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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

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

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.

Pica behavior, kaolin ingestion, in rats and mice can be used as an assessment of nausea and vomiting; however, we observed that the incidence of pica behavior in ICR strain mice varied markedly. We investigated the susceptibility of four strains of mice (ICR, BALB/c, C57BL/6, and DBA/2) to the development of pica behavior.Mice received cisplatin (7.5 mg/kg, i.p.) with or without a serotonin 5-HTAll mice except for ICR strain significantly increased kaolin intake after cisplatin administration. Among the tested strains, DBA/2 mice compared to BALB/c and C57BL/6 mice notably showed pica behavior on both days (P 0.0001). The expression of PPT-A mRNA was significantly increased 8 h after cisplatin administration in all strains, but the increase remained on the second day only in DBA/2 mice (P 0.05). Granisetron significantly inhibited pica behavior in DBA/2 mice on the first day (P 0.0001), but not the second day; however, fosaprepitant completely inhibited the pica behavior on both days (P 0.001).These results indicate that cisplatin-induced pica behavior in mice is likely to be influenced by the genotype, and that DBA/2 mice are useful to analyze the emetogenic or anti-emetic potential of drugs in preclinical studies.

Cancer chemotherapy often induces gastrointestinal symptoms such as anorexia, nausea, and vomiting. Antiemetic agents are effective in inhibiting nausea and vomiting, but patients still experience anorexia. We previously reported that chemotherapeutic agent-induced anorexia is associated with an increase of inflammatory cytokines. Other studies also reported that antagonism of the histamine H4 receptor is anti-inflammatory. In this study, we investigated the involvement of the H4 receptor in the development of chemotherapy-induced anorexia in mice. Cisplatin-induced anorexia occurred within 24 h of its administration and continued for 3 days. The early phase (day 1), but not the delayed phase (days 2 and 3), of anorexia was inhibited by the daily injection of a 5-HT3 receptor antagonist (granisetron). However, a corticosteroid (dexamethasone) or selective H4 receptor antagonist (JNJ7777120) abolished the delayed phases of anorexia. Cisplatin significantly increased TNF-α mRNA expression in the hypothalamus and spleen, and the period of expression increase paralleled the onset period of anorexia. In addition, pretreatment with JNJ7777120 completely inhibited the increased expression. These results suggest that TNF-α mRNA expression via H4 receptors may contribute to the development of cisplatin-induced anorexia, and that H4 receptor antagonists are potentially useful treatments.

This study examined Sal-like protein (SALL)1 methylation profiles in head and neck squamous-cell carcinoma (HNSCC) patients at diagnosis and follow-up, and evaluated their prognostic significance and value as a biomarker. SALL1 expression was examined in a panel of cell lines by quantitative reverse transcription PCR (qRT-PCR). Promoter methylation was determined by quantitative methylation-specific polymerase chain reaction (qMSP) and was compared to the clinical characteristics of 205 samples. SALL1 promoter methylation was associated with transcriptional inhibition and was correlated with disease recurrence in 31.7% of cases, with an odds ratio of 1.694 (95% confidence interval: 1.093-2.626; P = 0.018) by multivariate Cox proportional hazard regression analysis. SALL1 promoter hypermethylation showed highly discriminatory receiver operator characteristic curve profiles that clearly distinguished HNSCC from adjacent normal mucosal tissue, and was correlated with reduced disease-free survival in early stage T1 and T2 patients (log-rank test, P < 0.001). SALL1 methylation was significantly correlated with the methylation status of both SALL3 and CDH1. This study suggests that CpG hypermethylation is a likely mechanism of SALL1 gene inactivation, supporting the hypothesis that SALL1 might play a role in HNSCC tumorigenesis and could serve as an important biomarker.

