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PURPOSE This study aimed to compare patients with early oral cavity squamous cell carcinoma (OCSCC) (tumor category [T] 1-2, node-negative, and no distant metastasis) treated with traditional elective neck dissection (ND) with those managed by sentinel lymph node biopsy (SLNB) using survival and neck function and complications as end points. METHODS Sixteen institutions in Japan participated in the study (trial registration number: UMIN000006510). Patients of age ≥ 18 years with histologically confirmed, previously untreated OCSCC (Union for International Cancer Control TNM Classification of Malignant Tumors 7th edition T1-2, node-negative no distant metastasis), with ≥ 4 mm (T1) depth of invasion, were randomly assigned to undergo standard selective ND (ND group; n = 137) or SLNB-navigated ND (SLNB group; n = 134). The primary end point was the 3-year overall survival rate, with a 12% noninferiority margin; secondary end points included postoperative neck functionality and complications and 3-year disease-free survival. Sentinel lymph nodes underwent intraoperative multislice frozen section analyses for the diagnosis. Patients with positive sentinel lymph nodes underwent either one-stage or second-look ND. RESULTS Pathologic metastasis-positive nodes were observed in 24.8% (34 of 137) and 33.6% (46 of 134) of patients in the ND and SLNB groups, respectively ( P = .190). The 3-year overall survival in the SLNB group (87.9%; lower limit of one-sided 95% CI, 82.4) was noninferior to that in the ND group (86.6%; lower limit 95% CI, 80.9; P for noninferiority < .001). The 3-year disease-free survival rate was 78.7% (lower limit 95% CI, 72.1) and 81.3% (75.0) in the SLNB and ND groups, respectively ( P for noninferiority < .001). The scores of neck functionality in the SLNB group were significantly better than those in the ND group. CONCLUSION SLNB-navigated ND may replace elective ND without a survival disadvantage and reduce postoperative neck disability in patients with early-stage OCSCC.

The characteristic changes in the swallowing mechanism with aging are collectively termed presbyphagia. Although several studies have investigated presbyphagia in older adults, few have assessed oldest-old adults. We aimed to characterize the latent changes of swallowing function in oldest-old adults and to consider risk ages for presbyphagia.We analyzed the records of 85 individuals (44 males and 41 females, aged 25-101 years) who underwent videofluoroscopic swallowing studies. The included participants had penetration and aspiration scores of ≤ 2 and no history of aspiration, pneumonia, or diseases that affect swallowing. They were divided into four age groups: 25-64 years (non-older), 65-74 years (young-old), 75-84 years (middle-old), and ≥ 85 years (oldest-old). We analyzed and compared the pharyngeal delay time (PDT), duration of tongue base and posterior pharyngeal wall contact, duration and dimension of upper esophageal sphincter opening (UES-O), and maximal hyoid bone displacement between the age groups.Among the older groups, the oldest-old showed significantly longer PDT than younger-old adults, and the UES-O tended to be wider in the former. However, no other remarkable differences were found between the oldest-old and other old groups. Statistical comparisons between the 75 and ≥ 75-year age groups revealed significant age-related changes in the PDT and duration and dimension of UES-O.On videofluoroscopic evaluation, physiological changes with aging affected few parameters of swallowing in our cohort. These findings indicate that in non-aspirating oldest-old adults, any deterioration may be adjusted for by compensatory changes to maintain swallowing function.

BACKGROUND/AIM We have previously reported that alternate-day S-1 had comparable effects and milder adverse events than the respective consecutive-day regimen in head and neck cancer (HNC) patients. The aim of this study was to investigate the anticancer effects of both regimens and underlying mechanisms in vitro. MATERIALS AND METHODS Two head and neck squamous cell carcinoma (HNSCC) cell lines were treated with 5-FU given on an alternate-day or consecutive-day schedule. The relative inhibition (RI) of tumor growth was calculated. Cell cycle distributions and cyclin expression following 5-FU treatment were analyzed. RESULTS The RI of both regimens was almost identical. The percentage of cells in S phase was significantly increased in the alternate-day group compared to the consecutive-day group (p

