Interferon regulatory factor-5-dependent CD11c+ macrophages contribute to the formation of rupture-prone atherosclerotic plaques.

AIMS: Inflammation is a key factor in atherosclerosis. The transcription factor interferon regulatory factor-5 (IRF5) drives macrophages towards a pro-inflammatory state. We investigated the role of IRF5 in human atherosclerosis and plaque stability. METHODS AND RESULTS: Bulk RNA sequencing from the Carotid Plaque Imaging Project biobank were used to mine associations between major macrophage associated genes and transcription factors and human symptomatic carotid disease. Immunohistochemistry, proximity extension assays, and Helios cytometry by time of flight (CyTOF) were used for validation. The effect of IRF5 deficiency on carotid plaque phenotype and rupture in ApoE-/- mice was studied in an inducible model of plaque rupture. Interferon regulatory factor-5 and ITGAX/CD11c were identified as the macrophage associated genes with the strongest associations with symptomatic carotid disease. Expression of IRF5 and ITGAX/CD11c correlated with the vulnerability index, pro-inflammatory plaque cytokine levels, necrotic core area, and with each other. Macrophages were the predominant CD11c-expressing immune cells in the plaque by CyTOF and immunohistochemistry. Interferon regulatory factor-5 immunopositive areas were predominantly found within CD11c+ areas with a predilection for the shoulder region, the area of the human plaque most prone to rupture. Accordingly, an inducible plaque rupture model of ApoE-/-Irf5-/- mice had significantly lower frequencies of carotid plaque ruptures, smaller necrotic cores, and less CD11c+ macrophages than their IRF5-competent counterparts. CONCLUSION: Using complementary evidence from data from human carotid endarterectomies and a murine model of inducible rupture of carotid artery plaque in IRF5-deficient mice, we demonstrate a mechanistic link between the pro-inflammatory transcription factor IRF5, macrophage phenotype, plaque inflammation, and its vulnerability to rupture.

C-type lectin receptor CLEC4A2 promotes tissue adaptation of macrophages and protects against atherosclerosis.

Macrophages are integral to the pathogenesis of atherosclerosis, but the contribution of distinct macrophage subsets to disease remains poorly defined. Using single cell technologies and conditional ablation via a LysMCre+ Clec4a2flox/DTR mouse strain, we demonstrate that the expression of the C-type lectin receptor CLEC4A2 is a distinguishing feature of vascular resident macrophages endowed with athero-protective properties. Through genetic deletion and competitive bone marrow chimera experiments, we identify CLEC4A2 as an intrinsic regulator of macrophage tissue adaptation by promoting a bias in monocyte-to-macrophage in situ differentiation towards colony stimulating factor 1 (CSF1) in vascular health and disease. During atherogenesis, CLEC4A2 deficiency results in loss of resident vascular macrophages and their homeostatic properties causing dysfunctional cholesterol metabolism and enhanced toll-like receptor triggering, exacerbating disease. Our study demonstrates that CLEC4A2 licenses monocytes to join the vascular resident macrophage pool, and that CLEC4A2-mediated macrophage homeostasis is critical to combat cardiovascular disease.

CD200 Limits Monopoiesis and Monocyte Recruitment in Atherosclerosis.

[Figure: see text].

Management of chyle leakage after thyroidectomy, cervical lymph node dissection, in patients with thyroid cancer.

BACKGROUND: The purpose of this study was to evaluate the incidence and pattern of chyle leakage after thyroidectomy and/or cervical lymph node dissection and to establish management protocols for chyle leakage. METHODS: Patients who underwent surgical management for thyroid cancer were analyzed retrospectively. RESULTS: For this study, 131 patients with chyle leakage were identified; the overall incidence was 0.9%. Of them, 43.7% of patients underwent central neck dissection without lateral neck dissection, and chyle leakage was easily controlled with conservative management. Patients whose chyle drainage was reduced by >50% after dietary modification had a significantly shorter hospital stay (P < .001); NPO was the most effective dietary modification. CONCLUSION: The occurrence of chyle leakage after central compartment dissection even without lateral neck dissection was not rare, but was easily controlled with conservative management. Surgical management should be considered if the drainage amount does not decrease by >50% of the original amount of the day of detection after 2 days of NPO.

Functional diversity of macrophages in vascular biology and disease.

