Is total thyroidectomy with bilateral central neck dissection the only surgery for papillary thyroid carcinoma patients with clinically involved central nodes?

BACKGROUND: In clinical practice, we often observed that patients who underwent total thyroidectomy due to clinically involved nodal disease (cN1a) actually had less extensive CLNM on final pathology. This study investigates whether total thyroidectomy and therapeutic bilateral CND are necessary for all PTC patients with cN1a. METHODS: This study retrospectively reviewed 899 PTC patients who underwent total thyroidectomy with bilateral CND from January 2012 to June 2017. The patients were divided into two groups according to pre-operative central lymph node (CLN) status: cN0, no suspicious CLNM; cN1a, suspicious CLNM. We compared the clinicopathological features of these two groups. RESULTS: There was no significant difference in recurrence between cN0 and cN1a groups after a mean follow-up time of 59.1 months. Unilateral cN1a was related to the largest central LN size ≥ 2 mm (OR = 3.67, p < 0.001) and number of CLNM > 5(OR = 2.24, p = 0.006). On the other hand, unilateral cN1a was not associated with an increased risk of contralateral lobe involvement (OR = 1.35, p = 0.364) and contralateral CLNM (OR = 1.31, p = 0.359). Among 106 unilateral cN1a patients, 33 (31.1%) were found to be pN0 or had ≤ 5 metastatic CLNs with the largest node smaller than 2 mm. CONCLUSIONS: Most cN1a patients were in an intermediate risk group for recurrence and required total thyroidectomy. However, lobectomy with CND should have performed in approximately 30% of the cN1a patients. Pre-operative clinical examination, meticulous radiologic evaluation, and intra-operative frozen sections to check the nodal status are prerequisites for this approach.

Surgeon Volume and Long-Term Oncologic Outcomes in Patients with Medullary Thyroid Carcinoma.

BACKGROUND: Surgery is the most important curative treatment for medullary thyroid carcinoma (MTC). The relationship between surgeon volume (the number of surgeries performed) and short-term surgical outcomes, such as increased postoperative complication or costs, is well established. This study evaluated whether surgeon volume influenced long-term oncologic outcomes. METHODS: We retrospectively reviewed 246 patients diagnosed with MTC after initial thyroid surgery from 1995 to 2019. After exclusion, 194 patients were eligible for inclusion in the study. Surgeons were categorized as low/intermediate volume (fewer than 100 operations per year) or high volume (at least 100 operations per year). RESULTS: Of the 194 included patients, 60 (30.9%) developed disease recurrence, and 9 (4.6%) died of MTC during the median follow-up of 92.5 months. Having a low/intermediate-volume surgeon was associated with high disease recurrence (log-rank test, p < 0.001). After adjustment for age, sex, tumor type (sporadic versus hereditary), primary tumor size, presence of central lymph node metastasis (LNM), presence of lateral LNM, extrathyroidal extension, and positive resection margin, surgeon volume was a significant factor for disease recurrence (hazard ratio 2.28, p = 0.004); however, cancer-specific survival was not affected by surgeon volume (hazard ratio 4.16, p = 0.115). CONCLUSIONS: Surgeon volume is associated with long-term oncologic outcome. MTC patients will be able to make the best decisions for their treatment based on the results of this study.

Highly Sensitive and Specific Molecular Test for Mutations in the Diagnosis of Thyroid Nodules: A Prospective Study of BRAF-Prevalent Population.

