Rare Columnar Cell Variant of Papillary Thyroid Carcinoma with Cervical Spine Metastasis: A Case Report.

BACKGROUND: Columnar cell carcinoma is a rare subtype of papillary thyroid carcinoma (CCV-PTC) that accounts for only 0.15% to 0.2% of all Papillary Thyroid Carcinomas (PTCs). It has aggressive behavior but a better prognosis than anaplastic thyroid carcinoma. CASE PRESENTATION: A 64-year-old female presented with a huge thyroid mass resulting in compressive myelopathy and was diagnosed as CCV-PTC, not anaplastic carcinoma. After multidisciplinary discussions, we decided to proceed with otolaryngological, thoracic, and orthopaedic surgery. All tumours were unresectable, and we planned to proceed with R2 resection to resolve the gait disturbance and anterior fusion to resolve spinal instability. CONCLUSION: Advanced-stage thyroid cancer is relatively uncommon, but desirable treatment effects can be expected through accurate pathological diagnosis. Immunohistochemical staining and tissue-specific markers can be helpful.

Clinical Manifestations of Allergic Rhinitis by Age and Gender: A 12-Year Single-Center Study.

OBJECTIVES: Currently, epidemiological data on allergic rhinitis collected through the skin prick test are scarce. Moreover, the relationship of age and sex to allergic rhinitis is not comprehensively understood. This study aimed to characterize allergic rhinitis and the associated clinical manifestations by age and sex. METHODS: We retrospectively investigated data from 2883 patients who visited a single university hospital for rhinitis symptoms between January 2003 and December 2014. Of these 2883 patients, 1964 who underwent a skin prick test with 11 standardized allergen extracts and completed a nasal symptom questionnaire were enrolled. The clinical characteristics of allergen sensitization and nasal symptoms were analyzed by sex and age distribution. RESULTS: The prevalence of allergen sensitization progressively decreased with age after peaking at between 20 and 29 years. The sensitization rate was higher in males than in females (P = .046). The sensitization rate to house dust mites decreased with age, while sensitization to mugwort and ragweed increased. Six allergens (Dermatophagoides pteronyssinus, Dermatophagoides farinae, mugwort, trees, ragweed, and cats) were sufficient to identify >96% of patients with allergen sensitization. Nasal obstruction tended to decrease with age and was more prevalent in males (P = .002) than in females, while rhinorrhea (P = .007) and itching (P = .013) were more prevalent in females. Total nasal symptom scores did not differ by sex. CONCLUSIONS: The clinical characteristics of allergic rhinitis, including allergen-sensitization patterns and related symptoms, varied by age and sex. Six common allergens could be sufficient to generate a cost-effective tool to identify allergic rhinitis.

Clinical prognostic significance of cancer stem cell markers in patients with papillary thyroid carcinoma.

The recent development of the cancer stem cell (CSC) model has been heralded as a new era in thyroid cancer research. The aim of this study was to evaluate the presence of CD44+ and CD24- tumor cells in papillary thyroid carcinoma (PTC) as markers of aggressiveness and poor prognosis. Patients with PTC, who underwent successful surgical resections between January 2003 and December 2012 at a single tertiary hospital, were included in this study. Tissue arrays were prepared from 454 primary tumor tissues. Immunohistochemistry (IHC) was performed to detect the CSC markers CD24 and CD44 on the tissue arrays. IHC was graded using a semi-quantitative histology scoring system based on the extent and intensity of staining. Subsequently, the association between IHC results and clinicopathological characteristics and recurrence-free survival (RFS) was analyzed. In 454 patients, 39 cases recurred during the 70-month median follow-up period, with some patients exhibiting multiple sites of relapse. The results of a Kaplan-Meier survival analysis and univariate log-rank test demonstrated that sex (P=0.008), age (P=0.002), cN1b, defined as metastasis to unilateral, bilateral, or contralateral neck lymph nodes or retropharyngeal lymph nodes (P<0.001), pN1, defined as pathologically proven lymph node metastasis >5 (P<0.001), tumor size >2 cm (P<0.001), extrathyroidal extension (P=0.001) and CD24- (P<0.001) were prognostic factors for RFS. CSC marker combinations (CD44+/CD24-) also exhibited statistical significance in the log-rank test. In conclusion, expression of the CSC markers CD44+ and CD24- in PTC tissue samples was associated with RFS. The combination of CD44+ and CD24- exhibited a statistically significant negative association with RFS and a strong association with gross extra-thyroidal extension.

