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Chyle leakage (CL) due to lymphatic injuries is one of the rare complications that can develop after thyroidectomy. There are few studies on lymphatic embolization performed in case of CL after thyroid surgery. We report two cases of CL after thyroid surgery that were effectively treated by thoracic duct embolization. The patients had previously undergone total thyroidectomy with central compartment neck dissection with or without modified radical neck dissection. The amount of drainage from the operative site was ＞1000 mL per day in one patient and ＞500 mL per day in the other. In both cases, CL stopped after the thoracic duct embolization. Thoracic duct embolization seems to be an effective and important treatment option for CL after thyroid surgery.

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Whether chronic lymphocytic thyroiditis (CLT) influences the risk of development and the progression of papillary thyroid cancer (PTC) remains uncertain. We investigated the effects of CLT on the clinicopathologic features and prognosis of PTC. Two thousand nine hundred twenty-eight consecutive patients with PTC treated between 2009 and 2017 were divided into two groups: one with chronic lymphocytic thyroiditis and one without; 1174 (40%) of the patients had coincident CLT. In univariate analysis, CLT correlated positively with small tumor size, frequent extrathyroidal extension, multifocal diseases, and p53 but negatively with central lymph node (LN) metastasis and BRAF mutation. In multivariate analysis, CLT was associated with extrathyroidal extension and multifocal disease; however, it was not a prognostic factor for recurrence even though it was associated with two aggressive factors. Compared with patients with PTC alone, there were more retrieved central LNs in the PTC + CLT group, and these patients also underwent more invasive diagnostic tests such as fine needle aspiration cytology and frozen biopsy of LN. The CLT patients with PTC had better behavior features and prognoses than did those with PTC alone despite frequent multifocality and extrathyroidal extension. However, precaution may be necessary to avoid performing invasive diagnostic procedures for lateral LN metastasis and to manage the patients appropriately.

Purpose We investigated the risk factors of indeterminate response (IDR) in patients who underwent recombinant human thyroid-stimulating hormone (rhTSH)-aided radioactive iodine therapy (RAIT). Methods A total of 128 patients with papillary thyroid cancer were included in this retrospective study. The patients were classified into excellent response and IDR groups based on follow-up diagnostic whole-body scintigraphy (WBS) and TSH-stimulated thyroglobulin (Tg). Indeterminate response was defined as the presence of a faint uptake in the thyroid bed on the diagnostic WBS or a TSH-stimulated Tg detectable, but less than 10 ng/mL. Parameters that act as significant risk factors for IDR, including age, sex, stage, surgeon, time interval between surgery and RAIT, post-treatment WBS finding, urine iodine-to-creatinine ratio, TSH-unstimulated Tg, and rhTSH-stimulated Tg, were analyzed using a Cox proportional hazards regression method. Results After treatment, 64 patients showed IDR. Recombinant human TSH-stimulated Tg was the only independent risk factor for predicting IDR. Patients with an rhTSH-stimulated Tg greater than 2 ng/mL prior to RAIT were 3.75 times more likely (95% confidence interval, 1.61-8.72) to have an IDR than those with a lower rhTSH-stimulated Tg (≤2 ng/mL). Conclusions Pre-RAIT TSH-stimulated Tg levels are a risk factor for IDR after RAIT.

Background/objective The diagnostic accuracy of fine needle aspiration biopsy (FNAB) seems limited in large thyroid nodules with Bethesda Cat. 2 result. We aimed to determine the incidence of carcinoma with benign cytology and the reason for the high false-positive rate in thyroid nodules ≥4 cm. Methods The records of 103 patients with thyroid nodules ≥4 cm with preoperative cytological diagnosis of Bethesda Cat. 2 who underwent thyroidectomy were consecutively reviewed. Characteristics between patients with malignant vs. benign pathology were compared. Results Forty patients (38.8%) had malignancy. Malignancy was subclassified into follicular variant of papillary thyroid carcinoma (43%), minimally invasive follicular thyroid carcinoma (20.0%), and minimally invasive Hurthle cell thyroid carcinoma (10.9%). Patients with malignant cytology had significantly more suspicious ultrasound findings than those with benign cytology (p = 0.001). Conclusions Preoperative FNAB showed high false-negative rates in patients with thyroid nodules ≥4 cm with benign cytology. These nodules have a high malignancy rate with suspicious ultrasound findings.

