Utility and optimal management of planned drug holidays during lenvatinib treatment in patients with unresectable differentiated thyroid cancer: a real-world multi-center study.

PURPOSE: Lenvatinib achieves favorable therapeutic outcomes for patients with radioactive iodine therapy refractory differentiated thyroid cancer (DTC); however, its use is associated with a high incidence of adverse events. To avoid severe adverse events, planned drug holidays (PDH) have been proposed. This study aimed to evaluate treatment effects, identify prognostic factors, and investigate the usefulness of PDH in patients with unresectable DTC who received lenvatinib across the multi-institutions. METHODS: Fifty-one patients with unresectable DTC treated with lenvatinib were evaluated retrospectively. Overall survival (OS) and progression-free survival (PFS) were calculated, and prognostic factors were assessed. OS, PFS, and time to treatment failure (TTF) were compared between patients with and without PDH. Lenvatinib administration schedule was evaluated in PDH. RESULTS: The 3-year OS and PFS rate were 53.5% and 42.1%, respectively. Multivariate analysis revealed that presence of maximum size of lung metastasis ≥10 mm was independent prognostic factor for poorer OS and PFS, and histology other than papillary thyroid carcinoma was the independent prognostic factor for poorer PFS. Twenty-five patients (49%) treated with PDH. There were significant differences in OS, PFS, and TTF between patients with and without PDH. Various schedules were used in PDH. Eight (32%) patients required switch to the different administration schedule. CONCLUSION: Our results suggest that PDHs may extend OS, PFS, and TTF. In patients with PDH, various schedules used for lenvatinib administration highlight the difficulty in determining a uniform administration schedule. Therefore, it is crucial to consider the optimal lenvatinib administration schedule on a case-by-case basis.

Molecular basis of carotid body tumor and associated clinical features in Japan identified by genomic, immunohistochemical, and clinical analyses.

Carotid body tumor (CBT) is classified as a paraganglioma (PGL). Here, we report the genetic background, protein expression pattern, and clinical findings of 30 Japanese CBT cases. Germline pathogenic or likely pathogenic (P/LP) variants of genes encoding succinate dehydrogenase subunits (SDHs) were detected in 15 of 30 cases (50%). The SDHB variants were the most frequently detected, followed by SDHA and SDHD variants. One case with SDHAF2 variant was bilateral CBT, and other two multiple PGL cases were not detected P/LP variants. The three cases with germline variants that could be tested did not have somatic P/LP variants of the same genes. Immunohistochemical analysis showed negative SDHB signals in CBT tissues in five cases with germline P/LP variants of SDHB, SDHD, or SDHA. In addition, SDHB signals in CBT tissues were negative in four of nine cases without germline P/LP variants of SDHs. These findings suggest the involvement of unidentified molecular mechanisms affecting SDHs.

Tone Enhancement Electro-Fiberscope Combined with Strobe Light Source and Re-analysis Past Images-Tone Enhancement Dynamic Stroboscope.

Tone enhancement electro fiberscope combined with strobe light source is benefit for dynamic observation of vocal fold vibration, mucosal waves and voice, it also may be effective for early detection of cases of glottal cancer rather than ordinate stroboscopic examination or simple NBI observation. Laryngoscope, 132:2206-2208, 2022.

Carotid body tumor with neck metastasis due to germline SDHB variant: a case report and literature review.

Carotid body tumor involving the succinate dehydrogenase subunit B (SDHB) variant reportedly had a higher frequency of metastasis than other variants of succinate dehydrogenase. However, the correlation between genotype and phenotype among patients with carotid body tumor with SDHB gene variant remains unclear. Thus, we present a case of carotid body tumor with neck lymph metastasis caused by a novel SDHB variant, which resulted in long-term disease-free survival achieved after surgery. A 43-year-old man presented to our hospital with a 2-year history of a painless neck mass. Based on the radiographic findings, the patient was diagnosed with carotid body tumor with a possible Shamblin type III tumor. Another mass was detected and suspected to be a lymph node metastasis. The patient underwent resection of the tumor and lymph nodes. The common carotid artery, internal carotid artery, external carotid artery, internal jugular vein, vagal nerve, and hypoglossal nerve were resected with the tumor. Histopathological examination revealed a paraganglioma. The histological findings of the lymph nodes were similar to those of the carotid body tumor and were confirmed to be metastases of paraganglioma. To analyze the germline SDHx variant, a nonsense variant was detected in the SDHB gene at exon 2, c. 136C > T, p. Arg46*. During the follow-up 80 months after surgery, the patient exhibited no signs of recurrence, metastasis, or development of paragangliomas in other organs. This was the first case of carotid body tumor accompanied by neck metastasis caused by a germline nonsense SDHB variant at exon 2, c. 136C > T, p. Arg46*. Carotid body tumor with neck lymph metastasis caused by this nonsense variant could achieve long-term disease-free survival after surgery. Gene analysis, including SDHB variant, should be performed to predict the prognosis and future risk of metastasis. Genetic testing of SDHB may give a crucial information for the treatment and follow-up strategies of carotid body tumor. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1007/s13691-021-00522-x.

