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Oral aprepitant has a large interindividual variation in clinical responses in advanced cancer. This study aimed to characterize plasma aprepitant and its N-dealkylated metabolite (ND-AP) based on the cachexia progression and clinical responses in head and neck cancer patients. Fifty-three head and neck cancer patients receiving cisplatin-based chemotherapy with oral aprepitant were enrolled. Serum albumin level was negatively correlated with the plasma concentrations of aprepitant at 24 hours after a 3-day aprepitant treatment. The patients with Glasgow Prognostic Score (GPS) 1 or 2 had higher plasma concentrations of total and free aprepitant than those with GPS 0. No difference was observed in the plasma concentration of ND-AP between the GPS classifications. The plasma interleukin-6 level was higher in patients with GPS 1 or 2 than 0. The absolute plasma concentration of free ND-AP was higher in patients without the delayed nausea, and its concentration to determine the occurrence was 18.9 ng/mL. The occurrence of delayed nausea had no relation with absolute plasma aprepitant. In conclusion, cancer patients with a lower serum albumin and progressive cachectic condition had a higher plasma aprepitant level. In contrast, plasma free ND-AP but not aprepitant was related to the antiemetic efficacy of oral aprepitant.

Laryngeal papillomatosis is caused by infection with human papillomavirus (HPV) type 6 and/or 11. Laryngeal papillomatosis recurs frequently, and malignant transformation occurs in 1.6%-4% of the cases. Surgery is the treatment of first choice. While adjuvant therapies such as interferon, Chinese medicines, proton pump inhibitors, indole 3 carbinol, cidofovir and vaccines have been tried, none has come to be positioned as the standard of care.We report seven patients with laryngeal papillomatosis who underwent multiple surgeries. All were men. The surgery was performed in combination with two or three of the following: use of an electric scalpel, CO2 laser, YAG laser, sharp resection, and intralesional injection of cidofovir. Intralesional injection of cidofovir after resection was performed in four cases, and remission was achieved in three of these cases. Cidofovir is an unapproved drug in Japan and is not yet approved for use in cases of laryngeal papillomatosis in other countries. However, the outcomes in our cases and other reports suggest that intralesional injection of cidofovir is effective.HPV6 (n=5), HPV11 (n=1) and HPV negative (n=1) detected respectively. Malignant transformation occurred in one case and HPV negative. Moreover, p16 immunohistochemistry was performed in all cases. However, no relation with number of operations and HPV status was found.The life cycle of HPV in laryngeal papillomatosis is largely unknown, and there is no consensus on methods of treatment other than surgery. More research is needed to elucidate the life cycle of HPV and the pathophysiology of laryngeal papillomatosis., 浜松医科大学医学部耳鼻咽喉科・頭頸部外科学教室 峯田周幸教授退任記念論文集～症例から学ぶ～, Festschrift for Professor Hiroyuki Mineta In Hornor of His Retirement as Chairman of Hamamatsu University School of Medicine