Atherosclerosis is a multifactorial chronic inflammatory disease and is largely responsible for cardiovascular disease, the most common cause of global mortality. The hallmark of atherogenesis is immune activation following lipid accumulation in the arterial wall. In particular, macrophages play a non-redundant role in both the progression and regression of inflammation in the atherosclerotic lesion. Macrophages are remarkably heterogeneous phagocytes that perform versatile functions in health and disease. Their functional diversity in vascular biology is only partially mapped. Targeting macrophages is often highlighted as a therapeutic approach for cancer, metabolic and inflammatory diseases. Future strategies for therapeutic intervention in atherosclerosis may benefit from attempts to reduce local proliferation of pro-inflammatory macrophage subsets or enhance resolution of inflammation. Thus, characterisation of macrophage subsets during atherosclerosis would empower clinical interventions. Therefore, it would be of fundamental importance to understand how pathological factors modulate macrophage activity in order to exploit their use in the treatment of atherosclerosis and other diseases.

Paenibacillus arcticus sp. nov., isolated from Arctic soil.

A Gram-positive, endospore-forming, strictly aerobic and rod-shaped bacterium, designated strain MME2_R6T, was isolated from Arctic soil, and it was identified by using a polyphasic taxonomic approach. This strain was psychrotolerant, growing at 4‒24 °C. 16S rRNA gene sequence analysis showed that strain MME2_R6T was closest to Paenibacillus swuensis DY6T, with 93.9 % similarity. However, in phylogenetic analysis based on the 16S rRNA gene sequence, strain MME2_R6T showed that it clustered with Paenibacillus contaminans CKOBP-6T and the sequencing similarity between the two species was 93.7 %. Its major cellular fatty acid was anteiso-C15 : 0, like other Paenibacillus species. The major polar lipids were phosphatidylethanolamine, phosphatidylglycerol and diphosphatidylglycerol. The predominant isoprenoid quinone was menaquinone-7. The diagnostic diamino acid in the cell wall was meso-diaminopimelic acid. The genomic DNA G+C content was 44.2 mol%. Based on the results of phenotypic, chemotaxonomic and phylogenetic analyses, a novel species, Paenibacillus arcticus sp. nov., is proposed. The type strain is MME2_R6T (=JCM 30981T=PAMC 28731T).

Interferon Regulatory Factor 5 Controls Necrotic Core Formation in Atherosclerotic Lesions by Impairing Efferocytosis.

BACKGROUND: Myeloid cells are central to atherosclerotic lesion development and vulnerable plaque formation. Impaired ability of arterial phagocytes to uptake apoptotic cells (efferocytosis) promotes lesion growth and establishment of a necrotic core. The transcription factor interferon regulatory factor (IRF)-5 is an important modulator of myeloid function and programming. We sought to investigate whether IRF5 affects the formation and phenotype of atherosclerotic lesions. METHODS: We investigated the role of IRF5 in atherosclerosis in 2 complementary models. First, atherosclerotic lesion development in hyperlipidemic apolipoprotein E-deficient (ApoE-/-) mice and ApoE-/- mice with a genetic deletion of IRF5 (ApoE-/-Irf5-/-) was compared and then lesion development was assessed in a model of shear stress-modulated vulnerable plaque formation. RESULTS: Both lesion and necrotic core size were significantly reduced in ApoE-/-Irf5-/- mice compared with IRF5-competent ApoE-/- mice. Necrotic core size was also reduced in the model of shear stress-modulated vulnerable plaque formation. A significant loss of CD11c+ macrophages was evident in ApoE-/-Irf5-/- mice in the aorta, draining lymph nodes, and bone marrow cell cultures, indicating that IRF5 maintains CD11c+ macrophages in atherosclerosis. Moreover, we revealed that the CD11c gene is a direct target of IRF5 in macrophages. In the absence of IRF5, CD11c- macrophages displayed a significant increase in expression of the efferocytosis-regulating integrin-ß3 and its ligand milk fat globule-epidermal growth factor 8 protein and enhanced efferocytosis in vitro and in situ. CONCLUSIONS: IRF5 is detrimental in atherosclerosis by promoting the maintenance of proinflammatory CD11c+ macrophages within lesions and controlling the expansion of the necrotic core by impairing efferocytosis.

Predictive Factors of Lymph Node Metastasis in Follicular Variant of Papillary Thyroid Carcinoma.

