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Background: The purpose of this study was to analyze the relationship between pretreatment inflammatory markers and the prognosis of patients with oropharyngeal, hypopharyngeal, and laryngeal cancers., Methods: The data for 285 patients treated with curative intent by concurrent chemoradiotherapy (CRT) were obtained and their pretreatment inflammatory markers, including neutrophil-to-lymphocyte ratio (NLR), platelet-to-lymphocyte ratio (PLR), and lymphocyte-to-monocyte ratio (LMR) were calculated., Results: Significant relationships were observed between a high NLR and oropharyngeal or hypopharyngeal cancer, T3 to T4, N2b to N3, and clinical stage III to IV, whereas significant relationships were observed between a high LMR and laryngeal cancer, T1 to T2, and clinical stage I to II. With regard to survival outcomes, a high NLR, a high PLR, and a low LMR were all significantly associated with decreases in overall survival (OS) and disease-free survival (DFS). Furthermore, multivariate analysis showed that LMR was an independent prognostic factor., Conclusion: Pretreatment LMR was found to be an independent prognostic factor for patients with head and neck cancers treated by concurrent CRT. © 2016 Wiley Periodicals, Inc. Head Neck 39: 247-253, 2017., (© 2016 Wiley Periodicals, Inc.)

Background: The aim of this study was to investigate the expression of p53, p16, cyclin D1, epidermal growth factor receptor (EGFR) and Notch1 in temporal bone squamous cell carcinoma (TBSCC) tissue samples by immunohistochemistry (IHC), and to evaluate the association between these biomarkers and clinicopathological features., Methods: We performed a retrospective, single-institution review of 30 TBSCC patients treated with curative intent between April 2006 and March 2015. All tissue samples were obtained from pretreatment biopsy specimens or surgical specimens and using IHC staining., Results: Ten patients were categorized as T1, seven as T2, five as T3 and eight as T4. Nine patients had clinically positive lymph node metastasis. The positive expression of p53 and EGFR was significantly associated with T classification (P = 0.042 and P = 0.0039). EGFR expression was significantly more frequent in patients with positive lymph node metastasis compared with patients without node involvement (P = 0.017). In the analysis of the association between protein expression by IHC staining and prognosis, the positive expression of EGFR and Notch1 was significantly correlated with poor survival outcomes in TBSCC (P = 0.015 and P = 0.025) CONCLUSION: Overexpression of p53 and EGFR may be valuable biomarkers for identifying individuals at high risk of developing tumors in TBSCC. Furthermore, the positive expression of EGFR was significantly associated with poor survival outcome. Anti-EGFR therapy has potential for use as the treatment modality of choice for advanced-stage TBSCC as well as other head and neck squamous cell carcinomas.

We examined the capability of a gray-scale arterial spin labeling blood flow pattern variation (BFPV) map with two different post labeling delay (PLD) times to discriminate pannus in patients with rheumatoid arthritis (RA) at 3T. There was a statistically significant difference in the BFPV values between artery, pannus, and surrounding tissue. Furthermore, the color-coded BFPV map was able to accurately distinguish pannus from other tissues. These results suggest this approach may be capable of identifying pannus noninvasively.

It is assumed that resistance to ionizing radiation, as well as cross-resistance to other abiotic stresses, is a side effect of the evolutionary-based adaptation of anhydrobiotic animals to dehydration stress. Larvae of Polypedilum vanderplanki can withstand prolonged desiccation as well as high doses of ionizing radiation exposure. For a further understanding of the mechanisms of cross-tolerance to both types of stress exposure, we profiled genome-wide mRNA expression patterns using microarray techniques on the chironomid larvae collected at different stages of desiccation and after exposure to two types of ionizing radiation-70 Gy of high-linear energy transfer (LET) ions ( 4 He) and the same dose of low-LET radiation (gamma rays). In expression profiles, a wide transcriptional response to desiccation stress that much exceeded the amount of up-regulated transcripts to irradiation exposure was observed. An extensive group of coincidently up-regulated overlapped transcripts in response to desiccation and ionizing radiation was found. Among this, overlapped set of transcripts was indicated anhydrobiosis-related genes: antioxidants, late embryogenesis abundant (LEA) proteins, and heat-shock proteins. The most overexpressed group was that of protein-L-isoaspartate/D-aspartate O-methyltransferase (PIMT), while probes, corresponding to LEA proteins, were the most represented. Performed functional analysis showed strongly enriched gene ontology terms associated with protein methylation. In addition, active processes of DNA repair were detected. We assume that the cross-tolerance of the sleeping chironomid to both desiccation and irradiation exposure comes from a complex mechanism of adaptation to anhydrobiosis.

Objective: To determine the relationship between tumor glucose metabolism and tumor blood flow (TBF) in head and neck squamous cell carcinoma (HNSCC)., Methods: We retrospectively analyzed 57 HNSCC patients. Tumor glucose metabolism was assessed by maximum and mean standardized uptake values (SUVmax and SUVmean) obtained by 18F-fluorodeoxyglucose positron-emission tomography. TBF values were obtained by arterial spin labeling with 3-tesla MRI. The correlations between both SUVs and TBF were assessed in the total series and among patients divided by T-stage (T1-T3 and T4 groups) and tumor location (pharynx/oral cavity and sinonasal cavity groups). Pearson's correlation coefficients were calculated for significant correlations., Results: Significant correlations were detected: a negative correlation in the advanced T-stage group (TBF and SUV max: r, -0.61, SUVmean: r, -0.62), a positive correlation in the non-advanced T-stage pharynx/oral cavity group (TBF and SUVmax: r, 0.70, SUVmean: r, 0.73), a negative correlation in the advanced T-stage pharynx/oral cavity group (TBF and SUVmax: r, -0.62, SUVmean: r, -0.65), and a negative correlation in the advanced T-stage sinonasal cavity group (TBF and SUVmax: r, -0.61, SUVmean: r, -0.65)., Conclusion: Significant correlations between glucose uptake and TBF in HNSCC were revealed by the division of T-stage and tumor location., Competing Interests: The authors have declared that no competing interests exist.

Prophylactic neck dissection (PND) for patients with clinically N0 (cN0) tongue carcinoma remains controversial. We assessed the efficacy of PND for patients with cN0 tongue squamous cell carcinoma (SCC) and investigated the prognostic role of tumor thickness as assessed by diagnostic imaging in predicting the risk of nodal micrometastasis or late nodal recurrence. Eighty-eight patients with cN0 tongue carcinomas underwent surgical treatment. Tumor thickness was measured from magnetic resonance (MR) images or computed tomography (CT) scans. The overall survival rates of patients with or without PND were 94 and 81 %, respectively (p = 0.2857). MR images or CT scans were available for 68 patients. A tumor thickness ≥10 mm or ≥5 mm did not increase the probability of nodal metastasis, with late nodal metastasis observed in 15 % of patients with graphically undetected small tumors. PND appears to have the potential to improve overall survival for patients with cN0 tongue SCC. Careful follow-up management or PND is considered to be needed regardless of tumor thickness in the pre-treatment evaluation.

We sought to evaluate the efficacy and feasibility of superselective intra-arterial infusion of high-dose cisplatin with concomitant radiotherapy (hereafter RADPLAT) for head and neck squamous cell cancer (hereafter HNSCC) patients with retropharyngeal lymph node (hereafter RPLN) metastasis. A retrospective case series review was conducted at University medical center in Japan. Ten HNSCC patients with RPLN metastasis treated by RADPLAT were analyzed. The ascending pharyngeal artery was targeted for the treatment of RPLN metastasis in 9 patients. The median total dose of cisplatin was 26.6 mg/m(2) (mean 31.5 mg/m(2), range 11.7-87.9 mg/m(2)). In the remaining patient, the RPLN was supplied by the ascending palatine artery. As grade 3 and 4 adverse effects, leukopenia was observed in three, mucositis in four and nausea in one patient. No neurological complications were observed in any patients. Metastatic RPLNs were evaluated as a complete response in all patients. There was no recurrence of RPLN metastasis in any patients. Four patients remain alive without any evidence of disease and six patients died of disease. The 5-year overall survival rate was 50 %. We have shown that superselective intra-arterial cisplatin infusion for RPLNs was a feasible and effective approach for HNSCC patients with RPLN metastasis.