Objective To investigate whether the long-term presence of a patulous Eustachian tube (PET) is associated with sensorineural hearing loss (SNHL). Study design Retrospective chart review. Setting Tertiary referral center. Patients Ears (n = 100) were classified into two groups based on duration of PET symptom(s), i.e., Short (≤3 mo; n = 47 ears) and Long (≥48 mo; n = 53 ears). Contralateral ears without PET (n = 28 ears) were classified as the Contralateral group. Main outcome measures We used ISO 7029 to calculate the hearing thresholds of an age- and sex-matched population at a given frequency. Hearing loss was defined as >25% of these calculated values. Results At 4 kHz, the Long PET group showed a higher prevalence of hearing loss (47%) at 4 kHz than did the Contralateral (21%) and Short PET (19%) groups (p = 0.0280 and 0.0043, respectively). Ears with breathing autophony or a sonotubometric low probe tone level showed a higher prevalence of hearing loss at 4 kHz than those without this symptom or with a high probe tone level (p = 0.0329 or 0.0103, respectively). At low frequencies, ≥89% of the ears in all groups showed mild hearing loss. Conclusion Chronic PET was associated with SNHL at 4 kHz. PET patients showed low-frequency hearing loss regardless of disease duration. Further studies are needed to better understand the pathophysiology of SNHL in patients with PET.

In the current study, the utility of sentinel node (SN) identification using indocyanine green (ICG) was investigated for oral cancers in the clinical N0 stage. The current study was a prospective, multicentre, phase II clinical trial that was conducted in Japan. A total of 18 patients were included. Before surgery, the patients underwent lymphoscintigraphy to map the SNs. During surgery, radioactive isotope (RI) mapping was used to detect the SNs, and ICG was subsequently injected. ICG mapping of the SNs was then performed through the skin. The primary tumour was resected, and a neck flap was elevated for neck dissection, followed by SN biopsy (SNB) using RI or ICG mapping. With the RI method, a total of 63 SNs were detected. Among these SNs, 8 (12.7%) were positive for metastasis, including those with isolated tumour cells (ITCs). The median number of SNs per patient identified by SNB was 4. With the ICG method, a total of 67 SNs were detected. Among these SNs, 7 (10.4%) were positive for metastasis, including those with ITCs. The median number of SNs per patient identified by SNB was 4 (range, 1-6). The 5-year overall survival (OS) of all patients was 83.3%, and the 5-year disease-free survival (DFS) of all patients was 76.7%. The neck compression technique is a simple method that can be used to facilitate surgical procedures of ICG fluorescence navigated SNB for head and neck cancer.

International audience; Background : The eighth international symposium for sentinel node biopsy (SNB) in head and neck cancer was held in 2018. This consensus conference aimed to deliver current multidisciplinary guidelines. This document focuses on the surgical aspects of SNB for oral cancer.Method : Invited expert faculty selected topics requiring guidelines. Topics were reviewed and evidence evaluated where available. Data were presented at the consensus meeting, with live debate from panels comprising expert, nonexpert, and patient representatives followed by voting to assess the level of support for proposed recommendations. Evidence review, debate, and voting results were all considered in constructing these guidelines. Results/conclusion : A range of topics were considered, from patient selection to surgical technique and follow-up schedule. Consensus was not achieved in all areas, highlighting potential issues that would benefit from prospective studies. Nevertheless these guidelines represent an up-to-date pragmatic recommendation based on current evidence and expert opinion.

Introduction: Numerous surgical techniques for inferior turbinate hypertrophy have been reported, each with advantages and disadvantages. Submucosal turbinoplasty with removal of the bony component of the inferior turbinate is an excellent procedure to expand the nasal cavity. However, this procedure requires a large incision to remove the inferior turbinate bone and is associated with hemorrhage, crust formation, and adhesion. A smaller incision would avoid such complications. We developed a continuous suction irrigation method that maintains a clear view of the limited surgical field of the inferior turbinate. Only a single small incision is needed to insert the rigid endoscope. The Surgeon can flush blood with continuous water flow and perform inferior turbinate surgery without difficulty. We performed this method in 39 cases from January, 2016 to January, 2017. This video article demonstrates our new submucosal inferior turbinoplasty technique. Methods: Submucosal turbinoplasty using a continuous suction irrigation method was performed under general anesthesia. An irrigation-suction straw sheath system was used to create an underwater surgical field. Results: The inferior turbinate bone was removed safely with no severe complications. An expanded common nasal cavity was confirmed postoperatively on computed tomographic images. Conclusions: We resected the inferior turbinate bone safely using a continuous suction irrigation method without difficulty or complications. We believe that this method may become one of the best surgical options for inferior turbinate hypertrophy.

