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Purpose A fluorescence-based technique for the detection of parathyroid glands (PGs) intraoperatively was previously reported. The technique was based on the phenomenon in which PGs emit autofluorescence when exposed to near-infrared light and we undertook an evaluation to consider the pathological accuracy of the method. Methods The study comprised 17 patients (18 specimens) who underwent thyroid surgery at Kushiro City General Hospital between November 2018 and June 2019. We searched for PGs intraoperatively using a fluorescence spectroscopy system and evaluated the pathological accuracy of the system. We statistically evaluated the clinical factors associated with the accuracy of the system, including age, gender, body mass index, laterality, disease state, renal function, and comorbidity. Results Eighteen specimens were evaluated pathologically, with 13 specimens confirmed as PGs. These were evaluated as "true positive," giving a positive predictive value of 72.2% (13/18). Among the false-negative cases, one specimen was a metastatic lymph node in a patient with papillary thyroid carcinoma. There was a significant difference in the true-positive rates between malignant (25%) and benign (85.7%) disease (P = 0.044). Conclusion We consider that this technique is useful, however, we have to exercise care in malignant cases as the true-positive rate may be low.

Background: The purpose was to compare survival differences between patients with external auditory canal (EAC) cancer treated according to the University of Pittsburgh modified TNM staging system and those treated in accordance with the 8th edition of the American Joint Committee on Cancer (AJCC) staging manual on the TNM staging system for cutaneous cancers of the head and neck. Methods: We performed a retrospective, single-institution review of 60 patients with EAC cancer treated with curative intent between September 2002 and March 2018. Survival outcomes were measured on the basis of the two staging systems. Results: The C-index values for the overall survival (OS) rate revealed that the University of Pittsburgh staging system had higher prognostic accuracy than the 8th edition of the AJCC staging system. Univariable and multivariable analysis showed that T classification according to the University of Pittsburgh staging system was an independent predictor of the OS rate (hazard ratio 5.25; 95% confidence interval 1.38-24.9; P = 0.015). Meanwhile, the AJCC staging system could not differentiate T2 from T3-4 cancers. Conclusion: The University of Pittsburgh staging system for patients with EAC cancer is a valuable tool for use in clinical decision-making and predicting survival outcome.

Background: The revised 8th edition of the AJCC/UICC staging system was released in January 2017, and depth of invasion (DOI) was added to the new criteria for T classification in oral cavity cancer. In this study, we evaluated whether the 8th edition presents the prognosis and risk of nodal metastasis in patients with squamous cell carcinoma of tongue more accurately than did the 7th edition. Methods: The data for 112 patients were obtained and reclassified based on the criteria presented in the 8th edition. Results: Seven patients previously staged as T1 based on the criteria in the 7th edition were reclassified as T2 based on the 8th edition, while 19 T2 patients were reclassified as T3, and 9 T4a patients were reclassified as T3. T3 in the 8th edition represents a homogenous population showing the same prognosis, while T2 in the 8th edition represents a heterogenous population. Nodal metastasis was significantly correlated with T classification in both editions and DOI. However, neither the T classification in the 7th or 8th edition, nor DOI could predict the probability of potential nodal metastasis in patients with cN0 disease. Conclusions: The classification on T3 in the 8th edition can be seen as reasonable with regard to prognosis. Nodal metastasis was significantly correlated with T classification and DOI; however, the probability of subsequent nodal metastasis in patients with T2N0 was almost same for the criteria in the 7th and 8th editions, therefore, the same careful management as before is required for patients with N0 disease.

Purpose To evaluate the diagnostic power of hybrid intravoxel incoherent motion (IVIM)-diffusion kurtosis imaging (DKI) model parameters in pretreatment for the prediction of future distant metastasis in head and neck squamous cell carcinoma (HNSCC) patients. Materials and methods We retrospectively evaluated 49 HNSCC patients who underwent curative chemoradiation therapy. Diffusion-weighted image (DWI) acquired by single-shot spin-echo echo-planar imaging with 12 b-values (0-2000) was performed in all patients before any treatment. We calculated the IVIM-DKI parameters and the conventional apparent diffusion coefficient (ADC) in the ROI placed on the primary lesion. The presence of future distant metastasis was determined by histological findings or clinical follow-up. Results A univariate analysis revealed significant differences between the patients with distant metastasis and those without in slow diffusion coefficient (D) and kurtosis value (K). Highest diagnostic accuracy was obtained by the D value. In addition, a multivariate analysis revealed that the D value was an independent predictor of future distant metastasis. Conclusion The D and K values obtained by this hybrid IVIM-DKI model can be one of the diagnostic tools for the prediction of future distant metastasis in HNSCC patients.

