Multifocality of papillary thyroid carcinoma as a risk factor for disease recurrence.

OBJECTIVES: Tumor multifocality or bilaterality is associated with increased risk of papillary thyroid carcinoma (PTC) recurrence. However, its prognostic value in clinical outcomes remains controversial. This study aimed to evaluate the association of multifocality or bilaterality with recurrence and survival after total thyroidectomy. METHODS: This was a retrospective study of 2390 consecutive patients with pathologically confirmed PTC who underwent total thyroidectomy. Multifocality and bilaterality were decided based on the final pathology results, that is, if there were two or more tumor foci and bilateral location, respectively. Primary outcomes were recurrence-free survival (RFS). Cox proportional hazards regression analyses were used to assess the associations of multifocality, bilaterality, and other clinicopathological factors with RFS. RESULTS: Multifocal and bilateral PTC were found in 892 (37.3%) and 593 (24.8%) patients, respectively. Multivariate analyses showed that multifocality, lymphovascular invasion, N category, and number of positive lymph node (>5) were significant independent variables predictive of RFS (all P < 0.05). Multifocality was associated with adjusted hazard ratios for RFS of 1.93 (95% confidence interval = 1.33-2.80; P = 0.001). In a subset analysis, the prognostic value of multifocality was found to be significant in those patients with PTC > 1 cm, but not in papillary thyroid microcarcinoma. CONCLUSIONS: Tumor multifocality is an independent risk factor of PTC recurrence after total thyroidectomy. This indicate a more progressive state of disease, being included in risk stratification.

Risk Factors for Recurrence After Treatment of N1b Papillary Thyroid Carcinoma.

OBJECTIVES: To examine risk factors for posttreatment recurrence in papillary thyroid carcinoma (PTC) patients with initial presentation of lateral neck metastasis (N1b). SUMMARY OF BACKGROUND DATA: N1b PTC recurs after definitive treatment. METHODS: Study subjects were 437 consecutive PTC patients who underwent total thyroidectomy and therapeutic neck dissection of central and lateral compartments and postoperative radioactive iodine ablation therapy. The patients' demographics and pathological factors, including factors related to tumors and lymph nodes (LNs), and postoperative thyroglobulin levels were reviewed. Univariate and multivariate Cox proportional hazards regression analyses were used to identify factors associated with recurrence-free survival (RFS). RESULTS: During a median follow-up of 83 months (range, 32-135 months), recurrence occurred in 81 (18.1%) patients. Univariate analyses showed that male sex, tumor size, macroscopic extrathyroidal extension, perineural invasion, extranodal extension, LN involvement, LN ratio, MACIS score, and postoperative serum levels of thyroglobulin were significantly associated with RFS (P < 0.05). Multivariate analyses revealed that LN ratio (> 0.25) in the lateral compartment (adjusted hazard ratio = 2.099, 95% confidence interval = 1.278-3.448; P = 0.003), and postoperative serum levels of stimulated (>5.0 ng/mL; 3.172, 1.661-6.056, P < 0.001) and unstimulated (>0.1 ng/mL; 3.200, 1.569-6.526, P = 0.001) thyroglobulin were independent predictors of any-site RFS. Clinical and tumor factors were not independent predictors of RFS outcomes (P > 0.1). CONCLUSIONS: Posttreatment recurrence is predicted by the LN ratio in the lateral compartment and postoperative serum levels of thyroglobulin in patients with metastatic PTC in the lateral neck.

A comparison of the 7th and 8th editions of the AJCC staging system in terms of predicting recurrence and survival in patients with papillary thyroid carcinoma.