Objective: We aimed to evaluate the prognostic factors and efficacy of treatment modalities for patients with temporal bone cancer, and to determine if definitive chemoradiotherapy (CRT) for advanced-stage disease can provide a substitute for highly invasive surgeries., Study Design: Retrospective case series., Setting: Tertiary referral center., Patients: Sixty-six patients with previously untreated squamous cell carcinoma of the temporal bone treated with curative intent between April 1997 and March 2015., Intervention: Surgery alone, radiotherapy (RT) alone, surgery followed by RT or definitive CRT., Main Outcome Measure: The overall survival (OS) rate., Results: The 5-year OS rate for each T classification was 100% for T1, 76.2% for T2, 55.6% for T3, and 36.7% for T4. Univariable and multivariable analysis showed that T classification was an independent predictor of the OS rate (hazard ratio 5.66; 95% confidence interval 1.51-27.0; p = 0.015). Analysis by treatment modality revealed that the 5-year OS rate for patients with T1-2 was 100% for surgery and 81.3% for RT alone. The rate for patients with T3-4 was 52.1% for definitive CRT and 55.6% for surgery followed by RT with or without chemotherapy., Conclusions: Patients with T1-2 benefited from surgical intervention without significant morbidity or mortality. Our findings also suggested that definitive CRT might be appropriate as the first-line treatment for T3-4, especially in cases with unresectable tumors.

Objective: Late toxicity after concurrent chemoradiotherapy (CCRT), such as dysphagia, in patients with squamous cell carcinoma of the head and neck has received a good deal of attention recently. The gastrostomy tube (G-tube) dependence rate 1 year after CCRT was reported to be 16.7-42.9% in Western countries. We evaluated swallowing outcomes after CCRT in patients with hypopharyngeal cancer (HPC) treated in our hospital and compared them with previous reports., Methods: We reviewed 96 consecutive patients with a HPC treated by radiotherapy with intravenous or intra-arterial chemotherapy between 2006 and 2013 at Hokkaido University Hospital, Sapporo, Japan., Results: At 1 month after CCRT, 13 patients (13.7%) used a G-tube, whereas 5/91 (5.5%) and 4/81 (4.9%) used a G-tube at 3 and 6 months, respectively. Two patients used a G-tube at 12 and 24 months after CCRT (G-tube use rate: 2.8% at 12 months, and 3.2% at 24 months). The variables female, posterior wall primary, stage IV, ECOG performance status of 2, and smoking status were significantly associated with G-tube use at 12 months after CCRT, whereas the route of cisplatin administration was not related to G-tube use (p = 0.303)., Conclusions: The G-tube use rate up to 1year could be lower in Japanese patients than in Western patients according to previous reports. In particular, Japanese patients resume oral intake sooner than Western patients. Further study of the incidence of dysphagia after CCRT by ethnicity is required to clarify the differences in dysphagia after CCRT., Competing Interests: The authors have declared that no competing interests exist.

Objectives: To explore the long-term impact of a universal screening intervention for depression on suicide rates among older community-dwelling adults, with gender as an effect modifier., Design: Controlled cohort study reporting long-term follow-up of previous research., Setting: Two sets of three municipalities in Japan were assigned as intervention and control regions and compared with the surrounding zone and prefecture., Participants: Intervention area residents aged 60 years and older (14,291) were invited to participate in a 2-year intervention (2005-2006). Four population-based dynamic cohorts of residents aged 65 years and older (1999-2010) were included as subjects, 6 years before and after the intervention started., Intervention: At-risk residents within the intervention region (4,918) were invited for a two-step screening program; 2,552 participated in the program linked with care/support services for 2 years. An education program open to the public was held., Measurements: Changes in suicide from a 6-year baseline to the 2-year intervention and a 4-year follow-up in the intervention region (11,700 adults ≥65 years) were compared with a matched control and two comparison areas using mixed-effects negative binomial regression models. Suicide rates among older adults exposed to screening were compared with those of the control region., Results: Suicide rates in the intervention region decreased by 48%, which was significantly greater than in the three comparison areas. The program's benefits lasted longer for women than men. Screening exposure may be associated with decreased suicide risk over the 4-year follow-up., Conclusions: Universal screening may decrease suicide rates among older adults, with potential gender differences in treatment response., (Copyright © 2016 American Association for Geriatric Psychiatry. Published by Elsevier Inc. All rights reserved.)

Background: The purpose of this study was to compare the hearing outcomes after surgery with reconstruction of the external auditory canal in combination with tympanoplasty, radiotherapy (RT) alone, and surgery followed by postoperative RT for T1 to 2N0M0 external auditory canal cancer., Methods: We performed a retrospective, single-institution review of consecutive patients with early-stage external auditory canal cancer treated with surgery and/or RT between April 1997 and August 2013. Audiological data included the pretreatment hearing thresholds and those obtained at 12 months after the completion of therapy., Results: When we compared the functional gains for air-conduction pure-tone average thresholds and mean air-bone gaps, those in the surgery group (n = 10) were significantly higher than those in the RT (n = 13) and surgery + RT (n = 5) groups., Conclusion: Adequate techniques for reconstruction of the external auditory canal in combination with tympanoplasty after complete surgical resection is useful for hearing preservation in addition to good survival outcomes. © 2015 Wiley Periodicals, Inc. Head Neck 38: E1110-E1116, 2016., (© 2015 Wiley Periodicals, Inc.)

Background and Purpose: For the assessment of the treatment response in non-surgical treatment, tumor blood flow provides the functional information of the tumor which is different from the morphological information such as tumor volume. The purpose of this study was to evaluate the diagnostic value of tumor blood flow values obtained by pseudocontinuous arterial spin-labeling in patients with head and neck squamous cell carcinoma., Materials and Methods: Forty-one patients with head and neck squamous cell carcinoma were evaluated by using pseudocontinuous arterial spin-labeling. Quantitative tumor blood flow was calculated at the pretreatment and the early treatment periods in all the patients, and the percentage change of tumor blood flow between the two was calculated. At the early treatment period, based on their tumor volume reduction rate, we divided the patients into stable disease and partial response groups for a subgroup analysis. The local control or failure was confirmed either by histopathology or by radiologic evaluation within the follow-up., Results: Pretreatment tumor blood flow in patients in the failure group was significantly lower than that in patients in the local control group. In the subgroup analysis of patients with stable disease, the percentage change of tumor blood flow was significantly larger (due to the tumor blood flow increase from pretreatment value) in the local control group than in the failure group. In addition, in patients with a partial response, the percentage change of tumor blood flow was significantly smaller (due to the tumor blood flow decrease from the pretreatment value) in the local control group than in the failure group. The accuracy for determination of the local control group or the failure group in pretreatment tumor blood flow was 0.83 and that in the combination use of the percentage change of tumor blood flow and tumor volume in the early treatment period was 0.93., Conclusions: Tumor blood flow obtained by pseudocontinuous arterial spin-labeling can be useful for the determination of local control. The combined use of the percentage change of tumor blood flow and tumor volume had particularly high diagnostic accuracy., (© 2016 by American Journal of Neuroradiology.)

Objectives: In most Western and Asian countries, a higher risk of suicide is found among elderly people than those in other age groups. However, the treatment needs of elderly people who are at risk of committing suicide are not well understood. We conducted an overview of studies that assessed the impact of suicide prevention interventions on suicide rates in elderly people in Japan. We interpreted the results of these studies, as well as prominent findings associated with other successful interventions, within a framework of the suicidal process and preventive strategies., Method: We assessed six quasi-experimental studies of community-based interventions providing universal depression screening, subsequent care, and education to elderly people in Japan, and performed a combined analysis of outcome data., Results: Screening interventions were associated with lower suicide rates. We also found a gender difference in the response to subsequent psychiatric or primary care. Two types of interventions decreased the rate of suicide among elderly people: crisis helplines and screening interventions. These interventions featured a close link between universal, selective, and indicated prevention strategies, which reflect different approaches tailored to the size and risk profile of the target individuals., Conclusion: Successful interventions appear to hinge on systematic links between multi-level prevention interventions. Multi-level interventions for depression screening may result in lower suicide rates among elderly individuals in communities, although primary care interventions alone appear to be insufficient in men. The benefit of linked multi-level prevention interventions may highlight the importance of the multiple steps and components of the suicidal process.

