Systemically Administered D-allose Inhibits the Tumor Energy Pathway and Exerts Synergistic Effects With Radiation.

BACKGROUND/AIM: The present study investigated the anticancer effects of intraperitoneally administered D-allose in in vivo models of head and neck cancer cell lines. MATERIALS AND METHODS: To assess the direct effects of D-allose, its dynamics in blood and tumor tissues were examined. RESULTS: D-allose was detected in blood and tumor tissues 10 min after its intraperitoneal administration and then gradually decreased. In vivo experiments revealed that radiation plus D-allose was more effective than either treatment alone. Thioredoxin-interacting protein (TXNIP) mRNA over-expression was detected after the addition of D-allose in in vitro and in vivo experiments. D-allose inhibited cell growth, which was associated with decreases in glycolysis and intracellular ATP levels and the prolonged activation of AMPK. The phosphorylation of p38-MAPK was also observed early after the administration of D-allose and was followed by the activation of AMPK and up-regulated expression of TXNIP in both in vitro and in vivo experiments. CONCLUSION: Systemically administered D-allose appears to exert antitumor effects. Further studies are needed to clarify the appropriate dosage and timing of the administration of D-allose and its combination with other metabolic agents.

Assessment of eosinophilic rhinosinusitis cases that required secondary treatment (biologics or reoperation) during long-term postoperative courses.

OBJECTIVE: Endoscopic sinus surgery (ESS) is selected as the primary treatment for eosinophilic chronic rhinosinusitis (ECRS). Biologics or reoperation are sometimes required as secondary treatment after ESS. The present study examined the long-term postoperative courses of ECRS cases treated according to the current treatment concept, the frequency of secondary treatment, and its predictive factors. METHODS: Ninety-four patients with ECRS who underwent ESS and received continuous management for 1-5 years were retrospectively investigated. Patient characteristics, long-term changes in endoscopic scores and the results of olfactory function tests, and secondary treatment were evaluated. RESULTS: Five patients underwent reoperation and 11 received dupilumab during the follow-up period (35.9±19.2 months). Sixteen patients (17%) required secondary treatment due to the deterioration of sinus conditions. These patients were significantly younger, had higher comorbidity rates of allergic rhinitis and bronchial asthma, and a higher preoperative CT score than those who did not require secondary treatment. Three months after surgery, CT scores, endoscopic scores (E-scores), and the self-administered odor questionnaire (SAOQ) were significantly worse in patients who required secondary treatment. A multivariate regression analysis identified age, preoperative CT scores, and 3-month E-scores as predictive factors for secondary treatment. Three-month E-scores showed higher sensitivity and specificity, and the odds ratio was 11.3 when the cut-off value was set at 10. CONCLUSION: The early identification of patients for whom ESS may fail is important and additional treatments need to be provided at the appropriate timing where needed. Patients with the following factors need to be carefully followed up: a young age, high preoperative CT score, and high early postoperative E-score.

[LOWER RESPIRATORY TRACT SCREENING USING FRACTIONAL EXHALED NITRIC OXIDE IN PATIENTS WITH EOSINOPHILIC CHRONIC RHINOSINUSITIS].

BACKGROUND: It is known that eosinophilic chronic rhinosinusitis is often associated with adult-onset bronchial asthma, and undiagnosed bronchial asthma is also known to be included. The purpose of this study is to screen patients with eosinophilic chronic rhinosinusitis using fractional exhaled nitric oxide, and to examine its usefulness in detecting undiagnosed bronchial asthma. METHODS: We retrospectively examined the data of patients with eosinophilic chrnoic rhinosinusitis who underwent surgical treatment at Kagawa University from April 2015 to July 2022. Patients were included if they received examinations of fractional exhaled nitric oxide and spirometry before surgical treatment. RESULTS: Of the 127 subjects, 52 had no history of treatment or diagnosis of bronchial asthma at the initial consultation. Among them, 15 patients who had high fractional exhaled nitric oxide value were diagnosed with bronchial asthma by the respiratory medicine department. Comorbid of bronchial asthma was eventually increased to 70.9% even though it was 59.1% at initial consultation. CONCLUSION: A certain number of patients with eosinophilic chronic rhinosinusitis have undiagnosed bronchial asthma, which can be difficult to detect with basic examination alone therefore fractional exhaled nitric oxide is useful as an additional screening examination.