OBJECTIVES: The recently published 8th edition of the American Joint Committee on Cancer (AJCC) tumour-node-metastasis (TNM) staging system was significantly updated following the thyroid cancer-related guidelines to provide better predictability of survival but not focus on recurrence. Therefore, we compared the predictive values of the 7th and 8th editions of the AJCC staging systems for recurrence-free survival (RFS) and overall survival (OS) after thyroidectomy for papillary thyroid carcinoma (PTC). METHODS: This retrospective study included 2930 patients who underwent thyroidectomy and neck dissection for previously untreated PTC between 2006 and 2014. TNM stage was defined according to 7th and 8th editions. Univariate and multivariate Cox proportional hazard regression analyses were used to identify associations between variables and RFS or OS. Multivariate models for the AJCC TNM stages were adjusted for clinical and pathological variables. RESULTS: A significant number of patients classified as T3 with overall TNM stages II-IV in the AJCC 7th edition were down-staged in the 8th edition. Unadjusted T classification and overall TNM staging in both the 7th and 8th editions were significantly associated with RFS and OS rates (P < 0.001). After adjustment for clinicopathological factors, the overall TNM stage according to the AJCC 8th edition, but not the 7th edition, remained significantly associated with RFS and OS (P < 0.05), with better predictability of recurrence and survival, in patients with PTC. CONCLUSIONS: The 8th edition AJCC staging system down-staged a large proportion of PTC patients, resulting in better predictability of recurrence and survival compared to the previous staging system. CONDENSED ABSTRACT: This study compared the abilities of the 7th and 8th edition AJCC staging systems to predict recurrence and overall survival in 2930 patients with papillary thyroid carcinoma. The updated guidelines down-staged a large proportion of patients, resulting in better prediction of recurrence and survival than the previous staging system.

Novel cancer gene variants and gene fusions of triple-negative breast cancers (TNBCs) reveal their molecular diversity conserved in the patient-derived xenograft (PDX) model.

Despite the improved 5-year survival rate of breast cancer, triple-negative breast cancer (TNBC) remains a challenge due to lack of effective targeted therapy and higher recurrence and metastasis than other subtypes. To identify novel druggable targets and to understand its unique biology, we tried to implement 24 patient-derived xenografts (PDXs) of TNBC. The overall success rate of PDX implantation was 45%, much higher than estrogen receptor (ER)-positive cases. Immunohistochemical analysis revealed conserved ER/PR/Her2 negativity (with two exceptions) between the original and PDX tumors. Genomic analysis of 10 primary tumor-PDX pairs with Ion AmpliSeq CCP revealed high degree of variant conservation (85.0%-96.9%) between primary and PDXs. Further analysis showed 44 rare variants with a predicted high impact in 36 genes including Trp53, Pten, Notch1, and Col1a1. Among them, we confirmed frequent Notch1 variant. Furthermore, RNA-seq analysis of 24 PDXs revealed 594 gene fusions, of which 163 were in-frame, including AZGP1-GJC3 and NF1-AARSD1. Finally, western blot analysis of oncogenic signaling proteins supporting molecular diversity of TNBC PDXs. Overall, our report provides a molecular basis for the usefulness of the TNBC PDX model in preclinical study.

microRNA-155 positively regulates glucose metabolism via PIK3R1-FOXO3a-cMYC axis in breast cancer.

MicroRNA is an endogenous, small RNA controlling multiple target genes and playing roles in various biological processes including tumorigenesis. Here, we addressed the function of miR-155 using LC-MS/MS-based metabolic profiling of miR-155 deficient breast cancer cells. Our results revealed the loss of miR-155 hampers glucose uptake and glycolysis, via the down-regulation of glucose transporters and metabolic enzymes including HK2, PKM2, and LDHA. We showed this is due to the down-regulation of cMYC, controlled through phosphoinositide-3-kinase regulatory subunit alpha (PIK3R1)-PDK1/AKT-FOXO3a pathway. UTR analysis of the PIK3R1 and FOXO3a indicated miR-155 directly represses these genes. A stable expression of miR-155 in patient-derived cells (PDCs) showed activated glucose metabolism whereas a stable inhibition of miR-155 reduced in vivo tumor growth with retarded glucose metabolism. Furthermore, analysis of 50 triple-negative breast cancer (TNBC) specimens and specific uptake value (SUV) of PET images revealed a positive correlation between miR-155 level and glucose usage in human breast tumors via PIK3R1-PDK/AKT-FOXO3a-cMYC axis. Collectively, these data demonstrate the miR-155 is a key regulator of glucose metabolism in breast cancer.

