Predictive value of local control by 4'-[methyl-11C]-thiotymidine PET volume parameters in p16-negative oropharyngeal, hypopharyngeal, and supraglottic squamous cell carcinoma.

PURPOSE: We investigated the potential of baseline 4'-[methyl- 11 C]-thiothymidine ([ 11 C]4DST) PET for predicting loco-regional control of head and neck squamous cell carcinoma (HNSCC). METHODS: A retrospective analysis was performed using volumetric parameters, such as SUVmax, proliferative tumor volume (PTV), and total lesion proliferation (TLP), of pretreatment [ 11 C]4DST PET for 91 patients with HNSCC with primary lesions in the oral cavity, hypopharynx, supraglottis, and oropharynx, which included p16-negative patients. PTV and TLP were calculated for primary lesions and metastatic lymph nodes combined. We examined the association among the parameters and relapse-free survival and whether case selection focused on biological characteristics improved the accuracy of prognosis prediction. RESULTS: The area under the curves (AUCs) using PTV and TLP were high for the oropharyngeal/hypopharyngeal/supraglottis groups (0.91 and 0.87, respectively), whereas that of SUVmax was 0.66 ( P  < 0.01). On the other hand, the oral group had lower AUCs for PTV and TLP (0.72 and 0.77, respectively). When all cases were examined, the AUCs using PTV and TLP were 0.84 and 0.83, respectively. CONCLUSION: Baseline [ 11 C]4DST PET/CT volume-based parameters can provide important prognostic information with p16-negative oropharyngeal, hypopharyngeal, and supraglottic cancer patients.

Transoral robotic surgery (TORS) in Japan: procedures, advantages and current status.

Transoral robotic surgery (TORS), introduced by Weinstein et al. in 2005, has been widely adopted as a minimally invasive procedure, particularly for the treatment of patients with early stage oropharyngeal cancer. TORS is typically performed using the da Vinci Surgical System, similar to robot-assisted surgeries for other malignancies. The main difference between TORS and these other robot-assisted surgeries is that it is performed through the natural orifice of the mouth, which limits the surgical working space, and that it progresses from the lumen of the pharynx to the deeper tissues. The advantages of TORS are mainly due to the benefits of using the da Vinci Surgical System, such as three-dimensional high-definition images, magnification, multiple forceps articulation, tremor-stabilization function and motion scale function. To date, many big data and meta-analyses have shown that TORS is superior to conventional surgeries, such as open surgery, in terms of oncological outcomes, post-operative functionality and quality of life. In Japan, TORS is expected to spread across the country, as it has been covered by health insurance since April 2022. This review highlights the procedures of TORS, its unique aspects, its unparalleled advantages as a minimally invasive surgery for treating laryngeal and pharyngeal cancers, and its current status in Japan.

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.

Comparison of the accuracy of clinical prediction of survival and palliative prognostic index for patients with head and neck squamous cell carcinoma in the end-of-life setting.

OBJECTIVE: In the end-of-life stage of head and neck squamous cell carcinoma (HNSCC), predicting survival is essential to determine treatment procedure and place of care. Several reports have compared actual survival (AS) and clinical prediction of survival (CPS), a subjective prognostic prediction by attending physicians. However, specific studies focusing on patients with HNSCC are limited. Likewise, a comparison of the accuracy of CPS and palliative prognostic index (PPI), a prognostic tool using subjective assessment, has not been sufficiently investigated. This study aimed to clarify the correlation between AS and CPS/PPI and compare the accuracy of CPS and PPI in end-stage HNSCC. METHODS: This retrospective study included patients with HNSCC in the end-of-life setting. Patients were recruited from the National Hospital Organization Shikoku Cancer Center between April 2011 and March 2019. Data on basic demography and clinical parameters when patients decided to start end-of-life care at the head and neck oncology division were collected. We examined the correlation between AS and CPS using Spearman's correlation coefficients. The area under the receiver operating characteristic curve of CPS and PPI for 30-day survival prediction were compared for predictive accuracy. RESULTS: Among 98 eligible patients, 59 patients were enrolled in this study and analyzed. Of the 59 patients, CPS and PPI were calculated for 30 patients, whereas, only the PPI was calculated for 29 patients. The median AS and CPS were 35 (IQR: 9-73) days and 30 (IQR: 7-83) days, respectively. CPS and PPI (30 cases) were moderately correlated (r = 0.72, p<0.01). AS and CPS/PPI (30 cases) were significantly correlated (p<0.01) and showed a strong correlation (r = 0.86 and 0.80, respectively). In the 30-day survival prediction, the AUROCs of CPS and PPI (30 cases) were 0.967 (95%CI: 0.919-1) and 0.884 (95%CI: 0.767-1), respectively. Both CPS and PPI (30 cases) showed high accuracy in predicting the 30-day prognosis, with no significant difference (p = 0.077). The AUROC of PPI (59 cases) was 0.840 (95%CI: 0.711-0.969). CONCLUSIONS: AS and CPS/PPI showed significant correlations. The high accuracy of CPS may have been influenced by the fact that multiple head and neck cancer specialists at a comprehensive cancer center estimated CPS. Both CPS and PPI showed high prognostic accuracy in predicting 30-day survival. This suggests that PPI is useful in centers among physicians and healthcare workers unfamiliar with head and neck cancer.