Tinnitus Suppression Effect of Hearing Aids in Patients With High-frequency Hearing Loss: A Randomized Double-blind Controlled Trial.

INTRODUCTION: Hearing aids (HAs) with frequency lowering have been used for high-frequency hearing loss (HFHL), but their effects on tinnitus relief have not been studied extensively. This randomized double-blind trial was performed to investigate and compare tinnitus suppression effects of conventional type HAs and frequency-lowering HAs in patients with HFHL. METHODS: A total of 114 patients were randomized into three groups: conventional HA using wide dynamic range compression, HA with frequency translation, and HA with linear frequency transposition. Participants wore HAs for 3 months and then discontinued their use. The final evaluation was performed at 3 months after cessation of wearing HA (6 mo after the initial visit). The Tinnitus Handicap Inventory (THI) score and additional variables, such as matched tinnitus loudness and visual analog scale scores of subjectively perceived tinnitus loudness, daily awareness, and annoyance, were measured at the initial visit and at 3- and 6-month follow-ups. RESULTS: THI score and most of the additional outcomes were significantly improved at 3 and 6 months (3 mo after HA removal) compared with their initial values in all three groups. The incidence rates of patients with improvements in the THI score by 20% or more were 71.0, 72.7, and 74.3% at 3 months, and 54.8, 51.6, and 59.4% at 6 months for the three groups, respectively. There were no significant differences in primary or additional variables between hearing aid types at either 3 or 6 months. CONCLUSION: This is a consolidated standards of reporting trials-guided study providing direct evidence for tinnitus suppression effects of HA alone, without accompanying counseling or any other treatments, which lasted for at least 3 months after patients stopped using HAs. HAs effectively suppressed tinnitus in patients with HFHL regardless of the amplification strategy type.

Sequential versus Combination Treatment Using Steroids and Diuretics for Acute Low-Frequency Sensorineural Hearing Loss: A Noninferiority Trial.

OBJECTIVE: Acute low-frequency hearing loss (ALHL) is typically treated with combination therapy, including steroids and diuretics. To avoid unnecessary use of steroids we proposed a method of sequential administration using these two drugs, and compared the efficacy of our protocol with that of existing combination treatments. METHODS: A prospective, randomized, open-label, single-blind, noninferiority clinical trial was conducted to investigate whether the effectiveness of sequential treatment is noninferior to that of combination treatment for ALHL. Ninety-two patients with ALHL received either steroids and diuretics simultaneously for 2 weeks (combination group), or diuretics for 2 weeks followed by steroids for another 2 weeks if they did not respond to diuretic treatment (sequential group). The primary outcome measure was a change in mean hearing threshold at three frequencies (125, 250, and 500 Hz) at 4 weeks after treatment. RESULTS: The mean hearing threshold of the low frequencies improved 20.0 and 17.2 dB in the combination and the sequential group, respectively. The 95% lower confidence interval was -8.0 dB and noninferiority was established at p < 0.05. At 4 weeks after treatment, the complete recovery rate was 80.5 and 82.9% in the combination and sequential groups, respectively. CONCLUSION: This is the first study on ALHL treatment following the establishment of Consolidated Standards of Reporting Trials (CONSORT). The sequential treatment is not inferior to combination treatment for ALHL, and therefore may be a better treatment guideline for ALHL considering that patients receive less steroid exposure and smaller restrictions in diuretic use compared with steroids.

Characterization of the biomechanical properties of canine trachea using a customized 3D-printed apparatus.