The incidence rates of structural persistent disease (PD) and recurrent disease (RD) after thyroidectomy, and their clinicoradiological (CT) characteristics, remain poorly understood. Therefore, we characterized differentiated thyroid cancer (DTC) patients who underwent re-operations, with a focus on preoperative CT scans. We examined neck CT scans obtained prior to initial surgery and reoperation, and classified the disease into four categories according to the persistence/recurrence and neck dissection/non-dissection status. In total, 121 of 9,173 DTC patients underwent reoperations to treat PD or RD; the mean time to reoperation was 25.5 and 54.1 months, respectively. Of all reoperations, 19% (23/121) were performed to treat RD; 81% (98/121) were performed to treat PD. Compared to RD, PD was commonly detected in the non-dissected neck. Tumor multiplicity and the number of pathologically positive lymph nodes were greater in the non-dissected than dissected neck. A review of the CT data revealed more false-negative findings on the 60-s- versus 30–40-s-delay scans of PD patients with non-dissected necks. In conclusion, most of the reoperations performed on DTC patients were for management of PD. Improved preoperative CT assessments and initial surgery, based on the information of clinico-radiological characteristics, are required in the care of DTC patients.

An intermediate cervical plexus block (CPB) targets the posterior cervical space between the sternocleidomastoid muscle and the prevertebral fascia. The phrenic nerve descends obliquely on the surface of the anterior scalene muscle beneath the prevertebral fascia after originating from the C3–C5 ventral rami. Therefore, the phrenic nerve can be affected by a local anesthetic during an intermediate CPB, depending on the permeability characteristics of the prevertebral fascia. This study investigated whether an intermediate CPB affects the phrenic nerve, inducing hemidiaphragmatic paresis. In this prospective observational study, 20 patients undergoing single-incision transaxillary robot-assisted right thyroidectomy were enrolled. The intermediate CPB (0.25% ropivacaine 0.2 ml/kg) was performed at the C4–5 intervertebral level carefully, without penetrating the prevertebral fascia, before the patient emerged from general anesthesia. Diaphragmatic motions of the block side were measured by M-mode ultrasonography at three time points: before anesthesia (baseline) and at 30 and 60 min after the intermediate CPB. Hemidiaphragmatic paresis was divided into three grades, depending on the percentage of diaphragm movement compared to the baseline: none (> 75%), partial paresis (25–75%), and complete paresis (

This study investigated the correlation between basal thyroglobulin (Tg) and recombinant human thyroid-stimulating hormone (rhTSH)-stimulated Tg in differentiated patients with thyroid cancer, and sought to determine whether the basal Tg level predicts the rhTSH-stimulated Tg level. We retrospectively enrolled 177 patients with papillary thyroid cancer (mean age = 44 years; 50 males, 127 females) who received rhTSH before radioiodine therapy (RIT). Serum Tg levels were measured 7 days before the 1st rhTSH injection (basal Tg) and on the days of RIT (rhTSH-stimulated Tg). Patients were divided into 3 groups according to rhTSH-stimulated Tg cut-off levels of 2, 5, and 10 ng/mL. The correlation between basal Tg and rhTSH-stimulated Tg levels was assessed, and whether basal Tg was useful in predicting the rhTSH-stimulated Tg level was determined. A significant positive correlation was observed between basal and rhTSH-stimulated Tg levels (|rho| = 0.48, P 0.3 or 0.5 ng/mL, then the rhTSH-stimulated Tg level can be expected to be sufficiently high to necessitate clinical examination.

Calcification is important for the diagnosis of papillary thyroid carcinoma (PTC). Runt-related transcription factor 2 (RUNX2), a master transcription factor associated with osteogenic differentiation, is reportedly related to PTC calcification and invasiveness. However, its regulatory role in this process is somewhat uncharacterized. Here, we attempted to identify genes that regulate RUNX2 and clarify its function in PTC carcinogenesis and calcification. The expression of RUNX2-upstream genes was evaluated by real-time PCR in Nthy-Ori 3-1 normal thyroid cells and TPC1 and BHP10-3 PTC cell lines. Luciferase and chromatin immunoprecipitation assays were performed with candidate genes after cloning the RUNX2 promoter. We found that RUNX2 promoter activity was enhanced by homeobox family A9 (HOXA9). Over-expression of HOXA9 was found to enhance alkaline phosphatase activity, mineralization, and in vitro tumour cell migration and invasion, whereas downregulation had the opposite effects. These results indicate that HOXA9, a positive regulator of RUNX2, can enhance calcification, migration, and invasion in PTC. Our data improve the understanding of the molecular mechanisms of microcalcification in PTC as well as tumorigenesis.