Background We are currently undertaking a multi-institutional prospective trial of the superselective intra-arterial infusion of high-dose cisplatin with concomitant radiotherapy for patients with T4aN0M0 or T4bN0M0 locally advanced maxillary sinus squamous cell carcinomas (SCC). We herein report the results of the dose-finding phase. Methods The dose-finding phase sought to evaluate the incidence of dose-limiting toxicities and determine the recommended number of cycles of the intra-arterial infusion of cisplatin. In this phase, 100 mg/m2 of cisplatin was administered intra-arterially weekly for 7 weeks with concomitant radiotherapy (70 Gy). Results All 18 patients received a full dose of radiotherapy. The number of cycles of cisplatin was 7 in 13 patients and 6 in 5 patients. The dose-limiting toxicities were observed in 5 patients. Conclusion These results indicated that this therapy is safe and well-tolerated at 7 cycles of cisplatin, which was determined to be the recommended number of cycles for locally advanced maxillary sinus SCC.

Inverted papilloma (IP) is a benign tumor occurring in the nasal cavity and paranasal sinuses. It is reported that 5–15% of IPs undergo malignant transformation into squamous cell carcinoma (SCC), and the role of microRNAs (miRNA/miR) in this process remains to be elucidated. In the present study, whole miRNA profiles using samples of IP and SCC were investigated, in order to detect the function of miRNA in the carcinogenesis of IP. Samples from IPs (n=5) and SCC lesions (n=5), which arose from IPs, were used for miRNA analysis. A total of 200 miRNAs exhibited a >2-fold differential expression between IP and SCC. miR-296-3p was markedly upregulated in SCC with a 23-fold difference. Computational analysis indicated that miR-296-3p targeted PTEN, which regulates the phosphoinositide 3-kinase (PI3K)/protein kinase B (Akt) signaling pathway and PTEN is involved in the carcinogenesis of SCC. miR-296-3p directly regulated PTEN expression in head and neck cancer cells, with PTEN protein levels decreased in 4/19 the SCCs (21.0%), as compared with those in the IPs (76.4%). Positive p21 staining was observed in 64.7% of IPs; this was a significantly increased rate compared with that for SCCs (26.3%, P=0.0086). The results of the present study indicated that there were marked changes in the miRNA expression signature during the malignant transition. miR-296-3p may serve an important role in the malignant transformation of IPs via the regulation of PTEN, combined with the subsequent inhibition of the PI3K/Akt signaling pathway, and may be a novel agent for cancer prevention.

Purpose To evaluate the detectability of the residual tumour in post-treatment granulation tissue using parameters obtained with an advanced diffusion model in patients with head and neck squamous cell carcinoma (HNSCC) treated by chemoradiation therapy. Materials and methods We retrospectively evaluated 23 patients with HNSCC after the full course of chemoradiation therapy. The diffusion-weighted image (DWI) acquisition used single-shot spin-echo echo-planar imaging with 11 b-values (0–1000). We calculated 10 DWI parameters using a mono-exponential model, a bi-exponential model, a stretched exponential model (SEM), a diffusion kurtosis imaging (DKI) model and a statistical diffusion model (SDM) in the region of interest (ROI) placed on the post-treatment granulation tissue. The presence of residual tumour was determined by histological findings or clinical follow-up. Results Among the 23 patients, seven patients were revealed to have residual tumour. The univariate analysis revealed significant differences in six parameters between the patients with and without residual tumour. From the receiver operating characteristic curve analysis, the highest area under curve was detected in the center of the Gaussian distribution of diffusion coefficient (D s ) obtained by the SDM. The multivariate analysis revealed that the D s and diffusion heterogeneity (α) obtained by the SEM were predictors for the presence of residual tumour. Conclusion DWI parameters obtained by advanced fitting models will be one of the diagnostic tools for the detection of residual tumour.