Congenital cholesteatoma in the tympanic cavity can be divided into two types - the closed-type cholesteatoma, which takes the form of a keratotic cyst, and the open-type cholesteatoma, characterized by a flat surface of the epidermis on the middle ear mucosa. Closed-type cholesteatoma is usually identified as a globular white mass through a normal tympanic membrane; whereas the tympanic membrane appears normal in open-type cholesteatomas. Therefore, it is difficult to diagnose open-type cholesteatomas, which are often identified accidentally during exploratory tympanotomy for preoperative diagnoses such as conductive hearing loss. Herein, we report a case of open-type cholesteatoma, in which the diagnosis was suspected from the findings of diffusion-weighted MRI examination using the periodically rotated overlapping parallel lines with enhanced reconstruction (PROPELLER) technique.An 18-year-old male presented to our hospital with the complaint of right hearing loss, which was suspected at a previous ENT clinic to be caused by a congenital ossicular anomaly. Otoscopic examination failed to reveal any abnormalities. Pure-tone audiometry showed moderate conductive hearing loss in the right ear. Computed tomography of the temporal bone revealed a defect of the long process of the incus and superstructure of the stapes, with a surrounding shadow that appeared to be soft tissue. On the basis of these findings, we suspected an open-type cholesteatoma with a defect of the ossicles. Diffusion-weighted MRI examination using the PROPELLER technique showed a high-intensity in the temporal bone, suggestive of a cholesteatoma. We performed exploratory tympanotomy, and found the open-type cholesteatoma in the middle ear. The cholesteatoma was removed without ossiculoplasty, and until now, nine months after the surgery, there has been no sign of recurrence.Our case showed the usefulness of diffusion-weighted MRI using the PROPELLER technique for the diagnosis of the open-type cholesteatoma. The possibility of open-type cholesteatoma should be borne in mind in patients diagnosed preoperatively as having a congenital ossicular anomaly, and diffusion-weighted MRI with the PROPELLER technique is indicated in such patients towards confirming the diagnosis., 浜松医科大学医学部耳鼻咽喉科・頭頸部外科学教室 峯田周幸教授退任記念論文集～症例から学ぶ～, Festschrift for Professor Hiroyuki Mineta In Hornor of His Retirement as Chairman of Hamamatsu University School of Medicine

MALT lymphoma is a low-grade B-cell lymphoma. Although it can develop in any organ, laryngeal MALT lymphoma is extremely rare, and is reported to account for less than 1% of all laryngeal malignancies. An 80-year-old woman was admitted to our hospital after she was diagnosed as having a subglottic mass by a neighborhood doctor whom she consulted because of a few months’ history of hoarseness of voice. She underwent laryngeal microsurgery, and was referred to the hematology department because histopathology led to the laryngeal MALT lymphoma. Treatment was considered, but then, in consideration of her age, etc., it was decided to follow her up at the outpatient department. One and a half years after the operation, the subglottic mass had disappeared spontaneously, and it was considered as a case of spontaneous disappearance of a laryngeal MALT lymphoma., 浜松医科大学医学部耳鼻咽喉科・頭頸部外科学教室 峯田周幸教授退任記念論文集～症例から学ぶ～, Festschrift for Professor Hiroyuki Mineta In Hornor of His Retirement as Chairman of Hamamatsu University School of Medicine

Purpose: Cetuximab inhibits epidermal growth factor receptor (EGFR) signaling in cancer and skin cells, thereby inducing anti-cancer effects and skin disorders. The present study aimed to evaluate the relationships between serum cetuximab and EGFR-related markers, and adverse effects in head and neck cancer patients.Methods: Thirty-four head and neck cancer patients receiving weekly intravenous cetuximab were enrolled. Serum cetuximab levels were determined just before dosing. Blood samples for determination of serum EGFR-related markers including soluble epidermal growth factor receptor (sEGFR) and interleukin-6 (IL-6) were obtained. The severities of skin disorders, their medications, and hypomagnesemia treatment were also assessed.Results: Serum levels of cetuximab and sEGFR were negatively and positively correlated with that of IL-6, respectively. The serum cetuximab level was 2-fold higher in the patients with a grade 2–3 skin rash than with a grade 0–1 rash. The serum cetuximab cut-off value related to severe skin rash was 71 μg/mL (sensitivity, 59%; and specificity, 94%). The use of a strong topical corticosteroid for skin rash was also associated with a higher serum cetuximab level. Serum levels of sEGFR and IL-6 had no correlations with the skin disorder severities or their medications. Hypomagnesemia treatment using intravenous magnesium sulfate was not related to serum cetuximab and EGFR-related markers.Conclusions: Head and neck cancer patients with a higher serum IL-6 level tended to have a lower serum cetuximab level. Serum cetuximab had positive correlations to skin rash severity and its medication in the study population.