OBJECTIVES: The canine trachea is considered to be an excellent preclinical model for tracheal research due to its similar mechanical and dimensional characteristics to the human trachea. However, normative biomechanical properties have yet to be defined and it is one of the main reasons tracheal reconstruction has not succeeded in animal models at large scale. Variation and inaccurate measurement due to a lack of proper apparatus for mechanical tests further prevent determination of normative mechanical data of the trachea. The goal of this study was to overcome these shortcomings by designing the measuring apparatus using 3D-printing technology. Using this apparatus, we determined the normative biomechanical properties of the canine trachea. METHODS: Whole tracheas were obtained from thirteen mongrel dogs. Biomechanical measurements were performed to determine the radial compressive strength and tensile strength of the intact trachea, and the elastic modulus of the tracheal cartilage. RESULTS: Structural parameter data indicated the canine trachea to have inner-diameters similar to those of the human trachea and other widely used animal models. The compressive strength was 4.24N while the tensile strength was 29.96N. The elastic modulus of the cartilage portion of the trachea was 1.58N without showing a significant difference in value based on the location of the trachea. CONCLUSIONS: This study delineates a comprehensive and foundational characterization of the biomechanical properties of both the intact and cartilage portion of the canine trachea. The parameters were in agreement with those of the human trachea, confirming the canine trachea to be an excellent preclinical model for tracheal research.

Blood eosinophils may predict radiographic sinus opacification in patients with chronic rhinitis.

BACKGROUND: The association between chronic rhinosinusitis (CRS) and chronic rhinitis remains unclear. The aim of this study was to estimate the predictive factors for sinus opacification in chronic rhinitis patients without obvious CRS. METHODS: We retrospectively studied a total of 332 adult patients with chronic rhinitis who visited our clinic from January 2015 to December 2017. All of the patients underwent endoscopic examination, allergy test, and osteomeatal-unit computed tomography. The subjects were assigned to the normal sinus (NS) group (Lund-Mackay score [LMS] <5) and sinus opacification (SO) group (LMS ≥5). RESULTS: A total of 288 patients were eligible for this study. Of them, 183 (63.5%) were classified in the NS group and 105 (36.5%) in the SO group. Total immunoglobulin E (IgE) level and peripheral blood eosinophil count were significantly higher in the SO than NS group (p = 0.031 and p < 0.0001, respectively). Using Pearson correlation coefficients, we determined that eosinophil count had a positive correlation with the LMS (r = 0.282). In logistic analysis, the interquartile range increase (0.19 × 109 /L) of the eosinophil count was significantly associated with SO (odds ratio [OR] 1.76; 95% confidence interval [CI], 1.30 to 2.39). After adjusting for age, gender, smoking, drinking, and underlying disease, the interquartile range increase of the eosinophil count increased the odds of SO to 1.69-fold; this increase was statistically significant (p = 0.007; 95% CI, 1.17 to 2.43). CONCLUSION: Peripheral blood eosinophil count is an independent predictor of CRS in patients with chronic rhinitis.

Changes in the regional shape and volume of subcortical nuclei in patients with tinnitus comorbid with mild hearing loss.

PURPOSE: Tinnitus, the perception of sound without an external source, is a prevalent disease, but its underlying mechanism has not been fully elucidated. Recent studies have suggested the involvement of subcortical nuclei in tinnitus generation. We investigated changes in the local shape and volume of subcortical nuclei in relation to tinnitus. METHODS: The participants included 53 patients with tinnitus and 52 age- and gender-matched normal controls. Individual 3D T1-weighted structural images were obtained using 3-T magnetic resonance imaging. Surface-based vertex analysis (SVA) was performed with automated segmentation of the bilateral caudate nuclei, putamina, nucleus accumbens, thalami, pallidum, hippocampi, amygdalae, and brainstem. The scalar distances from the mean surface and volumes of 15 nuclei were compared between the tinnitus and control groups and correlated with tinnitus handicap score (THI) and tinnitus duration. RESULTS: SVA revealed regional contractions in the accessory basal and lateral nuclei of the right amygdala and expansions in the left medial and right ventral posterior nuclei and lateral dorsal nucleus of both thalami. The surface distances of the right nucleus accumbens were positively correlated with tinnitus duration, while those of the left nucleus accumbens and left hippocampus were negatively correlated with THI. CONCLUSION: Regional atrophy of the amygdala may indicate self-modulation of emotional response regulation to diminish tinnitus-related emotional distress. Thalamic regional expansion may signify dysfunctional auditory gating in the thalamus, where inhibition of the tinnitus signal at the thalamus level is disrupted due to abnormal changes in the limbic system, ultimately leading to the tinnitus percept.

