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Telomerase reverse transcriptase promoter (TERT-p) mutations are strongly associated with tumor aggressiveness and worse prognosis in papillary thyroid carcinomas (PTCs). Since the TERT-p promoter mutations have been reported to be subclonal, it is unclear how accurately they can be detected by preoperative fine needle aspiration (FNA). The objective of this study was to analyze the concordance rate of the TERT-p mutations between preoperative FNA and corresponding postoperative surgical specimens. The mutational status of the TERT-p in FNA samples detected by our ddPCR assay was highly concordant with that in postoperative FFPE specimens. The TERT-p mutation was significantly associated with age, tumor size, extrathyroidal extension, and the Ki-67 labeling index in multivariate analysis in both FNA and FFPE samples. The detection of the TERT-p mutations using FNA samples has a good ability to predict disease aggressiveness and, therefore, could be clinically useful in the determination of PTC management.

We report on the growth of papillary microcarcinoma during active surveillance and before clinical presentation.We conducted a retrospective study of 169 patients with papillary microcarcinoma who were enrolled in active surveillance at our hospital between 2000 and 2004. Patients were followed for a median of 10.1 years using serial ultrasonography (median, 12 examinations), used to calculate the tumor doubling time. To contextualize tumor growth rates during active surveillance, we calculated the hypothetical tumor doubling time before clinical presentation. To resolve the limitations in tumor doubling time, tumor doubling rates were inversely transformed into doubling rates.The doubling rates (per year) during active surveillance (median: 0.0) were0.5, 0.1 to 0.5, -0.1 to 0.1, and-0.1 in 5, 38, 97, and 29 cases, respectively. The proportions of tumors with rather rapid growth, slow growth, stable, and a decrease in size were 3%, 22%, 57%, and 17%, respectively.Tumor growth of papillary microcarcinomas varies from rather rapid growth to a decrease in size during active surveillance.

Background: Active surveillance (AS) of low-risk papillary thyroid microcarcinoma (PMC) was adopted as a management modality in both the Japanese guidelines in 2011 and the American Thyroid Association guidelines in 2015. AS was initiated at Kuma Hospital in 1993 but was not immediately accepted by all physicians. This study investigated the history of acceptance of AS at Kuma Hospital over time. The results should assist in the implementation of AS at other hospitals in Japan and other countries. Methods: This study included 4023 patients who were cytologically diagnosed with low-risk PMC at Kuma Hospital during the 24-year period between October 1993 and June 2016. The trend in the frequency of AS use over time was analyzed, dividing the 24-year study period into five parts based on the change in frequency of AS use: 1993–1997, 1998–2002, 2003–2006, 2007–2013, and 2014–2016. Results: The frequency of AS use in the present cohort was 65%. The frequency gradually increased from 30% in 1993–1997 to 88% in 2014–2016, with a slight decrease from 51% in 1998–2002 to 42% in 2003–2006. Until 2007, patients were mostly seen by surgeons, and the frequency of AS use varied remarkably among individual surgeons. Since 2007, the number of patients whose therapeutic strategies are determined by endocrinologists has increased, and the frequency of AS use for low-risk PMC by endocrinologists has been higher than that by surgeons. Conclusions: At Kuma Hospital, acceptance of AS for low-risk PMC gradually increased over the 24-year study period, but AS was not equally accepted by all physicians. Such variations in the acceptance of AS among individual physicians are also expected to exist in other hospitals. However, due to increasing evidence of the safety and superiority of AS over immediate surgery for this indolent disease, it is expected that AS will gain faster acceptance in other hospitals in Japan and around the world.