BACKGROUND: Compared with conventional papillary thyroid carcinoma (PTC), follicular variant of PTC (FV-PTC) shows less aggressive behavior and better prognosis. Nonetheless, regional lymph node (LN) metastasis was found in 22.8% of FV-PTC patients. Because LN metastasis is a proven predictor of recurrence in PTC, it is important to assess LN metastasis in FV-PTC patients. METHODS: We retrospectively reviewed 134 FV-PTC patients who underwent thyroidectomy with neck dissection. RESULTS: Central LN metastasis (CLNM) and lateral LN metastasis (LLNM) were found in 50 (37.3%) and 16 (11.9%) patients, respectively. In the multivariate analysis for CLNM, male sex (adjusted OR 4.735, p = 0.001), nonencapsulated form (adjusted OR 2.863, p = 0.022), and tumor size >1.0 cm (adjusted OR 3.157, p = 0.008) were independent predictors of high prevalence of CLNM in FV-PTC patients. In the multivariate analysis for LLNM, microscopic extrathyroidal extension (ETE) (adjusted OR 3.939, p = 0.041) and CLNM (adjusted OR 13.340, p = 0.001) were independent predictors of high prevalence of LLNM in FV-PTC patients. CONCLUSIONS: Meticulous perioperative evaluation and prophylactic central neck dissection may be beneficial for FV-PTC patients with male sex, nonencapsulated form, and tumor size >1.0 cm. Moreover, cautious perioperative evaluation of lateral neck LN may be mandatory for FV-PTC patients with microscopic ETE and CLNM.

Patterns, Predictive Factors, and Prognostic Impact of Contralateral Lateral Lymph Node Metastasis in N1b Papillary Thyroid Carcinoma.

BACKGROUND: Although the incidence among patients with bilateral lateral lymph node metastasis (LLNM) in N1b papillary thyroid carcinoma (PTC) is reported to be as high as 40%, only a few reports have addressed the characteristics of contralateral LLNM. Therefore, this study aimed to investigate the characteristics of patients with contralateral LLNM in N1b PTC. METHODS: This study retrospectively reviewed 834 patients with N1b PTC who underwent modified radical neck dissection between January 1997 and June 2015. RESULTS: Of the 834 N1b PTC patients, unilateral LLNM was found in 728 patients (87.3%) and bilateral LLNM in 106 patients (12.7%). The independent predictors of contralateral LLNM in N1b PTC patients were male sex (adjusted odds ratio [OR], 1.647; p = 0.039), tumor larger than 4 cm (adjusted OR, 6.700; p < 0.001), multiplicity (adjusted OR, 1.754; p = 0.040), bilobar involvement (adjusted OR, 1.971; p = 0.010), and bilateral central LN metastasis (CLNM) (adjusted OR, 2.829; p = 0.025). Moreover, contralateral LLNM significantly increased the risk of overall (adjusted hazard ratio [HR], 1.943; p = 0.016) and lateral neck (adjusted HR, 2.246; p = 0.015) locoregional recurrence. CONCLUSIONS: In the preoperative period, the meticulous evaluation of contralateral lateral neck may be required for male N1b PTC patients with tumor larger than 4 cm, multiplicity, bilobar involvement, and/or bilateral CLNM. In the postoperative period, N1b PTC patients may be re-stratified according to the contralateral LLNM, and meticulous follow-up assessment is required for N1b PTC patients with contralateral LLNM.

A novel robotic surgical technique for thyroid surgery: bilateral axillary approach (BAA).