Self-Administered Tinnitus Pitch Matching versus a Conventional Audiometric Procedure.

OBJECTIVE: Obtaining an accurate tinnitus pitch match is an initial and critical requirement for tinnitus evaluation and treatment, particularly for applying tailor-made notched music training. We investigated whether computer-based self-administered tinnitus pitch matching (CSTPM) is comparable with a conventional audiometric procedure (CAP). METHODS: In total, 82 patients (mean age 45.52 years; 42 females) with tonal tinnitus participated. The CAP was performed by the same audiologist using a 2-alternative forced choice method with a frequency range of 0.25-16 kHz. In the CSTPM, the subjects used personal computer software with a scrolling slider to select the sound closest to their tinnitus pitch. After each matching procedure, an octave challenge test was applied. A multivariate logistic regression was performed to determine factors associated with the difference between the CSTPM and CAP. RESULTS: The subjects' mean hearing threshold was 21.25 ± 17.61 dB HL; the mean tinnitus handicap inventory score was 35.56 ± 24.09. The mean pitches measured with the CSTPM and CAP were 6.29 ± 4.30 and 6.98 ± 5.33 kHz, respectively. In total, 57 (69.5%) subjects matched their tinnitus with less than half an octave difference between the procedures. The results of the 2 methods correlated significantly with each other (Pearson r = 0.793, p < 0.001). Octave confusion was a significant factor affecting the difference between the procedures (odds ratio 8.92, p < 0.05). CONCLUSIONS: The CSTPM appears to be as accurate as the standard audiological procedure, and may be used instead of the CAP when octave confusion is minimized.

Prevention of anterior glottis web with hyaluronic acid derivatives in rabbit model.

OBJECTIVES/HYPOTHESIS: Validating an antiadhesive strategy to prevent anterior glottic web (AGW) development. STUDY DESIGN: Prospective animal study in rabbits. METHODS: Fifteen New Zealand white rabbits were randomly divided into three equal groups (five rabbits each), applying either HyFence (HF: 0.1 g/vocal fold), an antiadhesive test agent; mitomycin-C (MMC: 1 mg/ml, 4 min) as reference therapy; or saline (control group) to AGWs induced by laryngofissure technique (previously reported by us). At week 8, the extent of AGW was measured to assess preventive effects of HF and MMC, and laryngeal specimens were sampled for high-speed recording and histologic analysis. RESULTS: AGW induction was successful in all five (100%) control rabbits, each demonstrating fibroconnective tissue and collagen fibers at anterior commissure, with AGW ratio averaging 0.57 ± 0.052. An AGW was seen in 100% of the rabbits survived in the MMC group (n = 2) with the 60% (n = 3) of the MMC rabbits expired due to postprocedure infections. The average AGW ratio was 0.28 ± 0.070 in the MMC group. AGW formation rate was 50% in HF group with one rabbit expired from infection. Mean AGW ratio was lowest in the HF group (0.23 ± 0.10; P = 0.013). Microscopically, AGW induction sites in HF-treated rabbits displayed significantly fewer collagen fibers (P = 0.009) by comparison. CONCLUSION: This is the first reported use of a cross-linked hyaluronic acid gel that may prevent AGW formation. LEVEL OF EVIDENCE: N/A. Laryngoscope, 126:2320-2324, 2016.