We assessed parameters of advanced diffusion weighted imaging (DWI) models for the prediction of the tumor growth rate in 55 head and neck squamous cell carcinoma (HNSCC) patients. The DWI acquisition used single-shot spin-echo echo-planar imaging with 12 b-values (0-2000). We calculated 14 DWI parameters using mono-exponential, bi-exponential, tri-exponential, stretched exponential and diffusion kurtosis imaging models. We directly measured the tumor growth rate from two sets of different-date imaging data. We divided the patients into a discovery group (n = 40) and validation group (n = 15) based on their MR acquisition dates. In the discovery group, we performed univariate and multivariate regression analyses to establish the multiple regression equation for the prediction of the tumor growth rate using diffusion parameters. The equation obtained with the discovery group was applied to the validation group for the confirmation of the equation's accuracy. After the univariate and multivariate regression analyses in the discovery-group patients, the estimated tumor growth rate equation was established by using the significant parameters of intermediate diffusion coefficient D2 and slow diffusion coefficient D3 obtained by the tri-exponential model. The discovery group's correlation coefficient between the estimated and directly measured tumor growth rates was 0.74. In the validation group, the correlation coefficient (r = 0.66) and intra-class correlation coefficient (0.65) between the estimated and directly measured tumor growth rates were respectively good. In conclusion, advanced DWI model parameters can be a predictor for determining HNSCC patients' tumor growth rate.

Recently it was reported that the parathyroid glands (PGs) emit autofluorescence when exposed to near infrared light, and a technique using fluorescence to detect the PGs intraoperatively was found to be useful. In some cases, however, it was difficult to detect the PGs. We sought to clarify the situation regarding such undetectable cases. The study comprised 45 patients (50 sides) who underwent thyroid or parathyroid surgery at Kushiro city general hospital between November 2018 and June 2019. We searched for the PGs intraoperatively using a fluorescence spectroscopy system. We statistically considered the factors related to the fluorescence patterns of background in cases in which two PGs could not be confirmed using Fisher’s exact test. Factors included age, gender, body-mass index, laterality, disease state, renal function, and comorbidity. In 41 sides (82%) fluorescence from at least one PG was determined. There was no significant difference in the detection rates among the other clinical factors. A “White out” pattern in which the background was too bright to detect PGs was observed in 11 sides (22%), and a “Black out” pattern in which the background and PGs were dark was observed in 18 sides (36%). Malignant disease was statistically associated with a “White out” pattern. No factors were found to be related to the “Black out” pattern. In malignant disease, we should use this novel approach carefully.

Purpose We assessed advanced fitting models of diffusion weighted imaging (DWI) in head/neck squamous cell carcinoma (HNSCC) patients to determine the best goodness of fit and correlations among diffusion parameters. We compared these results with those of dynamic contrast-enhanced (DCE) perfusion parameters. Materials and methods We retrospectively evaluated 32 HNSCC patients (12 sinonasal, 20 pharynx/oral cavity). The DWI acquisition used single-shot spin-echo echo-planar imaging (EPI) with 12 b-values (0 − 2000). We calculated 14 DWI parameters using mono-exponential, bi-exponential, and tri-exponential models, stretched exponential model (SEM) and diffusion kurtosis imaging (DKI) models. We compared each model's goodness of fit using the residual sum of squares (RSS), Akaike Information Criterion (AIC) and Bayesian information criterion (BIC) value. We determined the correlation between each pair of DWI parameters and between each DWI parameter and DCE perfusion parameter. Results The tri-exponential fit's RSS, AIC and BIC values were significantly smaller than those for bi-exponential fit. The RSS, AIC and BIC values of the SEM fit and DKI fit were significantly smaller than mono-exponential model. Significant correlations were observed in 30 pairs (sinonasal cavity) and 31 (sinonasal cavity group) among 91 DWI parameter combinations. Significant correlations were also observed in nine pairs (both sinonasal cavity and pharynx/oral cavity group) among 64 DWI/DCE perfusion parameter pairs, in particular, high positive correlations between the tri-exponential model's intermediate diffusion fraction (f 2 ) and the volume of the extracellular extravascular space per unit volume of tissue (v e ) were observed in both patient groups. Conclusion We identified several correlations between DWI parameters by advanced fitting models and correlations between DWI and DCE parameters. These will help determine HNSCC patients' detailed tissue structures.

Purpose. 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. Methods. Eighty-eight patients with cN0 tongue carcinomas underwent surgical treatment. Tumor thickness was measured from magnetic resonance (MR) images or computed tomography (CT) scans. Results. 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 ≧10mm or ≧5mm did not increase the probability of nodal metastasis, with late nodal metastasis observed in 15% of patients with graphically undetected small tumors. Conclusions. 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.

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, 2016

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 (100–120 mg/m 2 per week) with simultaneous intravenous infusions of thiosulfate to neutralize cisplatin toxicity and conventional radiotherapy (65–70 Gy). 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.

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, 2015

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/m2 was delivered 1 week before the start of radiotherapy. Seven weekly infusions of 250 mg/m2 of cetuximab followed during the definitive radiotherapy. In the CRT group, cisplatin was administered at a dose of 40 mg/m2 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).