The Japan Society for Head and Neck Surgery (JSHNS) started a board certification system for head and neck surgeons in 2010. To become certified, the following qualification and experiences are required: (1) board certification as otorhinolaryngologist, (2) 2 years of clinical experience in a board-certified training facility, (3) clinical care of 100 patients with head and neck cancer under the supervision of board-certified faculty and (4) surgical experience in 50 major head and neck surgical procedures, including 20 neck dissections, under the supervision of board-certified faculty. The following scientific activities are also required during the preceding 5 years: (1) two clinical papers on head and neck cancers presented at major scientific meetings, (2) one clinical paper on head and neck cancer published in a major journal, (3) attendance at two annual meetings of JSHNS and (4) enrolment in three educational programs approved by JSHNS. The qualifying examination consists of multiple choice tests and oral examinations. A total of 151 head and neck surgeons were certified in 2010 followed by 43 in 2011 and 34 in 2012, while the membership of JSHNS dramatically increased from 1201 in 2007 to 1748 in 2013. Although the board certification system for head and neck surgeons was started only recently, it has encouraged many residents and fellows as well as established head and neck surgeons. We believe that this system will contribute to further advancement in the clinical practice for head and neck cancers in Japan.

Human immunodeficiency virus (HIV) infection is associated with an increased risk of malignant disease. However, a case of diffuse large B-cell lymphoma arising in the submandibular gland in a patient with HIV infection has never been reported. This report describes a case of a patient with HIV infection and HIV-associated lymphadenopathy who developed diffuse large B-cell lymphoma (DLBCL) arising in the submandibular gland. Both the submandibular gland and its regional lymph nodes were positive by positron emission tomography/computed tomography (PET/CT), which led to radical neck dissection. The pathological diagnosis was DLBCL in the submandibular gland, however, that of regional lymph nodes was HIV-associated lymphadenopathy and was not malignancy. PET/CT-based staging can make a false-positive result in lymph nodes of patients with HIV infection due to HIV-associated lymphadenopathy.

Background The purpose of this study was to evaluate the efficacy of sentinel lymph node biopsy (SLNB) in early head and neck squamous cell carcinoma (HNSCC). Methods The PubMed database was searched for studies published before October 31, 2012. Pooled values for the sentinel lymph node identification rate, sensitivity, false-negative rate, negative predictive value, and accuracy were calculated. Results A total of 16 studies (987 patients) was included. The pooled identification rate, sensitivity, false-negative rate, negative predictive value, and accuracy were 95.2%, 86.3%, 13.7%, 94.2%, and 95.0%, respectively. The subgroup with high methodological quality showed a mean identification rate of 95.4% for SLNB validation trials and 94.2% for SLNB alone trials, and mean sensitivity of 91.0% for SLNB validation trials and 84.2% for SLNB alone trials. Conclusion The SLNB procedure has shown a high sensitivity rate, but the pooled sensitivity and false-negative rate were worse in SLNB alone trials than in SLNB validation trials. © 2014 Wiley Periodicals, Inc. Head Neck 37: 127–133, 2015

The incidence of tuberculosis patients is high in Japan compared with the other developed countries. The ratio of extrapulmonary tuberculosis patients, for example cervical tuberculous lymphadenitis, tends to increase. In otolaryngology, the number of tuberculosis patients (especially those with cervical tuberculous lymphadenitis) is high and followed by pleuritis patients in extrapulmonary tuberculosis. Although otolaryngologists often diagnose extrapulmonary tuberculosis, it is difficult for them to diagnose appropriately because of various clinical features. Thus, we examined and presented the clinical history of 9 cases of tuberculosis patients in our Otolaryngology department and added a review of the related literature. We diagnosed 9 patients as having cervical tuberculous lymphadenitis from April 2002 to December 2012. They were 30 to 90 years old (mean 57.9 years old), and the male/female ratio was 3 : 6. Five cases were diagnosed as the abscess types and 4 were the swelling types based on the imaging analysis of cervical tuberculous lymphadenitis. Four cases showed multiple lymphadenopathy and 5 showed a solitary involvement. Five sputum and 7 gastric fluid cultures were all negative, whereas 4 QuantiFERON tests were all positive. Fine-needle aspiration cytology was performed in 8 patients, and epithelioid cells were seen in 4 cases. Because tuberculosis presents various clinical features, if we obtained the atypical findings from those patients, it is important in the first instance to suspect tuberculosis. Based on the viewpoint for preventing the spread of infection, we should perform cellular analysis using ultrasound-guided fine needle aspiration after sufficient assessment of the spreading risk by sputum, gastric fluid culture and TB-PCR and QuantiFERON tests, and if a diagnosis remains difficult, the lymph node open biopsy need to be considered.