Clinical Implications of Septal Deviation in Lateralized Olfaction.

OBJECTIVES: Results of butanol threshold tests (BTTs) have shown that birhinal olfaction tends to converge toward monorhinal olfaction of the dominant nostril. However, birhinal olfaction may also be worse than dominant-side monorhinal olfaction. The goal of our study was to investigate the effect of deviated nasal septum on birhinal olfaction in patients with lateralized olfaction and to examine the effect of septoplasty in these patients. METHODS: A retrospective study with planned data collection was conducted in 518 patients who underwent BTTs. Lateralized olfaction was defined as monorhinal BTT scores that differed by >2 between sides. Underestimated birhinal olfaction was defined as a birhinal BTT score >2 lower than the dominant nostril monorhinal BTT score. Patients with lateralized olfaction were divided into 2 groups: group 1, underestimated birhinal olfaction; and group 2, without underestimated birhinal olfaction. RESULTS: Among 518 patients, 112 with lateralized olfaction were enrolled in this study. Group 1 included 23 patients (20.5%) and group 2 included 89 patients (79.5%). The severity of septal deviation (ratio of the distance of narrower side to wider side) did not differ between the 2 groups. Septal deviation to the dominant nostril was more common in group 1 than group 2 (73.9% vs. 37.6%; P=0.002). Five patients with septal deviation to the dominant nostril with underestimated birhinal olfaction underwent septoplasty. Improved lateralized olfaction occurred in all 5 patients postoperatively (P=0.041). CONCLUSION: Septal deviation of the dominant nostril in patients with lateralized olfaction is associated with underestimated birhinal olfaction. Septoplasty may improve olfaction by increasing airflow in the dominant olfactory side.

Modified Sistrunk operation: New concept for management of thyroglossal duct cyst.

OBJECTIVE: To describe a method of hyoid cartilage division during Sistrunk operation for management of thyroglossal duct cyst (TGDC) and compare postoperative outcomes with those of conventional hyoid bone cutting. METHODS: Fifty-nine patients who received operative treatment for TGDC from January 2005 to July 2013 were enrolled. The degree of fusion in the cartilaginous portion of the hyoid was evaluated by preoperative neck computed tomography and classified into (1) non-fusion, (2) partial fusion, and (3) complete fusion. Techniques of hyoid management, division of the cartilaginous portion of the hyoid or conventional hyoid bone cutting, during Sistrunk operation were analyzed according to the fusion classification. RESULTS: Of the 59 patients, 27 were pediatric patients and 32 were adults. In 32 adults undergoing TGDC, there were 13 cases (41%) of complete hyoid fusion and 7 (22%) of non-fusion. A total of 20 adult patients (63%) were treated with the cartilage division. Among the pediatric patients, 96% of cases were classified as non-fusion of the hyoid, and all of these were treated with the cartilage division. Patients who were treated with the cartilage division showed better postoperative results. However, there were no statistical differences. CONCLUSIONS: Our cartilage division technique at Sistrunk operation for TGDC is feasible and comparable to conventional hyoid cutting with regard to postoperative results.

Novel experimental rabbit model of anterior glottic web formation.

CONCLUSION: The rabbit model of anterior glottic web (AGW) formation using the laryngofissure technique resulted in reproducible and stable AGW formation that may facilitate research into this area. OBJECTIVE: To introduce and validate a novel experimental animal model of AGW formation using the rabbit. METHODS: The inner larynges of eight New Zealand white rabbits were exposed through the laryngofissure technique. The mucosa of the bilateral true vocal fold was stripped off using the bevel of a needle tip. On the basis of the laryngoscopic findings at 8 weeks postoperatively, the extent of AGW was measured, and the success of this procedure was validated. Laryngeal specimens were sampled at 8 weeks for high-speed recording and histological analysis. RESULTS: In seven (87.5%) rabbits, laryngoscopic examination revealed the formation of a scar band involving the anterior commissure. The mean extent of AGW ratio on the left and right sides was 0.58 ± 0.073 and 0.55 ± 0.075, respectively. The symmetric formation of AGW (p = 0.655, p = 0.128) and stability of the AGW procedure (p = 0.491, left; p = 0.501, right) were statistically validated. On high-speed recording, the vocal mucosal wave was hindered by AGW formation. Histologically, fibro-connective tissue, especially collagen fiber, was observed in the anterior commissure.