Nodal Factors Predictive of Recurrence After Thyroidectomy and Neck Dissection for Papillary Thyroid Carcinoma.

BACKGROUND: Lymph node (LN) yield and ratio are considered important predictors of post-treatment outcomes for several human cancers. This study examined the association between nodal factors, including the LN yield and ratio, with recurrence after thyroidectomy plus central compartment neck dissection (ND) for papillary thyroid carcinoma (PTC). MATERIALS AND METHODS: This retrospective study involved 2384 consecutive patients who underwent a thyroidectomy plus central compartment ND combined with (n = 440) or without lateral compartment ND at the authors' tertiary referral center between 2006 and 2012. The number of harvested LNs, as well as other tumor and nodal findings, were carefully reviewed. Univariable and multivariable Cox proportional hazards regression models were conducted to predict recurrence and its association with clinicopathologic variables. RESULTS: All nodal factors, including the positive number of LNs, ratio, and extranodal extension, were significantly associated with nodal and any-site recurrence after thyroidectomy, as well as the tumor size and multifocality (p < 0.01). The multivariable analysis showed that tumor size, multifocality, LN ratio, and extranodal extension were independent factors predictive of post-treatment recurrence (p < 0.05). The LN yield was higher in patients with nodal recurrence but did not significantly affect the nodal recurrence. Patients with a LN ratio >0.3 exhibited a 1.7-fold higher risk of post-treatment nodal recurrence than their counterparts (p < 0.01). CONCLUSIONS: LN ratio is an independent determinant predictive of nodal and any-site recurrence following thyroidectomy for PTC.

Risk Factors for Lateral Neck Recurrence of N0/N1a Papillary Thyroid Cancer.

BACKGROUND: Current guidelines advocate no prophylactic dissection of the lateral neck compartment for papillary thyroid carcinoma (PTC) without clinical evidence of lateral neck metastasis (cN1b). However, lateral neck recurrence can affect patient treatment outcomes and quality of life. Therefore, this study examined the risk factors for lateral neck recurrence after the definitive treatment of PTC without cN1b. METHODS: The study enrolled 1928 consecutive patients who underwent total thyroidectomy between 2006 and 2012 for PTC without cN1b. Logistic regression analysis was used to identify the relationship of clinicopathologic factors with lateral neck recurrence. Uni- and multivariate Cox-proportional hazards regression analyses were used to identify factors predictive of lateral neck recurrence-free survival (LRFS). RESULTS: During a median follow-up period of 94 months (range, 24-133 months), lateral neck recurrence occurred in 47 patients (2.4%). Binary logistic regression showed that tumor size (>2 cm), multifocality, clinical central neck metastasis (cN1a), number of positive lymph nodes (LNs, >5), and LN ratio (>0.5) were significantly associated with lateral neck recurrence (P < 0.05). Multivariate analyses showed that multifocality (hazards ratio [HR], 2.338; 95% confidence interval [CI], 1.126-4.858; P = 0.023), cN1a (HR, 5.301; 95% CI, 2.416-11.630; P < 0.001), LN ratio (HR, 2.628; 95% CI, 1.228-5.626; P = 0.013), extranodal extension (HR, 2.570; 95% CI, 1.063-6.213; P = 0.036), and MACIS (distant metastasis, patient age, completeness of resection, local invasion and tumour size) score (HR, 2.513; 95% CI, 1.211-5.216; P = 0.013) were independent factors for LRFS. CONCLUSIONS: Lateral neck recurrence after thyroidectomy is predicted by the clinicopathologic factors of multifocality, cN1a, LN ratio, extranodal extension, and MACIS score in N0/N1a PTC patients.