Background: Abnormal wound healing after thyroidectomy and a consequent scar is a common dermatologic consultation.Prevention of the possible hypertrophic scars and keloids is known to be challenging. Objectives: The objective of our study was to validate and confirm the efficacy and safety of low-level light therapy (LLLT) for the prevention of thyroidectomy scars on the neck. Methods: Fourty-one South Korean patients with linear surgical suture after thyroidectomy operation were treated with an 830/590nm light-emitting diode (Healite®). Each patient was treated daily of 60J/cm2(11 minutes) for a week starting on post-operation day one and treated 3 times per week for 3 more weeks. The control group consisted of 15 patients without any therapy except application of absorbent foam dressing. The scar prevention effects were evaluated at 1 month and 3 months after surgery.Colorimetric evaluation using a tristimulus color analyzer was done. The Vancouver Scar Scale (VSS), Global Assessment Score (GAS) and a subjective score ranging 1 to 4 was also measured. Results: The L* value and a* value decreased significantly on the 3 month follow up visit in the the treated groupcompared to the control group. Also, the average VSS and GAS was lower in the treated group. However, subjective measure did not show significant difference. Conclusion: LLLT using a 830/590nm light emitting diode may efficiently suppress the formation of thyroidectomy scars, and can be safely without noticeable side effects.

BACKGROUND Using a large set of genomic data from The Cancer Genome Atlas (TCGA), we classified BRAFwild papillary thyroid carcinomas (PTCs) into 2 subtypes with distinct molecular patterns and different clinical behaviors. We also suggested gene signatures (RAS-score) to predict molecular subtypes and clinical behaviors of BRAFwild PTC. METHOD Integrated genomic analysis was done using all genomic data of PTC in TCGA data portal (https://tcga-data.nci.nih.gov) and cancer browser (https://genome-cancer.ucsc.edu). Using Gene Ontology and a logistic regression test, we selected gene signatures (RAS-score) and applied this prediction model to the validation cohort (GSE60542). RESULT When we performed multiplatform genomic analysis, BRAFwild PTCs were divided into 2 molecular subtypes. Each subtype showed distinct molecular patterns and clinical behaviors. Gene signatures successfully predicted molecular subtype in another validation cohort. CONCLUSION We found that BRAFwild PTCs were divided into 2 molecular subtypes and each subtype showed distinct molecular patterns, different activated pathways, and different clinical behaviors.

Background and Objectives Single-incision transaxillary robotic thyroidectomy (START) requires substantial tissue disruption, which produces moderate-to-severe pain in the axilla and neck areas during the early postoperative period. This study aimed to investigate the analgesic effects of ultrasound-guided serratus-intercostal plane blocks and intermediate cervical plexus blocks (CPBs) on the early postoperative pain after START. Methods We randomized 22 patients to undergo either ultrasound-guided serratus-intercostal plane and intermediate CPBs (the block group, n = 11) or to not undergo any block (the control group, n = 11). We compared postoperative axillary pain, postoperative neck pain, and analgesic use between the groups during the first 24 hours. The rescue analgesics were intravenous fentanyl (0.5 μg/kg) in the postanesthesia care unit, and intravenous ketorolac tromethamine (30 mg) in the general ward. Results The block group showed consistently lower pain scores than the control group in the axillary area in the first 24 hours and in the neck area only in the first 3 hours after surgery. The numbers (proportions) of patients who required analgesics were 11 (100%) in the control group and 6 (54.5%) in the block group during the first 24 hours (P = 0.035). No adverse effect was observed related to the peripheral nerve blocks. Conclusions After START, a serratus-intercostal plane block performed at the level of the third rib was an effective analgesic technique for axillary pain; however, the clinical effectiveness of intermediate CPB for neck pain may be limited.

BACKGROUND AND AIMS Papillary thyroid cancer (PTC) is the most frequent subtype among thyroid cancers. Lymph node (LN) metastases are frequent in PTC and the incidence is 60% on average. Recent studies have shown that there has been an increase in the mortality or recurrence with LN metastases and that more than 5 metastatic LNs are clinically important. Therefore, we investigated clinicopathologic factors associated with clinically important LN metastases. METHODS From January 2010 to October 2013, we retrospectively enrolled 2,628 PTC patients who underwent thyroidectomy at Ajou University Hospital. Among 1,425 patients with LN metastasis, 325 had ≥ 5 LN metastases. RESULTS In univariate analysis, young age (< 45 year), male gender, capsular invasion, multiplicity, tumor size, and lymphovascular invasion (p < 0.001) were statistically associated with both LN metastasis and ≥ 5 LN metastases. However, Braking Action Fair (BRAF) mutation was not important to predict LN metastasis (p > 0.05). In multivariate analysis, lymphovascular invasion was the most important factor (odds ratio: 4.7, 4.0) among other clinicopathologic factors (odds ratio:< 2.1). CONCLUSION Braking Action Fair (BRAF) mutation was not useful to predict the LN metastasis. However, lymphovascular invasion was the most important factor to predict more than five cervical LN metastasis which is very important clinically.