6007 Background: The objective of the study is to evaluate the non-Inferiority of survival, the superiority of postoperative disability, and the complication of the neck in neck dissections based on sentinel lymph node navigation in early oral cancer patients, compared with standard selective neck dissections. Methods: This study was a randomized, multicenter, non-inferiority trial at 16 institutions in Japan. Eligibility criteria included histologically confirmed squamous cell carcinoma in the oral cavity; clinical categories T1 and T2, N0M0 by UICC TNM classification 7th edition, clinical depth of invasion (DOI) of T1 was over 4mm (defined as late T1); previously untreated; age at least 18 years; and written informed consent. We randomly assigned patients (1:1) to receive either sentinel lymph node biopsy (SNB) or standard selective neck dissections (ND) with stratification of T category (lateT1 vs T2) and subsite (tongue vs others). The primary endpoint was 3-year overall survival with a non-inferiority margin of 12%. Sentinel nodes (SNs) were detected using radioisotope method and examined with multislice frozen section analysis intraoperatively, following HE and cytokeratin stain for a final postoperative diagnosis. Patients with positive SNs had neck dissections in a one-stage or back up procedure. Results: Between November 2011 and January 2016, 271 patients were enrolled and randomized to SNB group (134 patients) and ND group (137 patients) with a median follow-up of 37 months (IQR 36-39). Pathological positive nodal status was 34% (46/132) in SNB group and 26% (34/133) in ND group (Chi-Square p = 0.10). 3-year overall survival in SNB group was 89% (95%CI 82-93%), which was non-inferior to that in ND group (86%, 95%CI 79-91%). 3-year relapse-free survival was 80% (95%CI 72-86%) in SNB group and 81% (95%CI 73-87%) in ND group. Arm abduction of postoperative 1 and 3 months in ND group was disturbed significantly compared with SNB group. Conclusions: SNB navigated ND could replace elective ND without survival disadvantage and reduce postoperative disability of the neck in patients with early oral cancer. Clinical trial information: 000006510.

Epstein-Barr virus (EBV) has many strains; however, it remains unclear whether a causal relationship exists between different regions and viral genetic variants in healthy persons. This study was designed to examine the relationship between EBV strains in tonsils and adenoids and peripheral blood lymphocytes of the same individuals using different measurements of EBV strain polymorphism. This study examined whether EBV contains two or three copies of a tandem repeat sequence in the first intron of the BZLF-1 gene. The genotype of the virus from P3HR-1, designated Z*, yielded a 415-bp product, and this was distinguished from the smaller, 386-bp product obtained with the B95-8 virus, designated the Z genotype. Simultaneous sequence infections with Z and Z* genotypes were also detected in one of the tonsils examined, suggesting that more than one strain or variant of EBV genotype may be present in a specimen from the same subject. Co-infection with Z and Z* was recognized in two subjects, so variation of the EBV gene may be seen in at least two different strains of EBV. It was seen that Z and Z* strain-infected cells are constantly in flux through lymph nodes and/or the blood stream in healthy persons; therefore, these results indicated that EBV genome variants probably show no specific tissue distribution.

Background: We previously reported on the regimen of S-1 plus nedaplatin (NDP), with S-1 was administered orally for 14 days and NDP intravenously on day 8. The maximum tolerated dose (MTD) of NDP was determined to be 90 mg/m2. The main toxicities were neutropenia and thrombocytopenia. This result was tolerated, but we believe there is a more effective and tolerable regimen. Thus, we investigated the S-1 regimen administered orally for 14 days, and NDP intravenously on day 1 in patients with locally advanced head and neck squamous cell carcinoma. Patients and Methods: Oral administration of S-1 (days 1-14) and intravenous NDP (day 1) were tested for patients with advance head and neck cancer in a phase I setting. The dose of S-1 was fixed and the dose of NDP was escalated from 70 mg/m2, with an increase of 10 mg/m2 per step, to find the MTD. Results: A total of 15 patients were registered. The MTD of NDP was determined to be 100 mg/m2. The main toxicities were neutropenia and thrombocytopenia. The response rate (RR) was 57.1%. Conclusions: The recommended dose of NDP for a phase II study was determined to be 100 mg/m2. We concluded that our regimen was well tolerated and that the RR was acceptable.