The tumor-node-metastasis (TNM) staging system is most commonly adopted to evaluate the prognosis of patients with thyroid carcinoma. The 8th edition of the TNM staging system, an extensively revised version of the 7th edition, was recently released. We aimed to investigate whether and how well the 8th edition reflects the cause-specific survival (CSS) of patients with papillary thyroid carcinoma by analyzing the cases in 5,892 patients who underwent initial surgery at Kuma Hospital between 1987 and 2005. The median postoperative follow-up duration was 178 months (range: 6-357 months). One patient with T4b disease was excluded from the analysis. Overall, 116 (2.0%) patients died of thyroid carcinoma. The proportion of variance explained (PVE) for CSS in the 7th and 8th editions was 10.69 and 10.97, respectively. Using the 7th edition, CSS of patients with stage IVA and stage III disease was similar (p = 0.32). In contrast, using the 8th edition, CSS was poorer in stage II than in stage I (p < 0.001), in stage III than in stage II (p < 0.001), and in stage IVB than in stage III (p < 0.001). Similar results were observed for disease-free survival. Although we could not establish any objective evidence that the 8th edition is superior to the 7th edition, the 8th edition is simpler and more convenient, as it includes fewer stages and addresses the issue of the 7th edition where stage IVA and III patients had similar prognoses.

Follicular thyroid carcinoma (FTC), a form of differentiated thyroid carcinoma, is the second most common malignancy arising from thyroid follicular cells. Recently, the tumor-node-metastasis (TNM) classification for differentiated thyroid carcinoma was revised from the 7th to the 8th edition. The diagnostic criteria for poorly differentiated carcinoma (PDC) were also updated in the latest World Health Organization (WHO) classification. In this study, we investigated whether these changes are appropriate for accurately predicting prognosis. Three hundred and twenty-nine patients diagnosed with postoperative pathologically confirmed FTC, who underwent initial surgery at our hospital between 1984 and 2004, were enrolled. For this study, patients were re-evaluated and diagnosed with FTC (N = 285) or PDC (N = 44) without typical nuclear findings of papillary thyroid carcinoma. For FTC, the 8th TNM classification was a more accurate predictor of prognosis than the 7th TNM classification. In the 8th TNM classification, cause-specific survival became significantly poorer from Stage I to IVB. The cause-specific survival of PDC based on the latest WHO classification was worse than, but did not significantly differ from, that of PDC based only on the former WHO classification. For PDC, neither of the TNM classifications could accurately predict prognosis. Taken together, we conclude that (1) the 8th TNM classification more accurately reflects the prognosis of FTC than the 7th TNM classification; (2) PDC based on the former WHO classification should be retained, at least in Japan; and (3) the TNM classification may not be suitable for predicting the prognosis of PDC.

The incidence of thyroid cancer is increasing rapidly in many countries, resulting in rising societal costs of the care of thyroid cancer. We reported that the active surveillance of low-risk papillary microcarcinoma had less unfavorable events than immediate surgery, while the oncological outcomes of these managements were similarly excellent. Here we calculated the medical costs of these two managements. We created a model of the flow of these managements, based on our previous study. The flow and costs include the step of diagnosis, surgery, prescription of medicine, recurrence, salvage surgery for recurrence, and care for 10 years after the diagnosis. The costs were calculated according to the typical clinical practices at Kuma Hospital performed under the Japanese Health Care Insurance System. If conversion surgeries were not considered, the 'simple cost' of active surveillance for 10 years was 167,780 yen/patient. If there were no recurrences, the 'simple cost' of immediate surgery was calculated as 794,770 yen/patient to 1,086,070 yen/patient, depending on the type of surgery and postoperative medication. The 'simple cost' of surgery was 4.7 to 6.5 times the 'simple cost' of surveillance. When conversion surgeries and recurrence were considered, the 'total cost' of active surveillance for 10 years became 225,695 yen/patient. When recurrence were considered, the 'total cost' of immediate surgery was 928,094 yen/patient, which was 4.1 times the 'total cost' of the active surveillance. At Kuma Hospital in Japan, the 10-year total cost of immediate surgery was 4.1 times expensive than active surveillance.

