[Emergency Care System in Otolaryngology].

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.

Epstein-barr virus diversity in immunocompetent healthy persons: reassessment of the distribution of genetic variants.

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.

[A study of 9 cases of cervical tuberculous lymphadenitis with the diagnosis of cervical tuberculous lymphadenitis].

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.

Phase I study of nedaplatin prior to S-1 in patients with locally advanced head and neck squamous cell carcinoma.

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 case of steroid psychosis caused by treatment for acute sensorineural hearing loss].

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.

Intraoperative molecular assessment for lymph node metastasis in head and neck squamous cell carcinoma using one-step nucleic acid amplification (OSNA) assay.

BACKGROUND: Conventional intraoperative pathological examination for Sentinel node navigation surgery (SNNS) has been controversial. We evaluated the efficacy of one-step nucleic acid amplification (OSNA) assay for intraoperative diagnosis of cervical lymph node (CLN) metastasis compared with histopathological examination in patients with head and neck squamous cell carcinoma (HNSCC). METHODS: A total of 175 CLNs dissected from 56 patients with HNSCC who underwent surgery at Aichi Cancer Center, Kyorin University, Gunma University or Fukushima Medical University, between April 2008 and December 2011 were enrolled. CLN samples were sectioned into four equal pieces, with two of each used for OSNA assay and other histopathological examinations. The diagnostic value of OSNA assay in HNSCC patients in predicting the results of histopathological diagnosis was evaluated using the area under the receiver operating characteristic (AUROC) curve. RESULTS: OSNA assay showed acceptable efficacy in the detection of pathological CLN metastasis (AUROC 0.918, 95 % confidence interval [CI] 0.852-0.984). Regarding the CK19mRNA cutoff value, the optimum cutoff point in HNSCC patients was 131 copies/µl (sensitivity: 82.4, 95 % CI 65.5-93.2; specificity: 99.3, 95 % CI 96.1-100.0; positive likelihood ratio 116.1; negative likelihood ratio 0.2]. CONCLUSIONS: We demonstrated that OSNA assay is useful in intraoperative diagnosis for CLN metastasis in patients with HNSCC. OSNA assay could be applied for SNNS in HNSCC patients.

[A case report - bisphosphonate-related osteonecrosis of the jaw(stage 0)successfully treated with sitafloxacin].

In recent years, many authors have reported that bisphosphonate-related osteonecrosis of the jaw(BRONJ)is a side effect of bisphosphonate therapy. However, clinicians have been confused by these reports, as no definitive criteria or treatment guidelines for BRONJ exist. In this paper, we report a patient who had BRONJ(stage 0)after dental extraction. She was successfully treated with sitafloxacin(STFX). A 73-year-old female had been taking 35 mg of alendronate per week for 24 months for the treatment of osteoporosis. She had a 1-month history of pain, suppuration, and a mandibular socket that would not heal after a left molar tooth extraction, despite the administration of antibiotics. A diagnosis of BRONJ(stage 0)was made without exposed bone, and she started 200 mg of STFX per day for 2 weeks, which was reduced to 100 mg per day for a week thereafter. After 3 weeks of STFX treatment, the mandibular wound healed. Furthermore, antimicrobial susceptibility testing against all of the organisms isolated from the pus indicated that STFX exhibited the most potent antimicrobial activity of all the agents. The results of these data suggested that STFX may be an effective antibiotic for BRONJ.

Latent changes in the pharyngeal stage of swallowing in non-aspirating older adults.

PURPOSE: 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. METHODS: 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. RESULTS: 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. CONCLUSION: 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.

Predictive factors for false negatives following sentinel lymph node biopsy in early oral cavity cancer.