Objective: To improve on the reproducibility and sensitivity of the assessment of patients with rheumatoid arthritis (RA), two semi-automated measurement methods of the area of enhancing pannus (AEP), based on thresholding (AEP_THRES) and pixel-by-pixel time-intensity curve analysis (AEP_TIC), were evaluated as an alternative for the gold-standard manual contouring method (AEP_MANUAL)., Methods: 8 patients (7 females and 1 male) with RA of the wrist or finger joints participated in the study. A three-dimensional contrast-enhanced dynamic sequence was used at 3 T. After identifying the most relevant time-intensity curve (TIC) shape in terms of synovitis by comparing with the synovitis score using the RA-MRI scoring system, three different approaches for measuring the AEP were performed. Spearman's test of rank correlation was used to compare AEPs via two semi-automated methods (AEP_THRES and AEP_TIC) against manual segmentation (AEP_MANUAL) in the entire hand region as well as the wrist and the finger regions., Results: The TIC shape of "washout after fast initial enhancement" had excellent correlation with synovitis score (r = 0.809). The correlation coefficient between AEP_TIC and AEP_MANUAL was evaluated to be better than that of AEP_THRES and AEP_MANUAL in the wrist region (AEP_THRES: r = 0.716, AEP_TIC: r = 0.815), whereas these were of comparable accuracy for the entire hand and the finger regions., Conclusion: This study suggests that TIC analysis may be an alternative to manual contouring for pannus quantification and provides important clinical information of the extent of the disease in patients with RA., Advances in Knowledge: TIC shape analysis can be applied for new quantitative assessment for RA synovitis in the wrist.

The anaplastic lymphoma kinase (ALK) fusion oncogene is observed in 3%-5% of non-small cell lung cancer (NSCLC). Crizotinib and ceritinib, a next-generation ALK tyrosine kinase inhibitor (TKI) active against crizotinib-refractory patients, are clinically available for the treatment of ALK-rearranged NSCLC patients, and multiple next-generation ALK-TKIs are currently under clinical evaluation. These ALK-TKIs exhibit robust clinical activity in ALK-rearranged NSCLC patients; however, the emergence of ALK-TKI resistance restricts the therapeutic effect. To date, various secondary mutations or bypass pathway activation-mediated resistance have been identified, but large parts of the resistance mechanism are yet to be identified. Here, we report the discovery of p-glycoprotein (P-gp/ABCB1) overexpression as a ceritinib resistance mechanism in ALK-rearranged NSCLC patients. P-gp exported ceritinib and its overexpression conferred ceritinib and crizotinib resistance, but not to PF-06463922 or alectinib, which are next-generation ALK inhibitors. Knockdown of ABCB1 or P-gp inhibitors sensitizes the patient-derived cancer cells to ceritinib, in vitro and in vivo. P-gp overexpression was identified in three out of 11 cases with in ALK-rearranged crizotinib or ceritinib resistant NSCLC patients. Our study suggests that alectinib, PF-06463922, or P-gp inhibitor with ceritinib could overcome the ceritinib or crizotinib resistance mediated by P-gp overexpression.

Background: Pyriform sinus squamous cell carcinoma (SCC) has one of the worst prognoses of all upper aerodigestive tract cancers. Improving clinical outcomes for patients with hypopharyngeal SCC has been particularly challenging for head and neck surgeons and oncologists., Methods: We investigated 30 patients with pyriform sinus SCC to verify the effectiveness of weekly cisplatin chemotherapy with concurrent radiotherapy. Cisplatin was administered at a dose of 40 mg/m(2) on weeks 1, 2, 3, 5, 6, and 7 during definitive radiotherapy with the aim of preserving the larynx., Results: All 30 patients achieved definitive radiotherapy at a median dose of 70 Gy (range 64-70 Gy). Cisplatin was administrated concomitantly a median of five times (range 2-6 times). Persistent or recurrent primary disease was observed in four patients (13 %). Persistent or recurrent nodal metastasis was observed in five patients (17 %). Nine salvage surgeries were performed for eight patients, of whom seven survived without any evidence of disease. Post-operative complications were observed in two patients (22 %). The 5-year overall survival and locoregional control rates were 87 and 96 %, respectively. The 5-year laryngeal preservation rate was 74 %., Conclusions: The regimen of weekly cisplatin CRT may be effective for pyriform sinus SCC; however, there were problems with strong selection bias in the current study due to the large number of T2 patients. Salvage surgery was safe and was able to improve the survival rate. This chemoradiation regimen was considered successful in preserving laryngeal function.

Objective: We retrospectively assessed the indications for superselective intra-arterial infusion of cisplatin with concomitant radiotherapy (RADPLAT) in patients with hypopharyngeal cancer (HPC)., Methods: Between April 2000 and March 2013, 41 previously untreated patients received superselective intra-arterial infusion of cisplatin (100-120mg/m(2) per week) with simultaneous intravenous infusions of thiosulfate to neutralize cisplatin toxicity and conventional radiotherapy (65-70Gy)., Results: During the median follow-up period of 5.5 years, a statistically significant difference in the 5-year overall survival was noted between patients with N0-1 (n=14) and N2b-3 disease (n=27). One-half of deaths were observed to be the result of distant metastasis. The 5-year local control and overall survival were significantly better in patients with unilateral than in those with bilateral primary tumors. All the patients with T4b disease (n=3) died of disease within 2 years., Conclusion: Indications for RADPLAT in patients with HPC were defined as patients with unilateral tumors staged as T3-4a and N0-1., (Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.)

Objectives: To investigate the diagnostic value of tumor blood flow (TBF) obtained with pseudo-continuous arterial spin labeling (pCASL) for the differentiation of squamous cell carcinoma (SCC) and malignant lymphoma (ML) in the nasal or sinonasal cavity., Methods: Thirty-three patients with SCC and 6 patients with ML in the nasal or sinonasal cavity were retrospectively analyzed. Quantitative TBF values were obtained using whole-tumor region of interest (ROI) from pCASL data. The histogram analysis of TBF values within the tumor ROI was also performed by calculating the coefficient of variation (CV), kurtosis, and skewness. The mean TBF value, histogram CV, kurtosis and skewness of the patients with SCC were compared with those of the ML patients. The diagnostic accuracy to differentiate SCC from ML was also calculated by receiver operating characteristic (ROC) curve analysis. In addition, multiple logistic regression models were also performed to determine their independent predictive value, and diagnostic accuracy with the combined use of these parameters., Results: Between the SCC and ML groups, significant differences were observed in mean TBF, CV, and kurtosis, but not in skewness. In ROC curve analysis, the diagnostic accuracy values for the differentiation of SCC from ML in mean TBF, CV, and kurtosis were all 0.87, respectively. Multiple logistic regression models revealed TBF and CV were respectively independent predictive value. With the combination of these parameters, the diagnostic accuracy was elevated to 0.97., Conclusions: The TBF value and its histogram analysis obtained with pCASL can help differentiate SCC and ML., (Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.)

Total laryngo-pharyngo-esophagectomy (TLPE) with gastric pull-up reconstruction is still considered to be associated with major complications and a significant risk of in-hospital death. Minimally invasive esophagectomy, avoiding thoracotomy and laparotomy, has been increasingly performed for esophageal malignancies with the hope of reducing mortality and morbidity, such as pulmonary complications. The aim in this study was to assess early and long-term morbidity as well as treatment outcomes in patients treated with TLPE with gastric pull-up reconstruction via thoracoscopy, laparoscopy and cervical incision. From 2004 to 2013, 10 patients with a median age of 64 years (range 47-71 years) underwent minimally invasive TPLE with gastric pull-up reconstruction. Seven of the 10 patients had previously received radiotherapy. As for early postoperative complications, no patient died during the early postoperative period, and pneumonia was observed in 1, skin necrosis in 1, pseudomembranous enterocolitis in 1, arrhythmia in 2, hemorrhage in the neck in 2, anastomotic leakage in the neck in 3, and tracheal necrosis in 6 patients. Three patients developed tracheostomal stenosis as a long-term postoperative complication, and an anastomotic stricture was observed in one patient. All patients were able to achieve oral intake, but 3 patients required feeding tube support. In conclusion, postoperative systemic complications during the early postoperative period were considered to be acceptable, although wound complications such as tracheal necrosis and anastomotic leakage were commonly observed. Therefore, this minimally invasive procedure might help reduce mortality and morbidity in patients requiring TLPE with gastric pull-up reconstruction.

