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1.  Clinical predictors of right upper paraesophageal lymph node metastasis from papillary thyroid carcinoma 
Background
Central and lateral lymph node metastases are quite common in patients with papillary thyroid carcinoma, and the predictors for those metastases have been well studied. Right upper paraesophageal lymph node metastasis has rarely been studied. The aim of this study was to identify the clinicopathological characteristics that may be risk factors for right upper paraesophageal lymph node metastasis in patients with papillary thyroid carcinoma.
Methods
This was a prospective observational study of 243 patients with papillary thyroid carcinoma (PTC) who underwent total thyroidectomy and comprehensive central lymph node dissection with or without lateral lymph node dissection between April 2008 and January 2010. The clinicopathologic findings from these patients were investigated and the patterns of lymph node metastasis were analyzed in the patients who had right upper paraesophageal lymph node disease.
Results
Of the 243 patients undergoing lymph node dissection, 14 had right upper paraesophageal lymph node metastases. Two of these patients had right upper paraesophageal lymph node metastasis only, without central compartment metastasis. Univariate analysis of clinicopathologic findings showed that right upper paraesophageal lymph node metastasis had significant association with larger primary tumors, multifocal tumors, extrathyroid extension, and lymphatic invasion (p <0.05 for each factor).
Conclusions
Although there were no independent predictors of right upper paraesophageal lymph node metastasis, it can be the only site of metastasis without other compartmental metastasis. Therefore, during surgery for patients with central or lateral lymph node metastases from PTC, it may be helpful to examine the right upper paraesophageal lymph nodes.
doi:10.1186/1477-7819-10-164
PMCID: PMC3490984  PMID: 22897890
Paraesophageal lymph node; Thyroid cancer; Papillary thyroid carcinoma
2.  Lymph Node Ratio Predicts Recurrence in Papillary Thyroid Cancer 
The Oncologist  2013;18(2):157-162.
This study aims to determine how the lymph node ratio may be used to predict the likelihood of recurrence for patients with papillary thyroid cancer.
Learning Objectives
Explain how lymph node ratio can be used to predict disease recurrence for papillary thyroid cancer.Cite the threshold total and central lymph node ratios that best predict recurrence.Describe ways in which lymph node ratio can be useful in guiding postoperative follow-up.
Background.
Lymph node metastasis occurs in 20%–50% of patients presenting for initial treatment of papillary thyroid cancer (PTC). The significance of lymph node metastases remains controversial, and the aim of this study is to determine how the lymph node ratio (LNR) may predict the likelihood of disease recurrence.
Methods.
We conducted a retrospective review of patients undergoing total thyroidectomy for PTC at our institution from 2005 to 2010. A total LNR (positive nodes to total nodes) and central lymph node ratio (cLNR) was calculated. Regression was used to determine a threshold LNR that best predicted recurrence. Multivariate logistic regression then determined the influence of LNR on recurrence while accounting for other known predictors of recurrence. Kaplan-Meier analysis and the log-rank test were used to compare differences in disease-free survival.
Results.
Of the 217 patients undergoing total thyroidectomy for PTC, 69 patients had concomitant neck dissections. Sixteen (23.2%) patients developed disease recurrence. When disease-free survival functions were compared, we found that patients with a total LNR ≥0.7 (p < .01) or a cLNR ≥0.86 (p = .04) had significantly worse disease-free survival rates than patients with ratios below these threshold values. Considering other known predictors of recurrence, we found that LNR was significantly associated with recurrence (odds ratio: 19.5, 95% confidence interval: 4.1–22.9; p < .01).
Conclusions.
Elevated total LNR and cLNR are strongly associated with recurrence of PTC after initial operation. LNR in PTC is a tool that can be used to determine the likelihood of the patient developing recurrent disease and inform postoperative follow-up.
doi:10.1634/theoncologist.2012-0240
PMCID: PMC3579599  PMID: 23345543
Thyroid cancer; Recurrence; Lymph node metastases; Quality measure; Lymph node ratio
3.  Total thyroidectomy without prophylactic central neck dissection in clinically node-negative papillary thyroid cancer: is it an adequate treatment? 