Early postoperative endoscopic score can predict the long-term endoscopic outcomes in eosinophilic chronic rhinosinusitis (ECRS) patients.

OBJECTIVE: Eosinophilic Chronic Rhinosinusitis (ECRS) is refractory and recurrent, requiring long-term follow-up after Endoscopic Sinus Surgery (ESS). Endoscopic evaluation is common during postoperative assessment, but how the findings vary over time in postoperative ECRS patients who were treated by the recent standardized management is unclear. We assessed the long-term change in postoperative endoscopic score in ECRS patients using a novel endoscopic scoring system (Escore). METHODS: This retrospective study included 80 ECRS patients who underwent full-house ESS and were followed for longer than 1-year. Endoscopic procedures were repeated at every follow-up visit and postoperative Escores were assessed from 3-months up to 5-years (median follow-up period was 3-years). RESULTS: The Escore did not significantly change from that at 3-months (3m-Escore). The Escore at the final observation point (f-Escore) among 80 patients was 9.2 ± 5.6 and there was no significant difference from the 3m-Escore (8.5 ± 4.1, p = 0.363). Twenty-one patients (21/80, 26.3%) were considered to have endoscopically uncontrolled ECRS at their final observation points and the 3m-Escore was identified as an independent predictive factor by multivariate logistic regression analysis. The 3m-Escore cut-off value that was able to predict endoscopically uncontrolled ECRS after long-term follow-up was ≥12. CONCLUSION: We demonstrated the long-term endoscopic outcomes after full-house ESS and continuous outpatient treatment. Early endoscopic findings (3m-Escore) were a potential predictive factor for the later endoscopic outcome, and a 3m-Escore of 12 or higher may be an indicator of the poor long-term prognosis of sinus mucosa.

A highly specific recurrent pleomorphic adenoma of the nasal septum.

A 90-year-old woman presented with the sudden onset of visual loss. She previously underwent surgery to treat a right septal pleomorphic adenoma (PA) at 77 years old. She initially presented to our hospital with severe nasal obstruction at 83 years old. A large tumor occupied the bilateral nasal cavities and, thus, surgery was performed using midfacial degloving and an endoscopic endonasal combined approach. A 60×45×43 mm tumor was completely removed; however, a small area of the tumor capsule was damaged. Six years after surgery, PA recurred in the posterior midline portion of the nasal cavity. Imaging examinations revealed a 48×42×45 mm mass, which compressed the bilateral optic canal, thereby causing severe visual loss. The recurrent tumor was endoscopically removed, and vision recovered after surgery. The lack of malignant transformation was pathologically confirmed throughout this period. The present case had several highly specific features: she was very elderly, the tumor was very large, and visual dysfunction was caused by nasal PA. We described surgical procedures in detail and considered the specific findings of the present case. En bloc resection with a sufficient margin was considered to be important in the present case because recurrence may be caused by incomplete excision.

The Utility of Glasgow Prognostic Score and Palliative Prognostic Index in Patients With Head and Neck Squamous Cell Carcinoma Under Palliative Care.

