Prognostic significance of T3b in papillary thyroid carcinoma: Appropriateness of classifying T3bN0M0 in patients aged 55 years or older into stage II.

BACKGROUND: 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. METHODS: 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). RESULTS: 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. CONCLUSIONS: T3bM0 patients are appropriate to be classified as stage II in patients ≥55 years but be kept in stage I in patients <55 years.

Deep learning-based video-analysis of instrument motion in microvascular anastomosis training.

PURPOSE: Attaining sufficient microsurgical skills is paramount for neurosurgical trainees. Kinematic analysis of surgical instruments using video offers the potential for an objective assessment of microsurgical proficiency, thereby enhancing surgical training and patient safety. The purposes of this study were to develop a deep-learning-based automated instrument tip-detection algorithm, and to validate its performance in microvascular anastomosis training. METHODS: An automated instrument tip-tracking algorithm was developed and trained using YOLOv2, based on clinical microsurgical videos and microvascular anastomosis practice videos. With this model, we measured motion economy (procedural time and path distance) and motion smoothness (normalized jerk index) during the task of suturing artificial blood vessels for end-to-side anastomosis. These parameters were validated using traditional criteria-based rating scales and were compared across surgeons with varying microsurgical experience (novice, intermediate, and expert). The suturing task was deconstructed into four distinct phases, and parameters within each phase were compared between novice and expert surgeons. RESULTS: The high accuracy of the developed model was indicated by a mean Dice similarity coefficient of 0.87. Deep learning-based parameters (procedural time, path distance, and normalized jerk index) exhibited correlations with traditional criteria-based rating scales and surgeons' years of experience. Experts completed the suturing task faster than novices. The total path distance for the right (dominant) side instrument movement was shorter for experts compared to novices. However, for the left (non-dominant) side, differences between the two groups were observed only in specific phases. The normalized jerk index for both the right and left sides was significantly lower in the expert than in the novice groups, and receiver operating characteristic analysis showed strong discriminative ability. CONCLUSION: The deep learning-based kinematic analytic approach for surgical instruments proves beneficial in assessing performance in microvascular anastomosis. Moreover, this methodology can be adapted for use in clinical settings.

Crossing a CRISPR/Cas9 transgenic tomato plant with a wild-type plant yields diverse mutations in the F1 progeny.

Generating CRISPR/Cas9-mediated mutants in tomato (Solanum lycopersicum L.) involves screening shoots regenerated from cultured cells transformed with a T-DNA harboring sequences encoding Cas9 and single guide RNAs (sgRNAs). Production of transformants can be inconsistent and obtaining transformants in large numbers may be difficult, resulting in a limited variety of mutations. Here, I report a method for generating various types of mutations from one transgenic plant harboring the CRISPR/Cas9 system. In this method, a wild-type plant was crossed with a T0 biallelic mutant expressing two sgRNAs targeting the RIPENING INHIBITOR (RIN) gene, and the resulting F1 seedlings were classified using a kanamycin resistance marker on the T-DNA. Genotyping of the RIN locus revealed that kanamycin-sensitive F1 seedlings, which carried no T-DNA, always harbored the wild-type allele and a mutant allele from the transgenic parent. Kanamycin-resistant F1 seedlings, which do carry the T-DNA, harbored a variety of novel mutant alleles, but not the wild-type allele, suggesting that it was mutated during crossing. The novel mutations included one-base insertions or short deletions at each target site, or large deletions across the two target sites. This method was also successfully applied to produce mutations in Geranylgeranyl pyrophosphate synthase 2 (GGPS2). Because this method involves crossing rather than transformation, it can be readily scaled up to produce numerous novel mutations, even in plant species or cultivars for which transformation is inefficient. Therefore, when initial transgene experiments fail to induce the desired mutation, this method provides additional opportunities for generating mutants.

Tumor volume-doubling rate is negatively associated with patient age in papillary thyroid microcarcinomas under active surveillance.

BACKGROUND: Active surveillance of low-risk papillary thyroid microcarcinomas has gained popularity worldwide as a management strategy. We previously reported that young age was associated with tumor enlargement by ≥3 mm. Here, we used the tumor volume-doubling rate to study the age-related tumor volume dynamics of papillary thyroid microcarcinomas under active surveillance. METHODS: Between 2005 and 2019, 2,896 patients diagnosed with low-risk papillary thyroid microcarcinomas underwent active surveillance. We excluded patients who underwent ultrasound examination fewer than 4 times, had coexisting Graves' disease, or were treated with levothyroxine at the time of diagnosis, and we enrolled 2,129 patients for this study. We divided them into 3 subsets based on the age at diagnosis: young (<40 years), middle-aged (40-59 years), and elderly (≥60 years). The tumor volume-doubling rate was calculated based on ultrasound-derived tumor sizes and the respective examination date for each patient. RESULTS: Overall, 140 patients (6.6%) had moderate or rapid growth (tumor volume-doubling rate ≥0.3/year), and the incidence significantly decreased with advanced age (P < .01): 11.3%, 7.1%, and 5.0% in the young, middle-aged, and elderly groups, respectively. Tumor regression (tumor volume-doubling rate <0/year) was detected in 1,200 patients (56.4%), and the incidence significantly increased with age (P < .01): 44.6%, 55.3%, and 60.0% in the young, middle-aged, and elderly groups, respectively. On multivariate analysis, both the ≥60 years and 40 to 59 years age groups were independent negative predictors of papillary thyroid microcarcinoma enlargement and positive predictors of tumor regression. CONCLUSION: Tumor volume-doubling rate analysis demonstrated that the incidence of tumor enlargement decreased and that of tumor regression increased with advancing age in patients with papillary thyroid microcarcinomas.