INTRODUCTION: Bilateral axillo-breast approach (BABA) robotic thyroidectomy (RT) is proven to be a feasible method for the treatment of well-differentiated thyroid cancers in terms of oncology as well as cosmesis. However, BABA RT causes postoperative sternal discomfort and needs an incision over the nipple areolar area. Here, we suggest a novel robotic surgical technique for thyroid surgery that does not need a breast incision-bilateral axillary approach (BAA). PATIENTS AND METHODS: We recruited 51 patients who were willing to undergo the novel BAA robotic thyroid surgery. We performed a propensity score-matched analysis to compare the BAA robotic thyroid surgery group (BAA group) with the conventional open thyroid surgery group (open group). RESULTS: Mean operation time in the BAA group (129.7 min) was significantly longer than that in the open group (103.1 min) (p < 0.001). However, no significant differences in the mean number of metastatic lymph nodes (LNs), mean number of retrieved LNs, vocal cord palsy, hypoparathyroidism, and mean stimulated thyroglobulin level were observed between the two groups. There was no case of postoperative bleeding or chyle leak. Of the 51 patients who had undergone the BAA procedure, 27 patients answered the questionnaire. The mean scale, ranging from 0 to 10, at postoperative 1 day/2 weeks was as follows: voice change score, 3.0/1.6; swallowing difficulty score, 4.0/2.0; anterior neck pain score, 4.6/3.6; anterior neck numbness score, 5.4/4.3; right chest pain score, 3.8/2.1; left chest pain score, 3.6/2.3; right chest numbness score, 3.2/2.8; left chest numbness score, 2.4/2.7; right breast pain score, 0.9/0; left breast pain score, 1.2/0; right breast numbness score, 1.7/0; and left breast numbness score, 2.6/0, respectively. CONCLUSION: BAA robotic thyroid surgery is a novel, safe, and feasible oncoplastic method, especially for patients who have fear of procedures around the nipple areolar complex.

A Novel Gel Pad Laryngeal Ultrasound for Vocal Cord Evaluation.

BACKGROUND: Laryngeal ultrasound (LUS) is a new method for vocal cord evaluation in patients with risk of vocal cord palsy (VCP). However, the previously described LUS reportedly had a high failure rate of vocal cord visualization in male patients. A novel gel pad LUS was devised to overcome the limitations of the previous method. METHODS: A total of 482 (100 male) consecutive LUS and direct laryngoscopy examinations were performed in thyroidectomy and other neck surgery patients. The conventional LUS and gel pad LUS were used for all patients. Findings were independently cross-validated with direct laryngoscopy. RESULTS: The conventional LUS and gel pad LUS methods had a 93.4% and 99.0% visualization rate, respectively, with a sensitivity of 98.0% for both methods, and a specificity of 99.7% and 99.8%, respectively. Among the 482 patients, 51 patients had VCP and 91 patients had diffuse thyroid cartilage calcification interrupting LUS. CONCLUSION: The new gel pad LUS method significantly enhances the visualization of vocal cords in patients who have diffuse thyroid cartilage calcification interrupting LUS and, therefore, the overall efficacy of LUS as a perioperative diagnostic tool for VCP.

Nomogram for predicting central node metastasis in papillary thyroid carcinoma.

BACKGROUND: There was a difficulty for detecting Central lymph node metastasis (CLNM) in papillary thyroid carcinoma (PTC) patients. Therefore, the purpose of this study was to design a nomogram for predicting CLNM. METHODS: A total of 10,763 PTC patients who underwent total thyroidectomy with central neck dissection (CND) in Samsung Medical Center were randomly assigned to the training set (n = 7,535) and to the internal validation set (n = 3,228). And, a total of 2,514 PTC patients who underwent total thyroidectomy with CND at Seoul National University Hospital were assigned to the external validation set. RESULTS: The values of the area under the receiver operating characteristic curve in the training set, internal validation set, and external validation set were 0.721 (95% confidence interval [CI], 0.709-0.732), 0.706 (95%CI, 0.688-0.724), and 0.706 (95%CI, 0.685-0.727), respectively. CONCLUSIONS: We recommend the use of our nomogram to enable clinicians and patients to easily personalize and quantify the probability of CLNM during the both pre- and postoperative period. Clinicians may consider the prophylactic CND and meticulous postoperative evaluation in PTC patients with a high nomogram score. J. Surg. Oncol. 2017;115:266-272. © 2016 Wiley Periodicals, Inc.

Comparison of ultrasound frequency in laryngeal ultrasound for vocal cord evaluation.