Molecular testing offers more objective information in the diagnosis and personalized decision making for thyroid nodules. In Korea, as the BRAF V600E mutation is detected in 70-80% of thyroid cancer specimens, its testing in fine-needle aspiration (FNA) cytology specimens alone has been used for the differential diagnosis of thyroid nodules until now. Thus, we aimed to develop a mutation panel to detect not only BRAF V600E, but also other common genetic alterations in thyroid cancer and to evaluate the diagnostic accuracy of the mutation panel for thyroid nodules in Korea. For this prospective study, FNA specimens of 430 nodules were obtained from patients who underwent thyroid surgery for thyroid nodules. A molecular test was devised using real-time PCR to detect common genetic alterations in thyroid cancer, including BRAF, N-, H-, and K-RAS mutations and rearrangements of RET/PTC and PAX8/PPARr. Positive results for the mutation panel were confirmed by sequencing. Among the 430 FNA specimens, genetic alterations were detected in 293 cases (68%). BRAF V600E (240 of 347 cases, 69%) was the most prevalent mutation in thyroid cancer. The RAS mutation was most prevalently detected for indeterminate cytology. Among the 293 mutation-positive cases, 287 (98%) were diagnosed as cancer. The combination of molecular testing and cytology improved sensitivity from 72% (cytology alone) to 89% (combination), with a specificity of 93%. We verified the excellent diagnostic performance of the mutation panel applicable for clinical practice in Korea. A plan has been devised to validate its performance using independent FNA specimens.

Superior Located Papillary Thyroid Microcarcinoma is a Risk Factor for Lateral Lymph Node Metastasis.

BACKGROUND: It is important to identify prognostic factors for lateral lymph node metastasis (LLNM) in papillary thyroid microcarcinoma (PTMC) because they determine the extent of surgery. Several similarly designed studies have investigated predictors of LLNM, but with no more than 1000 cases. In addition, there are no recommendations or guidelines covering the differences in risk by tumor location. This study is the largest, using a papillary thyroid microcarcinoma population with 2967 patients. The purpose of this study is to address predictive factors of LLNM, focusing on lesion location. PATIENTS AND METHODS: We retrospectively reviewed the data of 2967 PTMC patients who underwent total thyroidectomy and central neck dissection and/or lateral neck dissection (unilateral or bilateral) between January 1997 and June 2015. RESULTS: On multivariate analysis, superior lesion [adjusted odds ratio (OR) 3.32, p < 0.000], male gender (adjusted OR 1.39, p = 0.0047), age under 45 years (adjusted OR 1.42, p = 0.015), and central lymph node metastasis (adjusted OR 3.40, p < 0.000) were significant predictors of high-risk LLNM. Superior lesion [hazard ratio (HR) 2.32, p = 0.005] and central lymph node metastasis (CLNM, HR 7.12, p < 0.000) were significant risk factors for locoregional recurrence (LRR). To reduce the effect of selection bias, we performed propensity score matching analysis with regard to tumor location. With a total of 1138 patients with matched data and 569 patients for each location, superior lesion (adjusted OR 3.17, p < 0.000), age under 45 years (adjusted OR 1.73, p = 0.005), and CLNM (adjusted OR 2.77, p < 0.000) were independent predictive factors of LLNM. Superior lesion (HR 2.28, p = 0.04) and CLNM (HR 5.32, p = 0.001) were significant risk factors for LRR. CONCLUSIONS: In addition to young age, male gender, and CLNM identified in previous studies, meticulous assessment for LLNM is required in PTMC patients when lesions are located in the superior pole of the thyroid during preoperative evaluation or postoperative follow-up, because superior located papillary microcarcinoma is a risk factor for LLNM and LRR.

Evaluation of a Novel Collagen Hemostatic Matrix: Comparison of Two Hemostatic Matrices in a Rabbits Jejunal Artery Injury Model.