Summary Objectives We aimed to determine the most appropriate syllable number for analyzing the Acoustic Voice Quality Index for the Japanese-speaking population (AVQIv3-JP) and to validate AVQIv3-JP using the determined syllable number. Methods First, we counted how many syllables should be included in each continuous speech (CS) sample to achieve time-balanced analysis between CS and sustained vowel samples using our previous dataset including 336 CS samples with 58 syllables. From the descriptive statistics of the counted syllable numbers, the most appropriate syllable number was identified. Subsequently, we performed validation procedures of AVQIv3-JP using our latest dataset including 455 recordings. Results Thirty Japanese syllables were judged to be the most appropriate syllable number. The concurrent validity of the AVQIv3-JP using 30 syllables was confirmed by Spearman's rho of 0.873. Subsequently, the receiver operating characteristic analysis demonstrated the excellent discriminative capability of AVQIv3-JP, showing the area under the curve of 0.915. The AVQIv3's original threshold of 2.43 in the Dutch language corresponded to sensitivity and specificity of 64.6% and 97.3%, respectively. In the present study, a threshold of 1.41 achieved the best accuracy with balanced sensitivity and specificity of 84.4% and 85.6%, respectively. Furthermore, the 95th percentile of the control participants exhibited a threshold of 2.06, showing sensitivity and specificity of 72.1% and 93.8%, respectively, as well as reasonable positive and negative likelihood ratios of 11.7 and 0.298, respectively. Conclusion The AVQIv3 using 30 Japanese syllables is a reliable measurement tool for estimating the severity of voice quality and detecting abnormal voices.

Objective Genetic testing for RET germline mutation can be useful to distinguish whether a patient with medullary thyroid carcinoma (MTC) is genuinely sporadic or hereditary. Conducting a routine preoperative germline RET genetic screening for all patients with MTC has the clinical benefit, i.e., avoidance of unnecessary total thyroidectomy in the selected patients. We sought to clarify the incidence of germline RET mutation carriers in Japanese patients with apparently sporadic MTC and to address the differences in clinicopathological characteristics between true sporadic MTC and hereditary MTC in these patients, all of whom were treated at Kuma Hospital. Methods A total of 134 patients with apparently sporadic MTC who underwent surgery between 1996 and 2014 were enrolled. All patients underwent a germline RET gene mutation analysis preoperatively. Results Germline mutations in RET proto-oncogene were identified in 20 of the 134 (14.9%) apparently sporadic MTC patients. No significant difference in clinicopathological characteristics was observed between the patients with sporadic MTC ( n = 114) and those with hereditary MTC ( n = 20) except for the RET gene carriers’ younger age at diagnosis and presence of multifocal and bilateral lesions. Conclusion Germline RET mutations were identified in 14.9% of Japanese patients with apparently sporadic MTC. No clearly decisive clinicopathological characteristics was observed to distinguish whether an apparently sporadic MTC case was genuinely sporadic or unconsciously hereditary. For the treatment strategy decision, it is advantageous to conduct a routine preoperative germline RET genetic screening for all patients with MTC, even if their MTC is apparently sporadic.

The incidence of papillary microcarcinoma (PMC) of the thyroid is rapidly increasing globally, making the management of PMC an important clinical issue. Excellent oncological outcomes of active surveillance for low-risk PMC have been reported previously. Here, unfavorable events following active surveillance and surgical treatment for PMC were studied.From February 2005 to August 2013, 2153 patients were diagnosed with low-risk PMC. Of these, 1179 patients chose active surveillance and 974 patients chose immediate surgery. The oncological outcomes and the incidences of unfavorable events of these groups were analyzed.In the active surveillance group, 94 patients underwent surgery for various reasons; tumor enlargement and the appearance of novel lymph node metastases were the reasons in 27 (2.3%) and six patients (0.5%), respectively. One of the patients with conversion to surgery had nodal recurrence, and five patients in the immediate surgery group had a recurrence in a cervical node or unresected thyroid lobe. All of these recurrences were successfully treated. None of the patients had distant metastases, and none died of the disease. The immediate surgery group had significantly higher incidences of transient vocal cord paralysis (VCP), transient hypoparathyroidism, and permanent hypoparathyroidism than the active-surveillance group did (4.1% vs. 0.6%, p 0.0001; 16.7% vs. 2.8%, p 0.0001; and 1.6% vs. 0.08%, p 0.0001, respectively). Permanent VCP occurred only in two patients (0.2%) in the immediate surgery group. The proportion of patients on L-thyroxine for supplemental or thyrotropin (TSH)-suppressive purposes was significantly larger in the immediate surgery group than in the active surveillance group (66.1% vs. 20.7%, p 0.0001). The immediate surgery group had significantly higher incidences of postsurgical hematoma and surgical scar in the neck compared with the active surveillance group (0.5% vs. 0%, p 0.05; and 8.0% vs. 100%, p 0.0001, respectively).The oncological outcomes of the immediate surgery and active surveillance groups were similarly excellent, but the incidences of unfavorable events were definitely higher in the immediate surgery group. Thus, active surveillance is now recommended as the best choice for patients with low-risk PMC.

