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Objective: Tumor cells can acquire a large amount of energy and structural components by reprogramming energy metabolism; moreover, metabolic profiles slightly differ according to cancer type. This study compared and assessed the metabolic profile of head and neck squamous cell carcinoma (HNSCC) and normal tissues, which were collected from patients without cancer. Subjects and Methods: Overall, 23 patients with HNSCC and 6 patients without cancer were included in the analysis. Metabolomic profiles were analyzed using capillary electrophoresis‐mass spectrometry. Gene expression was evaluated using real‐time reverse transcription‐polymerase chain reaction. Results: Glycolysis, the pentose phosphate pathway, tricarboxylic acid cycle, and glutamine metabolism were upregulated in HNSCC tissues based on gene expression analysis. HNSCC could then have enhanced energy production and structural component. The levels of lactate, succinate, glutathione, 2‐hydroxyglutarate, and S‐adenosylmethionine, considered as oncometabolites, increased and these had accumulated in HNSCC tissues. Conclusions: The level of metabolites and the expression of enzymes differ between HNSCC and normal tissues. Reprogramming metabolism in HNSCC provides an energy source as well as structural components, creating a system that offers rapid proliferation, progression, and is less likely to be eliminated. [ABSTRACT FROM AUTHOR]

Background: The modified Glasgow prognostic score (mGPS) includes C‐reactive protein and serum albumin levels and is a useful prognostic tool for malignant tumors. The immune system affects cancer progression and recurrence and treatment response. We hypothesized that increasing the lymphocyte count improves mGPS, and we created a new prognostic marker termed immune‐mGPS (imGPS). Methods: This study included 461 patients with head and neck squamous cell carcinoma (HNSCC). The imGPS was calculated as the conventional mGPS with one additional point for a low lymphocyte count (<1250/μL). Results: Addition of the lymphocyte count to mGPS significantly increased the area under the time‐dependent receiver operating characteristic curve for overall and progression‐free survivals. The added predictive abilities of this tool were supported by improvement in both net reclassification and integrated discrimination. Conclusion: imGPS is a more accurate predictor of clinical outcome in patients with HNSCC than mGPS. [ABSTRACT FROM AUTHOR]

Background: This study aimed to reveal the influence of the invasion site of external auditory canal (EAC) cancer by analyzing the outcome of patients with advanced tumor. Methods: A total of 111 patients with T4 EAC cancer were enrolled in this study. Of these patients, 79 underwent chemoradiotherapy and 32 underwent surgery under curative intent. Univariate and multivariate analyses and the Kaplan–Meier method were used to focus on the tumor invasion sites and overall survival of the patients. Results: The 3‐year overall survival rate of all patients was 55.0%. In multivariate analysis, the only significant invasion site for overall survival was the facial nerve, with the dura mater being the next most influential site. When Kaplan–Meier survival curve was calculated, facial nerve and dura mater were the significant factors resulting in poor patient outcomes. Conclusion: The facial nerve and dura mater are crucial sites of EAC cancer for patient outcomes. [ABSTRACT FROM AUTHOR]

Objectives: This study aimed to evaluate the efficacy of chemoradiotherapy (CRT) for patients with advanced cancer of the external auditory canal (EAC) by analyzing the outcome of the patients. Methods: This is a multi‐institutional retrospective survey, and we reviewed the medical records of the subjects. A total of 181 patients with tumor (T)3 or T4 tumor in 17 institutions were enrolled. Further analysis was performed for 74 patients who underwent CRT under curative intent. Results: Overall 5‐year survival rates of the patients who underwent CRT (n = 74) were 54.6%. Those of the patients who underwent CRT with modified TPF (docetaxel, cisplatin [CDDP], and 5‐fluorouracil) regimen (n = 50) and CRT with CDDP regimens (n = 24) were 64.4% and 36.7%, respectively. Significant differences were observed between these two groups. Conclusion: Given the tendency that head and neck surgeons prefer CRT for advanced larger cancer of the EAC, CRT for advanced EAC cancer using the modified TPF regimen showed good clinical outcomes. Level of Evidence: 4 Laryngoscope, 131:E870–E874, 2021 [ABSTRACT FROM AUTHOR]

Background: The usefulness of apparent diffusion coefficient (ADC) and diffusion‐weighted magnetic resonance imaging (DWI) in the detection of malignant tumors has been reported. The purpose of this study is to clarify the role of ADC and DWI for diagnosis of skull base tumors. Methods: A total of 27 patients with head and neck tumors with skull base invasions undergoing skull base surgery were enrolled in this study. Pathological findings of dural invasion and bone invasion were compared with the diagnostic imaging. Results: Advanced magnetic resonance imaging techniques revealed that ADC values in regions of pathological bone and dural invasions were significantly lower than in regions of no invasion. The area under the curve of ADC in bone invasions and dural invasions were 0.957 and 0.894, respectively. Conclusions: Our findings indicate that ADC and DWI are useful tools for the diagnosis of head and neck tumors with skull base invasion. [ABSTRACT FROM AUTHOR]

