Video-Assisted Thyroidectomy Using a Surgical Energy Device: Initial Experience in a Japanese Single-Center Cohort

<b><i>Objective:</i></b> Video-assisted thyroidectomy (VAT) was approved for coverage under the Japanese public health insurance system in 2016. In our department, we introduced VAT in 2018, and we have since been performing the procedure with the assistance of surgical energy devices. We herein summarize our cases undergoing VAT, including a review of points to consider when introducing the procedure, and characteristics of the surgical energy devices. <b><i>Methods:</i></b> We enrolled 24 patients (14 women and 10 men; age: 24–83 years; mean: 59.0 years) with thyroid/parathyroid tumors who underwent VAT between January 2018 and March 2021 at our department. The medical records of the patients were reviewed, and demographic data, clinical characteristics, histological type, treatment outcomes, and complications were analyzed. <b><i>Results:</i></b> The surgical energy devices used were LigaSure® in the first 4 cases, Acrosurg®. Scissors S17 in the next 13 cases, and Acrosurg®. Revo S15 in the latest 7 cases. The operation time (range: 72–250 min; mean: 147 min), intraoperative blood loss (range: 5–370 mL; mean: 33 mL), indwelling time of wound drain (range: 2–6 days; mean: 3.5 days), and hospitalization period (range: 3–8 days; mean: 5.5 days) were within acceptable ranges. In this study, it is suggested that Acrosurg®. Revo S15 can shorten the indwelling time and the hospitalization period. There were no serious complications, but 1 patient developed transient vocal cord paralysis, which improved 3 months after surgery. It was suggested that the microwave energy devices, Acrosurg®. Scissors S17 and Acrosurg®. Revo S15, may be more effective with respect to sealing/hemostasis/coagulation capacity and controllability than the high-frequency electrosurgical device, LigaSure®. <b><i>Conclusion:</i></b> Based on this initial experience, VAT using surgical energy devices appeared to be a safe, effective, and minimally invasive procedure for the treatment of thyroid/parathyroid tumors. Further studies confirming these early findings are needed.

Parathyroid Tumors: Molecular Signatures

Parathyroid tumors are rare endocrine neoplasms affecting 0.1–0.3% of the general population, including benign parathyroid adenomas (PAs; about 98% of cases), intermediate atypical parathyroid adenomas (aPAs; 1.2–1.3% of cases) and malignant metastatic parathyroid carcinomas (PCs; less than 1% of cases). These tumors are characterized by a variable spectrum of clinical phenotypes and an elevated cellular, histological and molecular heterogeneity that make it difficult to pre-operatively distinguish PAs, aPAs and PCs. Thorough knowledge of genetic, epigenetic, and molecular signatures, which characterize different parathyroid tumor subtypes and drive different tumorigeneses, is a key step to identify potential diagnostic biomarkers able to distinguish among different parathyroid neoplastic types, as well as provide novel therapeutic targets and strategies for these rare neoplasms, which are still a clinical and therapeutic challenge. Here, we review the current knowledge on gene mutations and epigenetic changes that have been associated with the development of different clinical types of parathyroid tumors, both in familial and sporadic forms of these endocrine neoplasms.

The Core Stem Genes SOX2, POU5F1/OCT4, and NANOG Are Expressed in Human Parathyroid Tumors and Modulated by MEN1, YAP1, and β-Catenin Pathways Activation

Tumors of the parathyroid glands are the second most common endocrine neoplasia. Epigenetic studies revealed an embryonic signature involved in parathyroid tumorigenesis. Here, we investigated the expression of the stem core genes SOX2, POU5F1/OCT4, and NANOG. Rare cells within normal parathyroid glands expressed POU5F1/OCT4 and NANOG, while SOX2 was undetectable. Nuclear SOX2 expression was detectable in 18% of parathyroid adenomas (PAds, n = 34) involving 5–30% of cells, while OCT4 and NANOG were expressed at the nuclear level in a more consistent subset of PAds involving 15–40% of cells. Most parathyroid carcinomas expressed the core stem genes. SOX2-expressing cells co-expressed parathormone (PTH). In PAds-derived primary cultures, silencing of the tumor suppressor gene MEN1 induced the expression of SOX2, likely through a MEN1/HAR1B/SOX2 axis, while calcium-sensing receptor activation increased SOX2 mRNA levels through YAP1 activation. In addition, inducing nuclear β-catenin accumulation in PAds-derived primary cultures by short-term incubation with lithium chloride (LiCl), SOX2 and POU5F1/OCT4 expression levels increased, while NANOG transcripts were reduced, and LiCl long-term incubation induced an opposite pattern of gene expression. In conclusion, detection of the core stem genes in parathyroid tumors supports their embryogenic signature, which is modulated by crucial genes involved in parathyroid tumorigenesis.