Current Status of Transoral Surgery for Patients With Early-Stage Pharyngeal and Laryngeal Cancers in Japan.

As the laryngopharynx is closely related to swallowing, speech, and phonation, it is necessary to consider not only disease control but also a minimally invasive approach for the treatment of laryngopharyngeal cancer. Transoral surgery has been reported to be a minimally invasive method for treating these diseases. Transoral videolaryngoscopic surgery (TOVS) and endoscopic laryngo-pharyngeal surgery (ELPS) have been developed in Japan and recently emerged as treatments for patients with early stage pharyngeal and laryngeal cancers. However, securing an appropriate field of view and a narrow operating space during TOVS or ELPS are critical issues to be resolved for these surgeries. The clinical significance and safety of transoral robotic surgery (TORS) using the da Vinci Surgical System have been widely reported to provide surgeons with increased visualization and magnification, resulting in precise surgical margins and rapid functional recovery. In this context, a multi-institutional clinical study was conducted to evaluate the treatment outcomes of TORS for the treatment of laryngopharyngeal cancer in Japan, and the da Vinci Surgical System for oral robot-assisted surgery for these diseases was approved by the Pharmaceutical Affairs Agency in August 2018. This review provides an overview of the therapeutic effects of TOVS, ELPS, and TORS, with a particular focus on these therapeutic results in Japan.

Treatment outcomes of transoral robotic and non-robotic surgeries to treat oropharyngeal, hypopharyngeal, and supraglottic squamous cell carcinoma: A multi-center retrospective observational study in Japan.

OBJECTIVES: The aim of this multicenter retrospective cohort study was to compare efficacy and subsequent postoperative treatment between transoral robotic surgery (TORS) and any non-robotic transoral surgery in Japanese patients with early oropharyngeal squamous cell carcinoma (OPSCC), hypopharyngeal SCC (HPSCC), or supraglottic SCC (SGSCC). MATERIALS AND METHODS: Clinical information and surgical outcomes were compared between patients with early-stage OPSCC, HPSCC, and SGSCC who underwent TORS (TORS cohort) and those who underwent non-robotic transoral surgery, including transoral videolaryngoscopic surgery (TOVS), endoscopic laryngopharyngeal surgery (ELPS), and transoral laser microsurgery (TLM) (non-robotic cohort). The data of the Head and Neck Cancer Registry of Japan (registry cohort) were used to validate the comparison. The main outcomes were the presence of positive margins under pathology and the requirement for postoperative therapy, including radiotherapy or chemoradiotherapy. RESULTS: Sixty-eight patients in the TORS cohort, 236 patients in the non-robotic cohort, and 1,228 patients in the registry cohort were eligible for this study. Patients in the TORS cohort were more likely to have oropharyngeal tumor disease and T2/3 disease than those in the other cohorts (P<0.001 and P=0.052, respectively). The TORS cohort had significantly fewer patients with positive surgical margins than the non-robotic cohort (P=0.018), as well as fewer patients who underwent postoperative treatment, although the difference was not significant (P=0.069). In the subgroup analysis of patients with OPSCC, a total of 57 patients in the TORS cohort, 73 in the non-robotic cohort, and 171 in the registry cohort were eligible for the present study. Patients with OPSCC who underwent TORS were more likely to have lateral wall lesions than those in the other cohorts (P=0.003). The TORS cohort also had significantly fewer patients with positive surgical margins than the non-robotic cohort (P=0.026), and no patients in the TORS cohort underwent any postoperative treatment for OPSCC, although the difference was not significant (P=0.177). CONCLUSIONS: Our results suggest that TORS leads to fewer positive surgical margins than non-robotic transoral surgeries. The clinical significance of TORS may be further validated through the results of all-case surveillance for patients who underwent TORS running in Japan in the future.