OBJECTIVES: Palliative care patients with head and neck squamous cell carcinoma (HNSCC) often experience dysphagia and airway trouble; thus, each patient requires a specific palliative care plan based on their prognostication. However, no established specific prognostic tool performed on the day of starting end-of-life care is available for such patients. We assessed the accuracy of Glasgow prognostic score (GPS) and palliative prognostic index (PPI) and their combination to establish a specified prognostic tool for patients with HNSCC in end-of-life setting. METHODS: A retrospective clinical chart review was undertaken on patients with HNSCC in end-of life setting who were decided in Kagawa University Hospital and National Hospital Organization Shikoku Cancer Center between April 2011 and March 2019. The patients were divided into 2 categories according to GPS (0-1 and 2) and PPI (groups A-B and C). These were combined into 4 categories (PPI group A-B and GPS score 0-1: good; PPI group A-B and GPS score 2: intermediate; PPI group C and GPS score 2: poor; and PPI group C and GPS score 0-1: others). The survival curves were compared for the former 3 categories. RESULTS: The median survival of the scores 0-1 and 2 on GPS were 114 (72-148) and 39 (25-52) days, respectively (P < .01). These of groups A-B and C on PPI were 79 (64-99) and 16 (9-29) days, respectively (P < .01). The median survival of the good, intermediate, and poor categories was 127 (73-149), 64 (44-80), and 15 (9-27) days, respectively (P < .01 among all categories). CONCLUSIONS: In this study, the survival of terminally ill patients with HNSCC can be predicted by the GPS, PPI, and their combination with sufficient probability.

Early postoperative endoscopic score can predict the long-term endoscopic outcomes in eosinophilic chronic rhinosinusitis (ECRS) patients

Abstract Objective: Eosinophilic Chronic Rhinosinusitis (ECRS) is refractory and recurrent, requiring long-term follow-up after Endoscopic Sinus Surgery (ESS). Endoscopic evaluation is common during postoperative assessment, but how the findings vary over time in postoperative ECRS patients who were treated by the recent standardized management is unclear. We assessed the long-term change in postoperative endoscopic score in ECRS patients using a novel endoscopic scoring system (Escore). Methods: This retrospective study included 80 ECRS patients who underwent full-house ESS and were followed for longer than 1-year. Endoscopic procedures were repeated at every follow-up visit and postoperative Escores were assessed from 3-months up to 5-years (median follow-up period was 3-years). Results: The Escore did not significantly change from that at 3-months (3m-Escore). The Escore at the final observation point (f-Escore) among 80 patients was 9.2 ± 5.6 and there was no significant difference from the 3m-Escore (8.5 ± 4.1, p = 0.363). Twenty-one patients (21/80, 26.3%) were considered to have endoscopically uncontrolled ECRS at their final observation points and the 3m-Escore was identified as an independent predictive factor by multivariate logistic regression analysis. The 3m-Escore cut-off value that was able to predict endoscopically uncontrolled ECRS after long-term follow-up was ≥12. Conclusion: We demonstrated the long-term endoscopic outcomes after full-house ESS and continuous outpatient treatment. Early endoscopic findings (3m-Escore) were a potential predictive factor for the later endoscopic outcome, and a 3m-Escore of 12 or higher may be an indicator of the poor long-term prognosis of sinus mucosa. Level of evidence: 4.

Short-term outcomes of olfaction in patients with eosinophilic chronic rhinosinusitis after endoscopic sinus surgery and an assessment of prognostic factors.

BACKGROUND: Olfactory dysfunction is one of the common symptoms of eosinophilic chronic rhinosinusitis (ECRS), for which endoscopic sinus surgery (ESS) is the standard treatment. Although the success rates of ESS for restoring olfaction in CRS have been reported, those for ECRS, as defined by new Japanese diagnostic criteria, remain unclear and the parameters affecting improvement rates have not yet been identified. METHODS: Eighty-four patients with ECRS who underwent full-house ESS were retrospectively investigated. Olfactory function was examined using T&T recognition thresholds before and 3 months after surgery. RESULTS: The total positive improvement rate in olfaction was 76.2% (64 of 84) and the mean T&T recognition threshold decreased significantly from 5.2 ± 1.1 to 3.0 ± 1.8 after surgery (p < 0.001). Some factors, including negative intravenous olfaction test, presence of olfactory cleft (OC) lesions, a history of sinus surgery, age ≥ 45 years, and being male, were more frequent in the olfaction refractory group. Furthermore, improvement of the T&T recognition threshold was significantly lower for factors of negative intravenous olfaction testing, the presence of OC lesions, and being male. Age and the proportion of blood eosinophils correlated with improvement. CONCLUSION: Herein we examined prognostic factors for olfactory outcomes in ECRS treated with ESS. The intravenous olfaction test, presence of OC lesions, sex differences, and age (the cut-off value was 45 years) were identified as independent prognostic factors for olfactory outcomes 3 months after surgery.