Behcet’s disease is a chronic relapsing systemic inflammatory disease with four characteristic symptoms, including oral aphthous ulcers. In general, oral aphthous ulcers in Behcet’s disease are often confined to the oral cavity, but there have been reports of cases in which the aphthous ulcers have extended to the pharynx and larynx. Because there are no specific laboratory findings for the diagnosis of this disease, it is often difficult to diagnose. Herein, we report four cases of Behcet’s disease with intractable aphthous ulcers in the pharynx and larynx, including the epiglottis., 浜松医科大学医学部耳鼻咽喉科・頭頸部外科学教室 峯田周幸教授退任記念論文集～症例から学ぶ～, Festschrift for Professor Hiroyuki Mineta In Hornor of His Retirement as Chairman of Hamamatsu University School of Medicine

Schwannomas are rare benign tumors that arise from the neurolemmocytes. Among cases of schwannoma that arise from nerves, vagal nerve schwannoma is the most common in the head and neck region. Surgical resection is the treatment of choice. Postoperative complications such as hoarseness and dysphagia can affect the patients’ quality of life, so that attempts at nerve preservation should be made whenever possible.A 46-year-old female patient underwent resection of a vagal schwannoma under continuous intraoperative neuromonitoring (CIONM) that allows real-time intraoperative feedback. The recurrent laryngeal and vagal nerve activities were monitored using an electromyographic endotracheal tube. We also used Narrow Band Imaging (NBI) to detect the tumor capsule and performed intracapsular excision of the tumor. She had no postoperative complications. In conjunction with NBI, CIONM allows for successful preservation of the vagal nerve and a reduced risk of postoperative complications., 浜松医科大学医学部耳鼻咽喉科・頭頸部外科学教室 峯田周幸教授退任記念論文集～症例から学ぶ～, Festschrift for Professor Hiroyuki Mineta In Hornor of His Retirement as Chairman of Hamamatsu University School of Medicine

Objective and method: From the viewpoint of new otolaryngologists, cases of otitis media with effusion (OME) caused by Eustachian tube dysfunction tend to be overlooked, while the mechanism of OME is gradually understood. Children in lower grades with tonsillitis, adenoid hyperplasia, sinusitis, and an immature Eustachian tube have been encountered. Children in upper grades with a habit of sniffing (HS), presenting for treatment by general practitioners, are also encountered. The training involved one case where insertion of a tympanic ventilation tube was requested by the general practitioner and another case with atelectasis. The conditions of the patients were assessed based on interviews, eardrum views, and assessment of the degree of ventilation of the Eustachian tube.Result: The condition of children in lower grades improved with conservative treatment, and the condition of children in upper grades improved with cessation of HS.Discussion: According to the 2015 medical treatment guidelines of OME, tympanic ventilation tubes should be inserted in cases of atelectasis, based on recommendation level A. However, the condition of the patients has been shown to improve with cessation of HS. Young otorhinolaryngologists often perform the insertion of tympanic ventilation tubes. It is important to consider not only the phenomena of hearing loss and exudate retention in the tympanum, but also the mechanism of exudate retention. We should make a careful judgement about whether to insert tympanic ventilation tubes or not, because the complications of tympanic ventilation tube insertion cannot be ignored., 浜松医科大学医学部耳鼻咽喉科・頭頸部外科学教室 峯田周幸教授退任記念論文集～症例から学ぶ～, Festschrift for Professor Hiroyuki Mineta In Hornor of His Retirement as Chairman of Hamamatsu University School of Medicine