Objective: Here we report our experience of patients with squamous cell carcinoma (SCC) of the nasal cavity and ethmoid sinus (NC&ES) together with an analysis of treatment outcomes., Methods: A retrospective analysis was performed using data from 25 consecutive patients treated between 2000 and 2012. Four patients were diagnosed with T1, 3 with T2, 4 with T3, 7 with T4a, and 7 with T4b disease. No patient had lymph node metastasis., Results: Twelve patients were treated with surgery with/without radiotherapy and with/without chemotherapy. Of these, 4 underwent endoscopic surgery without an open approach and 3 required an anterior skull base approach. Thirteen were treated with radiotherapy; 1 with radiotherapy alone, and 4 and 8 with intravenous and intra-arterial chemotherapy, respectively. The 5-yr overall survival for T1-3, T4a, and T4b disease was 53.9%, 71.4%, and 29.0%, respectively. The 5-yr disease-specific survival for T1-3, T4a, and T4b disease was 74.1%, 71.4%, and 29.0%, respectively., Conclusion: Our treatment policy for patients with SCC of NC&ES, which basically follows the NCCN guideline, was considered to be appropriate. However, several points in terms of surgery and non-surgical approach remain to be solved through further research., (Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.)

Ionising radiation-induced bystander effects are well recognised, but its dependence on dose or linear energy transfer (LET) is still a matter of debate. To test this, 49 sites in confluent cultures of AG01522D normal human fibroblasts were targeted with microbeams of carbon (103 keV µm(-1)), neon (375 keV µm(-1)) and argon ions (1260 keV µm(-1)) and evaluated for the bystander-induced formation of micronucleus that is a kind of a chromosome aberration. Targeted exposure to neon and argon ions significantly increased the micronucleus frequency in bystander cells to the similar extent irrespective of the particle numbers per site of 1-6. In contrast, the bystander micronucleus frequency increased with increasing the number of carbon-ion particles in a range between 1 and 3 particles per site and was similar in a range between 3 and 8 particles per site. These results suggest that the bystander effect of heavy ions for micronucleus formation depends on dose., (© The Author 2015. Published by Oxford University Press. All rights reserved. For Permissions, please email: journals.permissions@oup.com.)

Conclusions: Superselective intra-arterial cisplatin infusion with concomitant radiotherapy (RADPLAT) is considered to be one of the treatments of choice for patients with adenoid cystic carcinoma (ACC) who prefer not to undergo radical surgery., Objective: To evaluate the efficacy of RADPLAT for patients with ACC of the head and neck., Patients and Methods: Between 2001-2010, nine patients with untreated ACC were given superselective intra-arterial infusion of cisplatin (100-120 mg/m(2)/week) with simultaneous intravenous infusion of thiosulfate to neutralize cisplatin toxicity and radiotherapy (65-70 Gy)., Results: Five patients had tumors arising in the base of the tongue, two in the maxillary sinus, and the remaining two in the nasopharynx. The median follow-up period was 9 years 7 months (9;7) (range = 4;6-12;5), and the 5-year local control (LC), overall survival (OS), and disease-free survival rates were 88.9%, 88.9%, and 55.6%, respectively. The 10-year OS rate was 57.1%, but all patients who remained alive for over 10 years are still alive with disease. Primary tumor recurrence was observed in five of the nine patients, with the median time to recurrence being 6 years (range = 4-9 years). Five of the nine patients had distant metastasis, and of these three patients also had primary recurrence.

Conclusion: Grade ≥ 3 mucositis/stomatitis and inability to feed orally were problematic for patients undergoing cetuximab-based bioradiotherapy (BRT) as well as platinum-based chemoradiotherapy (CRT). Severe mucositis/stomatitis and radiation dermatitis should be addressed carefully in patients undergoing cetuximab-based BRT as well., Objectives: The efficacy of cetuximab-based BRT in locally advanced head and neck squamous cell carcinomas has been established. However, the safety of cetuximab-based BRT in comparison with platinum-based CRT is currently under investigation., Method: This study retrospectively analyzed 14 patients undergoing cetuximab-based BRT and 29 patients undergoing platinum-based CRT to compare the incidence of acute toxicities. In the BRT group, an initial cetuximab loading dose of 400 mg/m(2) was delivered 1 week before the start of radiotherapy. Seven weekly infusions of 250 mg/m(2) of cetuximab followed during the definitive radiotherapy. In the CRT group, cisplatin was administered at a dose of 40 mg/m(2) weekly during the definitive radiotherapy., Results: The BRT group had a higher incidence of Grade ≥ 3 radiation dermatitis than did the CRT group (43% vs 3%, respectively, p < 0.01). The incidence rate of Grade ≥ 3 mucositis/stomatitis was 64.3% and 41.4% in the BRT and CRT group, respectively (p = 0.1484), while the incidence rate of the inability to feed orally was 38.5% and 55.2%, respectively (p = 0.2053).

A boy in his early teens visited our hospital with chief complaints of hematemesis and tarry stools. Upper gastrointestinal endoscopy identified a hemorrhagic duodenal ulcer, for which hemostasis was performed using a clip. Proton pump inhibitor (PPI) administration diminished the ulcer but relapse occurred after PPI discontinuation. The esophagus showed concentric rings and longitudinal linear furrows considered to be characteristic of eosinophilic esophagitis. Biopsies of the duodenal ulcer and the esophagus revealed marked infiltration of eosinophils, leading to a diagnosis of eosinophilic gastroenteritis with esophageal involvement. Steroid treatment was initiated, and the duodenal ulcer and esophagitis resolved. Endoscopic findings characteristic of eosinophilic esophagitis were key to the diagnosis of eosinophilic gastroenteritis.

Background: The aim of this study was to evaluate the feasibility of induction docetaxel, cisplatin, and 5-fluorouracil chemotherapy followed by concurrent weekly cisplatin chemoradiotherapy for patients with locally advanced head and neck squamous cell carcinoma (HNSCC)., Methods: Between 2010 and 2013, 30 patients with Stage IV HNSCC were treated in Hokkaido University Hospital with three cycles of induction chemotherapy (docetaxel 75 mg/m(2) and cisplatin 75 mg/m(2), day 1; and 5-fluorouracil 750 mg/m(2)/day 120 h continuous infusion, every 3 weeks) followed by concurrent weekly cisplatin (40 mg/m(2), on weeks 1, 2, 3, 5, 6 and 7) chemoradiotherapy., Results: Three courses of induction chemotherapy were performed in 25 patients (83%) with grade 3-4 toxicities during induction chemotherapy observed in 22 patients (73%). The major toxicities were hematologic, with 22 cases (73%) showing grade 3-4 neutropenia. Radiotherapy was completed (70 Gy) in 29 patients (97%), while a total of 19 patients (63%) completed five (13 patients) or six (6 patients) courses of chemotherapy. During concurrent chemoradiotherapy, no grade 4 hematological toxicities were observed. Grade 4 dermatitis was observed in one patient, and grade 3 mucositis was observed in 12 patients. There were no treatment-related deaths during the induction chemotherapy or concurrent chemoradiotherapy. The 1- and 2-year progression-free survival rates and the 1- and 2-year overall survival rates were 86%, 72%, and 89%, 81%, respectively., Conclusion: Sequential therapy composed of induction chemotherapy followed by concurrent weekly cisplatin chemoradiotherapy is feasible, showing encouraging results in patients with locally advanced HNSCC. Concurrent weekly cisplatin chemoradiotherapy following induction chemotherapy appears to be a suitable alternative to three-weekly high-dose cisplatin therapy.

Background: The purpose of this retrospective analysis was to evaluate ocular function and survival rates among treatment modalities in patients with maxillary sinus cancer with orbital invasion., Methods: Eighty-seven patients were classified according to the main treatment modality. Ocular function preservation rates and survival rates were evaluated for each therapeutic modality., Results: The 5-year overall survival rate for the en bloc resection, conservative surgery, superselective intra-arterial chemotherapy, and radiotherapy (RADPLAT), intravenous chemoradiotherapy (IV-CRT) was 70%, 35%, 49%, and 31%, respectively. The ocular function preservation rate for each group was 15%, 27%, 30%, and 17%, respectively. In the en bloc resection group, there was no significant difference in the 5-year overall survival rate between patients with orbital exenteration and those without orbital exenteration (72% vs 71%; p = .9321)., Conclusion: The en bloc resection group showed a favorable survival rate but a low preservation rate. Preservation of orbital contents did not reduce the survival rate., (© 2014 Wiley Periodicals, Inc.)

