Atsushi Hanamoto

Volumetric PET/CT parameters predict local response of head and neck squamous cell carcinoma to chemoradiotherapy

It is not well established whether pretreatment 18F‐FDG PET/CT can predict local response of head and neck squamous cell carcinoma (HNSCC) to chemoradiotherapy (CRT). We examined 118 patients: 11 with nasopharyngeal cancer (NPC), 30 with oropharyngeal cancer (OPC), and 77 with laryngohypopharyngeal cancer (LHC) who had completed CRT. PET/CT parameters of primary tumor, including metabolic tumor volume (MTV), total lesion glycolysis (TLG), and maximum and mean standardized uptake value (SUVmax and SUVmean), were correlated with local response, according to primary site and human papillomavirus (HPV) status. Receiver‐operating characteristic analyses were made to access predictive values of the PET/CT parameters, while logistic regression analyses were used to identify independent predictors. Area under the curve (AUC) of the PET/CT parameters ranged from 0.53 to 0.63 in NPC and from 0.50 to 0.54 in OPC. HPV‐negative OPC showed AUC ranging from 0.51 to 0.58, while all of HPV‐positive OPCs showed complete response. In contrast, AUC ranged from 0.71 to 0.90 in LHC. Moreover, AUCs of MTV and TLG were significantly higher than those of SUVmax and SUVmean (P < 0.01). After multivariate analysis, high MTV >25.0 mL and high TLG >144.8 g remained as independent, significant predictors of incomplete response compared with low MTV (odds ratio [OR], 13.4; 95% confidence interval [CI], 2.5–72.9; P = 0.003) and low TLG (OR, 12.8; 95% CI, 2.4–67.9; P = 0.003), respectively. In conclusion, predictive efficacy of pretreatment 18F‐FDG PET/CT varies with different primary sites and chosen parameters. Local response of LHC is highly predictable by volume‐based PET/CT parameters.

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.

Docetaxel, cisplatin, and fluorouracil for patients with inoperable recurrent or metastatic head and neck squamous cell carcinoma

OBJECTIVE The first-line treatment for inoperable recurrent or metastatic head and neck squamous cell carcinoma (HNSCC) has long been the combination of cisplatin and fluorouracil (PF). Recently, cetuximab has been shown to provide an additional survival benefit to PF. It remains unknown whether docetaxel adds additional benefits to PF. Therefore, we sought to evaluate the efficacy and toxicity of docetaxel, cisplatin, and fluorouracil (TPF) for inoperable recurrent or metastatic HNSCC. METHODS A retrospective chart review from January 2005 to March 2013 identified patients who were treated with docetaxel 60 mg/m(2) on day 1, followed by cisplatin 60 mg/m(2) on day 1, and fluorouracil 600 mg/m(2)/day on days 1-5 (modified TPF) every 4 weeks for inoperable recurrent or metastatic HNSCC. RESULTS Twenty-four patients were identified; seven and five patients had locoregional disease only and distant metastasis only, respectively, while 12 patients had locoregional disease and distant metastasis simultaneously. Of the 17 patients with distant metastasis, multiple organs were affected in 9 patients, with the most frequently affected organ being the lung (n=11). Three patients had no prior treatment, whereas 21 patients underwent intensive prior treatment. In 17 of 21 patients who had received prior treatment, the treatment included chemoradiotherapy and/or chemotherapy. The median number of cycles of modified TPF was two (range, 1-5). One patient showed complete response, four patients showed partial response, two patients had stable disease, and 17 patients had progressive disease. Overall, the rate of objective response was 21%, with a 95% confidence interval (CI) of 9-40%. Median overall survival was 8.0 months (95%CI, 4.4-10.6 months). The treatment efficacy differed significantly according to extent of disease. Objective response in patients with distant metastasis alone was better than in patients with locoregional disease with or without distant metastasis (60% vs. 11%, respectively; P=0.02). Median overall survival in the former patients was longer than in the latter patients (not reached vs. 7.0 months, respectively; P=0.02). Fifteen patients (63%) had Grades 3-4 neutropenia, and seven patients (29%) developed Grade 3 febrile neutropenia. There were no toxic deaths. CONCLUSION The efficacy of modified TPF in the setting of first-line treatment for recurrent or metastatic HNSCC is not very high, while the toxicity is acceptable with extensive care. The development of more efficacious chemotherapeutic regimen is required.