Genetic Alteration Profiles and Clinicopathological Associations in Atypical Parathyroid Adenoma

Genomic aberrations associated with atypical parathyroid adenoma (AA) are poorly understood. Thus, herein, we sought to expand our current understanding of the molecular basis of atypical parathyroid adenomas. We analyzed 134 samples that had been surgically obtained from parathyroid tumors, including parathyroid carcinomas, atypical parathyroid adenomas, and parathyroid adenomas. The tumors were harvested from formalin-fixed, paraffin-embedded tissues. Fifteen tumor-related genes from recently published genome sequencing data were subjected to targeted sequencing analysis, and an average sequencing depth of 500x was achieved. Sixteen (16/50, 32%) AA tumors harbored at least one of the following genomic alterations: CDC73 (12, 24%), EZH2 (4, 8%), HIC1 (1, 2%), and CDKN2A (1, 2%). Our study identified, for the first time, a relatively high frequency of genomic alterations in patients with AA in a Chinese population. This suggests that AA arises de novo, rather than developing from a parathyroid adenoma. Altogether, these findings will improve our understanding of the malignant potential of parathyroid tumors at the molecular level.

Yes-Associated Protein 1 Is a Novel Calcium Sensing Receptor Target in Human Parathyroid Tumors

The Hippo pathway is involved in human tumorigenesis and tissue repair. Here, we investigated the Hippo coactivator Yes-associated protein 1 (YAP1) and the kinase large tumor suppressor 1/2 (LATS1/2) in tumors of the parathyroid glands, which are almost invariably associated with primary hyperparathyroidism. Compared with normal parathyroid glands, parathyroid adenomas (PAds) and carcinomas show variably but reduced nuclear YAP1 expression. The kinase LATS1/2, which phosphorylates YAP1 thus promoting its degradation, was also variably reduced in PAds. Further, YAP1 silencing reduces the expression of the key parathyroid oncosuppressor multiple endocrine neoplasia type 1(MEN1), while MEN1 silencing increases YAP1 expression. Treatment of patient-derived PAds-primary cell cultures and Human embryonic kidney 293A (HEK293A) cells expressing the calcium-sensing receptor (CASR) with the CASR agonist R568 induces YAP1 nuclear accumulation. This effect was prevented by the incubation of the cells with RhoA/Rho-associated coiled-coil-containing protein kinase (ROCK) inhibitors Y27632 and H1152. Lastly, CASR activation increased the expression of the YAP1 gene targets CYR61, CTGF, and WNT5A, and this effect was blunted by YAP1 silencing. Concluding, here we provide preliminary evidence of the involvement of the Hippo pathway in human tumor parathyroid cells and of the existence of a CASR-ROCK-YAP1 axis. We propose a tumor suppressor role for YAP1 and LATS1/2 in parathyroid tumors.

Ultrasound combined with biochemical parameters can be used to differentiate parathyroid carcinoma from benign tumors in patients with primary hyperparathyroidism

BACKGROUND: Primary hyperparathyroidism (PHPT) results from excessive secretion of parathyroid hormone from parathyroid tumors. Differentiating parathyroid tumors can be challenging before operation. OBJECTIVES: To differentiate parathyroid carcinoma from benign tumors in patients with PHPT by the application of ultrasound and biochemical parameters. METHODS: This study is a retrospective study. The study enrolled 17 patients with parathyroid carcinoma (PC) and 57 patients with parathyroid adenoma (PA), confirmed by postoperative pathology, between September 2010 and July 2017. This study retrospectively compared the ultrasonic features of the tumors included echotexture, maximum lesion diameter, shape, margin, blood flow inside the mass, intralesional calcifications, cysts in the mass, and biochemical parameters included serum calcium, phosphorus, parathyroid hormone (PTH), alkaline phosphatase (ALP) levels, gender distribution and age of patients between patients with PC and those with PA. RESULTS: In the US images, the two groups showed significant differences in heterogeneity, the appearance of a taller-than-wide shape, irregular or lobulated margins, and intralesional calcifications (p < #x003C;< #x200A;0.05). However, no significant difference was found in echogenicity, maximum lesion diameter, blood flow, and cystic components of the mass (p > #x003E;> #x200A;0.05). The mean PTH levels were significantly different between the two groups (p < #x003C;< #x200A;0.05). The PC and PA patients did not differ significantly in terms of mean serum calcium, mean serum phosphorus, and mean ALP levels (p > #x003E;> #x200A;0.05). There were significant differences to distinguish PC from PA in calcifications in mass or/and taller-than-wide shape combine with PTH > #x003E;> #x200A;1000 pg/mL (p < #x003C;< #x200A;0.05). Significant difference existed in the age between the two groups (p < #x003C;< #x200A;0.001). No significant difference existed in the gender distribution between the two groups (p > #x003E;> #x200A;0.05). CONCLUSION: Ultrasound features especially intralesional calcifications and taller-than-wide shape combine with an extremely high serum PTH (>1000 pg/mL) are helpful in differentiating between benign and parathyroid tumors in patients with PHPT.