We previously reported that sevoflurane-induced pica, kaolin ingestion behavior, in rats has the potential to reflect postoperative nausea and vomiting (PONV) in humans. It is well-known that corticosteroids, which inhibit both prostaglandin and leukotriene syntheses due to phospholipase A2 inhibition, are effective for reducing PONV; however, the precise mechanisms remain unclear. We investigated the involvement of the prostaglandin or leukotriene pathway in the development of sevoflurane-induced pica. We found that sevoflurane-induced pica was effectively inhibited by pretreatment with a leukotriene receptor antagonist (montelukast) or an inhibitor of 5-lipoxygenase (zileuton), rather than an inhibitor of cyclooxygenase (flurbiprofen). Furthermore, we observed that sevoflurane significantly increased urinary leukotriene excretion and 5-lipoxygenase mRNA expression in the spleen, but not hypothalamus. These results suggest that the production of leukotriene may lead to the development of sevoflurane-induced pica in rats, and that inhibition of the leukotriene pathway could be potentially useful for the treatment of PONV.

We examined the effects of volatile anesthetics on pica, which can be used to assess nausea and vomiting in rats. We found that inhalation anesthesia with sevoflurane significantly induced pica in female but not male rats. Among the female rats, young rats (8 weeks old) were more susceptible to its induction than adult rats (20 weeks old) with ovariectomy or sham-surgery. Anti-emetic drugs that are used to prevent postoperative nausea and vomiting (PONV) inhibited the pica. These results suggest that sevoflurane-induced pica in young female rats has the potential to be an animal model of PONV in humans.

Background:There is limited information available regarding the benefits and outcomes of resection of pulmonary metastases arising from head and neck cancers.Methods:A retrospective review was performed of 21 patients who underwent resection of pulmonary metastases of primary head and neck malignancies at Hamamatsu University Hospital. Clinical staging, treatment methods, pathological subtype (particularly squamous cell carcinoma), disease-free interval and overall survival were evaluated.Results:The 5- and 10-year overall survival rates of the study participants were 67.0 per cent and 55.0 per cent, respectively, as determined by the Kaplan–Meier method. The prognosis for patients with a disease-free interval of less than 24 months was poor compared to those with a disease-free interval of greater than 24 months (p = 0.0234).Conclusion:Patients with short disease-free intervals, and possibly those who are older than 60 years, should be categorised as having severe disease. However, pulmonary metastases from head and neck malignancies are potentially curable by surgical resection.

Since the peripheral serotoninergic pathway is involved in the development of radiation-induced nausea and vomiting, referred to as radiation sickness, serotonin 5-HT3 receptor antagonists are used as a preventive measure, although patients still suffer from these symptoms. Glutamate is known as the excitatory neurotransmitter and is involved in various autonomic symptoms. We investigated the effect of radiation on glutamate release in rats, as measured by in vivo brain microdialysis, and the effects of glutamate receptor antagonists on radiation-induced pica, which can be used as a behavioral assessment of radiation sickness in rats. A microdialysis probe was inserted into the hypothalamus of rats that received 4 Gy total-body irradiation (TBI) with or without pretreatment of 5-HT3 receptor antagonist (granisetron, 0.1 mg/kg, i.p.), and dialysates were collected for 3 h after TBI and subjected to HPLC assay of glutamate. In addition, rats were intracerebroventricularly injected with NMDA receptor antagonist (MK-801: 3 μg/rat) or AMPA receptor antagonist (CNQX: 1 μg/rat) before TBI, and radiation-induced pica was determined. An increase in glutamate release was observed within 1 h postirradiation. The increased glutamate release was suppressed by granisetron. We also found that CNQX, but not MK-801, effectively inhibited radiation-induced pica. These results indicate that the hypothalamic glutamatergic system contributes to radiation-induced pica through the AMPA receptors.