Combined treatment with D-allose, docetaxel and radiation inhibits the tumor growth in an in vivo model of head and neck cancer.

The present study was designed to evaluate the effect of one rare sugar, D-allose, on normal human cells and cutaneous tissue, and to investigate the radiosensitizing and chemosensitizing potential of D-allose in an in vivo model of head and neck cancer. Results indicated that D-allose did not inhibit the growth of normal human fibroblasts TIG-1 cells, and no apoptotic changes were observed after D-allose and D-glucose treatment. The mRNA expression levels of thioredoxin interacting protein (TXNIP) in TIG-1 cells after D-allose treatment increased by 2-fold (50.4 to 106.5). Conversely, the mRNA expression levels of TXNIP in HSC3 cancer cells increased by 74-fold (1.5 to 110.6), and the thioredoxin (TRX)/TXNIP ratio was markedly reduced from 61.7 to 1.4 following D-allose treatment. Combined multiple treatments with docetaxel, radiation and D-allose resulted in the greatest antitumor response in the in vivo model. Hyperkeratosis, epidermal thickening and tumor necrosis factor-α immunostaining were observed following irradiation treatment, but these pathophysiological reactions were reduced following D-allose administration. Thus, the present findings suggest that D-allose may enhance the antitumor effects of chemoradiotherapy whilst sparing normal tissues.

Influence of volumetric 4'-[methyl-11C]-thiothymidine PET/CT parameters for prediction of the clinical outcome of head and neck cancer patients.

OBJECTIVE: This prospective study compared the value of pretreatment 4'-[methyl-11C]-thiothymidine (11C-4DST) volumetric parameters and those of 2-deoxy-2-[18F] fluoro-D-glucose (18F-FDG) in predicting the clinical outcome in patients with head and neck squamous cell carcinoma (HNSCC). METHODS: Fifty patients with HNSCC underwent 11C-4DST PET/CT and 18F-FDG PET/CT prior to anticancer therapy. 18F-FDG metabolic tumor volume (18F-FDG MTV) and total lesion glycolysis (TLG) were calculated from 18F-FDG PET, and 11C-4DST MTV and total lesion proliferation (TLP) were calculated from 11C-4DST PET. All parameters were measured for the primary lesion and metastatic lymph nodes. Associations between clinical factors and PET/CT parameters and prognostic value were analyzed. RESULTS: Receiver-operating characteristic analysis revealed that MTV, TLG, and TLP acquired from the primary lesion and metastatic lymph nodes were good parameters for predicting disease relapse and death. The area under the curves (AUCs) ranged from 0.63 to 0.71 for 18F-FDG PET/CT parameters. The AUCs of 11C-4DST PET/CT parameters were larger than those of 18F-FDG (range 0.72-0.81). Univariate analysis revealed that individuals with tumors showing a high value for any PET/CT parameter were at a significantly increased risk of relapse. Upon multivariate analysis, 18F-FDG MTV, 11C-4DST MTV and 11C-4DST TLP were significant independent factors for relapse-free survival (P = 0.04, P = 0.0001 and P = 0.0005, respectively). CONCLUSION: Pretreatment 11C-4DST PET/CT volume-based parameters can provide important prognostic information about patients with HNSCC.

Ion transport its regulation in the endolymphatic sac: suggestions for clinical aspects of Meniere's disease.

