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BackgroundFederated learning is a decentralized approach to machine learning; it is a training strategy that overcomes medical data privacy regulations and generalizes deep learning algorithms. Federated learning mitigates many systemic privacy risks by sharing only the model and parameters for training, without the need to export existing medical data sets. In this study, we performed ultrasound image analysis using federated learning to predict whether thyroid nodules were benign or malignant. ObjectiveThe goal of this study was to evaluate whether the performance of federated learning was comparable with that of conventional deep learning. MethodsA total of 8457 (5375 malignant, 3082 benign) ultrasound images were collected from 6 institutions and used for federated learning and conventional deep learning. Five deep learning networks (VGG19, ResNet50, ResNext50, SE-ResNet50, and SE-ResNext50) were used. Using stratified random sampling, we selected 20% (1075 malignant, 616 benign) of the total images for internal validation. For external validation, we used 100 ultrasound images (50 malignant, 50 benign) from another institution. ResultsFor internal validation, the area under the receiver operating characteristic (AUROC) curve for federated learning was between 78.88% and 87.56%, and the AUROC for conventional deep learning was between 82.61% and 91.57%. For external validation, the AUROC for federated learning was between 75.20% and 86.72%, and the AUROC curve for conventional deep learning was between 73.04% and 91.04%. ConclusionsWe demonstrated that the performance of federated learning using decentralized data was comparable to that of conventional deep learning using pooled data. Federated learning might be potentially useful for analyzing medical images while protecting patients’ personal information.

Background: Papillary thyroid carcinoma (PTC) occasionally invades the trachea and requires airway resection. Tracheal excision site recurrence (ESR) is a serious problem. We investigated predictors of ESR in patients with PTC who underwent airway resection for locally curative surgery. Methods: We enrolled 149 patients with PTC who underwent airway resection (median age at the initial surgery: 67 years), including partial‐thickness resection (n = 73) or full‐thickness resection (n = 76), for grossly curative surgery. The median postoperative follow‐up period was 93 months. Results: To date, 11 patients (6.7%) underwent ESR: 6 underwent full‐thickness resection and 5 underwent partial‐thickness resection. The time to ESR ranged from 14 to 113 months (median: 57 months) after the initial surgery. None of the 11 ESR patients underwent adjuvant external beam radiotherapy (EBRT) and none of the 4 airway resection patients who underwent EBRT developed ESR. The 5‐ and 10‐year ESR rates were 4.3% and 11.3%, respectively. In the multivariate analysis (forward–backward stepwise selection method), a Ki‐67 labeling index (LI) ≥5% (p = 0.048) and the thyroglobulin doubling rate (Tg‐DR) >0.33/year (p = 0.009) (for Tg‐antibody negative cases) were independent predictors of ESR. Nine of the 11 patients underwent ESR resection and only one developed a second recurrence. Conclusions: A high Ki‐67 LI was a static predictor, and high Tg‐DR was a dynamic predictor, of ESR in patients with PTC following airway resection. In such patients, careful postoperative monitoring for ESR is necessary and adjuvant therapies, such as EBRT, may be considered. [ABSTRACT FROM AUTHOR]

Familial nonautoimmune hyperthyroidism (NAH) is a rare type of autosomal dominant hyperthyroidism caused by constitutively active pathogenic variants of the thyrotropin receptor (TSHR) gene. Although affected family members present with varied levels of hyperthyroid features, even when the same pathogenic variant is present, total thyroidectomy followed by radioiodine therapy is recommended for long-term management. Herein, we present the case of an 18-year-old proband and her family members with NAH (TSHR-I640V), who presented with diverse thyroid dysfunctions: fluctuations between euthyroid and subclinical hyperthyroidism, mild hyperthyroidism, and overt hyperthyroidism. Almost all affected adult family members, except the proband, showed no progression of hyperthyroidism or thyroid enlargement. A family history of thyrotropin receptor antibodies (TRAb)-negative hyperthyroidism is important for the identification of NAH in adults before TSHR genetic testing can be performed. Ablative therapy is not necessary when familial NAH presents with late-onset mild hyperthyroidism without coexisting diseases. [ABSTRACT FROM AUTHOR]