Extranodal extension of lymph node metastasis as a prognostic indicator of recurrence and survival in papillary thyroid carcinoma.

BACKGROUND AND OBJECTIVES: Stratification of extranodal extension (ENE) extent has the potential to improve the accuracy of risk estimations in papillary thyroid carcinoma (PTC). This study examined the prognostic importance of nodal factors, including ENE, in PTC patients. METHODS: This study enrolled 2071 consecutive patients with treatment-naïve PTC who underwent thyroidectomy between 2006 and 2010. Microscopic/macroscopic ENE was determined by pathological and operative findings. Univariate and multivariate analyses were used to identify the relationship of factors with recurrence and survival in all study patients and in the node-positive subset. RESULTS: Of 2071 patients, 975 (47.1%) had positive lymph nodes, and 271 (13.1%) and 70 (3.4%) had microscopic and macroscopic ENE, respectively. During a median follow-up of 96 months, 114 (5.5%) patients had post-treatment recurrence. Multivariate analyses showed that, in all patients, the number of positive nodes, lymph node ratio, ENE status, and ATA risk group were independent variables affecting recurrence (P < 0.05). T4 and macroscopic ENE were independent variables associated with shorter overall survival (P < 0.05). Macroscopic ENE was significantly associated with macroscopic extrathyroidal extension. CONCLUSION: Macroscopic ENE has a significant adverse impact on recurrence and survival after treatment for PTC. ENE is considered a high risk factor for recurrence.

Extent of Extrathyroidal Extension as a Significant Predictor of Nodal Metastasis and Extranodal Extension in Patients with Papillary Thyroid Carcinoma.

BACKGROUND: Extrathyroidal extension (ETE) and extranodal extension (ENE) indicate poor prognosis for patients with papillary thyroid carcinoma (PTC). The relationships among ETE, ENE, and nodal metastasis (N1) have not been thoroughly studied. In this study, we examined the relationships among the extent of ETE, N1, ENE, and posttreatment recurrence in patients with PTC. METHODS: This study enrolled 1693 consecutive patients with previously untreated PTC who underwent thyroidectomy between 2006 and 2009. The extent of ETE was graded based on intraoperative and pathological findings, and central and lateral neck (N1b) nodal metastases and ENE were pathologically determined. Univariate and multivariate analyses were used to identify the association of clinicopathological factors with recurrence-free survival (RFS) and to define the relationships among the extent of ETE, N1, and ENE. RESULTS: Of 1693 patients, 1087 (64.2 %) had ETE and 201 (11.9 %) had ENE. Pathologically positive lymph nodes were found in 783 patients (46.2 %), of whom 236 (30.1 %) had N1b. During the median follow-up of 86 months, 90 (5.3 %) patients had recurrences. Multivariate analyses showed that multifocality, ETE, T and N classification, the risk of structural recurrence proposed by the American Thyroid Association, and ENE were independent variables for RFS (P < .05). Patients with macroscopic ETE had a 13-fold increased risk of recurrence, and ETE had significant relationships with N1, N1b, and ENE (all P < .001). CONCLUSIONS: Local extension, nodal involvement, and ENE contribute to posttreatment recurrence of PTC. Macroscopic ETE predicts nodal metastasis and ENE, which are adverse pathologic features.

Differences in the Recurrence and Survival of Patients with Symptomatic and Asymptomatic Papillary Thyroid Carcinoma: An Observational Study of 11,265 Person-Years of Follow-Up.