Impact of Preoperative Systemic Corticosteroids on the Histology and Diagnosis of Eosinophilic Chronic Rhinosinusitis.

BACKGROUND: The histological changes corticosteroids induce in nasal polyps, and whether these changes have an impact on the diagnosis of eosinophilic chronic rhinosinusitis (ECRS), currently remain unclear. OBJECTIVES: A prospective controlled multicenter trial was conducted to evaluate the efficacy of the low-dose and short-term oral prednisolone (oPSL) treatment for tissue eosinophil infiltrations in ECRS. METHODS: Subjects with ECRS diagnosed by previous biopsies received a low dose of oPSL for 3 days (PSL 3) or 7 days (PSL 7) before surgery. Changes in the tissue eosinophil count after these treatments were evaluated. Furthermore, the percent change of tissue eosinophil count from baseline and its impact on the diagnosis defined by the JESREC study were examined. RESULTS: There were 23 and 21 subjects in the PSL 3 and PSL 7 groups, respectively. Polyp scores, clinical symptom scores, and the proportion of blood eosinophils significantly decreased after the treatment, and no significant differences were observed between the groups. The entire tissue eosinophil count tended to be slightly decreased in both groups without reaching a statistically significant value. The median percent change of tissue eo-sinophil count from baseline was 83.6%, and only the posttreatment proportion of blood eosinophil showed a mild correlation with it. Seven out of 44 nasal polyp specimens collected from the superficial part of the middle meatus showed < 70 eosinophils/high-power field; therefore, the false negative rate was 15.9%, but decreased to 11.4% when other parts were included in the histological evaluation. CONCLUSIONS: Low-dose and short-term oPSL did not appear to markedly affect the tissue eosinophil count in ECRS patients; however, the potential for misdiagnoses due to the effects of oPSL cannot be rejected. The diagnosis of ECRS prior to the administration of corticosteroids or tissue evaluations using multiple tissue parts is desirable.

Assessment of Simultaneous Surgery for Odontogenic Sinusitis: Endoscopic Sinus Surgery With Endoscopic Apicoectomy.

Odontogenic sinusitis (OS) is a disease commonly encountered by otolaryngologists and oral surgeons. There is currently no standard consensus for the management of the causative teeth of OS, and the therapeutic outcomes of endodontic surgery remain unclear. The authors herein report the outcomes of simultaneous surgery for OS, endoscopic sinus surgery (ESS) with endoscopic apicoectomy. Twenty-one OS patients who underwent ESS were included in the intent-to-treat population. Eleven patients who simultaneously underwent endoscopic apicoectomy were included as the study group, and another 10 patients who were subjected to the extraction of the causative teeth preceding or during surgery were included as the control group. The postoperative tooth course after surgery in the study group was assessed as the primary outcome by periodic radiographs. The postoperative sinus course was compared between the 2 groups as the secondary outcome. Seventeen teeth were subjected to endoscopic apicoectomy concurrently with ESS, and the treatment success rate for periapical lesions was 94.1% (16 out of 17 teeth), which was consistent with previously reported outcomes for endodontic microsurgery. Ten of 11 patients (90.9%) had good postoperative sinus courses, and the mean wound-healing period of the sinus mucosa was 6.9 ±â€Š3.5 weeks. These results were not significantly different from those obtained for the control group (90% and 6.1 ±â€Š3.2 weeks). This surgical procedure may contribute to the preservation of causative teeth without having an impact on the successful treatment of sinusitis. A comprehensive surgical approach by otolaryngologists and oral surgeons is desirable for the treatment of OS.