BACKGROUND: We evaluated the hemostatic efficacy and immunogenicity of CollaStat compared with FloSeal in a rabbit jejunal artery injury model. METHODS: A total of 27 experimental rabbits were used in the study. For each hemostatic agent, an injury was created in one of the right angles of the jejunal arteries originating from the vascular arcs. Time to hemostasis was determined after applying manual compression to the wound for 30 s, which was repeated a maximum of three times in cases of persistent bleeding. On postoperative day 7, the concentration of serum antithrombin antibody was measured among agent-treated and nontreated control groups. RESULTS: The mean time to hemostasis for CollaStat was significantly shorter than for FloSeal (64.0 ± 5.0 versus 84.0 ± 7.8 s; P = 0.040). There were no significant differences in rabbit serum mean anti-thrombin Ab concentration between CollaStat-treated, FloSeal -treated, and the control groups (8.43 ± 0.44 versus 8.18 ± 7.8 versus 9.58 ± 1.11 ng/mL; P = 0.065). CONCLUSIONS: According to our study, CollaStat was more efficient in achieving hemostasis in a rabbit jejunal artery injury and exhibited nonsignificant immunogenicity compared with FloSeal. These findings suggest that CollaStat has acceptable hemostatic potential for controlling significant arterial bleeding.

Molecular genotyping of the non-invasive encapsulated follicular variant of papillary thyroid carcinoma.

AIMS: The non-invasive encapsulated follicular variant of papillary thyroid carcinoma (FVPTC) has been managed as a low-risk malignancy. Recently, a proposal was made to reclassify this tumour type as a premalignant lesion and rename it non-invasive follicular thyroid neoplasm with papillary-like nuclear features (NIFTP). This study aims to provide the first comprehensive study on molecular genotype-phenotype correlations of encapsulated FVPTC. METHODS AND RESULTS: This study was performed on 177 consecutive FVPTCs from January 2014 to April 2016. These were classified as non-invasive encapsulated FVPTC (n = 74) invasive encapsulated FVPTC (n = 51), and infiltrative FVPTC (n = 52), according to standard criteria, by two independent pathologists. Genetic alterations and other clinicopathological information were compared. BRAFV600E was found in 12.2% (non-invasive) and 11.8% (invasive) of encapsulated FVPTCs, and in 34.6% of infiltrative FVPTCs (P = 0.001). Mutation in encapsulated FVPTCs was limited to cases with rare or abortive papillae. RET-PTC1 and RET-PTC3 rearrangements were present (11.5%) only in infiltrative FVPTCs. In contrast, NRAS, HRAS and KRAS mutations were observed more often in encapsulated FVPTCs (48.6% in non-invasive and 66.7% in invasive) than in infiltrative FVPTCs (15.4%) (P < 0.001). Preoperative cytological examination did not distinguish between non-invasive and invasive encapsulated FVPTCs, whereas infiltrative FVPTC was more likely to be Bethesda class V/VI than the encapsulated type (60.4% versus 38.1%; P = 0.01). CONCLUSIONS: There were no differences in clinicopathological or molecular profiles between non-invasive and invasive encapsulated FVPTCs, except in vascular and capsular invasion. Therefore, the diagnosis of NIFTP, like that of follicular adenoma, may require surgical resection and exclusion of those tumours with any papillae.

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.

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.

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.

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.

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.

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.

Predictive Factors for Lymph Node Metastasis in Papillary Thyroid Microcarcinoma.

BACKGROUND: Because lymph node (LN) metastasis has been proven to be a predictor for locoregional recurrence (LRR) in papillary thyroid microcarcinoma (PTMC), better knowledge about the predictors for LN metastasis in PTMC is required. METHODS: We retrospectively reviewed 5656 PTMC patients who underwent total thyroidectomy and central neck dissection and/or lateral neck dissection between January 1997 and June 2015. RESULTS: Male gender (adjusted odds ratio [OR] 2.332), conventional variant (adjusted OR 4.266), tumor size >0.5 cm (adjusted OR 1.753), multiplicity (adjusted OR 1.168), bilaterality (adjusted OR 1.177), and extrathyroidal extension (ETE) (adjusted OR 1.448) were independent predictors for high prevalence of central LN metastasis (CLNM), whereas per 10-year age increment (adjusted OR 0.760) and chronic lymphocytic thyroiditis (adjusted OR 0.791) were independent predictors for low prevalence of CLNM. In addition, male gender (adjusted OR 1.489), tumor size >0.5 cm (adjusted OR 1.295), multiplicity (adjusted OR 1.801), ETE (adjusted OR 1.659), and CLNM (adjusted OR 4.359) were independent predictors for high prevalence of lateral LN metastasis (LLNM), whereas per 10-year age increment (adjusted OR 0.838) was an independent predictor for low prevalence of LLNM. There was a statistically significant difference in LRR with regard to nodal stage (p < 0.001). CONCLUSIONS: Meticulous perioperative evaluation of LN metastasis is required for PTMC patients with the above predictors.