Background: An active-surveillance clinical trial of low-risk papillary microcarcinoma (PMC) patients has been performed at the authors' institution, Kuma Hospital, since 1993. Favorable oncological results have been reported. During the trial, a few patients were encountered with PMC that showed enlargement during pregnancy, and these cases have been reported. During pregnancy, a large amount of human chorionic gonadotropin (hCG) having weak thyrotropin (TSH) activity is produced, possibly affecting the progression of PMC. This study investigated how pregnancy and delivery influenced the progression of PMC in the entire active surveillance PMC patient series. Methods: From 1993 to 2013, 1841 patients with low-risk PMC chose the active surveillance program. Fifty of the 1549 female PMC patients experienced 51 pregnancies/deliveries. To minimize observer variation, a single specialist sonographer re-evaluated the changes in the size of these 50 patients' PMCs before and after the pregnancies/deliveries. Results: Four patients (8%) showed enlargement of PMC by ≥3 mm; one patient (2%) showed a decrease by ≥3 mm, and the remaining 44 patients (45 events, 90%) showed stable disease. None of the patients had a novel appearance of lymph node metastases during pregnancy. Of the four patients with enlargement, two underwent surgery after delivery, and the other two continued the active surveillance, since their tumors did not grow after the delivery. After delivery, the PMC of one of these four patients remained stable, and another showed a decrease in PMC size. To date, six more PMC patients underwent surgery after delivery for reasons other than disease progression due to pregnancy and delivery: two opted out of active surveillance, two were identified with a nodal metastasis during active surveillance after delivery, one had Graves' disease, and one showed enlargement of nodules of the contralateral lobe. Conclusions: Pregnancy and delivery was associated with an increase in size of PMCs in only 8% of the 51 pregnancies/delivery cases. None of the patients developed nodal metastasis during pregnancy. Thus, a possible future pregnancy does not prevent such patients from undergoing active surveillance, although watchful observation during pregnancy is recommended.

Follicular thyroid carcinoma (FTC), a form of differentiated thyroid carcinoma, is the second most common malignancy arising from thyroid follicular cells. Recently, the tumor-node-metastasis (TNM) classification for differentiated thyroid carcinoma was revised from the 7

Background We reported that a minority of patients with low-risk papillary microcarcinoma of the thyroid showed disease progression during active surveillance and that older patients had significantly lower disease progression rates than younger patients. Here, we estimated lifetime (≤85 years old) probabilities of disease progression during active surveillance according to the age at presentation based on age decade-specific disease progression rates. Methods From 1993–2013, 1,211 low-risk papillary microcarcinoma patients aged 20–79 years underwent active surveillance at Kuma Hospital. We calculated the disease progression rate at the 10-year point of active surveillance for each age-decade group (20s to 70s) with the Kaplan-Meier method. The lifetime disease progression probability for each age group was calculated as (1 − cumulative probability of progression-free survival calculated with age decade-specific disease progression rates) until the patients reached their 80s (i.e., 85 years on average). Results The age decade-specific disease progression rates at 10 years of active surveillance were 36.9% (20s), 13.5% (30s), 14.5% (40s), 5.6% (50s), 6.6% (60s), and 3.5% (70s); the respective lifetime disease progression probabilities were 60.3%, 37.1%, 27.3%, 14.9%, 9.9% and 3.5% according to the age at presentation. Conclusion The estimated lifetime disease progression probabilities of papillary microcarcinoma during active surveillance vary greatly according to the age at presentation.