BACKGROUND: Laryngeal ultrasound is a new method of vocal cord evaluation in patients at risk for vocal cord palsy. However, the previously described laryngeal ultrasound reportedly has a high failure rate of vocal cord visualization in male patients. We compared 2 ultrasound frequencies in laryngeal ultrasound to improve on the limitations of this method. METHOD: A total of 301 (55 male, 246 female) consecutive laryngeal ultrasound and direct laryngoscopy exams were performed for patients with thyroidectomy and other neck operations. High-frequency transducer (12-5 MHz broad band spectrum) and low-frequency transducer (9-3 MHz broad band spectrum) were used for all laryngeal ultrasound. Findings were independently cross-validated with direct laryngoscopy. RESULTS: High-frequency and low-frequency laryngeal ultrasound had 88.4% and 97.7% visualization rates, respectively. In addition, low-frequency laryngeal ultrasound showed improved sensitivity of 97.6% and specificity of 96.5%, compared with a sensitivity of 92.9% and specificity of 86.5% for high-frequency laryngeal ultrasound in vocal cord evaluation. CONCLUSION: The low-frequency laryngeal ultrasound method significantly enhances the visualization of vocal cords, especially in patients who have diffuse thyroid cartilage calcification interrupting laryngeal ultrasound, and therefore enhances the overall efficacy of laryngeal ultrasound as a perioperative diagnostic tool for vocal cord palsy. Hence, we recommend using a low-frequency transducer (about 9-3 MHz) for laryngeal ultrasound if it is available.

Total thyroidectomy versus lobectomy in conventional papillary thyroid microcarcinoma: Analysis of 8,676 patients at a single institution.

BACKGROUND: Because there is a controversy regarding the management of papillary thyroid microcarcinoma, the purpose of this study was to compare lobectomy with total thyroidectomy as a primary operative treatment for papillary thyroid microcarcinoma. Loco-regional recurrence in the contralateral remnant lobe can be managed safely by completion thyroidectomy via the previous scar. However, reoperation for operation bed (thyroidectomy site) or regional lymph node (central or lateral) recurrence generally is associated with morbidity. Therefore, we analyzed overall loco-regional recurrence and loco-regional recurrence outside of the contralateral remnant lobe separately. METHODS: We retrospectively reviewed 8,676 conventional patients with papillary thyroid microcarcinoma who underwent thyroidectomy. RESULTS: Lobectomy was performed in 3,289 (37.9%) patients, and total thyroidectomy was performed in 5,387 (62.1%) patients. Total thyroidectomy significantly decreased the risk of overall loco-regional recurrence (adjusted hazard ratio 0.398, P < .001). However, total thyroidectomy did not significantly decrease the risk of loco-regional recurrence outside of the contralateral remnant lobe (adjusted hazard ratio 0.880, P = .640). Particularly in conventional papillary thyroid microcarcinoma patients with multifocality, total thyroidectomy significantly decreased the risk of overall loco-regional recurrence (adjusted hazard ratio 0.284, P = .002) and loco-regional recurrence outside of the contralateral remnant lobe (adjusted hazard ratio 0.342, P = .020). CONCLUSION: Although lobectomy is associated with contralateral remnant lobe recurrence, lobectomy did not increase the risk of loco-regional recurrence outside of the contralateral remnant lobe in patients with papillary thyroid microcarcinoma, except in those with multifocality. Because recurrence in the contralateral remnant lobe can be managed safely by completion thyroidectomy, lobectomy may be a safe operative option for select patients with papillary thyroid microcarcinoma without multifocality.

Propensity score-matched analysis of robotic versus endoscopic bilateral axillo-breast approach (BABA) thyroidectomy in papillary thyroid carcinoma.

PURPOSE: The da Vinci surgical robot system was developed to overcome the weaknesses of endoscopic surgery. However, whether robotic surgery is superior to endoscopic surgery remains uncertain. Therefore, the purpose of this study was to compare the surgical and oncologic outcomes between endoscopic and robotic thyroidectomy using bilateral axillo-breast approach (BABA). METHODS: Between January 2008 and June 2015, papillary thyroid carcinoma patients who underwent thyroidectomy with central neck dissection using endoscopic (n = 480) or robotic (n = 705) BABA were primarily reviewed. We performed 1:1 propensity score matching and 289 matched pairs were yielded. RESULTS: Operation time was significantly longer in the robotic thyroidectomy than in the endoscopic thyroidectomy (184.9 vs. 128.9 min, P < 0.001). A significantly higher number of central lymph nodes (CLNs) were resected in the robotic thyroidectomy than in the endoscopic thyroidectomy (5.3 vs. 4.4, P = 0.003). However, the incidence of other outcomes including hospital stay, postoperative duration, thyroglobulin level, radioactive iodine ablation, hemorrhage, chyle leakage, wound infection, recurrent laryngeal nerve injury, and loco-regional recurrence did not significantly differ between the endoscopic thyroidectomy and the robotic thyroidectomy. CONCLUSIONS: Endoscopic thyroidectomy is comparable with robotic thyroidectomy in view of surgical complications and LRR. Because robotic thyroidectomy resected a larger number of CLNs than did endoscopic thyroidectomy, further long-term follow-up studies will be required to clarify the possible prognostic benefits of robotic thyroidectomy.