We encountered two cases of refractory sniff-type patulous Eustachian tubes. Case 1, a 14-year-old girl visited our hospital with the chief complaint of “aural fullness”. The diagnosis of patulous Eustachian tube was made according to the diagnostic criteria for this condition. Conservative treatments, such as oral medicines, instillation of physiological saline, and application of adhesive tape on the tympanic membrane proved ineffective, and we performed ventilation tube insertion. Immediately after placement of the ventilation tube, the patient developed “auditory hyperacusis” (hypersensitivity to surrounding sounds), but this improved from the 16th day after insertion. Wearing earplugs was effective during this period when environmental noise was particularly noticeable. With the improvement of the auditory hyperacusis, the aural fullness also improved. It is important to explain to the patients about the possible development of auditory hyperacusis before the ventilation tube insertion. Case 2 was a 31-year-old woman with the chief complaint of “autophonia”. She also had anorexia nervosa. The diagnosis of patulous Eustachian tube was made according to the diagnostic criteria for this condition. We considered that the “sound invasion into the middle ear” had a greater effect on the pathology than the “pressure change in the middle ear” in this case, and inserted Kobayashi plugs into the Eustachian tube. We also inserted a ventilation tube in anticipation of continued sniffing and worsening of the tympanic membrane retraction due to negative pressure. Thereafter, the patient exhibited the behavior of sniffing while inserting a finger into the external auditory meatus, but we considered that there was no direct effect on the tympanic membrane. The Kobayashi plugs were replaced (sized up) during follow-up, and the ear symptoms, mainly autophonia, resolved., 浜松医科大学医学部耳鼻咽喉科・頭頸部外科学教室 峯田周幸教授退任記念論文集～症例から学ぶ～, Festschrift for Professor Hiroyuki Mineta In Hornor of His Retirement as Chairman of Hamamatsu University School of Medicine

Objective To investigate the effects of habitual sniffing on the postoperative course of pars flaccida cholesteatoma. Study design Retrospective case series study. Setting University hospital. Patients Forty-nine patients (53 ears) with pars flaccida cholesteatoma and history of habitual sniffing before the initial operation. Interventions Patients were divided into a "sniffing cessation group" characterized by sniffing cessation and a "continual sniffing group" characterized by continuation of sniffing despite instructions for conscious cessation. Main outcome measures Hearing level, tympanic membrane findings, tympanograms, mastoid cell development before the operation, and pneumatization 1 year postoperatively. Results The sniffing cessation and continual sniffing groups comprised 35 patients (38 ears) and 14 patients (15 ears), respectively. The average postoperative hearing was slightly better in the continual sniffing group. In the sniffing cessation group, retractions were evident in significantly fewer cases. Retractions were observed in all continual sniffing group cases, with a high percentage of severe retractions, wherein the bottom was not visible. Type A tympanogram was predominant in the sniffing cessation group. Mastoid cell development was not significantly different between the two groups. Satisfactory pneumatization was significantly more common in the sniffing cessation group (Fisher's exact test, p Conclusion Conscious cessation of the sniffing habit could reduce the risk of postoperative retraction and improve pneumatization in patients with pars flaccida cholesteatoma. The presence or absence of the sniffing habit after surgery is a defining factor in postoperative prognosis (retraction, recurrence), and may be a determinant for decisions regarding surgical approach.

Cervical nodal metastasis is the most important prognostic factor in patients with head and neck cancers. Unfortunately, nodal dissection at level IIb carries a risk of damage to the spinal accessory nerve. We aimed to determine the prevalence of level IIb metastasis and the relevance of nodal dissection at level IIb in patients with head and neck squamous cell carcinomas. During neck dissection, level IIb lymph nodes obtained from 181 patients with head and neck squamous cell carcinomas were removed, processed, and histopathologically examined. All specimens were divided into two groups according to the side (affected and unaffected sides). The number of dissected lymph nodes and prevalence of level IIb metastasis in each group were then determined and compared according to the preoperative clinical N stage (cN0 and cN+). The study included 158 men and 23 women with a median age of 65 years (range, 17–89 years). The prevalence of pathologically confirmed level IIb metastasis was 0% for clinically node-negative (cN0) necks on the unaffected side and 10.34% for clinically node-positive necks (cN+), with an overall prevalence of 2.4%. There was a significant association between clinically determined and pathologically confirmed node negativity at level IIb. Our findings suggest that level IIb neck dissection in patients with head and neck squamous cell carcinomas may be required only if preoperative examination reveals multilevel or level IIa metastasis or suspicious level IIb metastasis.