Clinical impact of coexistent chronic lymphocytic thyroiditis on central lymph node metastasis in low- to intermediate-risk papillary thyroid carcinoma: The MASTER study.

BACKGROUND: The clinicopathological impact of chronic lymphocytic thyroiditis on patients with papillary thyroid carcinoma patients is still controversial. This study aimed to evaluate the clinicopathologic differences and risk factors for central lymph node metastasis based on the presence of coexistent chronic lymphocytic thyroiditis in patients with low- to intermediate-risk papillary thyroid carcinoma. METHODS: The medical records of 1,022 patients with low- to intermediate-risk papillary thyroid carcinoma who underwent lobectomy and central neck dissection between June 2020 and March 2022 were reviewed. Differences in clinicopathological factors were analyzed in patients with papillary thyroid carcinoma with or without chronic lymphocytic thyroiditis. Furthermore, risk factors for central lymph node metastasis in patients with low- to intermediate-risk papillary thyroid carcinoma with or without chronic lymphocytic thyroiditis were evaluated. RESULTS: Among the 1,022 patients with low to intermediate-risk papillary thyroid carcinoma, 102 (10.0%) had coexisting chronic lymphocytic thyroiditis. Female sex (odds ratio = 3.536, P = .001, 95% confidence interval 1.781-8.069), a multifocal tumor (odds ratio = 2.162, P = .001, 95% confidence interval 1.358-3.395), and angiolymphatic invasion (odds ratio = 0.365, P < .001, 95% confidence interval 0.203-0.625) were independent factors associated with patients who had coexisting chronic lymphocytic thyroiditis compared to those without chronic lymphocytic thyroiditis. There were 358 (35%) patients who had central lymph node metastasis. Multivariate analysis showed that younger age (odds ratio = 0.667, P = .013, 95% confidence interval 0.482-0.555), male sex (odds ratio = 0.549, P < .001, 95% confidence interval 0.402-0.751), tumor size >1 cm (odds ratio = 1.454, P = .022, 95% confidence interval 1.053-2.003), extrathyroidal extension (odds ratio = 1.874, P < .001, 95% confidence interval 1.414-2.486), and angiolymphatic invasion (odds ratio = 3.094, P < .001, 95% confidence interval 2.339-4.101) were risk factors for central lymph node metastasis. Angiolymphatic invasion (odds ratio = 11.184, P < .001, 95% confidence interval 3.277-46.199) was identified as the sole independent risk factor for central lymph node metastasis in patients with papillary thyroid carcinoma with coexisting chronic lymphocytic thyroiditis. CONCLUSION: Our data suggest that patients with low to intermediate-risk papillary thyroid carcinoma with coexistent chronic lymphocytic thyroiditis exhibit different clinical features than patients with papillary thyroid carcinoma without chronic lymphocytic thyroiditis. Additionally, the presence of chronic lymphocytic thyroiditis may be considered a potential factor against central lymph node metastasis.

Feasibility of active surveillance in patients with clinically T1b papillary thyroid carcinoma ≤1.5 cm in preoperative ultrasonography: MASTER study.