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). 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. 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. 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.

Objective Although elevated anti-mumps IgM antibody levels were reported in 5.7%–7.2% of Japanese patients with sudden sensorineural hearing loss (SSNHL), there were several reports of false-positive cases, such as the continually IgM positive case and the IgM positive case in normal adults. To improve specificity, the new enzyme immuno assay (EIA) anti-mumps IgM antibody measurement kit was introduced in December 2009. This study re-examined the frequency of anti-mumps IgM antibody test positivity with SSNHL using the new measurement kit and compared the results with those from a previous report that used old kit. Methods This is a retrospective multi-institutional study involving patients diagnosed with SSNHL who exhibited the anti-mumps IgM antibody. We compared the positive rate of anti-mumps IgM antibody and the annual average number of mumps cases per sentinel in Hokkaido between the patients in the present study and patients previously evaluated. Results Overall, 100 patients with SSNHL were enrolled. One case (1.0%) was positive for anti-mumps IgM antibody. Of the 69 patients evaluated in the previous study, 5 cases (7.2%) were positive for anti-mumps IgM antibody. The positive rate of the anti-mumps IgM antibody in the present cases was significantly lower than that previously reported (p = 0.042). The annual average number of mumps cases per sentinel in Hokkaido of the present and previous surveillance period was 34.47 and 42.77, respectively; no significant difference was seen in these data (p = 0.4519). Conclusion The present study revealed that 1.0% of SSNHL was positive for the anti-mumps IgM antibody using the new EIA-IgM measurement kit. After the introduction of the new EIA-IgM measurement kit, anti-mumps IgM antibody positive rate with SSNHL significantly decreased, indicating that the proportion of asymptomatic mumps among etiology of SSNHL may be lower than those previously reported.

Background Osteoradionecrosis (ORN) of the hyoid bone sometimes induces severe front neck infection and can cause laryngeal stenosis and carotid rupture. Although ORN of the hyoid bone is known to be a complication of chemoradiotherapy for head and neck cancer, there has been no basis for its evaluation. Our purpose is to present the clinical and MR imaging features of ORN of the hyoid bone. Methods The study group comprised patients with advanced oropharyngeal cancer treated with targeted intra-arterial cisplatin infusion with concomitant radiotherapy. ORN of the hyoid bone was identified on the basis of decreased signal intensity of the bone marrow on T1WI images. Signal intensity on T2WI images was used to distinguish between inflammation and fibrosis. Results A total of 39 pre-treatment MR images and follow-up MR images were reviewed. ORN of the hyoid bone were detected in 30% of patients after treatment, with 23% of them showing inflammation and 7.7% fibrosis. Two patients developed severe neck infection and received antibiotics and underwent surgical intervention by tracheostomy and resection of the hyoid bone. Conclusion Our MR imaging study showed that ORN of the hyoid bone is not particularly rare in patients with oropharyngeal cancer treated with chemoradiotherapy. Clinicians should evaluate images carefully to prevent the development of severe complication due to infection associated with ORN of the hyoid bone.

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.

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.

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. (C) 2014 Elsevier Ltd. All rights reserved.

The suprasternal space is a narrow space between the superficial and deep layers of the investing layers of the deep cervical fascia above the manubrium of the sternum. The suprasternal space has been paid little attention as a space with the potential for lymph node metastasis from both thyroid cancer and head and neck cancer. We experienced 2 patients who were found to have a lymph node in the suprasternal space preoperatively. Both of them had well-differentiated thyroid papillary carcinomas and level III and IV lymph node metastases as well as metastasis in the suprasternal space. We have not previously dissected the suprasternal space prophylactically in other patients with thyroid papillary cancer, but no patient has developed metastasis in this space to date. The suprasternal space is not usually dissected in patients with thyroid cancer. However, suprasternal space metastasis has been reported to occur occasionally in patients with lymph node metastases in levels III and IV. We consider that dissection of the suprasternal space, which is not routinely performed, should be done when preoperative examination suggests lymph node metastasis in the suprasternal space as dissection of this space is less invasive, easy to achieve, and is not time consuming. Greater attention should be paid to the suprasternal space as an area with the potential for lymph node metastasis from thyroid cancer.

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. Head Neck 37: 537–542, 2015

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. (C) 2014 Elsevier Inc. All rights reserved.

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.