Intermittent subcutaneous injection of teriparatide, an active fragment of human parathyroid hormone, is clinically used for the treatment of osteoporosis. Patients suffer from nausea, which is one of the side effects teriparatide induces; however, the etiology of teriparatide-induced nausea remains unknown. We have reported pica, kaolin ingestion behavior, can be used as an assessment of nausea-related response in rats. In this study, we investigated the characteristics of teriparatide-induced pica and the abilities of anti-emetic drugs to inhibit teriparatide-induced pica. Male and female adolescent (4-week-old), young (8-week-old), and adult (30-week-old) naive rats, and ovariectomized (OVX: 17-week-old) and sham-operated (17-week-old) rats subcutaneously received teriparatide (0.4 mg/kg, n=4), and their kaolin and food intakes were monitored for 24 h after the injection. Among the tested rats, we found that OVX rats, rather than male, female, and sham-operated rats, showed marked teriparatide-induced pica (0 mg/kg: 0.17±0.07 g, 0.4 mg/kg: 6.18±0.91 g). Teriparatide-induced pica in OVX rats was inhibited by intraperitoneal pretreatment with serotonin 5-HT3 (granisetron 0.5 mg/kg), dopamine D2 (prochlorperazine 0.5 mg/kg), neurokinin NK1 (fosaprepitant 1 mg/kg), and histamine H1 (diphenhydramine 10 mg/kg) receptor antagonists to 70%, 11%, 19%, and 59% of that in vehicle-treated control, respectively. These results suggest that teriparatide-induced pica in OVX rats has the potential to reflect teriparatide-induced nausea; 5-HT3, D2, NK1, and H1 receptor activation is involved in the development of this behavior; antagonists of these receptors have the potential to be medical candidates used as treatments for teriparatide-induced nausea in human patients.

Gaucher disease is a lysosomal storage disorder that is caused by congenital defective function of the enzyme glucocerebrosidase. Glucocerebroside that is not hydrolyzed by glucocerebrosidase mainly accumulates in the reticular tissue. We describe a Japanese boy with Gaucher disease type 1 who developed bilateral profound sensorineural hearing loss within approximately 4years. We performed cochlear implantation initially on his right ear and again on his left ear 5 months later. The cochlear implants were successfully utilized with a speech discrimination score of 95% on a Japanese sentence recognition test. There are many reports of central hearing loss in Gaucher disease type 2 or 3. However, to the best of our knowledge, this is the first report of profound inner ear hearing loss with Gaucher disease. It also appears to be the first record of cochlear implantation for Gaucher disease. Cochlear implants may be useful for sensorineural hearing loss in patients with Gaucher disease without neurological symptoms other than hearing loss.

Habitual sniffing affects the pathogenicity and recurrence of cholesteatoma. Postoperative instructions requesting patients to cease sniffing may reduce the retraction and recurrence of cholesteatoma.To examine the relationship between tympanic membrane retraction and habitual sniffing in patients with cholesteatoma.We recruited 98 patients (102 ears) who were surgically treated for cholesteatoma by canal wall-down tympanoplasty (22 ears) or canal wall-down tympanoplasty with reconstruction methods (80 ears). We classified these patients into two groups on the basis of their preoperative habitual sniffing: habitual and non-habitual sniffers. The findings of the contralateral tympanic membrane were examined in each group and were classified according to the Tos classifications. Next, we evaluated the incidence of 1-year postoperative tympanic membrane retraction treated by the canal-down tympanoplasty with reconstruction method in the following three groups: non-habitual sniffing group, sniffing cessation group, and continual sniffing group.In habitual sniffers, the Tos classifications of contralateral tympanic membrane were normal in 7% (3/41). In contrast, for non-habitual sniffers, the findings were normal in 39% (21/54). These results indicate that sniffing causes tympanic membrane retraction. The tympanic membranes of patients in the sniffing cessation group were largely normal after surgery. However, more than 50% of the patients who continued to sniff after surgery showed retraction or recurrent cholesteatoma.

Objectives: We analyzed the clinical features and surgical techniques used in cases of childhood congenital cholesteatoma of the middle ear. Methods: We studied 26 patients (26 ears) who underwent surgery for congenital cholesteatoma between January 1998 and December 2009, focusing on the location and type of cholesteatoma, the surgical procedures involved, and the results obtained. Patients with prior otologic procedures were excluded. A 4-stage system was used to grade the cholesteatomas. Results: The frequency of posterior-quadrant involvement and open-type cholesteatomas increased in the more advanced stages. Second-look operations were performed in 60% of stage III and 75% of stage IV cases; and residual cholesteatomas were found in 20% of stage III and 75% of stage IV cases. Of the cases evaluated both before and after the operation, 100% of stage I and II cases, 86% of stage III cases, and 50% of stage IV cases showed improvement in hearing function. Conclusions: The staging system is relatively simple, while accurately reflecting clinical results. However, there are many differences between the anterior and posterior types of congenital cholesteatomas in surgical approach and postoperative progression that are not reflected in the classification systems and require further study. In addition, we reviewed the surgical procedures involved in anterior-quadrant cases, and propose a modified surgical procedure.