A 36 y/o female presented with the chief complaint of diarrhea and vomiting which had lasted for four days, and with a family history of suicide. The first general examination showed severe dehydration with hyponatremia. After admission, she was diagnosed as having isolated adrenocorticotropic hormone (ACTH) deficiency and mixed connective tissue disease, and the steroid replacement therapy was started with the dose equivalent to 7.5 mg/day of prednisolone (PSL). Three days later, she had right sensorineural hearing loss (SNHL). She was given 40 mg/day PSL in addition to the steroid replacement therapy. On the next day, she developed a persecutory type of paranoid disorder, and then was given psychiatric medication. After tapering off PSL for SNHL, the delusion began to improve with psychiatric medication. Three weeks after the onset of SNHL, her hearing level had partially recovered. Ten months later, she did not show any psychic instability. A family history of psychosis and the present history of malnutrition and connective tissue disease are risk factors of steroid psychosis. It can develop even with 5 mg PSL if the patient has a risk factor. Careful medical history taking and knowledge about the steroid psychosis will prevent the severe side effects associated with steroid treatment.

Objective Sentinel node (SN) biopsy in the head and neck region has not been widely used in Japan, except at a few facilities. However, almost all these facilities perform preoperative localization and intraoperative diagnosis by frozen section analysis of SN to select patients who must undergo neck dissection in a one-stage procedure. The objective of this study was to determine the actual status of SN biopsy at those facilities in Japan that have actively conducted this procedure, and to elucidate the usefulness and drawbacks of this technique in head and neck cancer. Methods We retrospectively reviewed 177 patients who had undergone SN biopsy at 7 facilities. The underlying pathology was laryngeal or hypopharyngeal cancer in 20 patients from one hospital, while the remaining 157 patients had oral cancer. Preoperative localization of SN was determined using conventional lymphoscintigraphy with or without single photon emission computed tomography with CT (SPECT-CT). Intraoperative localization and diagnosis of SN were performed by gamma probe and frozen section analysis. Results Conventional lymphoscintigraphy detected a mean of 2.6 SNs per patient in 137 patients with oral cancer, compared to 2.7 in 71 patients using SPECT-CT and 2.9 in 154 patients using the gamma probe. No significant differences were apparent between techniques. Forty of the 520 SNs (7.7%; 33 in oral cancer and 7 in laryngeal or hypopharyngeal cancer) were pathologically positive in the final diagnosis. Of these, 3 were not processed for frozen sectioning and were diagnosed only with hematoxylin and eosin staining. Among the others, 32 (86.5%) were diagnosed intraoperatively as showing metastasis. In terms of the false-negative rate, 144 patients were determined by SN biopsy to have no positive SNs. Of these, 2 patients had non-SN metastases found in their dissected neck and 8 patients without neck dissection showed late nodal recurrence. The false-negative rate was thus 6.9%. Conclusion Frozen section analysis, particularly multislice sectioning, offers a relatively reliable intraoperative diagnostic method. We were able to perform immediate neck dissection based on the results of multislice sectioning as a single-stage procedure.

Background The status of lymph nodes in the neck is the most important prognostic factor for the outcomes of patients with oral tongue cancer. However, surgical prophylaxis of the neck is controversial. Methods We reviewed 22 patients with clinically T1/T2, N0 Union Internationale Contre le Cancer oral squamous cell carcinoma of the tongue. Patients were assigned to groups according to the management strategy selected for the neck. One group underwent a “watchful waiting” policy and the other underwent sentinel node navigation surgery (SNNS). Results Three of 11 patients (27%) in the watchful waiting group developed regional recurrence and underwent neck dissection. Only 1 of 11 patients (9.1%) in the SNNS group developed regional recurrence. Although the groups did not significantly differ, the SNNS group tended to have less regional recurrence. Conclusion SNNS should be the third strategy formanaging early oral tongue carcinoma. © 2011 Wiley Periodicals, Inc. Head Neck, 2012

Pure tone auditory thresholds can change according to duration of interrupted tones in patients with mild to severe psychogenic hearing loss (PHL).To examine how the duration of stimulus tones affects the hearing thresholds of patients with PHL.Twelve patients with PHL (21 ears) were enrolled in this study. We initially measured their hearing thresholds using interrupted tones with a duration of 2 s and equal length of on-time and off-time, 225 ± 35 ms, respectively. After a 10 min interval, we measured their hearing thresholds using the same interrupted tones conditions lasting 5 s. The average threshold gains (2 s thresholds minus 5 s thresholds) were compared to those of 15 control subjects with normal hearing (25 ears), 15 patients with cochlear hearing loss (23 ears), and 4 patients with retrocochlear lesions (4 ears). Patients with profound PHL (4 patients, 6 ears) were analyzed separately.The average threshold gain of PHL patients (excluding profound PHL patients) at all frequencies was 18.3 dB, which was significantly larger than that of other groups: 0.3 dB (profound PHL patients), 3.8 dB (controls with normal hearing), 3.0 dB (patients with cochlear hearing loss), and 3.2 dB (patients with retrocochlear lesions).