BACKGROUND: Papillary thyroid carcinoma (PTC) generally has an indolent course and favorable prognosis. However, an optimal treatment strategy for asymptomatic PTC is not clear. We compared the recurrence and survival outcomes of patients with asymptomatic and symptomatic PTC and identified the associated risk factors. MATERIALS AND METHODS: Patients with previously untreated PTC of size ≤2 cm and who underwent curative surgery were included in this analysis. Asymptomatic PTC was defined as a tumor detected only by ultrasonography, computed tomography (CT), magnetic resonance imaging, and/or 18F-fluorodeoxyglucose positron emission tomography/CT. Clinical factors, operative and pathologic findings, and posttreatment outcomes were compared between the aforementioned two groups. Univariate and multivariate analyses were performed to identify the factors associated with recurrence-free survival (RFS) and overall survival (OS). RESULTS: Out of 1419 patients, 1259 patients (88.7%) were asymptomatic. Patients with symptomatic PTC had significantly larger tumor size, palpability, extrathyroidal extension, high tumor and node stages, and were more likely to undergo treatment with radioactive iodine therapy compared with patients with asymptomatic PTC (p < 0.05 each). Recurrence was significantly higher in the symptomatic PTC group than in the asymptomatic group (p < 0.001). Asymptomatic PTC was an independent predictor of RFS and OS and had higher five-year rates than those associated with symptomatic tumors: 97.3% and 90.6% for RFS (p < 0.001) and 99.4% and 96.9% for OS (p < 0.001), respectively. CONCLUSION: Symptomatic PTC is associated with higher recurrence and lower overall survival rates than asymptomatic PTC. Symptomatic PTC may require total thyroidectomy and close posttreatment surveillance.

Recurrence in patients with clinically early-stage papillary thyroid carcinoma according to tumor size and surgical extent.

BACKGROUND: To investigate whether post-treatment recurrence differs by tumor size or surgical extent in clinically early-stage papillary thyroid carcinoma (PTC) patients. METHODS: A total of 1,041 surgical patients with PTC 4 cm or less and no clinical evidence of metastases to regional or distant sites were included. Cox proportional hazard models were used to identify the clinicopathological variables predictive of post-treatment recurrence. RESULTS: Central nodal involvement was found in 313 (34.1%) of 918 patients who underwent prophylactic central lymph node dissection. For the median follow-up of 83 months, 25 (2.4%) of 1,041 patients had a regional recurrence and 12 (1.2%) patients died of other causes. Male gender, tumor size, extranodal extension, and positive resection margin remained independent variables predictive of recurrence by multivariate analysis (P < .05 each). There was no significant impact of age (<45 vs ≥45 years, P = .944) or surgical extent (unilateral vs bilateral thyroidectomy, P = .776) on recurrence. CONCLUSIONS: Tumor size in patients with PTC of 4 cm or less is an important predictive factor for post-treatment recurrence.

Treatment Outcomes and Risk Factors for Recurrence After Definitive Surgery of Locally Invasive Well-Differentiated Papillary Thyroid Carcinoma.

BACKGROUND: Papillary thyroid carcinoma (PTC) is generally an indolent tumor that has a favorable prognosis. However, locally invasive PTC can recur after treatment, and its optimal treatment is still controversial. This study aimed to evaluate treatment outcomes and identify risk factors for recurrence and survival in patients with locally invasive PTC. MATERIALS AND METHODS: All consecutive patients who underwent definitive surgery and radioactive iodine therapy for non-distant metastatic invasive PTC were included. Clinical factors, operative and pathological findings, surgical morbidity, and recurrences were recorded. Univariate and multivariate Cox proportional hazard models served to identify factors associated with recurrence-free survival (RFS) and overall survival. RESULTS: Of the 96 patients, 74 (77%), 52 (55%), 4 (4%), and 14 (15%) had invasion to the recurrent laryngeal nerve (RLN), trachea, larynx, and esophagus, respectively; 39 (41%) had preoperative vocal cord paresis or paralysis; and 24 (25%) developed recurrence during follow-up (median 77 months). The patients with single and multiple organ invasion did not differ significantly in terms of recurrence-free or overall survival (p > 0.05). The patients with and without recurrences did not differ in terms of surgical extent and involving nerve preservation. Multivariate analysis showed that high (≥1 ng/mL) post-ablation stimulated serum thyroglobulin concentration was an independent predictor of poor RFS (p = 0.013). CONCLUSION: Disease extent, surgical extent, and involving nerve preservation did not associate with recurrence or overall survival outcomes. The post-ablation stimulated thyroglobulin level may be an independent predictor for recurrence. Careful follow-up of patients with this risk factor is recommended.