There are no universally accepted treatment recommendations for elderly patients with head and neck carcinomas. This study investigated whether radical treatment in elderly patients resulted in better survival compared with palliative treatment. We retrospectively reviewed the medical records of 724 patients aged > 60 years who underwent treatment for primary head and neck carcinomas at Hamamatsu University Hospital. We evaluated the impact of the following: age, sex, the clinical stage, smoking history, alcohol use history, primary tumor site, performance status, and Osaka Head and Neck Comorbidity Index score on overall survival using a Cox proportional hazards model. The 5-year overall survival rate was significantly greater for the 646 patients initially treated with radical (curative) therapy than for the 78 patients treated with palliative therapy (p

An ameloblastoma is a locally aggressive odontogenic tumour that commonly develops from the odontogenic epithelium within the jawbone. Here we present for the first time a case of a rare primary ameloblastoma in the middle ear cavity, along with some consideration of its treatment and a new classification. A 65-year-old woman presented with a left middle ear cavity tumour. Pathological examination led to the diagnosis of an ameloblastoma. We resected the tumour along with an extensive part of the middle ear mucosa, which made it difficult to have an adequate margin. It is recommended that the remaining bone be ground 2–3 mm beyond the visible margin after resecting the gross tumour. Therefore, several cases are treated with conservative surgery, including physicochemical treatment. This factor should be considered when designing treatment strategies as good alternatives in cases where resection with an adequate margin is difficult.

BackgroundCervical nodal metastasis is a key prognostic factor in patients with papillary thyroid carcinoma. The role of lymph nodes in papillary thyroid carcinoma management and prognosis remains controversial.MethodsLevel IIb lymph nodes obtained from 44 patients with papillary thyroid carcinoma were histopathologically examined retrospectively. Specimens were classified as ipsilateral or contralateral. The number of dissected nodes and prevalence of level IIb metastasis were compared according to pre-operative clinical nodal stage.ResultsIn the node-negative neck, the prevalence of contralateral and ipsilateral IIb nodes was 0 out of 20 and 0 out of 3, respectively. In the node-positive neck, the prevalence of contralateral and ipsilateral IIb nodes was 1 out of 13 (7.70 per cent) and 3 out of 41 (7.32 per cent), respectively. Clinically determined and pathologically confirmed level IIb node negativity were significantly associated. Thirty-four patients (77.3 per cent) developed accessory nerve complications from level IIb dissection.ConclusionLevel IIb neck dissection for papillary thyroid carcinoma may be required if pre-operative examination reveals multilevel, level IIa or suspicious level IIb metastasis.

Background: Infants admitted to the neonatal intensive care unit (NICU) have a higher incidence of congenital hearing loss compared with the healthy newborn population. Objectives: To clarify the relationship between risk factors for hearing impairment in NICU-treated infants and deterioration of the auditory brainstem response (ABR) threshold during childhood. Method: We screened 1,071 high-risk infants admitted to the NICU for hearing impairment. One-hundred forty-eight infants exhibited an abnormal ABR threshold of ≥40 dB nHL. We analyzed the correlation of change in ABR threshold with risk factors for future hearing impairment. Results: Among infants treated in the NICU, 148 (13.8%) exhibited an ABR threshold of ≥40 dB nHL; 107 of these 148 (72.3%) showed hearing change in the process (102 showed improvement to normal hearing level, whereas 5 showed further deterioration). Our analysis showed that the factors contributing to the elevation of ABR threshold were oxygen administration and chromosomal aberrations. Conclusions: Factors related to the elevation of ABR threshold were oxygen administration and the presence of chromosomal aberrations. Awareness of risk factors that are more likely to cause hearing loss in infants may aid in follow-up treatment of these children.