Using a large set of genomic data from The Cancer Genome Atlas (TCGA), we classified BRAFIntegrated genomic analysis was done using all genomic data of PTC in TCGA data portal (https://tcga-data.nci.nih.gov) and cancer browser (https://genome-cancer.ucsc.edu). Using Gene Ontology and a logistic regression test, we selected gene signatures (RAS-score) and applied this prediction model to the validation cohort (GSE60542).When we performed multiplatform genomic analysis, BRAFWe found that BRAF

Cellular senescence has been perceived as a barrier against carcinogenesis. However, the senescence-associated secretory phenotype (SASP) of senescent cells can promote tumorigenesis. Here, we show senescent tumour cells are frequently present in the front region of collective invasion of papillary thyroid carcinoma (PTC), as well as lymphatic channels and metastatic foci of lymph nodes. In in vitro invasion analysis, senescent tumour cells exhibit high invasion ability as compared with non-senescent tumour cells through SASP expression. Collective invasion in PTC is led by senescent tumour cells characterized by generation of a C-X-C-motif ligand (CXCL)12 chemokine gradient in the front region. Furthermore, senescent cells increase the survival of cancer cells via CXCL12/CXCR4 signalling. An orthotopic xenograft in vivo model also shows higher lymphatic vessels involvement in the group co-transplanted with senescent cells and cancer cells. These findings suggest that senescent cells are actively involved in the collective invasion and metastasis of PTC., The senescence-associated secretory phenotype of stromal cells can promote tumorigenesis. Here, the authors show that senescent cancer cells are localized at the invasive front in human papillary thyroid carcinoma, and that senescent cancer cells drive collective invasion via CXCL12 in mouse models.

Midkine is a multifunctional, heparin-binding growth factor that is frequently expressed in patients with malignancies but is undetectable in healthy adults. In various cancers, high expression of midkine is associated with aggressive clinical behavior and a poor prognosis. In the present study, we investigated the expression of midkine in papillary thyroid carcinoma (PTC) and assessed its association with a BRAFV600E mutation and the clinicopathological parameters. We determined the presence of a BRAFV600E mutation in 79 cases of PTC and examined the effects of the BRAFV600E mutation on midkine expression in primary thyrocytes. In addition, we evaluated the association between midkine expression and various clinicopathological parameters. We found that midkine is more frequently expressed in BRAFV600E PTC (68.3%) than in BRAF wild-type PTC (18.8%). BRAFV600E transduction could up-regulate midkine expression in primary thyrocytes. Moreover, midkine expression was associated with multiple lymph node (≥5) metastases in BRAFV600E PTC. In conclusion, our results suggest that midkine expression could be a clinically useful marker in predicting the presence of multiple lymph node metastases in BRAFV600E PTC.

Objectives: We evaluated the utility of the VE1 antibody that can detect a mutant protein resulting from the BRAF V600E mutation as a diagnostic tool for thyroid fine-needle aspiration cytology (FNAC). Methods: We performed VE1 immunocytochemistry on 202 FNAC specimens from surgically confirmed thyroid nodules. The results were compared with the molecular analyses of the BRAF mutation in these specimens matched with their corresponding histology. Results: Diagnoses of FNAC specimens included benign (9.4%), atypia of undetermined significance/follicular lesion of undetermined significance (11.4%), follicular neoplasm/suspicious for follicular neoplasm (2.0%), suspicious for malignancy (9.4%), and malignancy (65.8%). VE1 immunostaining was positive in 71.3% of FNAC specimens. The overall sensitivity of the VE1 antibody was 88.8%, specificity was 71.2%, positive predictive value was 88.2%, negative predictive value was 72.4%, and diagnostic accuracy was 83.7%. Conclusions: VE1 immunocytochemistry in thyroid FNAC as a screening test for BRAF mutations is highly specific for malignant category cases but can be suboptimal due to its high false-positive rate for the nonmalignant cases.

Purpose: Papillary thyroid cancer (PTC) is the most frequent subtype among thyroid cancers. B-type Raf kinase (BRAF) mutation can be found in...