Prophylactic elective neck dissection (ND) with navigation surgery using radioisotope-based sentinel lymph node biopsy (SLNB) is non-inferior to elective ND in terms of survival but has an advantage in postoperative functional disability. We conducted a subgroup analysis to identify predictive factors for false-negative (FN)-SLNB in patients with early oral cavity cancer. This study is a supplementary analysis using the dataset of a previously reported randomized clinical trial on SLN navigation surgery for oral cancers. This study investigated the association of clinical and SLN-related factors with false-negative cases in the SLNB group. From 2011 to 2016, 275 patients were enrolled and randomly assigned to the ND and SLNB study groups, with 134 patients assigned to the SLNB group. In the SLNB group, seven cases with negative SLNs and neck recurrences were judged as FN-SLNBs according to the general definition. The number of detected SLNs with and without adjusting for the propensity score was significantly associated with FNs in the logistic analysis. FN-SLNB was associated with the number of identified SLNs, suggesting the need for careful postoperative monitoring for neck recurrence in patients with one or two identified SLNs after acquiring sufficient experience in the identification technique.

Feasibility of ICG fluorescence-guided sentinel node biopsy in animal models using the HyperEye Medical System.

BACKGROUND: The sentinel lymph node (SLN) concept is accepted for several types of cancers. Current methods for sentinel node detection involve radioisotopes and blue dye. They have shown good results, but some drawbacks remain. Indocyanine green (ICG) fluorescence using the HyperEye Medical System (HEMS) was evaluated as a new method. METHODS: This was a prospective, nonrandomized, experimental study in four Japanese white rabbits and six Yorkshire pigs. ICG and indigo carmine were injected into the tongue, larynx, or hypopharynx, and ICG fluorescence detection was evaluated using both transcutaneous visualization of lymphatic vessels and intraoperative identification of SLNs. RESULTS: The SLNs appeared as shining fluorescent spots with HEMS transcutaneously in rabbits, but no SLNs were detected transcutaneously in pigs. Eleven procedures identified SLNs, but one did not due to a technical problem. CONCLUSIONS: HEMS could become useful for predicting lymph node metastasis during surgery for head and neck cancer.

Risk of Sensorineural Hearing Loss in Patulous Eustachian Tube.

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.

Neck Dissections Based on Sentinel Lymph Node Navigation Versus Elective Neck Dissections in Early Oral Cancers: A Randomized, Multicenter, and Noninferiority Trial.

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.

Docetaxel suppresses invasiveness of head and neck cancer cells in vitro.

The combination of docetaxel, cisplatin, and fluorouracil significantly enhances the survival of head and neck cancer patients compared to cisplatin and fluorouracil. We hypothesized that docetaxel may affect invasiveness of the head and neck cancer cells in addition to its tumor-killing effect. Two different head and neck cancer cell lines (HEp-2 and Ca9-22) were treated with docetaxel at IC(10) and IC(50) concentrations. Cell migration and invasive growth was evaluated by wound healing assay and three-dimensional (3D) culture of multicellular tumor spheroids, respectively. Expression levels of possible downstream effectors for cell migration/invasiveness were measured by immunoblotting in conditions with or without docetaxel. Docetaxel, but not cisplatin, suppressed filopodia formation compared with no treatment (control) condition. Consistent with this, docetaxel suppressed two-dimensional (2D) cell migration and 3D cell invasion compared with control or cisplatin. Only docetaxel treated cells exhibited thick tubulin bundle and had lower activity of Cdc42, a member of the Rho family of small GTPases. In conclusion, Docetaxel treatment suppressed migration and invasiveness of head and neck cancer cells in vitro, which is likely to be mediated by regulating Cdc42 activity.

Phase I study of S-1 plus nedaplatin in patients with advanced/recurrent head and neck cancer.

BACKGROUND: Cisplatin plus fluorouracil is widely used for the treatment of head and neck cancer. However, the cisplatin plus fluorouracil regimen necessitates hospitalization. Therefore, we planned to develop a new regimen that can be administered on an outpatient basis and performed a phase I study of S-1 + nedaplatin. METHODS: S-1 was given orally at a fixed dose for 14 days, and nedaplatin was administered intravenously on day 8 of S-1 administration. The dose of nedaplatin was increased in 10-mg/m(2) steps to find the maximum tolerated dose, depending on the appearance of dose-limiting toxicities. RESULTS: A total of 14 patients were registered. The maximum tolerated dose of nedaplatin was determined to be 90 mg/m(2). The main toxicities were neutropenia and thrombocytopenia. The response rate was 57.1%. CONCLUSION: The recommended dose of nedaplatin for a phase II study was determined to be 80 mg/m(2). We concluded that our regimen was well tolerated and that the response rate was acceptable.