Advances in broad-spectrum antibiotics are enabling general physicians and pediatricians to treat acute middle-ear infection without otolaryngologists’ intervention. Most such subjects also recover without serious complications. Middle-ear infection remains potentially life-threatening, however, due to potential infectious intracranial complications, requiring surgery by otolaryngologists. We report two cases of acute pediatric mastoiditis following acute otitis media. Both had been initially treated by pediatricians and administered several antibiotics. One subject had masked mastoiditis when first seen and the other serious complications involving intracranial infection thought due to comorbid congenital cholesteatoma. Both were treated successfully with mastoidectomies followed by intravenous antibiotic therapy.

センチネルナビゲーション手術はリンパ節転移のステージングに非常に有効であるが，いくつかの問題点がある。それらを改善する取り組みのなかでも，ICG蛍光法を用いたセンチネルリンパ節生検とOSNA法に最適な遺伝子検索の観点から舌癌の免疫染色について述べてみる。

厚生労働省科学研究費補助金「頭頸部がんのリンパ節転移に対する標準的治療法の確立に関する研究」（斉川班）で作成した頸部郭清術後機能評価法を用いて，本研究班において見学調査され詳細な術式の情報が得られた症例を対象として，郭清範囲の縮小や非リンパ組織の温存，術後照射が，頸部郭清術後Quality of Lifeに与える影響を検討した。郭清範囲をレベルIIIまでに縮小することで，「肩や首の硬さ」や「締め付け感」などの悩みが減ること，レベルVを郭清しても胸鎖乳突筋や副神経を温存すれば，これらの後遺症を軽減させることができること，胸鎖乳突筋の切除により有意に「肩の下がり」がみられること，副神経切除例では「首の痛み」や「外観」での悩みが多いこと，50Gy以上の放射線治療例では「首が硬い」という訴えが強くなること等が確認された。

目的：この研究の目的は局所進行頭頸部扁平上皮癌（SCCHN）患者におけるS-1の隔日投与による同時化学放射線療法の有用性と毒性を評価することである。対象と方法：2008年1月から2010年2月にかけて10例のSCCHN患者を対象に，隔日でS-1の80mg/日の経口投与と三次元原体照射（three-dimensional conformal radiation therapy：3DCRT）による同時化学放射線療法を行った。放射線治療は内視鏡所見やCT，PET-CT所見にもとづく病巣部照射で，矩形照射野での回転照射と固定多門照射を複合させた3DCRTで行った。総線量の中央値は69Gy（66～74Gy）であった。結果：Grade 2の粘膜炎を2例で認めたが，その他のgrade 2以上の急性期・晩期有害事象を認めた症例はなく，予定された放射線治療も中断なく施行可能であった。一次治療後，9例（82%）で臨床的に完全奏効となり，それらの症例では現在のところ再発は認めていない。結論：局所進行頭頸部扁平上皮癌患者において，原体性を高めた3DCRTと隔日投与のS-1による同時放射線化学療法の有効性が示された。今後，症例数を重ねて遠隔成績を検討する必要がある。

化学放射線同時併用療法（Concurrent Chemoradiotherapy，CCRT）は，メタアナリシスにおいて有用性が示され，世界的に普及した。切除可能な頭頸部進行癌においてCCRTは外科的治療の代替であり，その目的は手術と同等の根治性を確保しつつ機能温存を図ることである。しかし，治療後の嚥下障害や，失敗例に対する救済手術の難しさなど，問題点も徐々に明らかとなってきた。近年では，導入化学療法が再び注目されている。導入化学療法をCCRTの効果予測に用いる試みや，導入化学療法によって上乗せ効果を図る試みがある。また，術後CCRT，根治治療後の補助化学療法，再発・転移頭頸部癌に対する化学療法など，さまざまな局面で化学療法は用いられている。本稿では多様化した頭頸部癌化学療法の現状を整理し，本邦における問題点を探る。