Objectives. The Acoustic Voice Quality Index ( AVQI) is a multivariate construct for quantification of overall voice quality based on the analysis of continuous speech and sustained vowel. The stability and validity of the AVQI is well established in several language families. However, the Japanese language has distinct characteristics with respect to several parameters of articulatory and phonatory physiology. The aim of the study was to confirm the criterion-related concurrent validity of AVQI, as well as its responsiveness to change and diagnostic accuracy for voice assessment in the Japanese- speaking population. Study Design. This is a retrospective study. Methods. A total of 336 voice recordings, which included 69 pairs of voice recordings ( before and after therapeutic interventions), were eligible for the study. The auditory- perceptual judgment of overall voice quality was evaluated by five experienced raters. The concurrent validity, responsiveness to change, and diagnostic accuracy of the AVQI were estimated. Results. The concurrent validity and responsiveness to change based on the overall voice quality was indicated by high correlation coefficients 0.828 and 0.767, respectively. Receiver operating characteristic analysis revealed an excellent diagnostic accuracy for discrimination between dysphonic and normophonic voices ( area under the curve: 0.905). The best threshold level for the AVQI of 3.15 corresponded with a sensitivity of 72.5% and specificity of 95.2%, with the positive and negative likelihood ratios of 15.1 and 0.29, respectively. Conclusions. We demonstrated the validity of the AVQI as a tool for assessment of overall voice quality and that of voice therapy outcomes in the Japanese- speaking population.

The primary treatment of nasopharyngeal carcinoma (NPC) has been external radiotherapy. Rupture of an internal carotid artery (ICA) pseudoaneurysm is a rare complication of irradiation therapy for a nasopharyngeal carcinoma. A 78 years old man had a history of NPC treated with radiotherapy in 1993. He was admitted to the hospital because of epistaxis. Angiography showed an ICA pseudoaneurysm pointing medially to the nasopharynx. Coil embolization of the ICA was performed, but cerebral infarction occurred. Internal carotid artery (ICA) pseudoaneurysms are an uncommon but potentially lethal condition. Angiography is the mainstay of diagnosis of the aneurysm and planning the embolization of the ICA. We should be more aware of this complication in NPC patients.

Isshiki's arytenoid adduction combined with thyroplasty type I is a useful procedure for correcting the membranous vocal fold atrophy and the height difference between the two vocal folds, particularly in patients with a large posterior glottal chink and atrophy. Conventional arytenoid adduction (Isshiki's arytenoid adduction) is designed to place a suture through the muscular process of the arytenoid attached anteriorly to the thyroid ala, stimulating the function of the thyroarytenoid muscle and lateral cricoarytenoid muscle. Combining with thyroplasty type I, the suture direction of conventional arytenoid adduction prevented inserting implant material into the pocket of the thyroid cartilage window. In contrast to conventional arytenoid adduction, the suture direction in our approach is anchored anteroinferiorly, mimicking only the action of the lateral cricoarytenoid muscle (the major adductor of the larynx). It is used the thyroid cartilage window in thyroplasty type I to determine the direction of the lateral cricoarytenoid muscle. After approaching the muscular process based on Isshiki's arytenoid adduction, two nylon sutures are tied across the muscular process or the lateral cricoarytenoid muscle nearby the muscular process. The cricoarytenoid joint is not dislocated. One of the sutures was anchored to the inferior rear corner of the thyroid cartilage window to be used with thyroplasty type I and the other was anchored to the rear lower margin of the thyroid lamina. Gore-tex medialization thyroplasty is done after tying the sutures on the thyroid ala. Subjects were 30 unilateral paralytic dysphonia. Maximum phonation of all patients improved significantly after surgery. The preoperative and postoperative mean maximum phonation times were 6.0 and 17.9 seconds. No major complications occurred in this study. Our approach effectively combined arytenoid adduction and thyroplasty type I for patients with severe insufficient glottic closure.

Objective To histologically evaluate the long-term outcomes of autologous fat grafts after injection laryngoplasty in the human larynx. Study design and setting We injected liposuctioned fat for vocal fold augmentation in patients with vocal fold paralysis. We suctioned autologous fat from the low abdomen with an 18-G disposable needle and a 20-mL disposable syringe under negative pressure. This is different from the conventional liposuction technique and avoids the use of special equipment. In this article, we report the histological evaluation of 2 patients (patient 1: 12 months, patient 2: 41 months) who required total laryngectomy after autologous fat injection into the vocal folds. Results Histological examination revealed normal-appearing viable adipocytes with minimal inflammatory response in both patients. Conclusions Our liposuctioned autologous fat injection histologically offered long-term improvement in patients with impaired glottal closure from vocal fold paralysis.