Clinical effects of submucosal middle turbinectomy for eosinophilic chronic rhinosinusitis.

OBJECTIVE: The preservation or resection of the middle turbinate (MT) during endoscopic sinus surgery (ESS) currently remains a matter of debate. The present study aimed to investigate the effects of submucosal middle turbinectomy (SMT) in ESS for eosinophilic chronic rhinosinusitis (ECRS). METHODS: The study included 38 ECRS patients (63 sides) who had undergone full-house ESS with SMT and 20 ECRS patients (40 sides) without SMT as a control group. Post-operative middle turbinate lateralization (MTL), synechia formation, and the patency grade of the olfactory cleft (OC) were assessed as the primary outcomes 3 months after surgery. CT scans and the T&T test were performed on the SMT group 3 months after surgery and assessed as secondary outcomes. RESULTS: MTL and synechia formation rates were slightly higher in the control group than in the SMT group (20% vs. 7.9%, p=0.072, 17.5% vs. 9.5%, p=0.235), although neither reached statistically significance. The mean patency score of OC was significantly better in the SMT group than in the control group (0.5±0.6 vs. 1.3±0.7, <0.001). CT findings and T&T test scores showed good improvements after SMT combined with ESS. No major adverse events occurred due to SMT. CONCLUSION: We demonstrated the potential advantages of SMT for ECRS patients. This method may avoid physiological functional loss through its preservation of the mucosa and structure of the MT.

Preference evaluation and perceived sensory comparison of fluticasone furoate and mometasone furoate intranasal sprays in allergic rhinitis.

OBJECTIVE: Intranasal corticosteroid sprays (INCSs) are commonly used for therapy of allergic rhinitis (AR). Adherence to regular use of INCSs is influenced by patient perception and preferences of products. The study objective was to compare perceived sensory attributes of fluticasone furoate nasal spray (FFNS) and mometasone furoate nasal spray (MFNS) in AR patients. METHODS: In a multicenter, randomized, crossover, prospective study, 40 seasonal AR patients were administered both FFNS and MFNS for 2 weeks each in a crossover fashion, for a total of 4 weeks. Patients completed questionnaires for each product regarding perceived sensory attributes at the end of each two-week period of product administration. RESULTS: FFNS was significantly preferred over MFNS. Significantly, fewer subjects perceived a bitter taste (p=0.01), medication running down their throat (p=0.033), and medication running out of their nose (p=0.002) with FFNS. MFNS was more frequently reported to induce nasal irritation (p=0.012), sneezing (p=0.017), and rhinorrhea (p=0.007) compared to FFNS. Interestingly, these findings were markedly observed in females. Medicine dripping out of the nose and nasal shooting were the most common problems reported for MFNS with a higher proportion of subjects who felt moderate-to-severe discomfort. Overall, 52.5% of patients expressed a preference for FFNS compared with 22.5% for MFNS. CONCLUSION: Several perceived sensory attributes of FFNS were rated significantly superior to MFNS. FFNS may contribute to enhanced treatment outcomes in AR patients due to improved treatment adherence.

Prognostic value comparison between (18)F-FLT PET/CT and (18)F-FDG PET/CT volume-based metabolic parameters in patients with head and neck cancer.