Background
Cervical lymph node metastases in papillary thyroid cancer are common. Although central neck dissection is indicated in clinically nodal-positive disease, it remains controversial in patients with no clinical evidence of nodal metastasis. The aim of this retrospective study was to determine the outcomes of clinically lymph node-negative patients with papillary thyroid cancer who underwent total thyroidectomy without a central neck dissection, in order to determine the rates of recurrence and reoperation in these patients compared with a group of patients submitted to total thyroidectomy with central neck dissection.
Methods
Two-hundred and eighty-five patients undergoing total thyroidectomy with preoperative diagnosis of papillary thyroid cancer, in the absence of suspicious nodes, were divided in two groups: those who underwent a thyroidectomy only (group A; n = 220) and those who also received a central neck dissection (group B; n = 65).
Results
Six cases (2.1%) of nodal recurrence were observed: 4 in group A and 2 in group B. Tumor histology was associated with risk of recurrence: Hürthle cell-variant and tall cell-variant carcinomas were associated with a high risk of recurrence. Multifocality and extrathyroidal invasion also presented a higher risk, while smaller tumors were at lower risk.
Conclusions
The role of prophylactic central lymph node dissection in the management of papillary thyroid cancer remains controversial. Total thyroidectomy appears to be an adequate treatment for clinically node-negative papillary thyroid cancer. Prophylactic central neck dissection could be considered for the more appropriate selection of patients for radioiodine treatment and should be reserved for high-risk patients only. No clinical or pathological factors are able to predict with any certainty the presence of nodal metastasis. In our experience, tumor size, some histological types, multifocality, and locoregional infiltration are related to an increased risk of recurrence. The potential use of molecular markers will hopefully offer a further strategy to stratify the risk of recurrence in patients with papillary thyroid cancer and allow a more tailored approach to offer prophylactic central neck dissection to patients with the greatest benefit. Multi-institutional larger studies with longer follow-up periods are necessary to draw definitive conclusions.
doi:10.1186/1477-7819-12-152
PMCID: PMC4032348  PMID: 24885654
Papillary thyroid carcinoma; Central neck dissection; Total thyroidectomy
4.  Video-Assisted Thyroidectomy for Papillary Thyroid Carcinoma 
Journal of Oncology  2010;2010:148542.
Background. The results of video-assisted thyroidectomy (VAT) were evaluated in a large series of patients with papillary thyroid carcinoma (PTC), especially in terms of completeness of the surgical resection and short-to-medium term recurrence. Methods. The medical records of all patients who underwent video-assisted thyroidectomy for PTC between June 1998 and May 2009 were reviewed. Results. Three hundred fifty-nine patients were included. One hundred twenty-six patients underwent concomitant central neck node removal. Final histology showed 285 pT1, 26 pT2, and 48 pT3 PTC. Lymph node metastases were found in 27 cases. Follow-up was completed in 315 patients. Mean postoperative serum thyroglobulin level off levothyroxine was 5.4 ng/mL. Post operative ultrasonography showed no residual thyroid tissue in all the patients. Mean post-operative 131I uptake was 1.7%. One patient developed lateral neck recurrence. No other recurrence was observed.
doi:10.1155/2010/148542
PMCID: PMC2952809  PMID: 20953412
5.  How the preoperative ultrasound examination and BFI of the cervical lymph nodes modify the therapeutic treatment in patients with papillary thyroid cancer 
BMC Surgery  2013;13(Suppl 2):S52.
Background
Ultrasound is considered the best diagnostic method for the detection of metastatic cervical lymph nodes (LNs) in patients with papillary thyroid carcinoma (PTC). According to current guidelines, all patients undergoing thyroidectomy for malignancy should undergo preoperative neck ultrasound of the thyroid and central and lateral neck LNs, followed by fine needle aspiration of suspicious LNs. Cervical LN involvement determenes the extent of surgery. Complete surgical resection disease at the initial operation decreases likelihood of future surgery for recurrent disease and may impact survival. We use a new technique, B-flow imaging (BFI), recently used for evaluation of thyroid nodules, to estimate the presence of BFI twinkling signs (BFI-TS), within metastatic LNs in patients with PTC.
