Norihiko Takemoto

Prognostic factors of peripheral facial palsy: multivariate analysis followed by receiver operating characteristic and Kaplan-Meier analyses.

Objective: To search for prognostic predictors and reexamine the usefulness of electroneurography (ENoG) in predicting the prognosis of peripheral facial palsy using statistical methods. Study Design: Prospective study. Setting: Tertiary referral center. Patients: Consecutive 142 patients with Bells palsy and 26 with Ramsay Hunt syndrome treated with steroid plus antiviral agents. Interventions: Multivariate analysis was used to identify which factors, including Yanagihara grading score and ENoG, predict better recovery. Receiver operating characteristic (ROC) curves were constructed for ENoG and grading score. The cumulative recovery rate by ENoG was calculated using Kaplan-Meier analysis. Recovery was defined as the improvement of grading score to 36 points or more (full score, 40) without synkinesis. Results: Multivariate analysis revealed that Ramsay Hunt syndrome, the worst grading score and ENoG were the significant prognostic predictors. The area under the ROC curve for ENoG was broader than those for grading score, indicating that ENoG was superior to grading score in terms of accuracy for prognosis prediction. The ROC curve revealed that more than 85% degeneration on ENoG had the best specificity (77.8%) and sensitivity (71.4%) to predict nonrecovery. When ENoG was subjected to the analysis of cumulative recovery rate using Kaplan-Meier plots, patients with more than 85% degeneration on ENoG had significantly poorer prognosis. Conclusion: ENoG was the most effective factor for prediction of the prognosis of peripheral facial palsy, and more than 85% degeneration had the best specificity and sensitivity to predict nonrecovery.

Prognostic significance of body mass index before treatment for head and neck cancer.

Patients with head and neck cancer frequently experience malnutrition. The purpose of this study was to examine the impact of nutritional status on prognosis and its association with treatment modalities.

Prognostic significance of serum squamous cell carcinoma antigen in patients with head and neck cancer

Abstract Conclusions: Serum squamous cell carcinoma antigen (SCC-Ag) level was an independent prognostic factor for survival in patients with head and neck squamous cell carcinoma (HNSCC), and the prognostic value depended on the carcinoma site. Objectives: To assess the value of SCC-Ag as a prognostic indicator in patients with HNSCC and to determine the effect of primary tumor site on prognosis. Methods: We reviewed 493 patients with HNSCC between 2004 and 2012. The chi-squared test was used to assess associations between SCC-Ag levels and TNM classification. A Cox proportional hazard model was used to assess the hazard ratio of SCC-Ag at different sites for death, and it was analyzed as a continuous variable. Results: The median serum level of SCC-Ag was 1.1 ng/ml (range 0–20). SCC-Ag was significantly higher in patients with advanced T and N classification tumors. Primary sites in the oral cavity, in the hypopharynx, advanced T and N classification, distant metastasis, and SCC-Ag were negatively associated with survival in univariate analysis. Multivariate analysis revealed that SCC-Ag was a significant risk factor for overall survival in cancers of the oral cavity, hypopharynx, and larynx, but not in oropharyngeal cancer.

Factors associated with malnutrition in patients with head and neck cancer

Abstract Conclusions: Comorbidities as well as T classification were the primary determinants for the nutritional status of patients with head and neck cancer. Objectives: We aimed to elucidate the underlying conditions of malnutrition in patients with head and neck cancer. Methods: We retrospectively reviewed 726 patients diagnosed with head and neck cancer between 2004 and 2013. Associations between malnutrition and clinical parameters were assessed using univariate and multivariate analyses. Results: Median body mass index was 21.5 (range 11.6–38.0). According to World Health Organization criteria, the nutritional status of these patients was classified into four groups: underweight (18%), normal (63%), overweight (17%), and obese (1%). Comorbidities were detected in 40% of patients. Multivariate analysis revealed the following factors to be independent factors associated with malnutrition: advanced T stage, metachronous cancer, collagen disease, gastrointestinal disease, and pulmonary disease.

Transaminase Activity Predicts Survival in Patients with Head and Neck Cancer.

Various serum biomarkers have been developed for predicting head and neck squamous cell carcinoma (HNSCC) prognosis. However, none of them have been proven to be clinically significant. A recent study reported that the ratio of aspartate aminotransaminase (AST) to alanine aminotransaminase (ALT) had a prognostic effect on non-metastatic cancers. This study aimed to examine the effect of the AST/ALT ratio on the survival of patients with HNSCC. Clinical data of 356 patients with locoregionally advanced HNSCC were collected. The effect of the AST/ALT ratio on overall survival was analyzed using a Cox proportional hazard model. Moreover, recursive partitioning analysis (RPA) was used to divide the patients into groups on the basis of the clinical stage and AST/ALT ratio. The prognostic ability of this grouping was validated using an independent data set (N = 167). The AST/ALT ratio ranged from 0.42 to 4.30 (median, 1.42) and was a prognostic factor for overall survival that was independent of age, primary sites, and tumor stage (hazard ratio: 1.36, confidence interval: 1.08−1.68, P = 0.010). RPA divided patients with stage IVA into the following two subgroups: high AST/ALT (≥2.3) and low AST/ALT (<2.3) subgroups. The 5-year survival rate for patients with stage III, stage IVA with a low AST/ALT ratio, stage IVA with a high AST/ALT ratio, and stage IVB were 64.8%, 49.2%, 28.6%, and 33.3%, respectively (p < 0.001). Compared with the low AST/ALT group, the adjusted hazard ratio for death was 2.17 for high AST/ALT group (confidence interval: 1.02–.22 P = 0.045). The AST/ALT ratio was demonstrated to be a prognostic factor of HNSCC. The ratio subdivided patients with stage IVA into low- and high-risk groups. Moreover, intensified treatment for the high-risk group may be considered.