Objective: Active surveillance (AS) is generally accepted as an alternative to immediate surgery for papillary thyroid carcinoma (PTC) measuring ≤1.0 cm (cT1a) without risk factors. This study investigated the clinicopathologic characteristics of PTCs measuring ≤2.0 cm without cervical lymph node metastasis (cT1N0) by tumor size group to assess the feasibility of AS for PTCs between 1.0 cm and 1.5 cm (cT1b≤1.5). Design: This study enrolled clinically T1N0 patients with preoperative ultrasonography information (n= 935) from a cohort of 1259 patients who underwent lobectomy and were finally diagnosed with PTC from June 2020 to March 2022. Results: The cT1b≤1.5 group (n = 171; 18.3 %) exhibited more lymphatic invasion and occult central lymph node (LN) metastasis with a higher metastatic LN ratio than the cT1a group (n = 719; 76.9 %). However, among patients aged 55 years or older, there were no significant differences in occult central LN metastasis and metastatic LN ratio between the cT1a, cT1b≤1.5, and cT1b>1.5 groups. Multivariate regression analyses revealed that occult central LN metastasis was associated with age, sex, tumor size, extrathyroidal extension, and lymphatic invasion in patients under 55, while in those aged 55 or older, it was associated only with age and lymphatic invasion. Conclusion: For PTC patients aged 55 years or older with cT1b≤1.5, AS could be a viable option due to the absence of a significant relationship between tumor size and occult central LN.

A new subfascial approach in open thyroidectomy: efficacy for postoperative voice, sensory, and swallowing symptoms. A randomized controlled study.

BACKGROUND: After open thyroidectomy, patients usually complain of voice, sensory, and swallowing symptoms. We approached the thyroid via the subfascial method to reduce these symptoms and compared postthyroidectomy symptoms with the conventional subplatysmal method. METHODS: Eighty-six patients undergoing thyroidectomy were recruited and randomized into either a conventional subplatysmal approach group (subplatysmal, 42 patients) group or a subanterior fascia of strap muscle approach group (subfascial, 44 patients). Voice symptoms were assessed using the Voice Handicap Index questionnaire and acoustic voice analysis. Sensory alterations were evaluated by the light touch and pain touch methods. Swallowing symptoms were assessed using the Swallowing Impairment Score (SIS) questionnaire, barium swallowing time, and hyoid bone movement range. Each variable was measured preoperatively, and at 2 weeks and 3 months after thyroidectomy. RESULTS: In both groups, the subjective symptoms of voice, sensation, and swallowing were significantly worsened at 2 weeks after operation, but improved 3 months after operation. Patients in the subplatysmal group had worse SIS scores than patients in the subfascial group (p = 0.016) and delayed barium swallowing time 2 weeks after operation (p = 0.008 compared to preoperative level). In the cohort over 50 years of age, SIS score did not recover to preoperative levels in the subplatysmal group 3 months after operation (p = 0.005 compared to preoperative level). CONCLUSIONS: The subfascial approach may be an effective method for reducing postthyroidectomy swallowing symptoms based on swallowing impairment score, especially in patients over 50 years of age.

The clinical meaning of intramammary lymph nodes.

OBJECTIVE: The clinical meaning of intramammary lymph nodes (iMLNs) is uncertain. We wanted to describe the clinical characteristics and understand the implications of iMLNs detected by sentinel LN biopsy (SLNB). METHODS: We reviewed the clinical, radiological and pathological records of women diagnosed with invasive carcinoma of the breast at the Samsung Medical Center between January 2001 and January 2011. A total of 69 patients were identified, and SLNB was performed in 31 patients. RESULTS: Of the 69 patients included in the study, 22 (31.9%) had metastases in iMLNs. The presence of lymphovascular invasion and the number of axillary LN metastases were associated with iMLN metastasis. Of the 31 patients who underwent SLNB, there were no cases with axillary LN metastasis when axillary SLNB was negative, even in cases of iMLN-positive patients. Of the 10 patients in whom intramammary SLNs (iMSLNs) were detected during SLNB, 8 patients without iMLN metastases were also negative for axillary LNs. CONCLUSION: Patients with metastatic iMLNs had more aggressive cancers with lymphovascular invasion and increased axillary LN metastases. When iMSLN was detected by SLNB, performing of axillary dissection could be determined by the status of the iMSLN itself.