Risk Factors for Re-recurrence After First Reoperative Surgery for Locoregional Recurrent/Persistent Papillary Thyroid Carcinoma.

BACKGROUND: Papillary thyroid carcinoma (PTC) is generally an indolent tumor indicative of favorable prognosis. However, post-treatment recurrences may be problematic, and management strategies for recurrent disease have not been established. This study investigated risk factors associated with re-recurrence of PTC after reoperative surgery. MATERIALS AND METHODS: This study included 151 patients with pathologically confirmed recurrent/persistent PTC who underwent reoperation. Clinical factors, operative and pathologic findings, serum thyroglobulin levels, postoperative complications, and recurrences were examined. Univariate and multivariate analyses were performed to identify factors associated with re-recurrence-free survival (RFS) after reoperative surgery. RESULTS: Recurrent tumors were found in thyroid remnants or previous resection bed (n=28), central nodes (n=48), and lateral neck nodes (n=102). Biochemical complete remission (stimulated thyroglobulin<1 ng/mL) was achieved in 69 (51.5%) patients after reoperative surgery. Permanent vocal fold paralysis and hypoparathyroidism developed in 6 (4.1%) and 4 (2.8%) patients, respectively. Vocal fold paralysis occurred primarily due to intentional nerve resection following tumor invasion. During a median follow-up of 57.5 months, 41 (27.2%) patients had re-recurrences. Univariate analyses showed that extranodal extension (p=0.028), recurrent laryngeal nerve invasion (p=0.037), as well as stimulated (p=0.001) and unstimulated (p=0.015) serum thyroglobulin were significant predictors of RFS. Multivariate analyses showed that postoperative biochemical remission independently predicted RFS (p=0.014). CONCLUSIONS: Postoperative thyroglobulin after reoperative surgery predicted re-recurrence. Careful follow-up of these patients after reoperation is recommended.

Bioinformatic and metabolomic analysis reveals miR-155 regulates thiamine level in breast cancer.

microRNA-155 (miR-155) is one of the well-known oncogenic miRNA implicated in various types of tumors. Thiamine, commonly known as vitamin B1, is one of critical cofactors for energy metabolic enzymes including pyruvate dehydrogenase, alpha ketoglutarate dehydrogenase, and transketolase. Here we report a novel role of miR-155 in cancer metabolism through the up-regulation of thiamine in breast cancer cells. A bioinformatic analysis of miRNA array and metabolite-profiling data from NCI-60 cancer cell panel revealed thiamine as a metabolite positively correlated with the miR-155 expression level. We confirmed it in MCF7, MDA-MB-436 and two human primary breast cancer cells by showing reduced thiamine levels upon a knock-down of miR-155. To understand how the miR-155 controls thiamine level, a set of key molecules for thiamine homeostasis were further analyzed after the knockdown of miR-155. The results showed the expression of two thiamine transporter genes (SLC19A2, SLC25A19) as well as thiamine pyrophosphokinase-1 (TPK1) were decreased in both RNA and protein level in miR-155 dependent manner. Finally, we confirm the finding by showing a positive correlation between miR-155 and thiamine level in 71 triple negative breast tumors. Taken altogether, our study demonstrates a role of miR-155 in thiamine homeostasis and suggests a function of this oncogenic miRNA on breast cancer metabolism.

Risk factors for recurrence of papillary thyroid carcinoma with clinically node-positive lateral neck.