LAT1, a subunit of heterodimeric system L transporter responsible for transporting neutral amino acids into cells, has been investigated in several cancers because of its onco-fetal nature. Based on the studies of its functional inhibition, LAT1 has been proposed to be a new molecular target of a cancer therapy. We have shown here that human head and neck cancer cell line, Hep-2, expresses both LAT1 and 4F2hc, another subunit of system L transporter. An inhibitor of system L, 2-aminobicyclo-(2,2,1)-heptane-2-carboxylic acid (BCH), inhibited leucine uptake by the cells. BCH administration or restriction of essential amino acid leucine decreased viability of Hep-2 cells. Co-administration of cisplatin with BCH reduced the viability of the cells more than either agent alone. When BCH treatment preceded cisplatin administration, reduction in Hep-2 cell viability was additive. In contrast, when BCH was given after cisplatin treatment, synergistic effect in decreasing the number of viable cells was obtained. BCH treatment decreased the phosphorylation of mTOR, p70S6K and 4EBP1, suggesting that BCH enhanced anti-tumor action of cisplatin by inhibiting mTOR pathway. This potentiation may be used to reduce cisplatin exposure to alleviate many unwanted toxicity of the drug.

クリニカルパスは，医療サイドでは施設内での治療の標準化やリスクマネージメントの観点から導入する施設が増加しているが，このことは同時に患者サイドのインフォームドコンセントや治療に対する関心の高まりのニーズにうまく合致している。耳鼻咽喉科・頭頸部領域では，対象は良性腫瘍の手術や薬物治療が中心の突発性難聴，顔面神経麻痺などの疾患に限定され，集学的治療が必要な癌患者には余り用いられてこなかった。その中でも，癌化学療法の分野では，多種なレジメンが存在し，同一薬剤でも併用薬剤や投与量が異なり，また患者バリアンスが大きいと考えられるためパスの導入は遅れていた。今回我々は頭頸部悪性腫瘍症例に対する導入化学療法のパスを作成，運用したので報告する。

Background Despite improved survival by the addition of a monoclonal antibody against epidermal growth factor receptor (EGFR), cetuximab, to chemotherapy or radiotherapy for squamous cell carcinoma of the head and neck (SCCHN), cetuximab by itself is not a potent antiproliferative agent against SCCHN. We aimed to elucidate working mechanism of cetuximab in SCCHN. Methods The effect of cetuximab on the proliferation, migration, invasion, epithelial-mesenchymal transition, and signaling events downstream of the EGFR were investigated in 4 SCCHN cell lines. The in vivo efficacy of cetuximab was evaluated in a xenotransplant model. Results Cetuximab inhibited migration, invasion, epithelial-mesenchymal transition, and lymph node metastasis by suppressing EGFR-GEP100-Arf6-AMAP1 pathway, but it did not inhibit cancer cell proliferation. Conclusion The improved survival by the addition of cetuximab is likely to be attributable to the antiepithelial-mesenchymal transition action of cetuximab via inhibiting EGFR-GEP100-Arf6-AMAP1 pathway. © 2016 Wiley Periodicals, Inc. Head Neck, 2016

Otolaryngologists play a very important role in the field of emergency care in otolaryngology because their field requires a particular expertise in dealing with a variety of diseases. However, the emergency medical service system at night or during holidays has not yet been completely organized. Clarification of the present problems is essential to improve our emergency medical service system. Thus, we investigated the present state of otolaryngological emergency care in Tokyo and in Kyorin University Hospital. In Tokyo, outpatient clinics and hospitals see the emergency patients in the otolaryngology field by rotation during holidays. More than 13,000 patients were referred to the outpatient clinics, and more than 2, 000 patients were referred to the hospitals per year using this emergency care system. There are some problem with this system. One is that patients have to rush to a hospital in consecutive holidays and the other is that only a few clinics and hospitals see patients at night. Otolaryngologists have to regard these problem as an otolaryngologist-wide issue. For both public administration or academic societies a site for discussion needs to be provided.

This study was designed to assess the validity of sentinel lymph node (SLN) biopsy using either the combination of indocyanine green (ICG) fluorescence and radioisotope (RI) or ICG-alone in SLN mapping for early head and neck cancer patients.Nineteen patients received SLN biopsy with the following method. Thirteen patients received SLN biopsy with only RI, 2 patients with only ICG and 4 patients with the combination of ICG and RI. Detection time for each method of SLN biopsy was measured to evaluate the validity of SLN with the combination of ICG and RI.A total of 41 SLNs were identified by RI or ICG. All SLNs identified by ICG could be localized intraoperatively. The number of SLNs identified by the combination of ICG and RI was greater than that of SLNs identified by RI-alone. One of the patients who underwent SLN biopsy by RI-alone was diagnosed with a metastatic lymph node one year later, then underwent neck dissection. Mean detection time for SLN biopsy with ICG or with the combination of ICG and RI tended to be shorter than that of RI-alone.SLN biopsy with the combination of ICG and RI enabled us to identify SLNs more easily and rapidly than by using RI alone.