Long term-follow-up multicenter feasibility study of ICG fluorescence-navigated sentinel node biopsy in oral cancer.

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.

Concurrent chemoradiotherapy for organ function preservation in advanced patients with hypopharyngeal and laryngeal cancer.

Preservation of the larynx is the most critical factor influencing quality of life in the treatment of head and neck cancer. This clinical study focuses on laryngeal function-preserving chemoradiotherapy for locally advanced hypopharyngeal and laryngeal cancer. Thirty-two resectable cases with histologically proven squamous cell carcinoma undergoing function-preserving therapy were examined. Induction chemotherapy comprised cisplatin and 5-fluorouracil, and another cycle of chemotherapy was performed for responders. Chemoradiotherapy comprised conventional irradiation and weekly chemotherapy (nedaplatin plus docetaxel). Non-responder patients were excluded from further chemotherapy and were changed to other surgical treatment. Three patients were non-responders for induction chemotherapy, and 29 patients were treated with chemoradiotherapy. Thus, 21 out of 29 patients obtained preserved laryngeal function. Initial larynx preservation rate with these treatment strategies was 93.8%. This study provides a new concept for laryngeal function-preserving treatment that should be considered for locally advanced laryngeal and hypopharyngeal cancer.

Acute-onset unilateral psychogenic hearing loss in adults: report of six cases and diagnostic pitfalls.

We encountered 6 rare cases of acute-onset unilateral psychogenic hearing loss in adults. All were women in their 20s and 30s. Three cases had severe hearing impairment characterized by hearing loss at every frequency; 2 cases had profound hearing impairment, and 1 case had low-frequency hearing impairment. Of the 6 cases, 3 had a history of hearing loss, and 1 had a history of psychogenic visual disturbance. All 6 cases were initially diagnosed as having idiopathic sudden sensorineural hearing loss; all subsequently received steroid therapy. Three cases were not diagnosed as being psychogenic in origin until otoacoustic emissions and auditory brain responses were performed. Although the presence of distinctive clinical features (age, gender, and past history) is important for suspecting psychogenic hearing loss, objective audiological tests such as otoacoustic emissions are essential for diagnosing some cases. Compared to the existing reports of similar cases, our cases had a poorer prognosis (only 2 cases were cured).

[Emergency care of vertigo patients: suggestions for efficient management].

Some diseases in which persons show vertigo or dizziness may be life-threatening, regardless of symptom severity, and require careful attention. These include diseases of the inner ear, central nervous system, and cardiovascular manifestation. In May 2006, a group in charge of primary emergency consultation began work enabling physicians to treat vertigo patients more efficiently and safely, as detailed in this report. Of the 173 persons with vertigo hospitalized from January 2004 to March 2008, six had cerebrovascular manifestations clarified only after hospitalization, underscoring the importance of careful examination, especially of those 75 years of age older, having continuous headache, having severe trunk ataxia despite apparently mild eye nystagmus, or reporting a history of high blood pressure, diabetes mellitus, hyperlipidemia, or ischemic heart disease.

In Vitro Study of the Anti-cancer Effect of Alternate-day 5-Fluorouracil in Head and Neck Cancer Cells.

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<0.001). CONCLUSION: The cytotoxic effect of alternate-day was equivalent to that of consecutive-day. S-phase arrest was more prominently observed with the alternate-day regimen, which may help maintain 5-FU sensitivity in head and neck cancer cells.

Surgical consensus guidelines on sentinel node biopsy (SNB) in patients with oral cancer.

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.