PURPOSE: The present study compared the potential of pretreatment 3'-deoxy-3'-[F]-fluorothymidine (F-FLT) uptake parameters and those of F-FDG to predict the clinical outcome of head and neck squamous cell carcinoma treated with chemoradiotherapy. METHODS: A total 53 patients undergoing pretreatment F-FLT PET/CT and F-FDG PET/CT from May 2006 to April 2013 were evaluated. The SUVmax, metabolic tumor volume (MTV), total lesion glycolysis, and total lesion proliferation (TLP) were determined semiquantitatively. Associations between clinical factors and PET/CT parameters and prognostic value were analyzed. RESULTS: In univariate analyses, F-FLT SUVmax, MTV, TLP, F-FDG MTV, and total lesion glycolysis correlated with locoregional control (P = 0.02, P = 0.0007, P = 0.0001, P = 0.007, and P = 0.013, respectively). Clinical T stage, F-FLT SUVmax, MTV, TLP, and F-FDG SUVmax correlated with overall survival (P = 0.012, P = 0.0057, P = 0.0018, P = 0.0012, and P = 0.047, respectively). On multivariate analyses, F-FLT TLP was an independent factor for locoregional control (P = 0.002; hazards ratio [HR], 5.13; 95% confidence interval [CI], 1.81-14.54), as were F-FLT SUVmax and MTV for overall survival (P = 0.021; HR, 3.47; 95% CI, 1.2-10.01 and P = 0.029; HR, 3.17; 95% CI, 1.12-8.95). CONCLUSIONS: Pretreatment F-FLT PET/CT volume-based metabolic parameters are superior prognostic predictors to those of F-FDG PET/CT. F-FLT SUVmax and MTV can provide important prognostic information for patients with head and neck squamous cell carcinomas administered with chemoradiotherapy.

Predictive value of SUV-based parameters derived from pre-treatment (18)F-FLT PET/CT for short-term outcome with head and neck cancers.

OBJECTIVE: The aim of this study was to investigate the predictive potential of pre-treatment 3'-deoxy-3'-[18F]-fluorothymidine (FLT) uptake parameters for short-term outcome of primary head and neck squamous cell cancer (HNSCC) patients. PATIENTS AND METHODS: A total of 32 patients undergoing pre-treatment FLT positron emission tomography/computed tomography (PET/CT) from May 2010 to May 2013 were evaluated. Semi-quantitative assessment was used to determine mean, peak and maximum standardized uptake values (SUVmean, SUVpeak and SUVmax), metabolic tumor volume (MTV) and total lesion proliferation (TLP). Clinicopathologic factors and PET/CT parameters were analyzed for their association with 2-year loco-regional control (LRC) and overall survival (OS). RESULTS: The mean (± SD) SUVmean, SUVpeak, SUVmax, MTV and TLP were 5.97 ± 3.16, 6.71 ± 3.75, 10.05 ± 5.37, 7.31 ± 8.05 and 44.95 ± 52.82, respectively. In univariate analyses, N category was associated with OS (P = 0.037). Increased MTV ≥13 ml was associated with decreased LRC and OS (P < 0.0001). TLP ≥69.3 g was also linked with both LRC and OS (P = 0.009 and 0.015, respectively). Regarding SUVs, only the SUVpeak was associated with LRC and OS (P = 0.035 and 0.049, respectively). CONCLUSIONS: Pre-treatment MTV is the most useful parameter with FLT PET/CT. TLP and SUVpeak may also provide important prognostic information for patients with HNSCCs.

Blindness caused by septic superior ophthalmic vein thrombosis in a Lemierre Syndrome variant.

A 65-year-old man presented with right facial cellulitis and right blindness. Enhanced CT and MRI showed right facial cellulitis involved with pterigopalatine fossa. Additionally, orbital cellulitis, superior ophthalmic vein thrombosis, and pulmonary multiple nodules were observed. (18)F-FDG PET/CT supported these findings. He was diagnosed with septic superior ophthalmic vein thrombosis accompanied with Lemierre Syndrome variant and was treated mainly by the administration of intravenous antibiotics. His symptoms and image findings improved after a few days of treatment, but the right visual loss has not recovered. Since septic superior ophthalmic vein thrombosis and Lemierre Syndrome both have life-threatening potential, early diagnosis and appropriate treatment are important and may contribute to reduce the incidence of severe complications. Septic superior ophthalmic vein thrombosis accompanied with Lemierre Syndrome is exceeding rare, and this case is the first report of blindness in Lemierre Syndrome. A literature review and discussion of septic superior ophthalmic vein thrombosis and Lemierre Syndrome are included.