Na(+), K(+)-ATPase (Na,K-ATPase) is an ubiquitous enzyme in the inner ear and a key factor in the maintenance of the osmotic gradient of the endolymph. This study uses Na,K-ATPase α1 subunit immunoreactivity (IR) to identify cellular structures in the normal and disease human cochlea. Formalin-fixed celloidin-embedded (FFCE) human temporal bone sections were immunoreacted with mouse monoclonal antibodies against Na,K-ATPase α1 subunit. Na,K-ATPase α1 IR was examined in the cochlea of 30 patients: four with normal hearing, 5 with Meniere’s disease, and 21 with other inner ear diseases: 11 male, 19 female; ages 42 to 96 years-old (yo), average age of 77 yo. Na,K-ATPase α1 IR area was quantified using the ImageJ software program. Na,K-ATPase α1 IR was located in the stria vascularis, and in type I, II and IV fibrocytes of the spiral ligament in the cochlea from patients with normal hearing. Na,K-ATPase α1 IR was seen in Deiter’s cells and inner phalangeal cells of the organ of Corti. Na,K-ATPase α1 IR was present in satellite cells that surround the neurons of the spiral ganglia. In the inner ear of pathological specimens, Na,K-ATPase IR area was decreased (compared to the normal) in the stria vascularis, supporting cells in the organ of Corti and satellite cells of the spiral ganglia. These results show that Na,K-ATPase α1 IR is a good marker to identify cellular structures of the human inner ear and may be used to study cellular changes in the cochlea associated with aging and disease. The ubiquitous localization of Na,K-ATPase α1 in the human cochlea is consistent with the Na,K-ATPase role in ionic homeostasis and osmolarity, similar to that seen in animal models.

Background Photodynamic therapy (PDT) is a minimally invasive treatment for malignant tumors. The aim of this study was to determine the efficacy of PDT in patients with head and neck squamous cell carcinoma (HNSCC). Methods Thirty-three patients with HNSCC were treated with porfimer sodium-mediated PDT followed by intraoperative light activation at 630 nm via fiber optic microlens delivered after 48 hours of injection. Results The complete response (CR) rate was 72.7%, while the efficacy (CR + partial response) rate was 97.0%. The rate of good local control (i.e., CR without recurrence after PDT) achieved after the initial PDT (82.6%) was significantly higher than that achieved after the second or third PDT (10%); this rate remained at 62.1% without functional disturbance and disfigurement even after excluding four previously untreated patients. The final local control rate following PDT plus additional therapies was 73.8%. Conclusions PDT is an effective therapy to treat HNSCC, and leads to an improved quality of life in patients with residual or recurrent disease. Lasers Surg. Med. 50:420-426, 2018. © 2018 Wiley Periodicals, Inc.

We analyzed 356 patients with idiopathic sudden sensorineural hearing loss treated with hyperbaric oxygen therapy and systemic steroids (n = 161), systemic steroids alone (n = 160), or intratympanic and systemic steroids (n = 35). The main outcome measure was the hearing recovery rate. The effect of other variables, including the initial averaged 5-frequency hearing level, patient age, interval between the onset of symptoms and treatment, presence of vertigo as a complication, presence of diabetes mellitus, smoking history, and presence of hypertension, on the hearing recovery rate was also evaluated. The overall hearing recovery rate was significantly higher for the patients treated with hyperbaric oxygen therapy and systemic steroids than for those treated with systemic steroids alone (p < 0.001) or systemic and intratympanic steroids (p < 0.001). The presence of vertigo negatively affected hearing recovery. Our findings suggest that hyperbaric oxygen therapy confers a significant additional therapeutic benefit when used in combination with steroid therapy for idiopathic sudden sensorineural hearing loss.