This study analyzed the safety and feasibility of alternate-day S-1, a mixture of tegafur, dehydroxypyrimidine and potassium oxonate, as adjuvant chemotherapy for head and neck cancers.Patients with head and neck squamous cell carcinoma (HNSCC) who underwent primary treatment received alternate-day S-1 (80 mg/day for 1 year). The primary end-point was treatment completion rate. The secondary end-point was adverse events. Three-year overall survival (OS) and disease-free survival (DFS) were calculated using the Kaplan-Meier method.One-year completion rate was 65.6%. Out of 26 patients, 19.0% had grade III adverse events. All adverse reactions were tolerable and reversible. Three-year OS and DFS were 74.8% and 57.3%, respectively.S-1 therapy is an effective adjuvant treatment for head and neck cancer patients with relatively mild side-effects and does not adversely affect quality of life. A phase I/II study is warranted to investigate the appropriate dose for an alternate-day S-1 regimen.

Background Sentinel node navigation surgery is gaining popularity in oral cancer. We assessed application of sentinel lymph node navigation surgery to pharyngeal and laryngeal cancers by evaluating the combination of contrast-enhanced ultrasonography and indocyanine green fluorescence in animal models. Methods This was a prospective, nonrandomized, experimental study in rabbit and swine animal models. A mixture of indocyanine green and Sonazoid was used as the tracer. The tracer mixture was injected into the tongue, larynx, or pharynx. The sentinel lymph nodes were identified transcutaneously by infra-red camera and contrast-enhanced ultrasonography. Detection time and extraction time of the sentinel lymph nodes were measured. The safety of the tracer mixture in terms of mucosal reaction was evaluated macroscopically and microscopically. Results Sentinel lymph nodes were detected transcutaneously by contrast-enhanced ultrasonography alone. The number of sentinel lymph nodes detected was one or two. Despite observation of contrast enhancement of Sonazoid for at least 90 minutes, the number of sentinel lymph nodes detected did not change. The average extraction time of sentinel lymph nodes was 4.8 minutes. Indocyanine green fluorescence offered visual information during lymph node biopsy. The safety of the tracer was confirmed by absence of laryngeal edema both macro and microscopically. Conclusions The combination method of indocyanine green fluorescence and contrast-enhanced ultrasonography for detecting sentinel lymph nodes during surgery for head and neck cancer seems promising, especially for pharyngeal and laryngeal cancer. Further clinical studies to confirm this are warranted.

A 62-year-old man with an NK/T lymphoma originating in the right side of the upper jaw showed destruction of the hard palate and sino-nasal cavity. Intraoral examination revealed an ulcer with necrotic mucosa covering the area from the right side of the upper gingiva to the midline of the palate. CT scanning demonstrated a lesion on the right side of the sino-nasal cavity, and other clinical findings suggested a lethal midline granuloma. A biopsy specimen was positive for CD3, CD56, and Epstein-Barr virus (EBV), but negative for CD20. On the basis of these findings, a definitive diagnosis of NK/T lymphoma was established, and a course of radiation treatment was prescribed. Thereafter, his general condition deteriorated rapidly, and the patient died approximately 4 months later. In this disease, it is very difficult to establish a correct diagnosis. In situ hybridization study for EBV can contribute to the diagnosis because it can detect very small numbers of neoplastic cells in the early stage of disease.

頭頸部癌において頸部リンパ節は重要な予後因子である。センチネルリンパ節（SLN）とは腫瘍原発巣からのリンパ流を初めに受け止めるリンパ節である。したがって，SLNに最初に頸部転移が起こる事になる。そこでこのSLNに関する概念が頭頸部癌に成立し頸部郭清手術の指標になるかを検討した。放射線同位元素で標識されたトレーサーを腫瘍周辺粘膜に注入しシンチグラム（LS），ガンマプローベ（GP）で検索した。頸部郭清手術後に病理組織検査を行い相関を調べた。LSとGPの結果は良く相関した。そしてSLN検索の結果と摘出したリンパ節は15例中14例（93.3%）で一致した。微小転移は5例（33.3%）で同定された。これはSLNの検索を行う事により66.7%の症例では郭清手術を省略出来ることになる。したがってSLNの概念はT2，T3でN0症例の頸部郭清術適応の決定に有効である。しかしながら本法が確立された標準治療となるためには，症例の蓄積と長期の予後調査が必要と思われた。