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. i 2014 S. Karger AG, Basel

Background: The purpose of this study was to evaluate the efficacy of superselective cisplatin infusion with concomitant radiotherapy (RADPLAT) for previously untreated patients with the squamous cell carcinoma of maxillary sinus (SCC-MS). Methods: Between 1999 and 2010, 54 patients were given superselective intra-arterial infusions of cisplatin (100-120mgm(-2) per week) with simultaneous intra-venous infusions of thiosulfate to neutralise cisplatin toxicity and conventional radiotherapy (65-70 Gy). Results: One patient (1.9%) was diagnosed with T2, 14 (25.9%) with T3, 27 (50%) with T4a, and 12 (22.2%) with T4b disease. Lymph-node involvement was present in 12 patients (22.2%). During the median follow-up period of 6.4 years, the 5-year local progression-free and overall survival rates were 65.8 and 67.9% for all patients, respectively. No patient died as a result of treatment toxicity or experienced a cerebrovascular accident. Osteonecrosis (n-5), brain necrosis (n-1), and ocular/ visual problems (n = 14) were observed as late adverse reactions. Conclusion: We have shown excellent overall survival and local progression-free rate in SCC-MS patients treated by RADPLAT with acceptable rates of acute and late toxicity. A multi-institutional trial is needed to prove that this strategy is a feasible and effective approach for the treatment of SCC-MS.

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. J. Magn. Reson. Imaging 2014;40:920–928. © 2013 Wiley Periodicals, Inc.

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).

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.

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.

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.

Squamous cell carcinoma of the nasal vestibule (SCC-NV) is rare among head and neck malignancies. It behaves differently from cancers arising in the nasal cavity and paranasal sinuses, and skin cancer of the external nose. Prognosis is more favorable than nasal cavity tumors and less favorable than skin cancers. We experienced two cases of SCC-NV who were treated with rapid superselective high-dose cisplatin infusion with concomitant radiotherapy (RADPLAT). A 56-year-old male and a 68-year-old female with SCC-NV, classified as T4aN0M0 according to UICC and T2 according to Wang classification, were given superselective intra-arterial infusions of cisplatin, with simultaneous intravenous infusions of thiosulfate to neutralize cisplatin toxicity, together with conventional radiotherapy. In both cases, the internal maxillary artery and the facial artery were considered to be feeders of the tumor. No serious adverse events have been observed in either patient to date during follow-up of 7.3 and 5.3 years, respectively. Both patients are alive without disease and show excellent cosmetic results. RADPLAT is considered to be useful for the treatment of patients with SCC of the nasal vestibule.

下咽頭喉頭全摘頸部食道切除（咽喉食摘術）に施行される気管傍の郭清では，気管軟骨壊死をおこさないように，気管の虚血には細心の注意をはらう必要がある。われわれは下甲状腺動脈から，あるいは上甲状腺動脈から甲状腺を介した気管への血流の，左右4系列いずれかを温存することをこころがけている。この手技によって郭清の質を落とすことなく，安全な気管孔の作製をすることが両立しえた。この手技は特殊な技術を必要とせず，気管孔の管理・狭窄予防に有用であり，QOLの向上に寄与すると考えられた。

This retrospective study aimed to compare the accuracy of two nodal evaluation criteria using computed tomography after intra-arterial chemoradiation in node-positive head and neck squamous cell carcinomas. Computed tomography was used to evaluate radiographic nodal response 4-8 weeks after intra-arterial chemoradiation. We compared the accuracy of two different criteria: criterion 1 (radiographic complete response was recorded in the absence of focal abnormalities and if the maximum diameter of the metastatic node was less than 15 mm), and criterion 2 (radiographic complete response was recorded in the absence of focal abnormalities and if the minimum diameter of metastatic nodes was less than 7 mm in level II and if the minimum diameter of metastatic nodes in the rest of the neck was less than 6 mm). Positive predictive values were criterion 1: 69.2%, criterion 2: 47.8%; negative predictive values were criterion 1: 88.5%, criterion 2: 90.5%. Positive likelihood ratios were criterion 1: 7.50, criterion 2: 3.06. The difference between each criteria was statistically significant using McNemar's test (p = 0.0016). Computed tomography evaluation accuracy of nodal response after intra-arterial chemoradiation was comparable to recent reports, and it was feasible to perform salvage neck dissection by computed tomography evaluation for nodal response. We recommend using criterion 1 because of its simplicity and reliability.

Concomitant radiotherapy and superselective arterial infusion of cisplatin for laryngeal cancer has shown excellent therapeutic outcomes. It is expected to be a reasonable treatment option for laryngeal cancer, especially in locally advanced cases.