Proteomic approaches using liquid chromatography coupled to tandem mass spectrometry (LC-MS/MS) without an immunopurification technique have not been applied to the determination of serum cetuximab. This study developed a simple and rapid LC-MS/MS method for the absolute determination of cetuximab in human serum and applied it to clinical settings. Surrogate peptides derived from cetuximab digests were selected using a Fourier transform mass spectrometer. Reduced-alkylated serum cetuximab without immunopurification was digested for 20minutes using immobilized trypsin, and the digestion products were purified by solid-phase extraction. The LC-MS/MS was run in positive ion multiple reaction monitoring mode. This method was applied to the determination of serum samples in head and neck cancer patients treated with cetuximab. The chromatographic run time was 10minutes and no peaks interfering with surrogate peptides in serum digestion products were observed. The calibration curve of absolute cetuximab in serum was linear over the concentration range of 4-200μg/mL. The lower limit of quantification of cetuximab in human serum was 4μg/mL. The intra-assay and inter-assay precision and accuracy were less than 13.2% and 88.0-100.7%, respectively. The serum concentration range of cetuximab was 19-140μg/mL in patients. The serum cetuximab concentrations in LC-MS/MS were correlated with those in ELISA (r=0.899, P

// Kiyoshi Misawa 1 , Atsushi Imai 1 , Daiki Mochizuki 1 , Yuki Misawa 1 , Shiori Endo 1 , Seiji Hosokawa 1 , Ryuji Ishikawa 1 , Masato Mima 1 , Kazuya Shinmura 2 , Takeharu Kanazawa 3 and Hiroyuki Mineta 1 1 Department of Otolaryngology/Head and Neck Surgery, Hamamatsu University School of Medicine, Shizuoka, Japan 2 Department of Tumour Pathology, Hamamatsu University School of Medicine, Shizuoka, Japan 3 Department of Otolaryngology/Head and Neck Surgery, Jichi Medical University, Tochigi, Japan Correspondence to: Kiyoshi Misawa, email: kiyoshim@hama-med.ac.jp Keywords: neuropeptide receptors, GPCR, head and neck cancer, epigenetic markers, metastases Received: March 15, 2017 Accepted: June 29, 2017 Published: July 18, 2017 ABSTRACT Staging and pathological grading systems are useful but imperfect predictors of recurrence in head and neck squamous cell carcinoma (HNSCC). To identify potential prognostic markers, we examined the methylation status of eight neuropeptide receptor gene promoters in 231 head and neck squamous cell carcinomas. The NPFFR1 , NPFFR2 , HCRTR1 , HCRTR2 , NPY1R , NPY2R , NPY4R , and NPY5R promoters were methylated in 80.5%, 79.2%, 67.1%, 73.2%, 35.1%, 36.4%, 38.5%, and 35.9% of the samples, respectively. In a multivariate Cox proportional hazards analysis, the odds ratio for recurrence was 2.044 (95% confidence interval [CI], 1.323–3.156; P = 0.001) when the NPY2R promoter was methylated. In patients without lymph node metastasis (n = 100), methylation of NPY2R (compared with methylation of the other seven genes) best correlated with poor disease-free survival (DFS) (odds ratio, 2.492; 95% CI, 1.190–5.215; P = 0.015). In patients with oral cancer (n = 69), methylated NPY1R and NPY2R were independent prognostic factors for poor DFS, both individually and, even more so, in combination (odds ratio, 3.90; 95% CI, 1.523–9.991; P = 0.005). Similar findings were observed for NPY2R and NPY4R in patients with oropharyngeal cancer (n = 162) (odds ratio, 5.663; 95% CI, 1.507–21.28; P = 0.010).

Huge cervical and mediastinal masses may lead to acute respiratory failure caused by laryngotracheal compression and airway obstruction. Thyroid storm is also a life-threatening endocrine emergency originating almost exclusively from uncontrolled Graves’ disease. We report a case of a 42-year-old man with acute upper airway obstruction and tachycardia from progressive swelling of a giant thyroid, in conjunction with thyroid storm resulting from uncontrolled Graves’ disease. Fibreoptic-assisted nasal intubation was performed while the patient was awake, immediately followed by emergency total thyroidectomy via a cervical and sternal approach. The patient had an uneventful postoperative course and recovered well. Respiratory failure due to swelling of a giant thyroid is a life-threatening condition and should be treated immediately with endotracheal intubation while the patient is awake following emergent total thyroidectomy, even with a sternotomy.