Diagnostic role of core needle biopsy in cervical lymphadenopathy.

BACKGROUND: The purpose of this study was to evaluate the value of core needle biopsy (CNB) compared to fine-needle aspiration cytology (FNAC) in cervical lymphadenopathy. METHODS: This consecutive case series enrolled 208 patients with cervical lymphadenopathy. Sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV) were evaluated and the necessity of an additional open biopsy was compared. RESULTS: The sensitivity and NPV for critical disease (lymphoma, carcinoma, and tuberculosis) were significantly higher with CNB (p = .006, p = .001, respectively) than with FNAC. In the analysis based on specific disease, the sensitivity of CNB was statistically significantly higher (p = .009) for the diagnosis of lymphoma. The rate of open biopsy for confirmative diagnosis was significantly lower with CNB (p = .014). CONCLUSION: CNB is beneficial for initial examination in cervical lymphadenopathy and showed higher sensitivity and NPV than FNAC. It is especially useful for screening for lymphoma.

De novo large genomic deletions involving POU3F4 in incomplete partition type III inner ear anomaly in East Asian populations and implications for genetic counseling.

OBJECTIVE: The aim of this study was to understand the prevalence and molecular genetic etiology of incomplete partition type III (IP type III) anomaly in Koreans. We also attempted to verify the prevalence of genomic deletions in the DFNX2 locus and to look for association between inheritance patterns and mutation type in East Asian IP type III subjects. STUDY DESIGN: Retrospective case review. SETTING: Tertiary referral center. PATIENTS: Subjects with IP type III anomaly and their biological mothers. INTERVENTIONS: Sanger sequencing, array-comparative genomic hybridization (aCGH), and PCR were performed. We also analyzed the type and inheritance of the causative genetic abnormality in East Asian DFNX2 patients. MAIN OUTCOME MEASURE: Mutation type and occurrence. RESULTS: We identified IP type III in 10 (4.8%) of 206 patients with an inner ear abnormality. We confirmed an etiologic homogeneity, DFNX2, of the IP type III in this Korean population. Two (20%) of the 10 DFNX2 carried a large genomic deletion affecting POU3F4, as proved by aCGH. PCR confirmed that the 2 deletions occurred de novo. Genetic alteration occurred de novo in 29.4% (5/17) of all reported Korean IP type III cases. From this study and literature review, we observed a striking difference of de novo occurrence rate (75% versus 12.5%, p = 0.032) between large genomic deletions and point mutations in East Asian population. CONCLUSIONS: Our data suggest that different POU3F4 mutations might show different recurrence rate in siblings of the IP type III families, especially in East Asian population. Genetic counseling should be provided accordingly.

Detection and identification of Mycobacterium tuberculosis in joint biopsy specimens by rpoB PCR cloning and sequencing.

Osteoarticular tuberculosis (OAT) is an extrapulmonary tuberculosis and accounts for 1 to 3% of all tuberculosis cases. We used an rpoB PCR-plasmid TA cloning-sequencing method to detect and identify tubercle bacilli in surgical specimens from patients suspected of having OAT. By comparing the similarities of the rpoB sequences determined with those in GenBank, Mycobacterium tuberculosis was detected in 23 of 43 samples. Three of the 23 positive samples had mutations at codon 531, which are commonly observed in rifampin-resistant M. tuberculosis strains. Our results suggest that the rpoB PCR-TA cloning-sequencing method developed, which detects M. tuberculosis and which simultaneously determines its rifampin susceptibility, can also be used efficiently for the diagnosis of OAT.