Purpose: To investigate the feasibility of tumor blood flow (TBF) measurement in head and neck squamous cell carcinoma (HNSCC) using pseudo-continuous arterial spin labeling (pCASL) in a comparison with dynamic contrast-enhanced (DCE) perfusion., Materials and Methods: We prospectively scanned 18 patients with HNSCC using 3T magnetic resonance imaging (MRI) with both pCASL and DCE perfusion. Quantitative TBF value in the whole-tumor region of interest (ROI), and regional TBF in the ROIs of the central and peripheral areas in the tumor were respectively measured. Relative TBF value in the whole-tumor ROI was also calculated. We determined the correlation and agreement between each measured TBF by pCASL and DCE perfusion using Pearson's correlation coefficients, intraclass correlation coefficients (ICC), and Bland-Altman analysis., Results: In the whole-tumor ROIs, significant correlation was observed between the absolute TBF values (r = 0.72, P < 0.01), with an ICC of 0.72; moreover, higher correlation was observed in the relative TBF (r = 0.79). The correlation was higher in the peripheral ROI (r = 0.70) than the central ROI (r = 0.65), with an ICC of 0.62 and 0.54, respectively. Bland-Altman plots revealed the underestimation of TBF by pCASL in central ROIs., Conclusion: TBF measurement by pCASL was feasible in patients with HNSCC., (© 2014 Wiley Periodicals, Inc.)

Objectives: To investigate the diagnostic value of tumour blood flow (TBF) obtained with pseudocontinuous arterial spin labelling for the differentiation of squamous cell carcinoma (SCC) and inverted papilloma (IP) in the nasal or sinonasal cavity., Methods: We retrospectively analysed the cases of 33 patients with SCC and 8 patients with IP in the nasal or sinonasal cavity. Pseudocontinuous arterial spin labelling scanning was performed for all patients using a 3.0-T MR unit. Quantitative TBF values were measured by two neuroradiologists by respectively delineating the whole-tumour regions of interest, and the mean of them was determined as TBF value in each patient. Additionally, the presence of imaging findings of convoluted cerebriform pattern (CCP) on MR T2 weighted images was determined in all patients. As a subgroup analysis, patients with IP were divided into aggressive and non-aggressive IPs depending on their progression range. First, an intraclass correlation coefficient (ICC) of TBF values between two neuroradiologists was determined. Next, a statistical comparison of the TBF value by a Mann-Whitney U test between the patients with SCC and IP was performed. Additionally, the comparison by an ANOVA with a post hoc test of Tukey's method among the SCC, non-aggressive IP and aggressive IP groups was also performed. If significance was observed, the diagnostic accuracy to differentiate SCCs from IPs was calculated. Diagnostic accuracy by CCP findings alone and by the combination of CCP findings and TBF were also assessed., Results: The ICC of TBF values between two neuroradiologists was 0.82. The mean TBF values in the patients with SCC, all patients with IP, those with aggressive IP and those with non-aggressive IP were 141.2 ± 33.1, 77.8 ± 31.5, 109.4 ± 16.7 and 58.8 ± 19.9 ml 100 g⁻¹ min⁻¹, respectively. A significant difference was observed between SCC and IP (p < 0.001), SCC and non-aggressive IP (p < 0.01) and non-aggressive IP and aggressive IP (p < 0.01). The diagnostic accuracy values obtained with receiver operating characteristic curve analysis for the differentiation of SCC from IP and for SCC from non-aggressive IP were 0.90 and 0.92, respectively. The diagnostic accuracy was elevated (0.95 from 0.88) by adding the TBF value to CCP findings., Conclusions: The pseudocontinuous arterial spin labelling technique can be a useful non-invasive diagnostic tool to differentiate SCC from IP in nasal or sinonasal cavity.

Purpose: To investigate the correlation between perfusion-related parameters obtained with intravoxel incoherent motion (IVIM) and classical perfusion parameters obtained with dynamic contrast-enhanced (DCE) magnetic resonance imaging in patients with head and neck squamous cell carcinoma (HNSCC), and to compare direct and asymptotic fitting, the pixel-by-pixel approach, and a region of interest (ROI)-based approach respectively for IVIM parameter calculation., Materials and Methods: Seventeen patients with HNSCC were included in this retrospective study. All magnetic resonance (MR) scanning was performed using a 3T MR unit. Acquisition of IVIM was performed using single-shot spin-echo echo-planar imaging with three orthogonal gradients with 12 b-values (0, 10, 20, 30, 50, 80, 100, 200, 400, 800, 1000, and 2000). Perfusion-related parameters of perfusion fraction 'f' and the pseudo-diffusion coefficient 'D*' were calculated from IVIM data by using least square fitting with the two fitting methods of direct and asymptotic fitting, respectively. DCE perfusion was performed in a total of 64 dynamic phases with a 3.2-s phase interval. The two-compartment exchange model was used for the quantification of tumor blood volume (TBV) and tumor blood flow (TBF). Each tumor was delineated with a polygonal ROI for the calculation of f, f∙D* performed using both the pixel-by-pixel approach and the ROI-based approach. In the pixel-by-pixel approach, after fitting each pixel to obtain f, f∙D* maps, the mean value in the delineated ROI on these maps was calculated. In the ROI-based approach, the mean value of signal intensity was calculated within the ROI for each b-value in IVIM images, and then fitting was performed using these values. Correlations between f in a total of four combinations (direct or asymptotic fitting and pixel-by-pixel or ROI-based approach) and TBV were respectively analyzed using Pearson's correlation coefficients. Correlations between f∙D* and TBF were also similarly analyzed., Results: In all combinations of f and TBV, f∙D* and TBF, there was a significant correlation. In the comparison of f and TBV, a moderate correlation was observed only between f obtained by direct fitting with the pixel-by-pixel approach, whereas a good correlation was observed in the comparisons using the other three combinations. In the comparison of f∙D* and TBF, a good correlation was observed only with f∙D* obtained by asymptotic fitting with the ROI-based approach. In contrast, moderate correlations were observed in the comparisons using the other three combinations., Conclusion: IVIM was found to be feasible for the analysis of perfusion-related parameters in patients with HNSCC. Especially, the combination of asymptotic fitting with the ROI-based approach was better correlated with DCE perfusion., (Copyright © 2014 Elsevier Inc. All rights reserved.)

Background: As the suicide rate in Japan has remained high since 1998, various suicide prevention measures have been implemented in Japanese local communities., Aims: To report our findings on the effect of a psychoeducational video as a suicide prevention measure in a Japanese rural town., Methods: Questionnaires were randomly mailed to 2,000 residents aged between 30 and 79 years. Within 4 weeks, volunteers in the town visited the residents individually and collected the questionnaires. The variables reported in this study are demographics, awareness of suicide prevention measures available in the town, whether the residents watched the video, help-seeking from advisers regarding suicidal ideation and financial problems and attitudes towards suicide., Results: We analysed data collected from 1,118 people who reported their demographics (i.e. sex, age, and job) and whether they had watched the video. By conducting a series of logistic regression and multiple regression analyses and controlling for demographic variables, we found that watching the video had substantial psychoeducational effects., Conclusion: Despite conducting a cross-sectional study, our new suicide prevention measures were considered effective for psychoeducation. However, further studies using a longitudinal design are needed., (© The Author(s) 2014.)

In the case of oropharyngeal carcinoma, patients may present with symptoms similar to cervical lymphadenopathy, and the primary lesion may only be diagnosed after cervical mass extirpation/biopsy. We retrospectively analyzed the clinical course in 11 oropharyngeal carcinoma patients that were diagnosed after cervical mass extirpation/biopsy between 1998 and 2013. Before the diagnosis was made of oropharyngeal carcinoma, a cervical lymph node biopsy was performed in six patients; the lymph node was extirpated due to an initial diagnosis of lateral cervical cyst in four patients; and neck dissection was performed due to an initial diagnosis of primary unknown carcinoma in one patient. The primary tumor site in the oropharynx was the palatine tonsil in six patients and the lingual tonsil in five patients. Five of six patients with palatine tonsil carcinoma and three of five patients with lingual tonsil carcinoma were found to be positive for human papillomavirus (HPV). The duration from cervical lymph node extirpation/biopsy to final diagnosis was 1 to 13 months. All patients finally underwent radiation therapy or chemoradiotherapy, and they had no recurrence or metastasis. As the incidence of HPV-related oropharyngeal carcinoma increases, the number of oropharyngeal carcinomas assumed to be cervical lymphadenopathy due to the presenting symptoms may increase. It is important to investigate the oropharynx thoroughly so as to adequately differentiate the possibility of oropharyngeal carcinoma from that of cervical lymphadenopathy. Metastatic lymph nodes might present as cysts in cases of oropharyngeal carcinoma, it is therefore necessary to take the potential for metastatic lymph nodes in the oropharyngeal cancer into consideration when differentiating this disease from cervical cyst-shaped lesions.