Clinical implication of cancer adhesion in papillary thyroid carcinoma: clinicopathologic characteristics and prognosis analyzed with degree of extrathyroidal extension.

BACKGROUND: Macroscopic extrathyroidal extension (ETE) is a poor prognostic factor in papillary thyroid carcinoma (PTC). However, intraoperative inspection for ETE is often inaccurate and could lead the surgeon to misconstrue simple adhesion as gross ETE. Such confusion could result in more aggressive treatment than necessary. In the present study we investigated the frequency and clinical implication of simple adhesions. METHODS: We identified 858 patients who underwent total thyroidectomy for papillary thyroid carcinoma (PTC). Clinicopathologic features, prognosis, and stimulated serum thyroglobulin (Tg) levels were compared between four groups divided according to degree of ETE: no ETE (n = 335), simple adhesion (n = 16), microscopic ETE (n = 378), and macroscopic ETE (n = 129). RESULTS: In the total of 145 cases, which were recognized as gross ETE under intraoperative inspection, 16 cases (11.0 %) were diagnosed as cancer confined to the thyroid without ETE by definite histology. The simple adhesion group showed no statistical differences in postoperative stimulated Tg levels from the no ETE and microscopic ETE groups (p > 0.05). In contrast, the distribution of postoperative Tg levels in the macroscopic ETE group was significantly higher than in the other groups (p < 0.001). During the 54-month median follow-up period, the macroscopic ETE and microscopic ETE groups showed poorer relapse-free survival than the no ETE and simple adhesion groups (p < 0.05). CONCLUSIONS: The findings of the present study indicate that the discrepancy between intraoperative inspection and definite histology is not negligible when dense adhesions are present. When no tumor is found, the patient with inflammatory or fibrotic adhesions has a favorable prognosis.

ERK phosphorylation is not increased in papillary thyroid carcinomas with BRAF(V600E) mutation compared to that of corresponding normal thyroid tissues.

BACKGROUND: An association between a BRAF(V600E) mutation and upregulation of mitogen-activated protein kinase (MAPK) pathways in human papillary thyroid carcinoma (PTC) tissues has not been demonstrated well outside of in vitro studies. The aims of this study were to evaluate the activation status of extracellular signal-regulated kinase 1/2 (ERK1/2) in human PTCs with BRAF(V600E) mutations compared to that of corresponding normal thyroid tissue and to determine the expressions of Raf kinase inhibitor protein (RKIP) and MAPK phosphatase 3 (MKP-3), possible regulators of ERK1/2 activation. METHODS: We analyzed the presence of BRAF(V600E) mutation and the expressions of BRAF, total ERK, p-ERK, RKIP, and MKP-3 in 33 PTCs and corresponding normal thyroid gland tissues using western blot analysis. RESULTS: BRAF(V600E) mutation was found in 28 (84.8%) of 33 PTCs, 96.4% (27/28) of which showed decreased p-ERK activity, while 75% (21/28) showed increased MKP-3 expression. There were significant differences in p-ERK and MKP-3 expressions between BRAF(V600E) (+) PTCs and normal thyroid glands (p < 0.001). There were no differences in expressions of BRAF, total ERK, and RKIP between PTCs and normal thyroid tissue, irrespective of the presence of BRAF(V600E) mutation. CONCLUSIONS: In human BRAF(V600E) (+) PTCs, ERK phosphorylation is decreased compared to normal thyroid glands and the observed decrease in ERK1/2 MAPK phosphorylation in BRAF(V600E) (+) PTCs may be associated with increased MKP-3 activity.