Differences between Acute Embolic and Atherosclerotic Middle Cerebral Artery Occlusion in Multiphase Arterial Spin-labeling Imaging.

Arterial spin-labeling magnetic resonance imaging (ASL-MRI) is widely used for evaluating collateral development in patients with acute ischemic stroke (AIS). This study aimed to characterize the findings of multiphase ASL-MRI between embolic and atherosclerotic large vessel occlusion (LVO) to aid in the differential diagnosis. Among 982 patients with AIS, 44 who were diagnosed with acute, symptomatic, and unilateral occlusion of the horizontal segment of the middle cerebral artery (MCA) were selected and categorized into embolic stroke (ES) and atherosclerosis (AT) groups. Using ASL-MRI (postlabeling delay [PLD] of 1.5, 2.0, and 2.5 s) at admission, the ipsilateral to contralateral ratio (ICR) of the signal intensity and its time-course increasing rate (from PLD 1.5 to 2.0 and 2.5, ΔICR) were measured and compared between the two groups. The mean ICR was significantly higher in the AT group than in the ES group (AT vs. ES: 0.49 vs. 0.27 for ICR1.5, 0.73 vs. 0.32 for ICR2.0, and 0.92 vs. 0.37 for ICR2.5). The ΔICR of PLD 1.5-2.0 (ΔICR2.0) and 2.5 (ΔICR2.5) were also significantly higher in the AT group than in the ES group (AT vs. ES: 50.9% vs. 26.3% for ΔICR2.0, and 92.6% vs. 42.9% for ΔICR2.5). Receiver operating characteristic curves showed moderate-to-strong discriminative abilities of each ASL-MRI parameter in predicting MCA occlusion etiology. In conclusion, multiphase ASL-MRI parameters may aid in differentiating intracranial LVO etiology during the acute phase. Thus, it is applicable to AIS management.

A Prospective Cohort Study Exploring the Effect of Lenvatinib Planned Drug Holidays in Treatment of Differentiated Thyroid Cancer.

Background: Although lenvatinib is the preferred treatment for unresectable radioactive iodine-refractory differentiated thyroid cancer (RR-DTC), this agent exerts considerable toxicities, which can lead to frequent dose interruptions and modifications. The adoption of planned drug holidays has been recently suggested as one means of minimizing or avoiding these severe adverse events. Our retrospective study demonstrated that planned drug holidays appear to be a promising strategy for continuing of lenvatinib. However, the benefits of planned drug holidays in a prospective study have yet to be clarified. Here, we investigated the impact of planned drug holidays on clinical outcomes in patients treated with lenvatinib in the COLLECT study. Methods: In COLLECT, a prospective observational study, patients with RR-DTC were treated with lenvatinib in a real-world clinical setting. Lenvatinib was administered orally at a dose of 24 mg daily. Dose modification for toxicities was permitted. Furthermore, planned drug holidays were allowed to avoid severe or intolerable toxicities. The present post hoc analysis focused on evaluating the impact of planned drug holidays on clinical outcomes, including overall survival (OS), time to treatment failure (TTF), time to failure strategy (TFS), and progression-free survival (PFS), in patients in the COLLECT study who were treated with lenvatinib. Results: In total, 262 patients were included. Of the 253 patients evaluable for efficacy, 73 undertook a planned drug holiday at the discretion of the attending physician. OS, TTF, TFS, and PFS were significantly longer in patients who used a planned drug holiday than in those who did not. The planned drug holiday group demonstrated notable clinical outcomes, with a 1-year OS of 95.8% and a 1-year PFS of 94.5%. Moreover, planned drug holidays demonstrated a clinically meaningful advantage in clinical outcomes. The planned drug holiday group had a significantly longer duration of administration at a dose of ≥10 mg. Conclusions: Planned drug holidays for lenvatinib were associated with significantly improved clinical outcomes compared to daily oral administration. Further investigation of the optimal treatment schedule for lenvatinib is warranted. Clinical Trial Registration: UMIN000022243.

Ansa Cervicalis External Branch Anastomosis to Restore High Tone Voice in Thyroid Surgery.

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.