Objectives: The purposes of this study were to validate the Acoustic Breathiness Index (ABI) for the Japanese-speaking population and to determine whether it is independent of factors such as sex, age, and perceptual ratings of roughness. Method: First, the concurrent validity of the ABI for perceptual breathiness was evaluated on the concatenations of continuous speech and sustained vowels from 288 patients with varying degrees of dysphonia. The diagnostic accuracy was examined on 343 samples with 55 additional normophonic speakers. Second, the validity related to responsiveness-to-change was estimated on 222 samples obtained before and after interventions for 111 voice-disordered patients. Third, the relationships between the ABI and other variables (i.e., perceptual hoarseness/breathiness/roughness, sex, and age) were explored using bivariate and multivariate analyses for the 288 patients. Results: First, the concurrent validity and the responsiveness-to-change validity were confirmed by strong correlation coefficients of 0.890 and 0.878, respectively. Second, the receiver operating characteristic analysis showed the area under the curve to be 0.939, indicating excellent accuracy. The ABI of 3.44 exhibited a sensitivity of 76.3% and a specificity of 94.1%. Third, although bivariate analyses revealed a weak relationship between ABI and roughness and an ABI difference by age, multiple regression analyses showed a strong relation between only ABI and breathiness, without a meaningful contribution from roughness, sex, and age factors. Conclusion: The study confirmed that the ABI is an accurate and specific tool to estimate breathiness levels in the Japanese-speaking population and neither roughness, sex, nor age significantly affects the ABI.

Objectives: Injury to the external branch of the superior laryngeal nerve (EBSLN) causes low‐pitch voice and voice fatigue, particularly in female subjects, and available treatments are limited. Here, we assess a novel surgical procedure to restore a high‐tone voice: ansa cervicalis to EBSLN anastomosis (A‐E anastomosis). Methods: Between November 2012 and April 2022, 13 patients (12 female) underwent unilateral EBSLN resection and A‐E anastomosis, while 20 (16 female) underwent EBSLN resection during thyroid surgery. Patients (4494 women and 1025 men) with normal laryngoscopy scheduled for thyroid surgery served as normal controls. Phonatory function was examined using a Phonation Analyzer PA‐1000 preoperatively and intermittently postoperatively. Results: In patients who underwent A‐E anastomosis, high‐tone voice pitch decreased significantly postoperatively (673.9–471.5 Hz, p = 0.047), with restoration achieved within 5 months. The mean voice pitch in female patients who underwent A‐E anastomosis, EBSLN resection, and controls were 580.4, 522.8, and 682.0 Hz, respectively, indicating a significant decrease in EBSLN resection patients than controls (p = 0.002). The (mean – 1SD) of high‐tone voice pitch in female controls was 497 Hz; exceeding this may indicate recovery to a high‐tone voice. Overall, 73% (8/11) of A‐E anastomosis patients exceeded this value, which was marginally larger than the 43% (6/14) who underwent EBSLN resection. Data on male subjects are limited. There were no cases of adverse functional or cosmetic events. Conclusions: A‐E anastomosis, a novel simple procedure, restored high‐tone voice to some extent without any adverse events and thus warrants further investigation. Level of Evidence: 3 Laryngoscope, 134:3868–3873, 2024 [ABSTRACT FROM AUTHOR]