High-risk human papillomavirus (HPV) infection is associated with carcinogenesis in oropharyngeal squamous cell carcinoma (OPSCC) and patients with HPV-positive tumors have a significantly favorable prognosis. However, the underlying mechanism of this favorable clinical outcome remains unclear. Epithelial-mesenchymal transition (EMT) causes aggressiveness of cancer cells and we investigated the expression of the EMT markers and analyzed their correlation with HPV status and prognosis in order to examine the treatment response of HPV-positive OPSCCs. A total of 79 patients with OPSCC were examined in the present study. All high-risk HPV infections were determined with the multiplex PCR kit from each formalin-fixed paraffin-embedded (FFPE) sample. We performed immunohistochemical staining for E-cadherin and vimentin. Expression of the markers was graded and we statistically analyzed the correlation between tumor, node, metastasis (TNM) stages and prognosis. High-risk HPV-positive tumors were detected in 23 cases. The five‑year survival rate in HPV-positive and -negative tumors was 82.7 and 48.3%, respectively. High E-cadherin expression rate in HPV-negative samples was 76.7% and 43.4% in HPV-positive samples (p=0.007). Vimentin expression did not show a difference between HPV-positive and -negative tumors. HPV-negative patients presented significantly greater heterogeneity of E-cadherin expression compared to HPV-positive patients (p=0.0349). HPV-positive OPSCCs originally lost their epithelial cell phenotype compared with HPV-negative tumors. Therefore, the paradoxical favorable prognosis of HPV-positive OPSCC may be due to the intratumor homogeneity in EMT.

Purpose: To evaluate the feasibility of arterial spin-labeling (ASL) in head and neck cancer for noninvasive measurement of tumor blood flow (TBF), by comparing 1) the TBF change before and after the treatment, and 2) posttreatment TBF and its reduction rate between residual and nonresidual tumors after treatment., Materials and Methods: Twenty-two patients with head and neck cancer were evaluated using ASL on 3.0-T magnetic resonance imaging (MRI) before and after nonsurgical treatment. A pulsed ASL sequence with Look–Locker readout was used to calculate quantitative TBF. TBF reduction rates between pre- and posttreatment values were also calculated. Residual tumors were confirmed when present with either histopathologically or clinical follow-up., Results: Pre- and posttreatment mean TBF values were 121.4 ± 27.8 (standard deviation) and 24.9 ± 14.9 mL/100g/min, respectively. Pre- and posttreatment TBF differed significantly. Posttreatment TBF was significantly higher in patients with residual tumors (five patients, 46.9 ± 7.1 mL/100g/min) than in those without (17 patients, 18.4 ± 9.2 mL/100g/min). The TBF reduction rate was significantly lower in patients with residual tumors (0.540.55 ± 0.120.12) than in those without (0.85 ± 0.06)., Conclusion: ASL allows quantitative assessment of TBF in head and neck cancer. ASL may be useful for noninvasive assessment of tumor viability in head and neck cancer.

The efficacy of elective neck irradiation (ENI) for patients with N0 carcinoma of the maxillary sinus has been controversial. The purpose of our study was to investigate the incidence of late neck recurrence and the mortality rate from regional disease in patients with N0 maxillary sinus cancer after superselective cisplatin infusion and concomitant radiotherapy (RADPLAT) without ENI. We retrospectively analyzed 48 patients with N0 maxillary sinus cancer who underwent RADPLAT. Chemotherapy consisted of 100-120 mg/m(2) superselective intra-arterial cisplatin administered at a median rate of four times weekly. Concurrent radiation therapy was administered at a median dose of 65 Gy without ENI. Late neck recurrence was observed in 8.3% (4/48). Three patients underwent salvage neck dissection and survived without any evidence of disease. The remaining patient did not undergo neck dissection due to coexistence with distant metastasis, and he died of regional disease. The mortality rate from regional disease was calculated to be 2% (1/48). The incidence of late neck recurrence was not frequent, and the mortality rate from regional disease was low. Salvage neck dissection was considered to be feasible for patients with late neck recurrence. When definitive radiotherapy and concomitant chemotherapy are applied, it is considered that ENI is not required for cases of N0 maxillary sinus cancer.

Objective: Fine-needle aspiration cytology (FNAC) is considered to be the most reliable method of examination for thyroid nodules. However, when thyroid nodules are evaluated as Bethesda I-V, the role of ultrasonography is considered to be enhanced. We investigated the association between a number of ultrasonographic (US) characteristics and the risk of thyroid malignancy, and assessed the optimal compromise on the number of US characteristics for predicting thyroid malignancy., Methods: Seventy-three patients, whose thyroid nodules were evaluated as Bethesda I-V by FNAC prior to surgery, were treated surgically. A number of US characteristics, such as microcalcification, irregular margins, hypoechogenicity, a taller-than-wide shape, and the absence of halo sign, were assessed before surgery. The optimal compromise on the number of US characteristics was analyzed using a receiver operating characteristics (ROC) curve. The area under the ROC curve (AUC) represents the overall discriminatory ability of a test., Results: The risk of malignancy was 11.8% in patients without any US characteristics, 44.4% in those with one characteristic, 61.5% in those with two characteristics, 75% in those with three characteristics, 90% in those with four characteristics, and 100% in those with five characteristics. The AUC was favorable (0.81599). At least two US characteristics were revealed to be the optimal compromise on the number of US characteristics based on the ROC curve., Conclusion: We proved the role of the number of US characteristics in predicting thyroid malignancy. It was thought that a surgical approach should be considered for patients with at least two US characteristics.

Background: The current study sought to assess the role of initial neck dissection (ND) for patients with node-positive oropharyngeal squamous cell carcinomas (OPSCC)., Methods: The data for 202 patients with previously untreated node-positive OPSCC were gathered from 12 institutions belonging to the Head and Neck Cancer Study Group in the Japan Clinical Oncology Group. These patients were categorized into two groups, consisting of the initial ND group and the wait-and-see group, according to treatment policy., Results: Regional recurrence was observed in 17 of 93 patients undergoing initial ND, whereas, recurrent or persistent diseases were observed in 40 of 109 patients who did not undergo initial ND. The 4-year overall survival rates (OS) for the wait-and-see group and initial ND groups were 74.0% and 78.7%, respectively, and the 4-year regional control rates (RC) for each group were 77.6% and 84.9%. There were no significant differences in either OS or RC (p=0.3440 and p=0.2382, respectively). However, for patients with N3 disease, the 4-year OS of the initial ND group (100%) was favorable. For patients with N2a disease, the 4-year RC of the initial ND group was higher than that of the wait-and-see group statistically (100% vs 62.5%, p=0.0156)., Conclusions: The role of initial ND was limited in patients with node-positive OPSCC. The treatment strategy not involving initial ND is considered feasible and acceptable when nodal evaluation after definitive radiotherapy or chemoradiotherapy is applied adequately. However, it is possible that initial ND improves outcomes in patients with resectable large-volume nodal disease., (Copyright © 2014 Elsevier Ltd. All rights reserved.)

Objective: Abnormalities in circulating angiogenic factors and endothelial progenitor cells (EPCs) have been reported in patients with preeclampsia and placental abruption. The objective of this study was to determine whether the number of EPCs is altered in patients with placental abruption., Design: A case control study., Setting: Hiroshima University Hospital in Japan., Sample: Pregnant Japanese women with preeclampsia (n=27) and those without any complications (n=15)., Method: The EPC (CD45(low)CD34(+)CD133(+) cells) counts were examined using flow cytometry in peripheral blood collected from 27 women with preeclampsia and 15 normal pregnant women. Among the 27 women with preeclampsia, five subsequently developed placental abruption. All subjects were divided into three groups: normal pregnancy (NP, n=15), preeclampsia without placenta abruption (PE, n=22) and preeclampsia with placental abruption (PA, n=5)., Main Outcome Measures: The EPC counts were measured in pregnant women with preeclampsia who subsequently developed placental abruption., Results: The EPC count in the PE group significantly decreased in comparison to that observed in the NP group (620cells/ml versus 1918 cells/ml, P<0.01). In the PA group, the EPC count was found to markedly decrease in comparison to that observed in the PE group (221cells/ml, P<0.05)., Conclusions: The number of EPCs was found to significantly decrease in preeclamptic women who subsequently developed placental abruption., (Copyright © 2014 International Society for the Study of Hypertension in Pregnancy. Published by Elsevier B.V. All rights reserved.)

