the effect of HBO for MRONJ.

Objective Roles of aging or immune responses mediated by Toll-like receptors and natural killer cell in the onset or progression of human candidiasis remain unclear. This study was designed to elucidate the roles using peripheral blood mononuclear cells from healthy donors and patients with oral candidiasis. Subjects and methods Subjects tested were healthy volunteers and patients who visited Dental Clinical Division of Hokkaido University Hospital. The patients with oral candidiasis included 39 individuals (25–89 years of age) with major complaints on pain in oral mucosa and/or dysgeusia. Healthy volunteers include students (25–35 years of age) and teaching staffs (50–65 years of age) of Hokkaido University Graduate School of Dental Medicine. Results Functions of Toll-like receptors 2 and 4 were downregulated significantly and the natural killer activity was slightly, but not significantly downregulated in aged healthy volunteers compared with healthy young volunteers. Functions of Toll-like receptors 2 and 4 and the natural killer activity were significantly downregulated in patients with oral candidiasis compared with healthy volunteers. Conclusion Downregulation of functions of Toll-like receptors 2 and 4 as well as natural killer activity is suggested to be associated with the onset or progression of oral candidiasis in human.

Objective To evaluate gradual dose escalation and tolerability of paroxetine in patients with burning mouth syndrome (BMS). Methods This 12-week, open-label, non-comparative, prospective study involved 43 subjects with depressive condition. The initial dosage of paroxetine was 10 mg/day, but was raised to 20 mg/day and 30 mg/day if efficacy was not sufficient. Pain was assessed using the visual analog scale (VAS) at baseline and at weeks 2, 4, 8, and 12 of the study treatment. Results The mean VAS score at each time point was significantly lower than at baseline ( P t -test) after paroxetine treatment. The effects of paroxetine were dose-dependent. The cumulative improvement rates for daily doses of 10 mg, 20 mg, and 30 mg were 37.2%, 67.4%, and 74.4%, respectively. The cumulative proportion of responders was significantly higher for patients with maximal daily doses of 20 mg and 30 mg than in patients receiving 10 mg/day ( P χ 2 test). Adverse events were observed in 26 of 49 (53%) patients evaluated for safety, with most adverse events appearing when patients were taking 10 mg/day. The incidence of adverse events did not show a time- or dose-dependent increase, except for constipation. No serious safety issues were noted. Conclusions Dose escalation of paroxetine may be useful in treating patients with BMS and depressive conditions.

Hypoxia, a prognostic factor in many types of cancer, can be detected by 18F-fluoromisonidazole (FMISO) positron emission tomography (PET). It is unclear whether hypoxia reflects the response to chemotherapy in patients with oral squamous cell carcinoma (OSCC). The correlations of FMISO-PET and FDG-PET with histological response to preoperative chemotherapy were therefore assessed in patients with OSCC. This study enrolled 22 patients with OSCC undergoing preoperative chemotherapy. The T-stages were T2 in 6 patients, T3 in 3, and T4a in 13, and the N-stages were N0 in 14 patients, N1 in 3, and N2 in 5. Each patient was evaluated by both FMISO-PET and FDG-PET before surgery, and the maximum standardized uptake value (SUVmax) of FDG- and FMISO-PET and tumor-muscle ratio (TMR) of FMISO-PET were measured. The threshold for the hypoxic volume based on TMR was set at 1.25. The histological response to preoperative chemotherapy was evaluated using operative materials. FMISO-PET and FDG-PET detected uptake by primary OSCCs in 15 (68 %) and 21 (95 %) patients, respectively, and median SUVmaxs of FMISO- and FDG-PET in the primary site were 2.0 (range, 1.3–3.5) and 16.0 (range, 1.0–32.2), respectively. The median of FMISO TMR was 1.5 (range, 0.99–2.96). There were five cases whose FMISO TMR was less than 1.25. Histological evaluation showed good response to preoperative chemotherapy in 7 patients (32 %) and poor response in 15 (68 %). Good response was significantly more prevalent in patients with negative than positive FMISO uptake (P

Background Although taxanes (TAX) are effective for advanced cutaneous angiosarcoma (CAS) and stand as a current first-line treatment, no standardized second-line treatment has yet been established. Eribulin methylate (ERB), a non-taxane microtubule inhibitor, improved the overall survival (OS) of patients with advanced sarcoma compared to dacarbazine in a randomized, phase 3 trial. Based on this study, ERB was approved to use for all types of sarcoma in Japan. We hypothesized that ERB would be most active in patients with TAX-resistant CAS as both TAX and ERB target microtubules but through different mechanisms. Methods We designed a single-arm, prospective observational study of ERB administered at a dose of 1.4mg/m2 on days 1 and 8 in a 21-day cycle. Advanced, TAX-resistant CAS patients scheduled for ERB use were enrolled. The primary endpoint was OS and the secondary endpoints were response ratio (RR), progression-free survival (PFS), and toxicity assessment. Results The last patient was enrolled in January 2018 and the data was locked at the end of March 2019. In total, 25 patients with CAS (median age 74) were enrolled. All patients had prior TAX exposure and 5 patients had 2 or more prior therapy courses. All patients except 1 had their primary tumours in the head and neck while 10 patients had distant metastasis. Performance status (PS) was generally good; 14 were PS0, 8 were PS1, and 3 were PS2. The median follow-up period was 250 (16-849) days. The rate of OS and PFS at 6 months estimated by Kaplan-Meier method was 67% and 24%, respectively. Median OS and PFS were 8.6 and 3.0 months, respectively. RR at week 7, 13, and 25 were 24% (6/25), 16.7% (4/25) and 13% (3/23), respectively. Although 10 patients experienced severe toxicity (8 had neutropenia, 2 had anemia and 1 had a retroperitoneal abscess), they all recovered. Conclusions ERB showed a promising and durable response and was well-tolerated in TAX-resistant CAS. Both RR and OS were comparable to previous results where ANGIOTAX was used as a second-line treatment. The most common toxicity was neutropenia but this was manageable. Taken together, this study provides evidence to support ERB use in TAX-resistant CAS cases. Clinical trial identification UMIN000023331. Legal entity responsible for the study The authors. Funding Maruho Takagi Dermatology Foundation. Disclosure All authors have declared no conflicts of interest.

Mucin core protein (MUC) 5AC is a gel-forming glycoprotein that is expressed in different types of tumour cells. MUC5AC expression in cultured cells is regulated through the extracellular matrix and through remodelling by other membranous proteins such as type IV collagen (COL4) and E-cadherin. However, it has not been elucidated whether COL4 and E-cadherin affect MUC5AC expression in tumours in vivo. Here, by analysing a single individual with concomitant neoplasms in the skin [extramammary Paget disease (EMPD)] and the stomach (gastric cancer), we show that MUC5AC expression is reduced in COL4 and membranous E-cadherin-expressing EMPD specimens whereas MUC5AC is not abolished in gastric cancer with COL4 negativity and E-cadherin cytoplasmic localization. As the EMPD and gastric cancer specimens were derived from a single patient, each specimen had the same genetic background. These in vivo results support previous in vitro studies which showed that COL4 and E-cadherin downregulated MUC5AC expression. Our study suggests that concomitant neoplasms in different organs of the same individual can serve as a strong tool for uncovering functional diversity in tumour markers in distinct cancer cells.