Background: Induction chemotherapy (IC) in locally advanced squamous cell carcinoma of the head and neck (LA‐SCCHN) often compromises compliance with subsequent chemoradiotherapy (CRT), which negatively affects outcomes. Here, we assessed the combination of paclitaxel (PTX), carboplatin (CBDCA), and cetuximab (Cmab) as IC for unresectable LA‐SCCHN. Methods: Induction chemotherapy consisted of weekly CBDCA area under the plasma concentration‐time curve = 1.5, PTX 80 mg/m2 and Cmab with an initial dose of 400 mg/m2 followed by 250 mg/m2 for 8 weeks. Following IC, CDDP (20 mg/m2, 4 days × 3 cycles) and concurrent radiotherapy (70 Gy/35 fr) were started. Primary endpoint was the proportion of CRT completion (%CRT completion). PCE was planned to be deemed effective if the Bayesian posterior probability (PP), defined as the probability that %CRT completion was larger than the threshold value of 65%, exceeded 84%. Results: Thirty‐five patients were enrolled. Cases were hypopharynx/oropharynx/larynx in 17/17/1 patients, all at Stage IV. Of 35 patients, 34 (97%) completed IC and 32 received CRT and met the criteria of full analysis set (FAS). In FAS, the %CRT completion was 96.9%, and PP was 99.9%, exceeding the prespecified boundary of 84%. Mean cumulative dose and relative to dose intensity of CDDP in CRT was 232.5 mg/m2 and 100%, respectively. Response rate was 88.6% by IC and 93.8% in the CRT phase. Three year overall survival was 83.5%. Main grade 3 toxicities included neutropenia (11.4%) and skin rash (5.7%) during IC; and oral mucositis (31.3%) and neutropenia (12.5%) during CRT. No grade 4 toxicity or treatment‐related death was seen. Conclusions: PCE as IC was feasible, with promising efficacy and no effect on compliance with subsequent CRT in unresectable LA‐SCCHN. [ABSTRACT FROM AUTHOR]

Background and Aim Dysphagia caused by pharyngo-upper esophageal stricture is a complication of treatment for head and neck cancer. Endoscopic balloon dilation ( EBD) is in widespread use as an effective and safe treatment for stricture in many areas of the gastrointestinal tract. In the present study, we investigated the efficacy and safety of EBD for pharyngo-upper esophageal strictures that developed after treatment for head and neck cancer. Methods From January 2010 to December 2013, the medical records and endoscopic findings of 19 consecutive patients with pharyngo-upper esophageal strictures occurring after surgery and/or chemoradiotherapy for head and neck cancer were retrospectively examined. Results Mean number of EBD sessions per patient was 6.6 (1-30), and mean maximum diameter of dilation was 15.8 (11-20) mm. Technical success was achieved in 16 of 19 (84.2%) patients, and only two major complications (bleeding and pha ryngeal edema) occurred in a total of 125 dilatation sessions (1.6%). Regarding the influence of chemoradiotherapy on the outcome of EBD, patients who had undergone chemoradiotherapy plus surgery experienced significantly more restenosis during the follow-up period compared to those who had undergone surgery alone (50% vs 0%, P < 0.05). Conclusions This retrospective analysis demonstrated the efficacy and safety of exclusive EBD for pharyngo-upper esophageal strictures occurring after treatment for head and neck cancer, indicating that the therapeutic application of EBD could be extended to such strictures. Patients who underwent chemoradiotherapy and surgery experienced more restenosis; hence, such patients should be carefully followed up after EBD treatment. [ABSTRACT FROM AUTHOR]

Background Mucosal melanoma of the head and neck is rare and is associated with a poor prognoses because of locoregional failure and distant metastasis. The aim of our study was to review the characteristics of these patients in northern Japan and to analyze their outcomes. Methods The medical records of 94 patients who had been provided initial treatment in 12 institutes from 1998 to 2007 were reviewed. Results When the 5-year overall survival rates of patients were evaluated, we found that the survival rates of patients treated by chemotherapy were significantly lower than those of patients treated by surgery or radiation. The survival rates of the single-treatment modality, 2-modality, and ≥3-modality groups were 23.4%, 38.0%, and 33.6%, respectively. Conclusion Our results suggest that patients who underwent combined treatment had better prognoses. However, we found that chemotherapy had no additional survival benefits. © 2012 Wiley Periodicals, Inc. Head Neck, 2012 [ABSTRACT FROM AUTHOR]