Our aim was to evaluate the feasibility of salvage operations for patients with persistent or recurrent cancer of the maxillary sinus after superselective intra-arterial infusion of cisplatin with concurrent radiotherapy. We retrospectively analysed the records of 61 patients with cancer of the maxillary sinus who were treated in this way. Chemotherapy comprised 100-120 mg/m(2) superselective intra-arterial infusions of cisplatin given a median of 4 times weekly (range 2-5). Concurrent radiotherapy was given in a median dose of 65 Gy (range 24-70 Gy). Persistent or recurrent cancer of the maxillary sinus was found in 17 patients, of whom 11 had salvage surgery. The disease was controlled in 8 of the 11, and 7 of the 11 survived with no evidence of disease. Their 5-year overall survival was 61%. Two of the 11 developed serious operative complications. Salvage surgery for patients with persistent or recurrent cancer of the maxillary sinus treated by superselective chemoradiotherapy is both safe and successful. Salvage surgery is a good option when this sort of persistent or recurrent cancer is followed up after the regimen of chemoradiotherapy described., (Copyright © 2014 The British Association of Oral and Maxillofacial Surgeons. Published by Elsevier Ltd. All rights reserved.)

We examined the effect of a community-based screening program on depression in middle-aged individuals. Ten subdistricts constituting a rural township (2400 inhabitants aged 40-64 years) in northern Japan with a high suicide rate were randomly assigned to intervention (four) and control (six) groups. A 2-year depression-screening program entailing identification and subsequent care support was offered to adults aged 40 to 64 years in the intervention group, accompanied by 4-year ongoing dissemination of educational information in both groups. Change in depressive symptom prevalence was assessed through before-and-after cross-sectional surveys using the Center for Epidemiologic Studies-Depression Scale. Of the 900 targeted individuals, 49.2% participated in the screening. Comparison of data from these surveys after controlling for district-level clustering indicated a greater difference in prevalence between baseline and 5-year follow-up in the intervention group than that in the control. Universal screening and subsequent support seem effective to decrease depressive symptom prevalence among middle-aged individuals in a community setting.

Purpose: This study investigated changes in depressive symptoms after the implementation of a universal screening for depression and subsequent care support., Methods: A cluster-randomized study design used 10 subdistricts (2,400 inhabitants aged 40-64 years) in northern Japan randomly assigned in a 2:3 ratio to intervention and control conditions. All 900 residents aged 40-64 in the intervention districts were invited to participate in a 2-year depressive screening program, with a participation rate of 49.2%. A 4-year ongoing education program occurred in both intervention and control districts. The Center for Epidemiologic Studies Depression Scale (CES-D) was used to assess depressive symptomatology. Repeated cross-sectional samples were surveyed before (n = 1,516, response rate 63.6%) and after (n = 1,596, 66.4%) intervention, and the data, clustered according to district, were analyzed at the individual level using a mixed-effects model., Results: Significant changes in mean scores between baseline and 5-year follow-up in the intervention group were observed in the Depressive Affect, Somatic Symptoms, and Interpersonal Problems subscales. The difference between the changes over time in the two groups was significant for the three subscales and marginally for the CES-D total scale, but not for the Positive Affect subscale., Conclusions: Universal depression screening and subsequent support can be effective in preventing general depressive symptoms, but may not influence psychological well-being, among middle-aged adults in a community setting.

Objective: To evaluate postoperative hearing outcomes after lateral temporal bone resection (LTBR) with reconstruction of the external auditory canal (EAC) and conductive function for early-stage EAC carcinoma., Methods: We retrospectively examined patients diagnosed with early-stage EAC carcinoma treated with surgery alone between January 2006 and December 2012. Patients who had postoperative adjuvant chemotherapy and/or radiotherapy were excluded. Patients receiving LTBR in combination with tympanoplasty were divided into two groups based on the reconstruction of the EAC with and without (w/o) split-thickness skin grafts (STSGs). Audiological data included the preoperative hearing thresholds and the most recent postoperative hearing thresholds obtained at least 12 months after surgery. The hearing outcome was evaluated based on pure-tone audiograms using the Committee on Hearing and Equilibrium guidelines of the American Academy of Otolaryngology-Head and Neck Surgery for the evaluation of the results of treatment of conductive hearing loss. The postoperative quality of life (QOL) for patients was evaluated using the Glasgow Benefit Inventory (GBI)., Results: All patients (n = 15) achieved disease-free survival without significant morbidity or mortality. When we compared the mean air-bone gaps after surgery, those in the STSG group (n = 8) were found to be significantly lower than those in the w/o STSG group (n = 7; p < 0.001). The success rate for postoperative hearing was 75.0% in the STSG group, which was significantly higher than that in the w/o STSG group (p = 0.014). All patients in the w/o STSG group showed stenosis and closure of the EAC at fewer than 10 months after surgery. In contrast, all patients in the STSG group showed preserved conformation of the new EAC for more than 12 months after surgery. When we compared the mean GBI score between the two groups of patients, the overall and general health scores in the STSG group were found to be significantly higher than those in the w/o STSG group (p = 0.021, p = 0.001)., Conclusions: Reconstruction of the EAC using a rolled-up STSG technique in combination with tympanoplasty after LTBR is useful for hearing preservation and the observation of locoregional lesions after surgery, resulting in improved QOL for patients., (© 2014 S. Karger AG, Basel.)

Previously, we isolated a new enzyme, N-substituted formamide deformylase, that catalyzes the hydrolysis of N-substituted formamide to the corresponding amine and formate (H. Fukatsu, Y. Hashimoto, M. Goda, H. Higashibata, and M. Kobayashi, Proc. Natl. Acad. Sci. U. S. A. 101:13726-13731, 2004, doi:10.1073/pnas.0405082101). Here, we discovered that this enzyme catalyzed the reverse reaction, synthesizing N-benzylformamide (NBFA) from benzylamine and formate. The reverse reaction proceeded only in the presence of high substrate concentrations. The effects of pH and inhibitors on the reverse reaction were almost the same as those on the forward reaction, suggesting that the forward and reverse reactions are both catalyzed at the same catalytic site. Bisubstrate kinetic analysis using formate and benzylamine and dead-end inhibition studies using a benzylamine analogue, aniline, revealed that the reverse reaction of this enzyme proceeds via an ordered two-substrate, two-product (bi-bi) mechanism in which formate binds first to the enzyme active site, followed by benzylamine binding and the subsequent release of NBFA. To our knowledge, this is the first report of the reverse reaction of an amine-forming deformylase. Surprisingly, analysis of the substrate specificity for acids demonstrated that not only formate, but also acetate and propionate (namely, acids with numbers of carbon atoms ranging from C1 to C3), were active as acid substrates for the reverse reaction. Through this reaction, N-substituted carboxamides, such as NBFA, N-benzylacetamide, and N-benzylpropionamide, were synthesized from benzylamine and the corresponding acid substrates.

α-Halocarbonyl compounds undergo β-hydrogen elimination to give conjugated olefins in the presence of a transition-metal catalyst. However, a copper/triamine catalyst system can induce the alkylative Mizoroki–Heck reaction of styrenes with tertiary-alkyl halides possessing a withdrawing group under very mild conditions. This reaction provides an efficient synthetic methodology for tertiary-alkylated styrenes.

In daily communication, we can usually still hear the spoken words as if they had not been masked and can comprehend the speech when spoken words are masked by background noise. This phenomenon is known as phonemic restoration. Since little is known about the neural mechanisms underlying phonemic restoration for speech comprehension, we aimed to identify the neural mechanisms using magnetoencephalography (MEG). Twelve healthy male volunteers with normal hearing participated in the study. Participants were requested to carefully listen to and understand recorded spoken Japanese stories, which were either played forward (forward condition) or in reverse (reverse condition), with their eyes closed. Several syllables of spoken words were replaced by 300-ms white-noise stimuli with an inter-stimulus interval of 1.6-20.3s. We compared MEG responses to white-noise stimuli during the forward condition with those during the reverse condition using time-frequency analyses. Increased 3-5 Hz band power in the forward condition compared with the reverse condition was continuously observed in the left inferior frontal gyrus [Brodmann's areas (BAs) 45, 46, and 47] and decreased 18-22 Hz band powers caused by white-noise stimuli were seen in the left transverse temporal gyrus (BA 42) and superior temporal gyrus (BA 22). These results suggest that the left inferior frontal gyrus and left transverse and superior temporal gyri are involved in phonemic restoration for speech comprehension. Our findings may help clarify the neural mechanisms of phonemic restoration as well as develop innovative treatment methods for individuals suffering from impaired speech comprehension, particularly in noisy environments., (© 2013 The Authors. Published by Elsevier B.V. All rights reserved.)