Docetaxel, a taxane derivative, is frequently used for the treatment of advanced breast cancer, non-small cell lung cancer, and metastatic prostate cancer. Clinical reports demonstrated that docetaxel-based chemotherapy often induces anorexia, but the etiology is not completely understood. To elucidate possible mechanisms, we investigated the involvement of central interleukin (IL)-1β, cyclooxygenase (COX)-2, and pro-opiomelanocortin (POMC) in the development of docetaxel-induced anorexia in rats. Rats received docetaxel (10mg/kg, i.p.) with or without pretreatment with selective COX-2 inhibitors, NS-398 (10 and 30 mg/kg, i.g.) or celecoxib (10 and 30 mg/kg, i.g.), and a non-selective COX inhibitor, indomethacin (10mg/kg, i.g.), then food intake was monitored for 24h after administration. We also examined expression of IL-1β, COX-2, and POMC mRNA in hypothalamus of docetaxel-treated rats and the effect of a COX-2 inhibitor on docetaxel-induced POMC mRNA expression. Food consumption in rats was significantly decreased 24h after administration of docetaxel and anorexia was partially reversed by all COX inhibitors. Administration of docetaxel increased IL-1β, COX-2, and POMC mRNA expression in the hypothalamus of rats. The time required to increase these gene expressions was comparable to the latency period of docetaxel-induced anorexia in rats. In addition, pretreatment with COX-2 inhibitors suppressed docetaxel-induced expression of POMC mRNA. These results suggest that IL-1β and COX-2 mRNA expression and subsequent activation of POMC in the hypothalamus may contribute to the development of docetaxel-induced anorexia in rats.

Background We report a rare case of a patient with a hypopharyngeal metastasis from breast cancer. Case presentation Isolated breast cancer metastasis to the hypopharynx has been previously reported in only one autopsy case. Herein, we report a 56-year-old woman with metastases to the hypopharynx almost 24 years after receiving a mastectomy and chemotherapy to treat primary breast carcinoma. We believe that she is the first patient to be treated for metastatic breast carcinoma to the hypopharynx. The hypopharyngeal tumor reduced in size after administration of an oral aromatase inhibitor. The patient has remained alive with a preserved larynx for three years. Conclusions Breast cancer metastasis to the hypopharynx is an extremely rare event.

Conclusions This study suggests that long-term ventilation tube insertion is the first-choice surgical treatment for a 'sniff-type' patulous Eustachian tube (PET). When treating a refractory PET, it is important to determine whether the patient had a habitual sniff. Objectives PET patients were divided into two groups: patients with a habitual sniff (sniff-type PET) and those without a habitual sniff (non-sniff-type PET). This study examined the effects of ventilation tube insertion or silicone plug insertion in each group. Methods Surgical procedures such as ventilation tube insertion or trans-tympanic silicone plug insertion were performed for these patients. Tubotympanoaero-dynamic graphy (TTAG) was also performed to determine the mechanisms underlying these treatments. Results There were 11 cases (17 ears) of sniff-type PET and 20 cases (27 ears) of non-sniff-type PET. An improvement in symptoms was found in 72.7% of the patients who underwent silicone plug insertion (66.7% for sniff-type PET and 74.1% for non-sniff-type PET) and in 90.9% of the patients who underwent ventilation tube insertion for sniff-type PET. In TTAG assessments, many sniff-type PET patients showed significant synchronous changes at high levels of pressure (over 40 daPa) in the external auditory meatus and nasopharynx when performing a slight Valsalva manoeuvre (below 200 daPa).