Pretherapeutic Predictive Factors for Histological High-Grade Parotid Gland Carcinoma.

OBJECTIVE: The histological grade of parotid gland carcinoma (PGC) is an important prognostic factor; however, the diagnosis prior to treatment has been challenging to make. This study aimed to investigate whether the pretreatment clinical findings, including hematological inflammatory, nutritional, and immune markers, could predict the histological grade of PGC. STUDY DESIGN: Retrospective study. METHODS: We retrospectively enrolled 111 patients with PGC and evaluated the correlation between histological grade and pretreatment clinical findings such as age, sex, tumor staging, facial nerve paralysis, pain or tenderness, adhesion to the surrounding tissues or tumor immobility, and hematological markers. RESULTS: Sixty patients (54%) were diagnosed with histological high-grade PGC. Univariate analysis revealed that age, T classification, N classification, TNM stage, facial nerve paralysis, adhesion/immobility, C-reactive protein (CRP), and CRP-to-albumin ratio (CAR) were significant predictors of PGC histological grade. On multivariate analysis, high T classification (T3, 4), high N classification (≥1), and elevated CRP (≥0.22 mg/dL) were independent predictors of high-grade PGC. CONCLUSIONS: Pretreatment T classification, N classification, and CRP are significant predictors of the histological grading of PGC. Our results are useful for treatment planning and obtaining appropriate informed consent from the patients before treatment. LEVEL OF EVIDENCE: 4 Laryngoscope, 132:96-102, 2022.

Vocal Hygiene Education Program Reduces Surgical Interventions for Benign Vocal Fold Lesions: A Randomized Controlled Trial.

OBJECTIVES/HYPOTHESIS: Vocal fold polyps and nodules are common benign laryngeal lesions. Currently, the Japanese health insurance system covers surgical interventions. However, the establishment of more cost-effective conservative methods is required, because healthcare costs are viewed as a major concern, and the government and taxpayers are demanding more economical, effective treatments. In this situation, more suitable vocal hygiene education may be important for the success of cost-effective conservative treatment. In this study, we developed a novel reinforced vocal hygiene education program and compared the results of this program with those of previous methods of teaching vocal hygiene. STUDY DESIGN: Multicenter randomized controlled trial. METHODS: Patients who visited a National Hospital Organization (NHO) hospital for the surgical indication of hoarseness were included in the study. Before undergoing surgery, 200 patients with benign vocal fold lesions (vocal fold polyps/nodules) were enrolled and randomly allocated to the NHO-style vocal hygiene educational program (intervention group) or control education program (control group). Two months after enrollment, the patients in both groups underwent laryngeal fiberscopic examinations to determine whether the benign lesions had resolved or whether surgery was indicated for the vocal fold polyps/nodules. RESULTS: After 2 months, in the intervention group, the proportion of lesion resolution (61.3%) was significantly greater than that in the control group (26.3%) (P < .001, Fisher exact test). CONCLUSIONS: Our results clearly indicate that the quality and features of the education program could affect the outcome of the intervention. We found that a reinforced vocal hygiene education program increased the rate of the resolution of benign vocal fold polyps and nodules in a multicenter randomized clinical trial. LEVEL OF EVIDENCE: 1b Laryngoscope, 2593-2599, 2018.

A Case of Undiagnosed Sleep Disorder with Hearing Difficulty and Dizziness.

INTRODUCTION: The aim of this case report was to investigate the relationship between sleep disorders and audio vestibular symptoms. CASE REPORT: A case of undiagnosed sleep disorder, presenting as a temporary auditory processing difficulty, is presented. The disorder was initially treated as sudden deafness with dizziness. A 23-year-old male patient complained of acute hearing disturbance despite normal results on pure tone audiometry. The patient was initially administered a steroid injection in the hospital. After treatment, his hearing symptoms improved only slightly and he reported balance difficulty with rightward spontaneous nystagmus. Vestibular rehabilitation was performed. We also suspected that his hearing symptom was due to an auditory processing difficulty. Despite steroid treatment and vestibular rehabilitation, neither of his symptoms improved. We subsequently identified the presence of insomnia. He was prescribed zolpidem 5 mg, which slightly improved his symptoms, and referred to a sleep specialist for further examination. Polysomnography was performed, which identified restless leg syndrome and sleep disturbance with delayed sleep phase syndrome. After pharmacological treatment, his sleep disturbance, hearing difficulty, and balance disorder completely resolved. CONCLUSION: Sleep disorders may provoke reversible auditory processing difficulties. We should carefully evaluate patients for a potentially undiagnosed sleep disorder, even in patients chiefly complaining of intractable sensory dysfunction such as hearing or balance disturbance.