Ion transport and its regulation in the endolymphatic sac (ES) are reviewed on the basis of recent lines of evidence. The morphological and physiological findings demonstrate that epithelial cells in the intermediate portion of the ES are more functional in ion transport than those in the other portions. Several ion channels, ion transporters, ion exchangers, and so on have been reported to be present in epithelial cells of ES intermediate portion. An imaging study has shown that mitochondria-rich cells in the ES intermediate portion have a higher activity of Na+, K+-ATPase and a higher Na+ permeability than other type of cells, implying that molecules related to Na+ transport, such as epithelial sodium channel (ENaC), Na+-K+-2Cl- cotransporter 2 (NKCC2) and thiazide-sensitive Na+-Cl- cotransporter (NCC), may be present in mitochondria-rich cells. Accumulated lines of evidence suggests that Na+ transport is most important in the ES, and that mitochondria-rich cells play crucial roles in Na+ transport in the ES. Several lines of evidence support the hypothesis that aldosterone may regulate Na+ transport in ES, resulting in endolymph volume regulation. The presence of molecules related to acid/base transport, such as H+-ATPase, Na+-H+ exchanger (NHE), pendrin (SLC26A4), Cl--HCO3- exchanger (SLC4A2), and carbonic anhydrase in ES epithelial cells, suggests that acid/base transport is another important one in the ES. Recent basic and clinical studies suggest that aldosterone may be involved in the effect of salt-reduced diet treatment in Meniere's disease.

Clinical outcomes of nedaplatin and S-1 treatment with concurrent radiotherapy in advanced head and neck cancer.

CONCLUSION: Nedaplatin and S-1 treatment with concurrent radiotherapy was effective, with acceptable toxicities. This regimen does not require extensive intravenous hydration and continuous infusion. Nedaplatin and S-1 may contribute to better clinical outcomes and improve quality of life for patients. OBJECTIVES: We retrospectively analyzed the clinical efficacy and toxicity of concurrent chemoradiotherapy with nedaplatin and S-1 for head and neck squamous cell cancer. METHODS: Forty-six patients with oropharyngeal, hypopharyngeal, and laryngeal cancer were treated with S-1 on days 1 through 14 and nedaplatin on day 1 every 4 weeks for two cycles of radiotherapy. Therapeutic responses and adverse events were assessed. RESULTS: Primary site tumors and neck lymph nodes exhibited complete response rates of 91% and 64.3%, respectively. The 4-year relapse-free survival and overall survival rates were 76.2% and 85.3%, respectively. The main grade 3 and 4 toxicities were mucositis (30%), leukopenia (30%), anorexia (22%), dermatitis (15%), and thrombocytopenia (9%).

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.

[Significant factors for surgical site infection: analysis of 203 head and neck surgeries].

Surgical site infection (SSI) is a common complication in head and neck surgeries. The aim of this study was to assess the rate of, and risk factors for SSI following surgical procedures of the head and neck. The study population comprised 206 patients who underwent surgery of head and neck region in NTT West Osaka Hospital between 2009 and 2011. The incidence rate and risk factors were estimated by the chi-square test and a logistic regression analysis. SSI occurred in 22 cases (10.8%) of 203 patients. A broad range of putative risk factors was recorded in each patient and statistically analyzed to elucidate SSI related factors. Univariate analysis indicated that low BMI, diabetes mellitus, anemia, hypoalbuminemia, surgical wound classification, duration of operation, blood loss, left implants and preoperative radiotherapy were risk factors associated with SSI. Multivariate statistics revealed four independent risk factors: surgical wound classification (odds ratio (OR) 5.88, p = 0.02), hypoalbuminemia (OR 11.48, p < 0.01), duration of operation (OR 18.66, p < 0.01) and left implants (OR 20.24, p < 0.01). Thus, to achieve a reduction in SSI, we need to take care of not only the factors related with surgical technique such as the duration of the operation or left implants, but the preoperative nutrition status.

The value of 18F-FLT PET for detecting second primary cancers and distant metastases in head and neck cancer patients.

OBJECTIVE: Diagnostic efficacy of (18)F-FLT PET was compared with that of (18)F-FDG PET regarding second primary cancers and distant metastases of head and neck squamous cell cancers (HNSCCs). METHODS: A total of 88 patients with HNSCCs were qualitatively examined with FLT PET and FDG PET for regions of focally increased metabolism. Final diagnoses of second primary cancer and distant metastasis were established on the basis of histological findings or clinical follow-up. RESULTS: FDG PET had 1 false-negative finding with lung metastasis, and FLT PET had 4 false-negative findings with 1 liver metastasis, 1 bone metastasis, and 2 lung metastases. There were no false-positive findings with FLT PET in contrast to 9 with FDG PET (1 in lung, 4 in mediastinum, 1 in rectum, and 3 in stomach). Overall accuracy of FDG PET and FLT PET for pretreatment metastasis staging was 92% and 98%, respectively. Five distant metastases in 3 patients occurred after the initiation of chemoradiotherapy. FLT PET missed 2 metastatic lesions (1 in liver and 1 in lung), whereas FDG PET could not discriminate intracranial metastasis because of FDG uptake in the brain. CONCLUSIONS: FLT PET does not appear to be recommendable to replace FDG PET for pretreatment metastasis staging in HNSCC cases because of its lower sensitivity and higher background activity in the liver and bone marrow. However, it might provide additional diagnostic specificity and biological information.