腺房細胞癌acinic cell carcinomaは，稀な疾患であり，耳下腺に好発するとされている。当科で経験した耳下腺腺房細胞癌6症例について年齢，性別，病期，治療法および治療成績などの臨床的検討を行った。年齢は23歳～78歳（平均64.2歳），男女比は5：1であった。全例手術治療とした。術式は，拡大耳下腺全摘術を2例に施行し，神経温存した全摘術を1例に施行した。腫瘍が限局していた3例については部分切除術を施行した。頸部郭清術は2例に施行した。顔面神経は4例温存できた。観察期間は，1年5ヶ月～19年11ヶ月（中央値5年11ヶ月）であった。非担癌生存は4例で，追跡不能が1例あった。死亡例1例は，術後19年11ヶ月で多発転移により死亡した。長期経過観察が必要と思われた。

Predictive strategies for the treatment efficacy of cetuximab are currently not available for head and neck cancer. We investigated the correlation between the expression of epidermal growth factor receptor (EGFR) ligands and EGFR expression, and the growth inhibitory activity of cetuximab in a panel of head and neck squamous cell carcinoma (HNSCC) cell lines.The growth inhibiting effect of cetuximab was measured for eight HNSCC cell lines and correlated with the autocrine production of five EGFR ligands as measured by ELISA, and the mRNA expression of two ligands, as measured by quantitative RT-PCR. EGFR expression was assessed by western blot analysis.There was a good correlation between the expression of four of the EGFR ligands (TGF-α, amphiregulin, epiregulin and epigen) and the growth inhibiting effect of cetuximab. TGF-α had the highest predictive potential but had to be combined with epigen for full prediction. EGFR expression also correlated with cetuximab sensitivity but less clearly.The results indicate that the expression of several EGFR ligands has to be used to predict sensitivity to cetuximab in HNSCC. This has to be further evaluated in clinical samples.

1995年1月から2009年12月までの15年間に，浜松医科大学耳鼻咽喉科で治療した甲状腺未分化癌7症例について検討した。全例女性であり，年齢は60歳から81歳（平均70.0歳）であり，臨床症状，術前診断，治療方法，在宅期間，生存期間，転帰などについて検討した。治療方法は，4例に根治手術療法を行った。退院後在宅生活が可能であった3例は，手術施行例であった。放射線療法は5例に行ったが，化学療法を施行した例はなかった。生存期間は3日～1年6か月（平均8.2か月）で，全例が原病死であった。その内訳は原発巣死2例，転移巣死4例，およびその両者による死亡が1例であった。甲状腺未分化癌でも，手術可能な症例もあり，在宅生活の可能性が示唆された。

Malignant external otitis is an invasive infection of the external auditory canal mostly caused by Pseudomonous aeruginosa. The syndrome mainly affects elderly patients with diabetes mellitus. Though the patients were usually cured with conservative treatment using antibiotics, we present herein two cases of malignant external otitis in whom otological surgery was performed. Case 1 was a 35-year-old male with diabetes mellitus type 1. He was referred to our hospital after having been treated for several months with oral antibiotics for the left ear pain and discharge. On examination, the ear canal was severely edematous and erythematous. Cultures of aural drainage demonstrated P. aeruginosa and high-resolution computed tomography (HRCT) showed defects in the external auditory canal. Malignant external otitis was diagnosed, and the patient was treated with cefozopran. Because the patient suffered from ear discharge despite the treatment, surgery was eventually performed. His postoperative course was satisfactory and there is no sign of recurrence. Case 2 was a 63-year-old male with diabetes mellitus type 2. He was admitted after having been treated for 2 months with oral antibiotics for the swelling around the right temporomandibular joint and right ear pain and discharge. On examination, the ear canal was edematous and the retraction pocket on the Pars flaccida of the tympanic membrane was filled with keratinized debris. Cultures demonstrated P. aeruginosa. HRCT showed defects of the temporomandibular joint and the attic and tympanic cavity were filled with soft tissue. Malignant external otitis caused by cholesteatoma was diagnosed, and tympanoplasty with mastoidectomy was performed. The patient improved immediately and shows no sign of recurrence.

Salivary duct carcinoma (SDC) is rare, and originating mainly in the parotid gland. In the 15-years from 1995 to 2010, we treated nine subjects with parotid gland SDC. None undergoing fine-needle aspiration biopsy or frozen section was diagnosed with SDC preoperatively. One had partial parotidectomy and the remainder wide resection of parotid gland masses. All nine underwent surgery, but only two remained cancer-free. Neither postoperative radiation nor chemotherapy was effective in tumor control. SDC prognosis thus requires new diagnositic techniques, therapeutic modalities, and surgical procedures.