Should Level V Be Routinely Dissected in N1b Papillary Thyroid Carcinoma?

BACKGROUND: For N1b papillary thyroid carcinoma (PTC) patients, modified radical neck dissection (MRND) encompassing levels II-V is generally recommended. However, routine level V dissection is controversial because of the low incidence of metastasis/recurrence in level V and the increased morbidities associated with level V dissection. METHODS: This study retrospectively reviewed 646 N1b PTC patients who underwent unilateral MRND between January 1997 and June 2015. Specifically, to assess surgery-related outcomes of level V dissection, outcomes from N1b PTC patients who underwent unilateral MRND (levels II-V) were compared with those who underwent unilateral selective neck dissection (SND; levels II-IV) using propensity score matching. RESULTS: Overall and occult level V metastases were observed in 13.9% and 8.6% of patients, respectively. Level V recurrences were observed in only 2.26 (7.7%) recurred N1b PTC patients who underwent unilateral MRND. In multivariate analysis, three-level (II, III, and IV) simultaneous metastasis (adjusted odds ratio = 3.079, p = 0.003) was an independent predictor for level V metastasis. Under a matched condition, "shoulder syndrome" encompassing shoulder dysfunction and pain (9.1% vs. 2.7%, p = 0.002) was significantly more frequent in the MRND group than it was in the SND group. CONCLUSIONS: Because of the low incidence of metastasis/recurrence in level V and the clear evidence of increased morbidities, level V dissection in N1b PTC patients may be reserved for those with three-level simultaneous metastasis or clinically/radiologically evident level V metastasis.

Computed Tomography-Detected Central Lymph Node Metastasis in Ultrasonography Node-Negative Papillary Thyroid Carcinoma: Is It Really Significant?

BACKGROUND: Because of the limitations in ultrasonography (US), the advantages of computed tomography (CT) for detecting central lymph node (LN) metastasis have been suggested in papillary thyroid carcinoma (PTC). METHODS: First, we compared the diagnostic accuracy of US and CT for detecting central LN metastasis in 6577 central neck levels from 3668 PTC patients. Second, to examine the clinical impact of CT-detected central LN metastasis (CT cN1a) in PTC patients with clinically node negative in US (US cN0), we selected two groups: group I comprised 1245 US cN0 PTC patients who did not have CT scans and did not undergo central neck dissection (CND), while group II comprised 348 US cN0 and CT cN1a PTC patients who underwent CND. After propensity score matching, 254 matched pairs were yielded. RESULTS: For detecting central LN metastasis, CT showed significantly higher sensitivity (38.9 vs. 27.5 %; p < 0.001) and accuracy (66.1 vs. 63.2 %; p < 0.001) than US. Furthermore, US + CT showed significantly higher sensitivity (47.8 vs. 27.5 %; p < 0.001) and accuracy (69.0 vs. 63.2 %; p < 0.001) than US. After matching, radioactive iodine ablation (81.5 vs. 85.8 %; p = 0.235) and locoregional recurrence (p = 0.663) were not significantly different between groups I and II. CONCLUSIONS: Despite the diagnostic advantages of preoperative CT, 'CT-based CND' in US cN0 PTC patients did not significantly influence postoperative management and locoregional recurrence. The strategy for the management of central neck in PTC patients can be sufficiently determined by US only.

Predicting Factors for Bilaterality in Papillary Thyroid Carcinoma with Tumor Size <4 cm.