Background Methods Results Conclusions Papillary thyroid carcinoma (PTC) often extends to adjacent organs. According to the 8th Tumor‐Node‐Metastasis Classification, extension to the strap muscles was graded as T3b. We investigated the prognostic impact of T3b and the appropriateness of T3b in patients aged ≥55 years who were classified as stage II.We enrolled 7811 patients with M0 PTC who underwent initial surgery at the Kuma Hospital (Kobe, Japan) between January 2007 and December 2016. Tumor extension was divided into T3b, T4a1 (extension to the tracheal adventitia, tracheal cartilage, esophageal muscle layer, recurrent laryngeal nerve, cricothyroid, and inferior constrictor muscles), and sT4a2 (extension to the subcutaneous soft tissues, tracheal mucosa, esophageal mucosa, internal jugular vein, brachiocephalic vein, larynx, pharynx, and sternocleidomastoid muscle).In patients ≥55 years, the local recurrence‐free survival (LR‐FS), distant recurrence‐free survival (DR‐FS), and cause‐specific survival (CSS) rates of T3bN0M0 were significantly poorer than those of T1/T2N0M0 but did not significantly differ from those of T3aN0M0. The LR‐FS, DR‐FS, and CSS rates of T3b stage II patients did not differ from those of T4a1 stage III patients but were significantly better than those of T4a2 stage III patients. T3b was an independent predictor of local recurrence and distant recurrence but not of death due to carcinoma in the multivariate analysis. In patients aged <55 years with M0 PTC, T3b had no prognostic value in both analyses.T3bM0 patients are appropriate to be classified as stage II in patients ≥55 years but be kept in stage I in patients <55 years. [ABSTRACT FROM AUTHOR]

Objectives: The acoustic voice quality index (AVQI) is a reliable tool that objectively assesses dysphonia levels using six acoustic parameters. Despite its high criterion‐related concurrent validity, diagnostic accuracy, and minimal detectable change derived from test–retest reliability, the minimal important difference (MID) of the AVQI has not been tested before. This study aimed to estimate the MIDs of AVQI for improvement audibly perceived by clinicians and self‐reported improvement by patients. Methods: A retrospective study was conducted on 110 patients who received treatment for voice disorders. Patients completed AVQI and Voice Handicap Index‐10 (VHI‐10) questionnaires before and after the therapy. The MIDs of the AVQI were estimated using the anchor of either auditory–perceptual judgment of total dysphonia levels by clinicians or the VHI‐10 questionnaire by patients. A distribution‐based approach was also used to complement the results. Results: First, using the auditory–perceptual anchor, a decrease of 0.95 in the AVQI was estimated as the MID for clinicians' perception, as a result of the receiver operating curve. Then, using the patient‐reported anchor, an improvement of 1.36 in the AVQI was estimated as the MID for patients' voice‐related disability. The distribution‐based approach also ensured the anchor‐based results of both the MIDs. Conclusions: The AVQI is a reliable and valid tool for evaluating voice quality, and a 0.95 decrease in the AVQI represents a meaningful improvement for clinicians' perception, whereas a 1.36 decrease in the AVQI influences patients' self‐reported disability. This study contributes to understanding the minimal change necessary for clinicians to make informed decisions and ensure patient satisfaction. Level of Evidence: 3 Laryngoscope, 134:2805–2811, 2024 [ABSTRACT FROM AUTHOR]

Activating rearranged during transfection (RET) proto‐oncogene alterations can be identified using next‐generation sequencing (NGS) of tumor DNA/RNA. We assessed factors associated with NGS (Oncomine Dx Target Test [ODxTT]) success for resected thyroid cancer (TC) specimens, including sample age, processing conditions, and DNA/RNA quality. TC samples were from three Japanese hospitals, with sample age <1–<10 years, fixative 10%/15% neutralized buffered formalin (NBF), and fixation time ≤48 h/>48 h–≤72 h. NGS success rate was defined as the percentage of samples returning validated NGS results (RET fusion‐positive/negative [RNA] or RET mutation‐positive/negative [DNA], detected using ODxTT). DNA/RNA quality was assessed with indexes based on electrophoresis (DNA/RNA integrity number, DV200) and quantitative polymerase chain reaction (DNA/RNA integrity score [ddCq/ΔCq]). NGS success rate (N = 202) was 90%/93% (DNA/RNA) overall, 98%–100% (DNA and RNA) for samples <3 years old, and 91% (DNA and RNA) for samples ≥3–<5 years old fixed in 10% NBF for ≤48 h. Multivariate logistic regression analysis identified ddCq and ΔCq as significant predictors of DNA and RNA NGS success rates, respectively. Quality assessment of nucleic acid extracted from archival tissue samples is important for achieving high NGS success rates in clinical practice, especially for samples ≥3 years old. [ABSTRACT FROM AUTHOR]