For the purpose of analyzing mechanisms related to the cis-diamminedichloroplatinum resistance in head and neck squamous cell carcinoma, we analyzed RPMI2650 and its derived previously established cis-diamminedichloroplatinum resistant cell line RPMI2650 CR. To identify resistant phenotype-related micro RNAs, we compared micro RNA expressions between RPMI2650 CR and RPMI2650 by microarray. One of the micro RNAs as downregulated, mi R-34a, was further investigated. Decreased expression of mi R-34a in RPMI2650 CR was confirmed by quantitative reverse transcription-polymerase chain reaction, but introduction of the mi R-34a precursor into RPMI2650 CR or the inhibitor of mi R-34a into RPMI2650 did not change cis-diamminedichloroplatinum sensitivities. However, 24 patients with sinonasal squamous cell carcinomas treated with intra-arterial infusion of cis-diamminedichloroplatinum showed a significant association between decreased expression of mi R-34a and poor disease specific survival ( P = 0.0015), poor disease free survival ( P = 0.0019), and poor local control rates ( P = 0.017) (median follow-up period: 53 months). Furthermore, multivariate analyses demonstrated significant associations between mi R-34a expression and the hazard ratios of disease free survival at 0.005 (95% confidence interval [ CI] 0.00-0.29, P = 0.011) and local control rate at 0.008 (95% CI 0.00-0.44, P = 0.019), although other parameters such as age, gender, treatment method, T and N stages did not show any similar association. These results strongly suggest that mi R-34a expression can be an independent prognostic biomarker in patients with sinonasal squamous cell carcinoma who are undergoing treatment with cis-diamminedichloroplatinum. [ABSTRACT FROM AUTHOR]

BACKGROUND: A growing proportion of head and neck squamous cell carcinoma (HNSCC) is caused by the human papillomavirus (HPV). In light of the unique natural history and prognosis of HPV-related HNSCCs, routine HPV testing is being incorporated into diagnostic protocols. Accordingly, there is an escalating demand for an optimal detection strategy that is sensitive and specific, transferrable to the diagnostic laboratory, standardized across laboratories, cost-effective, and amenable to broad application across specimen types including cytologic preparations. METHODS: Cytologic preparations (fine-needle aspirates [FNAs] and brushes) were obtained from surgically resected HNSCCs and evaluated for the presence of high-risk HPV using the Hybrid Capture 2 assay. HPV analysis was also performed on the corresponding tissue sections using HPV in situ hybridization and p16 immunohistochemistry. In cases in which the immunohistochemical and in situ hybridization results were discordant, HPV status was determined by real-time polymerase chain reaction detection of E7 expression. HPV status in the tissues and corresponding cytologic samples was compared. RESULTS: Based on benchmark HPV testing of the tissue sections, 14 HNSCCs were classified as HPV positive and 10 as HPV negative. All corresponding cytologic preparations were correctly classified using the Hybrid Capture 2 assay. CONCLUSIONS: The Hybrid Capture 2 strategy, already widely used for the detection of high-risk HPV in cervical brushes, is readily transferrable to HNSCCs. Consistent accuracy in cytologic preparation suggests its potential application in FNAs from patients who present with lymph node metastases, and may eliminate the need to obtain tissue solely for the purpose of HPV testing. Cancer (Cancer Cytopathol) 2012. © 2011 American Cancer Society. [ABSTRACT FROM AUTHOR]

Head and neck paragangliomas are tumors derived from parasympathetic paraganglia. Familial cases account for 10% or more of these tumors, and mutations of the genes encoding subunits for the mitochondrial respiratory chain complex II, SDHD, SDHB, and SDHC, have been reported. We analyzed mutations in the all four SDH genes, SDHA through SDHD, in a Japanese family with cervical paraganglioma that include a father with bilateral tumors and his daughter with a malignant left carotid body tumor with nodal metastasis. This pedigree harbored a germline G106D alteration in exon 4 of the SDHD gene that has not previously been reported to date. The tumors of the father expressed biallelic SDHD, but the SDHD expression was highly suppressed by an unknown mechanism(s) in tumors of his daughter, and the wild-type allele was predominantly suppressed in the metastatic node. These results suggest that the missense dysfunction of SDHD prepares neoplastic condition and that expressional silencing, particularly of the wild-type allele, plays an important role in the malignant transformation of the paragangliomas. Our results may lead to a better understanding of this disease and to the development of methods for prevention of this disease., ((c) 2006 Wiley-Liss, Inc.)