Small Cell Carcinoma of the Larynx Treated by Concurrent Chemoradiotherapy: A Case Report

Small cell carcinoma (SmCC) generally occurs in the lung and extrapulmonary SmCC is a relatively rare entity. Here, we present a case of a 42-year-old male with SmCC of the larynx diagnosed as cT3N0M0. Concurrent chemoradiotherapy using cisplatin (CDDP) and etoposide (VP-16) was given, which achieved complete response (CR). Lung metastasis became evident in 16 months whereas the locoregional control remained good. In spite of intensive chemotherapy using CDDP and irinotecan (CPT-11), the patient died of disease in 34 months after the first interview. Since the prognosis of laryngeal SmCC is extremely poor, organ preservation therapy should be considered instead of radical laryngectomy.

CLICK: one-step generation of conditional knockout mice

BackgroundCRISPR/Cas9 enables the targeting of genes in zygotes; however, efficient approaches to create loxP-flanked (floxed) alleles remain elusive.ResultsHere, we show that the electroporation of Cas9, two gRNAs, and long single-stranded DNA (lssDNA) into zygotes, termed CLICK (CRISPR with lssDNA inducing conditional knockout alleles), enables the quick generation of floxed alleles in mice and rats.ConclusionsThe high efficiency of CLICK provides homozygous knock-ins in oocytes carrying tissue-specific Cre, which allows the one-step generation of conditional knockouts in founder (F0) mice.

Metabolic tumor volume of primary tumor predicts survival better than T classification in the larynx preservation approach

We aimed to determine whether pretreatment metabolic tumor volume of the primary tumor (T‐MTV) or T classification would be a better predictor of laryngectomy‐free survival (LFS) and overall survival (OS) after chemoradiotherapy in patients with locally advanced laryngeal or hypopharyngeal cancer requiring total laryngectomy. We analyzed 85 patients using a Cox proportional hazards model and evaluated its usefulness by Akaikes information criterion. A T‐MTV cut‐off value was determined by time‐dependent receiver operating characteristic curve analysis. Interobserver reliability for measuring T‐MTV was estimated by the intraclass correlation coefficient (ICC). After adjustment for covariables, T‐MTV, irrespective of whether a continuous or dichotomized variable, and T classification remained independent predictors of LFS and OS. Large T‐MTV (>28.7 mL) was associated with inferior LFS (hazard ratio [HR], 4.16; 95% confidence interval [CI], 1.97–8.70; P = 0.0003) and inferior OS (HR, 3.18; 95% CI, 1.47–6.69; P = 0.004) compared with small T‐MTV (≤28.7 mL). The T‐MTV model outperformed the T classification model in predicting LFS and OS (P = 0.007 and 0.01, respectively). Three‐year LFS and OS rates for patients with small versus large T‐MTV were 68% vs 9% (P < 0.0001) and 77% vs 25% (P < 0.0001), respectively, whereas those for patients with T2‐T3 versus T4a were 61% vs 31% (P = 0.003) and 71% vs 48% (P = 0.10), respectively. ICC was 0.99 (95% CI, 0.99–1.00). Given the excellent interobserver reliability, T‐MTV is better than T classification to identify patients who would benefit from the larynx preservation approach.

Factors predicting severe infections during chemotherapy in head and neck cancer patients.

Abstract Conclusions: The head and neck cancer patients with more co-morbidities and those dependent on tube feeding are at a high risk of severe infections during chemotherapy. Therefore, prophylaxis with colony-stimulating factors and/or antibiotics should be considered for those patients. Objectives: To investigate the risk factors for severe infection during chemotherapy in head and neck cancer patients. Methods: A retrospective study was conducted of 129 patients with head and neck cancer who received taxane-based and platinum-based chemotherapy between 2008–2013. Logistic regression models were used to evaluate risk factors. Results: Febrile neutropenia occurred in 50 patients out of the 129 (39%), severe infections occurred in 24 patients (19%), and bacteremia in two patients (2%). In univariate analysis, low serum albumin levels and tube feeding were significantly associated with severe infections (p = 0.015 and < 0.001, respectively). In multivariate analysis, the odds ratios for a higher modified Charlson co-morbidity index and tube feeding were 2.80 and 9.74, respectively. These two were independent predictive factors for severe infections (p = 0.020 and 0.001, respectively).

Development and validation of a new comorbidity index for patients with head and neck squamous cell carcinoma in Japan

Due to habitual drinking and smoking and advanced age at diagnosis, patients with head and neck squamous cell carcinoma (HNSCC) frequently present with comorbidities. Several comorbidity indices have been developed and validated for HNSCC. However, none have become the standard method. In this study, we developed a new comorbidity index for Japanese patients with HNSCC, which was validated against an independent data set. A Cox proportional hazards analysis of 698 patients identified dementia, connective tissue diseases, and second primary malignancies in the oesophagus, head and neck, lungs, and stomach as prognostic comorbidities for overall survival. The Osaka head and neck comorbidity index (OHNCI) was generated from the weighted points of these comorbidities. In the independent data set, the 5-year overall survival rates for the low, moderate, and high scoring OHNCI groups were 62.1%, 64.3%, and 37.7%, respectively. In the multivariate analysis, the high scoring OHNCI group was an independent prognostic factor for overall survival (hazard ratio: 1.81, 95% confidence interval: 1.05–3.13; P = 0.031). The model including the OHNCI exhibited a higher prognostic capability compared to those including other commonly used comorbidity indices. The OHNCI could become the primary choice for comorbidity assessment in patients with HNSCC in Japan.