BACKGROUND: In the 2015 American Thyroid Association guidelines, either lobectomy or total thyroidectomy was recommended for thyroid cancer <4 cm without extrathyroidal extension (ETE) and lymph node (LN) metastasis. Therefore, the purpose of this study was to investigate factors predictive of bilaterality in papillary thyroid carcinoma (PTC) patients with tumor size <4 cm. METHODS: This study retrospectively reviewed 3296 conventional PTC patients who underwent total thyroidectomy with central neck dissection and/or lateral neck dissection between January 2008 and June 2015. RESULTS: In overall conventional PTC patients, per 10-year age increment (adjusted odds ratio [OR] = 1.153, p < 0.001), BRAF mutation positivity (adjusted OR = 1.447, p = 0.002) and multifocality (adjusted OR = 3.895, p < 0.001) were independent predictors for bilaterality. In conventional PTC patients with tumor size 1-4 cm, per 10-year age increment (adjusted OR = 1.289, p < 0.001), BRAF mutation positivity (adjusted OR = 1.560, p = 0.012), multifocality (adjusted OR = 4.220, p < 0.001), and N1b (adjusted OR = 1.570, p = 0.007) were independent predictors for bilaterality. In conventional PTC patients with tumor size <1 cm, BRAF mutation positivity (adjusted OR = 1.327, p = 0.042) and multifocality (adjusted OR = 3.530, p < 0.001) were found to be independent predictors for bilaterality. CONCLUSIONS: When multifocality and BRAF mutation positivity are observed in PTC patients with tumor size <4 cm, total thyroidectomy may be considered. If lobectomy is performed in PTC patients with multifocality and BRAF mutation positivity, meticulous follow-up is needed to detect hidden malignancies in the contralateral lobe.

Routine Level 2b Dissection may be Recommended Only in N1b Papillary Thyroid Carcinoma with Three- or Four-Level Lateral Lymph Node Metastasis.

BACKGROUND: Due to the low incidence of level 2b metastasis and the risk of spinal accessory nerve injury, previous studies have argued against routine level 2b dissection for N1b papillary thyroid carcinoma (PTC). However, other studies have suggested the importance of including level 2b during lateral neck dissection. Therefore, this study aimed to determine the necessity of routine level 2b dissection. METHODS: The study retrospectively reviewed 327 N1b PTC patients who underwent unilateral modified radical neck dissection between January 1997 and May 2016. RESULTS: The incidence of level 2b metastasis was 10.4 %, compared with 53.5 % for level 2a metastasis. The univariate analysis showed that large tumor size (p = 0.027) and simultaneous lateral lymph node metastasis (LLNM) (p = 0.002) were significantly associated with level 2b metastasis. The multivariate analysis showed that three-level (adjusted odds ratio [OR] 6.032; p = 0.020) and four-level (adjusted OR 9.398; p = 0.012) simultaneous LLNM were independent predictors for level 2b metastasis. CONCLUSIONS: Due to the low incidence of level 2b metastasis, routine level 2b dissection may not be necessary for N1b PTC patients. Level 2b dissection may be reserved for patients with more than three-level simultaneous LLNM or clinical/radiological evidence of level 2b metastasis.

Follicular and Diffuse Sclerosing Variant Papillary Thyroid Carcinomas as Independent Predictive Factors of Loco-Regional Recurrence: A Comparison Study Using Propensity Score Matching.

BACKGROUND: Only about half of papillary thyroid carcinoma (PTC) cases are classified as conventional PTC (CV-PTC), whereas various histologic variants constitute the remaining cases. Since controversies about the clinical behavior and outcomes of PTC variants continue, the purpose of this study was to compare the outcomes of patients with PTC variants who were treated at a large tertiary referral center in Korea. METHODS: The medical records for 15,598 CV-PTCs, 435 follicular variants of PTC (FV-PTCs), and 66 diffuse sclerosing variants of PTC (DSV-PTCs) were retrospectively reviewed. Loco-regional recurrences (LRR) among PTC variants were compared using propensity score matching. RESULTS: Analysis I compared CV-PTC with FV-PTC. After rigorous matching, 367 pairs were established. Recurrence-free survival (RFS) rates in CV-PTC were 96.1% at 5 years, 92.2% at 10 years, and 92.2% at 15 years, while those for FV-PTC were 98.8% at 5 years, 98.8% at 10 years, and 98.8% at 15 years (p = 0.026). Analysis II compared CV-PTC with DSV-PTC. Rigorous matching yielded 56 pairs. RFS rates for CV-PTC were 87.4% at 5 years, 87.4% at 10 years, and 87.4% at 15 years, while those for DSV-PTC were 68.9% at 5 years, 57.5% at 10 years, and were not available at 15 years (p = 0.013). CONCLUSIONS: Compared with CV-PTC, FV-PTC showed less aggressive behaviors and more favorable outcomes. However, DSV-PTC showed more aggressive behaviors and a less favorable outcome than CV-PTC did. Therefore, the management strategy and follow-up plan for PTC should be differentiated according to the histologic variant.