Background: The prevalence of oropharyngeal carcinoma is rising in western Europe and the United States, where there appears to be a strong association between human papillomavirus (HPV) and oropharyngeal squamous cell carcinoma (OPSCC). However, such a correlation has not yet been fully evaluated in Japan., Methods: We performed a retrospective analysis of the association between tumour HPV status and the demographic and clinicopathological parameters of 71 patients with OPSCC at Hokkaido University Hospital, Japan, between 1998 and 2009. The parameters included age, gender, survival, tumour subsite, tumour-node-metastasis (TNM) stage, smoking history, second primary tumour status, recurrence/residual disease at the primary site, and overall survival. HPV status was established by multiplex polymerase chain reaction (PCR) analysis., Results: Of the 71 oropharyngeal cancers, 20 were positive for HPV-16, two for HPV-18, and one for HPV-58. Kaplan-Meier survival analysis showed improved overall survival rates in patients with HPV-positive tumours (p = 0.0038) compared with HPV-negative tumours. Of the 45 patients who received chemoradiotherapy, HPV-positive patients experienced better overall survival than HPV-negative patients (p = 0.0032). In a multivariate analysis, the survival benefit of HPV-positive patients was independent of age and T and N classification., Conclusions: HPV status is a significantly favourable prognostic factor in oropharyngeal cancer and could be used as a marker to optimize the treatment of patients with this type of cancer in Japan.

Conclusion: It was proved that cyclin D1-positive status in surgical margins was an independent prognostic indicator of local recurrence. The expression of cyclin D1 in tumor-free surgical margins may better predict local recurrence in patients with head and neck squamous cell carcinoma (HNSCC) after surgical treatment with curative intent., Objective: This retrospective study aimed to determine the prognostic indicators for local recurrence in HNSCC., Methods: A total of 116 HNSCC patients who underwent surgical treatment with curative intent and had histopathologically tumor-free margins were eligible for this study. The expression of p53 and cyclin D1 was assessed by immunohistochemical staining in surgical margins as well as in tumor specimens., Results: In all, 63 patients (54.3%) had p53-positive tumor specimens and 34 patients (29.3%) had p53-positive margins. Seventy-six patients (65.6%) had cyclin D1-positive tumor specimens and 54 patients (46.6%) had cyclin D1-positive margins. A significant difference in local control rates was observed between patients with cyclin D1-positive and -negative margins (77.2% vs 91.5%, log rank test, p = 0.0139). Multivariate Cox proportional hazards testing indicated that the hazard ratio of cyclin D1-positive margins for local recurrence was 4.58 (95% confidence interval 1.14-21.69, p = 0.0304).

Background: Clonogenicity gives important information about the cellular reproductive potential following ionizing irradiation, but an abortive colony that fails to continue to grow remains poorly characterized. It was recently reported that the fraction of abortive colonies increases with increasing dose. Thus, we set out to investigate the production kinetics of abortive colonies using a model of branching processes., Methodology/principal Findings: We firstly plotted the experimentally determined colony size distribution of abortive colonies in irradiated normal human fibroblasts, and found the linear relationship on the log-linear or log-log plot. By applying the simple model of branching processes to the linear relationship, we found the persistent reproductive cell death (RCD) over several generations following irradiation. To verify the estimated probability of RCD, abortive colony size distribution (≤ 15 cells) and the surviving fraction were simulated by the Monte Carlo computational approach for colony expansion. Parameters estimated from the log-log fit demonstrated the good performance in both simulations than those from the log-linear fit. Radiation-induced RCD, i.e. excess probability, lasted over 16 generations and mainly consisted of two components in the early (<3 generations) and late phases. Intriguingly, the survival curve was sensitive to the excess probability over 5 generations, whereas abortive colony size distribution was robust against it. These results suggest that, whereas short-term RCD is critical to the abortive colony size distribution, long-lasting RCD is important for the dose response of the surviving fraction., Conclusions/significance: Our present model provides a single framework for understanding the behavior of primary cell colonies in culture following irradiation.

Conclusion: The Japanese version of the Tinnitus Handicap Inventory-12 (THI-12), Tinnitus Rating Scale (TRS), TRS 1-week version (TRSw), Tinnitus Severity Scale (TSS), and TSS 1-week version (TSSw), which were developed in this study, showed high reliability and validity, suggesting their usefulness in clinical practice. Based on the THI severity grades, we propose that the severity grades of THI-12 (draft) are categorized into four groups: 0-4 points, 5-9 points, 10-14 points, and 15-24 points., Objectives: We developed Japanese versions of new questionnaires for evaluating the level of psychological distress and difficulty in activities of daily living due to tinnitus, and performed their psychometric validation to determine the reliability and validity. The THI-12 is an assessment consisting of 12 items, each of which is rated on a 3-point scale that was created by reducing the number of questions from the 25 items of the THI. The TRS, TRSw, TSS, and TSSw, which were self-evaluation questionnaires of tinnitus on an 11-grade integer Likert scale from 0 to10 points, were used as additional instruments to assess tinnitus severity and distress., Methods: The subjects were healthy adults, and patients with subjective tinnitus who were examined at the Otolaryngology Department of Keio University Hospital, Osaka City University Hospital, or Nagoya City University Hospital with a chief complaint of tinnitus between September 2010 and January 2011. In all, 38 healthy adult subjects and 113 patients with subjective tinnitus were included. We examined the reproducibility and the internal consistency for reliability. We also examined the relationship with the available scales (THI and Hospital Anxiety and Depression Scale, HADS) and group divergence for validity., Results: The psychometric validation showed high reliability and validity of the THI-12, TRS, TRSw, TSS, and TSSw.

Objectives: Although three-weekly high-dose (100mg/m(2)) cisplatin (three cycles) chemoradiotherapy has been considered a standard regimen for patients with advanced head and neck squamous cell carcinomas (HNSCC), this protocol is associated with significant acute and late toxicities. Therefore, weekly cisplatin at a dose of 40mg/m(2) has been used at our institution since 2006. This retrospective study was aimed at assessing the oncologic efficacy of weekly cisplatin chemoradiotherapy for the control of nodal metastasis., Methods: We analyzed 28 patients with node-positive HNSCC treated with weekly cisplatin and concurrent radiotherapy. Computed tomography was performed 4-8 weeks after the completion of chemoradiotherapy to evaluate nodal response. If residual neck disease was apparent or suspected, we performed early salvage neck dissection (ND). In cases with a complete response (CR), we took a "wait and see" approach. When no viable tumor cells were observed in the surgical specimens obtained by ND, nodal metastasis was defined as controlled by weekly cisplatin chemoradiotherapy alone., Results: Nodal metastasis was evaluated as having a CR in 20 patients (71%). Eight patients (29%) underwent early salvage ND. Recurrent primary tumors were observed in the other four patients (14%). Salvage primary resection and associated ND were performed for these four patients. In 7 of 12 patients undergoing ND, no viable tumor cells were observed. In 23of 28 patients, neck diseases were controlled by chemoradiotherapy alone (not including salvage by ND). In 27 of 28 patients, neck diseases were controlled by the overall treatment (including salvage by ND). The rate of nodal control by chemoradiotherapy alone and by the overall treatment was found to be 82.0% and 96.3%, respectively, using the Kaplan-Meier method. The three-year overall and disease free survival rates were 86.8% and 80.8%, respectively., Conclusion: Concomitant weekly cisplatin at a dose of 40mg/m(2) chemoradiotherapy showed a good control rate of not only primary lesions but also neck diseases., (Copyright © 2012 Elsevier Ireland Ltd. All rights reserved.)

We report the strictest observational verification of CPT invariance in the photon sector, as a result of γ-ray polarization measurement of distant gamma-ray bursts (GRBs), which are the brightest stellar-sized explosions in the Universe. We detected γ-ray polarization of three GRBs with high significance levels, and the source distances may be constrained by a well-known luminosity indicator for GRBs. For the Lorentz- and CPT-violating dispersion relation E(±)(2) = p(2) ± 2ξp(3)/M(Pl), where ± denotes different circular polarization states of the photon, the parameter ξ is constrained as |ξ|