A case of anaplastic lymphoma kinase‐positive large B‐cell lymphoma: Aspiration cytology findings

Anaplastic lymphoma kinase‐positive (ALK+) large B‐cell lymphoma (LBCL) is a rare subtype of non‐Hodgkin B‐cell lymphoma that exhibits a more aggressive clinical course and poorer prognosis than the typical diffuse large B‐cell lymphoma. In this study, we report the case of a 67‐year‐old man with left cervical lymph node swelling. Aspiration cytology revealed many clusters of cohesive, large, and solitary cells. The tumor cells had abundant cytoplasm and large round‐to‐oval nuclei with prominent nucleoli. The Giemsa staining specimens exhibited amorphous global bodies adjacent to some clusters. Histologically, large tumor cells occupied the lymph nodes in a sinusoidal pattern, and immunohistochemically, these cells were cytokeratin−, CD19−, CD20−, CD79a−, CD3−, CD30−, CD138+, IgG−, IgA+, and ALK+. Chromogenic in situ hybridization revealed restricted immunoglobulin light‐chain expression. Fluorescent in situ hybridization demonstrated translocation of the ALK gene. The tumor cells were negative for Epstein–Barr virus and human herpesvirus 8. It is important to differentiate ALK+LBCL from metastatic carcinoma and other lymphoma subtypes with similar histological features to ensure a proper treatment strategy and prediction of prognosis. Diagn. Cytopathol. 2014;42:69–72.

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).

Shock Sensitization and Fear Potentiation of Auditory Startle Response in Hamsters

It is well known that an auditory startle response can be modulated by several processes. In the present study shock sensitization and fear potentiation were examined in 17 hamsters to assess whether response enhancement is similar for another rodent. Immediately after presentation of electrical foot shocks, the auditory startle response increased significantly. This response was also enhanced after fear conditioning in the Experimental group using a light as a conditioned stimulus (CS) and the foot shock as the unconditioned stimulus (US). The auditory startle response remained unchanged in the Control group after nonpaired presentation of CS and US. Significant correlation between enhancement of the auditory startle response in sensitization and fear conditioning was found for the Experimental group. Shock sensitivity and effect of fear on modulation of the auditory startle response in hamsters are similar to those of other rodents. Further, neural mechanisms underlying enhancement of the auditory startle response seem not to be responsible for the deficit of prepulse inhibition in hamsters.

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.

A Case of Paraneoplastic Cerebellar Degeneration and Lambert-Eaton Myasthenic Syndrome Associated with Neuroendocrine Carcinoma of the Oropharynx

Paraneoplastic cerebellar degeneration and Lambert-Eaton myasthenic syndrome (PCD-LEMS) are usually associated with small-cell lung carcinoma (SCLC). PCD-LEMS with extrapulmonary non-SCLC tumors; however, has not been previously reported. A 78-year-old man presented with dysarthria, dysphagia, staggering gait, and lower extremity muscle fatigue. He was diagnosed with PCD-LEMS associated with neuroendocrine carcinoma of the oropharynx, based on the histological findings of the biopsy, the existence of antibodies against P/Q-type voltage-gated calcium channels, and an incremental response of the compound muscle action potentials during repetitive nerve stimulation tests. Thus, PCD-LEMS should be included in the differential diagnosis of neurological dysfunction, even in extrapulmonary non-SCLC patients.

Efficacy and safety of management by only falecalcitriol for patients with postoperative hypoparathyroidism

Efficacy and safety of management by only falecalcitriol for patients with postoperative hypoparathyroidism: Susumu Nakahara1), Atsushi Hanamoto1), Toshimichi Yasui2), Yukinori Takenaka2), Yoshifumi Yamamoto2), Takahito Fukusumi1), Takahiro Michiba1) and Hidenori Inohara1). 1)Department of OtorhinolaryngologyHead and Neck Surgery, Graduate School of Medicine, Osaka University, 2)Department of Otorhinolaryngology-Head and Neck Surgery, Osaka General Medical Center