Changes in (18)F-fluorothymidine and (18)F-fluorodeoxyglucose positron emission tomography imaging in patients with head and neck cancer treated with chemoradiotherapy.

OBJECTIVE: This study compared change of (18)F-fluorothymidine (FLT) uptake with that of (18)F-fluorodeoxyglucose (FDG) in head and neck squamous cell cancer (HNSCC) patients during and after treatment and evaluated the utility for early monitoring of response to chemoradiotherapy. METHODS: Thirty patients with newly diagnosed HNSCCs treated with concurrent chemoradiotherapy underwent FLT and FDG PET in pre-treatment (PET1), mid-treatment (PET2) and post-treatment (PET3) stages. The PET images were evaluated quantitatively using maximum standardized uptake values (SUVs). Ratios between SUVs at PET2 and PET3 were also calculated. RESULTS: According to the SUVs, no significant differences were found with primary site location, cellular differentiation and T category in all PET scans. About a 78 % median decrease in FLT SUV was observed at the total dose (TD) of 30 Gy and no apparent change was observed thereafter. About a 40 % decrease in FDG SUV was observed at TD 30 Gy and significant decreases were then found at the 4- and 6-week time points after the therapy. FLT PET demonstrated no recurrence regions in patients with a PET3/PET2 ratio of <1.5. In comparison, FLT SUVs in PET3 with recurrence were increased more than three times. However, no significant difference was found between the values with recurrence and those with no recurrence in FDG PET. CONCLUSION: FLT PET signal change preceded FDG PET change and the increase of FLT uptake after the therapy can imply recurrence or a residual tumor. FLT PET seems promising for early evaluation of chemoradiation effects in HNSCCs.

Comparison of ( 18 ) F-FLT PET and ( 18 ) F-FDG PET for detection of cervical lymph node metastases in head and neck cancers.

CONCLUSION: Despite low uptake of tracer, 3'-deoxy-3'-(18)F-fluorothymidine (FLT) PET could detect cervical lymph node metastases as well as 2-deoxy-2-(18)F-fluoro-d-glucose (FDG) PET. OBJECTIVE: The diagnostic efficacy of FLT PET was compared with that of FDG PET regarding nodal staging of head and neck squamous cell cancers. METHODS: Twenty-three patients were examined with FLT PET and FDG PET. PET images were evaluated qualitatively for regions of focally increased metabolism and maximum standardized uptake values (SUV) were calculated for semiquantitative analysis. RESULTS: The mean (± SD) FLT SUV in visualized metastatic lymph nodes was 4.8 ± 2.9 as compared with 6.9 ± 4.9 for FDG SUV (p < 0.001). Significant correlations were found between the area of metastatic lymph nodes and both FLT SUV (r = 0.8; p < 0.0001) and FDG SUV (r = 0.84; p < 0.0001). The false-positive (over-staged) and false-negative (under-staged) rates for lymph node staging by FLT PET were 4% (1/23) and 17% (4/23), respectively. Those for FDG PET were 9% (2/23) and 13% (3/23). All metastatic lymph nodes measuring more than 9 mm in short-axis diameter were correctly detected by FLT PET. However, both FLT and FDG PET had low sensitivity for detecting the lymph node metastases ≤ 9 mm in short-axis diameter and tumor deposits < 5 mm.

The mRNA of claudins is expressed in the endolymphatic sac epithelia.

OBJECTIVE: Claudins are a family of membrane proteins which localize to tight junctions (TJs). Recent studies have shown that claudins can form pores for ions in the TJs and regulate the permeability of epithelial paracellular ion transport. The endolymphatic sac (ES) is a part of the inner ear, absorbing the endolymphatic fluid. ES dysfunction may result in endolymphatic hydrops. In this study, we focused on the paracellular transport and examined claudin mRNA expression in the ES epithelia. MATERIALS AND METHODS: Total RNA was isolated from whole ES epithelia of rats by laser capture microdissection. RT-PCR was used to evaluate the expression of claudins. The expression of each claudin mRNA in the epithelial cells of rat ES was confirmed by in situ hybridization. RESULTS: RT-PCR indicated the expression of cldn2, cldn4, cldn6, cldn7, cldn9, cldn11, cldn12, and cldn14. The expression of these claudin mRNAs in the epithelial cells of rat ES was confirmed by in situ hybridization. CONCLUSION: We demonstrated mRNA expression of multiple claudins in the rat ES epithelia. These results in the ES epithelia were consistent with a role of claudins in paracellular ion transport.