This multi‐institutional study investigated non‐invasive follicular thyroid neoplasm with papillary‐like nuclear features (NIFTP) frequency and its diagnostic significance in Japan. We reviewed 4008 thyroid nodules resected in six institutions before NIFTP was proposed. Overall, 26 cases diagnosed as non‐invasive encapsulated follicular variant of papillary thyroid carcinoma (PTC) and 145 cases of follicular thyroid adenoma (FTA) were included. Of these nodules, 80.8% and 31.0%, respectively, were NIFTPs. In five institutions, NIFTPs were more commonly found in FTA than in PTC nodules. When NIFTP was included with PTC, the overall prevalence was 2.3%, with rates in five institutions below 5.0% (0.8%–4.4%). One NIFTP case with nuclear score 3 revealed nodal metastasis 2.5 years post‐resection, and the carcinoma cells were immunohistochemically positive for BRAF. FTAs or NIFTPs with nuclear score 2 did not metastasize. NIFTP was more common among FTA than among PTC nodules, possibly due to underdiagnosis of PTC on nuclear findings. Considering the clinical findings, molecular pathogenesis, and therapeutic strategy in Japan, NIFTP with nuclear score 2 is not different from FTA, and use of this entity terminology is not meaningful. In contrast, NIFTP with nuclear score 3 has potential for metastasis and BRAFV600E mutation. Therefore, in NIFTP cases, nuclear scores 2 and 3 should be separately reported. [ABSTRACT FROM AUTHOR]

Background: During active surveillance (AS), serum thyrotropin (TSH) levels may affect papillary thyroid microcarcinoma (PTMC) progression. We investigated AS outcomes according to whether levothyroxine (LT4) treatment was administered. Patients and Methods: From 2005 to 2019, 2896 patients with low-risk PTMC underwent AS. Of these, 2509 patients were included: 2187 patients did not receive LT4 at diagnosis (group I), 1935 patients did not receive LT4 during AS (group IA), and 252 patients started LT4 during AS (group IB). The remaining 322 patients were administered LT4 before or at diagnosis (group II). The tumor volume doubling rate (TVDR) and tumor size based on ultrasound examination results and time-weighted detailed TSH scores were calculated. Disease progression was defined as tumor enlargement ≥3 mm and/or the appearance of novel lymph node metastasis. Results: At diagnosis, group II had more high-risk features, such as younger age and larger tumors, than group I. However, group II had a lower disease progression rate (2.9% at 10 years) than group I (6.1%) (p = 0.091). The disease progression rate of group IB (13.8% at 10 years) was significantly higher than that of groups IA (5.0%) and II (2.9%) (p < 0.01). The TVDR of group IB before LT4 administration was significantly higher than that of groups IA and II (0.095 per year, −0.0085 per year, and −0.057 per year, respectively; p < 0.01), suggesting that patients with progression signs during AS were selectively prescribed LT4. The time-weighted detailed TSH score of group IB significantly decreased after LT4 administration compared with those before administration (3.35 and 3.05, respectively; p < 0.01). The TVDR also decreased from 0.13 per year to 0.036 per year (p = 0.08). The proportions of patients with rapid or moderate growth decreased significantly after LT4 (from 26.8% to 12.5%, p < 0.01). A multivariable analysis revealed group IB status was independently associated with disease progression (odds ratio [OR] = 3.42 [CI 2.15–5.44], p < 0.01), whereas age ≥40 years and <60 years and age ≥60 years were independently negatively associated with this outcome (OR = 0.23 [CI 0.14–0.38, p < 0.01 and OR = 0.16 [CI 0.10–0.27], p < 0.01). Conclusion: LT4 treatment may be associated with decreased tumor growth during AS of PTMC, but further confirmatory research is needed. [ABSTRACT FROM AUTHOR]