BACKGROUND: Papillary thyroid carcinoma (PTC) with clinically node-positive lateral neck is more likely to recur after surgery than node-negative PTC. The present study investigated the risk factors for recurrence in PTC patients with clinically node-positive lateral neck. MATERIALS AND METHODS: This study involved 136 patients with pathologically confirmed PTC and a clinically lymph node (LN)-positive lateral neck but no initial distant metastasis who underwent total thyroidectomy with therapeutic central and lateral neck dissection. Clinicopathologic characteristics, intraoperative findings, postoperative thyroglobulin (Tg) levels, and post-treatment recurrences were examined. Univariate and multivariate analyses were performed to identify factors associated with recurrence-free survival (RFS). RESULTS: During a median follow-up of 62 months (range 33-90 months), 27 (19.9 %) patients had locoregional or distant recurrences. Univariate analyses showed that primary tumor size (p = 0.049), recurrent laryngeal nerve invasion (p = 0.035), the maximal size of metastatic LN foci (≥1.5 cm; p = 0.012), extranodal extension (p = 0.025), total LN ratio (≥0.26; p = 0.008), American Thyroid Association (ATA) risk categories (p < 0.001), and stimulated serum Tg level (≥4.4; p < 0.001) at the time of radioactive iodine ablation therapy just after thyroidectomy were significant predictors of RFS. Multivariate analyses showed that the maximal size of metastatic foci (p = 0.037), ATA risk categories (p < 0.001), and stimulated Tg level (p < 0.001) were independent predictors of RFS. CONCLUSIONS: Maximal size of metastatic foci, ATA risk categories, and stimulated serum Tg levels are predictive of recurrence after surgery. Careful follow-up of patients with these risk factors is therefore recommended.

Intraoperative diagnosis of central compartment lymph node metastasis predicts recurrence of patients with papillary thyroid carcinoma and clinically node-negative lateral neck and may guide extent of initial surgery.

BACKGROUND: Although lymph node (LN) metastasis (LNM) of papillary thyroid carcinoma (PTC) is common, routine prophylactic LN dissection (LND) is still controversial. The purpose of this study was to investigate risk factors for recurrence of PTC with clinically node-negative lateral neck to determine the utility of intraoperative LN biopsy. MATERIALS AND METHODS: This study involved 185 patients with pathologically confirmed PTC and clinically node-negative lateral neck. All patients underwent thyroidectomy with or without ipsilateral or bilateral central LND after intraoperative central LN biopsy. Routine lateral neck LND was not performed. Clinicopathologic and intraoperative findings and post-treatment recurrences were recorded. Univariate and multivariate analyses with Cox-proportional hazards model were used to identify factors associated with recurrence. RESULTS: During a follow-up of 50-96 months, six (3.2 %) patients had recurrences in lateral cervical LNs at a median 28 months (range 7-57 months) after surgery. Overall, 2- and 5-year RFS rates were 98.4 and 96.7 %, respectively. Univariate analyses revealed that tumor size (P = 0.005), bilaterality (P = 0.033), T4 disease (P < 0.001), and intraoperative diagnosis of central LNM (P = 0.001) were significantly predictive of recurrence. Multivariate analyses showed that T4 disease (P = 0.049) and intraoperative diagnosis of central LNM (P = 0.027) were independently predictive of recurrence. CONCLUSIONS: Prophylactic lateral neck LND is not advocated for PTC with clinically node-negative lateral neck. Intraoperative LN biopsy may help identify patients at risk for recurrence and those who would benefit from LND.

Characteristics of BRCA1/2 Mutation-Positive Breast Cancers in Korea: A Comparison Study Based on Multicenter Data and the Korean Breast Cancer Registry.