A 65-year-old man complained of severe otalgia, occipital pain, hearing loss and otorrhea was referred to our hospital. Otoscopic examination demonstrated hyperemia and bulging of the left ear drum. The bacteria isolated from otorrhea was a mucoid type of Streptococcus pnemoniae. It was also penicillin-resistant Streptococcus pneumoniae (PRSP). The patient was diagnosed as having mucoid otitis media. Intravenous administration of piperacillin sodium (PIPC) diminished otalgia, occipital pain and otorrhea. However, the patient continued complain of hearing loss and a sensation of ear fullness. Due to acute sensorineural hearing loss, the patient was administered steroids. Nevertheless, bone conduction hearing loss persisted. This is the first report of otitis media demonstrating not only the mucoid type of Streptococcus pnemoniae but also PRSP.

A 10-year-old boy complaining of severe sore throat, left cervical pain, left cervical swelling and high fever was referred to our hospital. Local findings demonstrated swelling of the posterior wall on the left side of the pharynx and swelling of the neck with severe tenderness. The patient had trismus and the distance between upper and lower molar on opening was only ten millimeter. Fiberscopy demonstrated that there was no swelling or edema in the larynx (epiglottis and arytenoids). The patient did not demonstrate dyspnea. Computed tomography (CT) demonstrated a massive soft tissue swelling in the retropharyngeal space. We could easily diagnose his disease as retropharyngeal abscess. It was supposed that transoral intubation into the trachea would be difficult due to trismus. Therefore, we did not schedule surgery on his first examination. Appropriate intravenous administration of antibiotics was performed. Trismus was improved and difficulty in transoral intubation into the trachea was supposed to have decreased. Seven days after the first examination, surgery was successfully performed via transoral incision under general anesthesia. The patient was discharged on the 7th day after surgery without complications such as mediastinitis.We reviewed 50 cases of retropharyngeal abscess including our case reported in Japan since 1990. The incidence of retropharyngeal abscess in infants has decreased due to developments in antibiotic chemotherapy, however the incidence in adults has increased due to complications such as diabetes mellitus. The management of retropharyngeal abscess including surgical treatment was discussed. Although retropharyngeal abscess is rare, understanding of this disease and appropriate treatment are required.

We report a case of giant pleomorphic adenoma of the left parotid gland. The patient was a 72-year-old female who had noticed the mass 20 years ago. At that time she visited a hospital and was recommended for surgical treatment. The tumor was not treated becouse of fear of the surgery. The tumor gradually enlarged. She suddenly noticed pain and visited our hospital. Initial examination revealed a giant tumor in the left parotid gland without facial palsy. The giant tumor was extirpated under general anesthesia. The tumor originated from the deep lobe of the parotid gland. Histopathologically, the tumor was diagnosed as pleomorphic adenoma without evidence of malignancy. The extirpated tumor was 14cm in diameter and weighed 720g. Postoperatively, palsy of the mandibular marginal branch of the facial nerve occurred. The palsy improved within 3 months. There has been no recurrence for 8 months.

痙攣性発声障害 (以下SD) は非常に特徴的な音声症状を呈するにもかかわらず多くの患者は症状の自覚から長い期間を経て診断されることが多い.また現在治療には保存的治療であるボツリヌストキシン注入術をはじめとしてその他さまざまな外科的治療もあり, その選択は患者に委ねられている.今回われわれはSD患者17名 (うちボツリヌストキシン注入術, 音声治療など保存的治療を受けているのは12名, 外科的治療である甲状披裂筋切除術を受けたのは5名) に対し病悩期間や現在行っている治療およびその満足度などについてアンケートを行い, その実態について調査した.結果, 甲状披裂筋切除術を受けた5名の満足度は高かったのに対して, 保存的治療を受けている患者の満足度は半数を下回った.ただ現段階ではおのおのの治療法に一長一短があり, その選択をすることは困難であると思われた.

We treated 4 patients with hypopharyngeal cancer, each of whom had a complete response after 2 cycles of chemotherapy with docetaxel, cisplatin, and 5-FU followed by radiation and/or neck dissection. Twenty-one months to 2 years after this therapy, 3 patients had no recurrence and no metastasis with their laryngeal framework and function preserved. Chemotherapy including docetaxel, cisplatin, and 5-FU is a useful treatment for early head and neck cancer.