Enhancement of the radiation effects by D-allose in head and neck cancer cells.

The aim of this study was to investigate the radiosensitizing potential of D-allose in human head and neck cancer cells. HSC-3 cells were treated with or without D-allose for 6 h and then irradiated (2-6 Gy). The combination of D-allose and radiation was more effective than either agent alone. The radiation enhancement ratios at the 37% survival level were 1.61 and 2.11 for 10 mM and 25 mM D-allose treatment, respectively. The combination of D-allose and radiation also reduced the cell proliferation in 3D culture experiments. Although the mRNA expression of TXNIP was not increased by radiation alone, combined use with D-allose markedly elevated TXNIP expression. The combination of D-allose and radiation significantly induced intracellular reactive oxygen species (ROS) and apoptosis compared to that induced by either agent alone. This study shows that D-allose enhances the effect of radiation, suggesting a potential clinical application of combination treatment with D-allose and radiation for head and neck cancer.

In vitro and in vivo effects of D-allose: up-regulation of thioredoxin-interacting protein in head and neck cancer cells.

OBJECTIVES: This study was aimed to investigate the relationship between the antiproliferative effects of D-allose and the up-regulation of thioredoxin-interacting protein (TXNIP) in head and neck cancer cells. METHODS: For the in vitro study, 5 oral squamous cell carcinoma cell lines (Ca9-22, HSC-3, HSC-4, SAS, and KON) were treated with 25 mmol/L D-allose. For the in vivo study, HSC-3 cells were used in a xenograft model with female athymic nude mice (BALB/c nu/nu; 5 to 6 weeks old). RESULTS: Inhibition of cell growth by D-allose was noted in HSC-3 and Ca9-22 cells, along with significant induction of TXNIP. Although TXNIP up-regulation was also evident, albeit to a lesser extent, in the remaining cell lines, D-allose did not inhibit their growth. With the HSC-3 line, the cell survival fractions decreased and TXNIP expression increased in a D-allose dose-dependent manner. The antiproliferative effects were partially suppressed by concomitant D-glucose treatment, which also reduced TXNIP expression. In the in vivo experiment, the tumor volume at day 15 after D-allose treatment was reduced to 61% of that of the control group. CONCLUSIONS: This study showed that D-allose exerts growth inhibitory effects on head and neck cancer cells in vitro and in vivo. The sugar may act as an antiproliferative agent via TXNIP induction and thus may be useful as a novel anticancer drug.

Expression and localization of 11beta-hydroxysteroid dehydrogenase (11betaHSD) in the rat endolymphatic sac.

CONCLUSIONS: 11beta-Hydroxysteroid dehydrogenase type 2 (11bHSD-2) enables aldosterone to bind to mineralocorticoid receptors (MRs) selectively by converting cortisol (corticosterone) into inactive metabolites. Its expression in the endolymphatic sac (ES) suggests that aldosterone may selectively act on the ES through its binding to MRs by the action of 11betaHSD-2, and supports the notion that ES is an aldosterone target organ. We propose that 11betaHSD-2 is a dominant isoform of 11betaHSDs in the ES, and the ES (especially the intermediate portion of the ES) may be the main aldosterone target in the inner ear. OBJECTIVE: The purpose of this study was to examine 11bHSD isoform expression in the rat inner ear, mainly 11betaHSD-2 in the ES. MATERIALS AND METHODS: In the ES and whole cochlea, 11betaHSDs were examined by RT-PCR using highly specific ES RNA by laser capture microdissection. In addition, 11betaHSD-2 localization in the rat ES was determined by immunohistochemistry. RESULTS: RT-PCR demonstrated 11betaHSD-2 expressed in the rat ES. In addition, its localization was observed mainly in the intermediate portion and a faint immune positive signal was observed in other parts of the ES. In contrast, 11bHSD-1 was undetectable in the ES by RT-PCR. Both types of 11betaHSDs were expressed in rat cochlea.