PURPOSE: Mutations in BRCA genes are the main cause of hereditary breast cancer in Korea. The aim of this study was to investigate the characteristics of breast cancers involving BRCA1 (BRCA1 group) and BRCA2 (BRCA2 group) mutations. METHODS: We retrospectively reviewed the medical records of patients with BRCA1 (BRCA1 group) or BRCA2 (BRCA2 group) mutation positive breast cancer from multiple centers and compared the data to that of the Korean Breast Cancer Society registry (registry group). RESULTS: The patients of the BRCA1 group were diagnosed at a younger age (median age, 37 years) and had tumors of higher histological (61.3% with histological grade 3) and nuclear (37.5% with nuclear grade 3) grade than those of the registry group. In addition, the frequency of ductal carcinoma in situ in the BRCA1 group was lower (3.7%) than in the registry group, and the BRCA1 group were more likely to be triple-negative breast cancer (61.3%). Patients in the BRCA2 group were also younger at diagnosis (mean age, 41 years) and were more likely to have involvement of the axillary node than the registry group (45.5% vs. 33.5%, p=0.002). The BRCA1 and BRCA2 groups did not show a correlation between tumor size and axillary node involvement. CONCLUSION: We report the characteristics of BRCA mutation positive breast cancer patients in the Korean population through multicenter data and nation-wide breast cancer registry study. However, BRCA-mutated breast cancers appear highly complex, and further research on their molecular basis is needed in Korea.

Long-term survival of a patient with pulmonary artery intimal sarcoma after sequential metastasectomies of the thyroid and adrenal glands.

Cancer metastases to the thyroid or adrenal gland are uncommon. Furthermore, cases showing long-term survival after surgical resection of those metastatic tumors are rare. We report a case of pulmonary artery intimal sarcoma with metastases to the thyroid and adrenal glands sequentially that was successfully treated with sequential metastasectomies. A 62-year-old woman presented with a 4-week history of dyspnea on exertion and facial edema in November 1999. Echocardiography and chest computed tomography (CT) revealed an embolism-like mass in the pulmonary trunk. Pulmonary artery endarterectomy with pulmonary valve replacement was performed, and histopathology revealed pulmonary artery intimal sarcoma. A thyroid nodule was found by chest CT in November 2001 (2 years after initial surgery). During follow-up, this lesion showed no change, but we decided to obtain fine needle aspiration cytology (FNAC) in August 2004 (4.7 years after initial surgery). FNAC revealed atypical spindle cells suggestive of metastatic intimal sarcoma. She underwent total thyroidectomy. During follow-up, a right adrenal gland mass was detected by chest CT in March 2006 (6.3 years after initial surgery), and adrenalectomy was done, which also revealed metastatic sarcoma. She has been followed up without any evidence of recurrent disease until May 2012 (12.5 years after initial surgery).

Lymphovascular invasion is associated with lateral cervical lymph node metastasis in papillary thyroid carcinoma.

OBJECTIVES: The objective of this retrospective study to evaluate whether lymphovascular invasion (LVI) is associated with lateral cervical lymph node metastasis and tumor recurrence in papillary thyroid carcinoma (PTC). METHODS: We evaluated the medical records of patients with PTC who had undergone total thyroidectomy and subsequent I remnant ablation at Asan Medical Center, Seoul, Korea, from January 1997 thorough December 2000. RESULTS: A total of 662 patients (585 women and 77 men; mean age, 44.8 years) with PTC were enrolled in the study. Of these patients, 33 were found to have LVI. We found a significant association between LVI and lateral cervical lymph node metastasis at the time of initial surgery (P = .001). Multivariate analyses adjusting for clinicopathologic parameters known to predict recurrence such as age, gender, tumor size, extrathyroid extension, and multifocality also showed a significant association between LVI and lateral cervical lymph node metastasis. For the 633 patients without distant metastasis at the time of initial surgery, LVI was also significantly associated with tumor recurrence during the follow-up period (median, 68 months; range, 3-108 months): 29% versus 13.6% for patients with and without LVI, respectively (P = .048 by log-rank test). However, this association was lost on multivariate analyses adjusting for conventional clinicopathologic predictors of recurrence. CONCLUSIONS: In patients with PTC, LVI is associated with lateral cervical lymph node metastasis and clinical recurrence.