Methods
Between September 2006 and December 2012, 304 patients with known PTC were examined for preoperative sonographic evaluation with gray-scale US, color Doppler US and BFI. Only 157 with at least one metastatic LN were included in our study. All patients included underwent surgery, and the final diagnosis was based on the results of histologic examination of the resected specimens. The following LN characteristics were evaluated: LN shape, abnormal echogenicity, the absent of hilum, calcifications, cystic appearance, peripheral vascularization and the presence of BFI-TS.
Results
A total of 767 LNs were analyzed. 329 out of 767 were metastatic, according to the histopathologic findings. BFI-TS, showed 99.5% specificity and 81,5% sensitivity. We detected BFI-TS in 6 metastatic LNs that were negative to the other conventional US features.
Conclusions
Our results indicate that the BFI-TS has a diagnostic accuracy higher than the other conventional sonographic signs. Our findings suggest that BFI can be helpful in the selection of suspicious neck LNs that should be examined at cytologic examination or open biopsy for accurate preoperative staging and individual therapy selection.
doi:10.1186/1471-2482-13-S2-S52
PMCID: PMC3851007  PMID: 24267705
6.  Impact of Routine Unilateral Central Neck Dissection on Preablative and Postablative Stimulated Thyroglobulin Levels after Total Thyroidectomy in Papillary Thyroid Carcinoma 
Annals of Surgical Oncology  2011;19(1):60-67.
Background
Prophylactic central neck dissection (CND) remains controversial in papillary thyroid carcinoma (PTC). Because postsurgical stimulated thyroglobulin (sTg) level is a good surrogate for recurrence, the study aimed to evaluate the impact of prophylactic CND on preablative and postablative sTg levels after total thyroidectomy.
Methods
Of the 185 patients retrospectively analyzed, 82 (44.3%) underwent a total thyroidectomy and prophylactic CND (CND-positive group) while 103 (55.7%) underwent total thyroidectomy only (CND-negative group). All patients had no preoperative or intraoperative evidence of lymph node metastases. Clinicopathological characteristics, postoperative outcomes, and preablative and postablative sTg levels were compared between the two groups. Preablative sTg level was taken at the time of radioiodine ablation, while postablative sTg level was taken 6 months after ablation. A multivariable analysis was conducted to identify factors for preablative athyroglobulinemia (sTg < 0.5 μg/L).
Results
Relative to the CND-negative group, the CND-positive group had larger tumors (15 mm vs. 10 mm, P < 0.005), more extrathyroidal extension (26.8% vs. 14.6%, P < 0.003), more tumor, node, metastasis system stage III disease (32.9% vs. 9.7%, P < 0.001), and more temporary hypoparathyroidism (18.3% vs. 8.7%, P = 0.017). Fourteen patients (17.1%) in the CND-positive group were upstaged from stages I/II to III as a result of prophylactic CND. The CND-positive group experienced lower median preablative sTg (<0.5 μg/L vs. 6.7 μg/L, P < 0.001) and a higher rate of preablative athyroglobulinemia (51.2% vs. 22.3%, P = 0.024), but these differences were not observed 6 months after ablation. Prophylactic CND was the only independent factor for preablative athyroglobulinemia.
Conclusions
Although performing prophylactic CND in total thyroidectomy may offer a more complete initial tumor resection than total thyroidectomy alone by minimizing any residual microscopic disease, such a difference becomes less noticeable 6 months after ablation.
doi:10.1245/s10434-011-1833-x
PMCID: PMC3251780  PMID: 21681379
7.  Video-assisted thyroidectomy: lessons learned after more than one decade 
Summary
In selected patients, video-assisted thyroidectomy can be considered a safe and validated procedure offering significant advantages over conventional surgery, with no additional morbidity. Aim of this study was to evaluate the results obtained in a series of patients selected for video-assisted thyroidectomy over a 10-years period. All patients who underwent video-assisted thyroidectomy from June 1998 to June 2009 were considered. The eligibility criteria for video-assisted thyroidectomy are: thyroid nodules ≤ 35 mm; estimated thyroid volume < 30 ml; no previous conventional neck surgery and/or radiation therapy; small, low-risk papillary thyroid carcinoma. A total of 1363 video-assisted thyroidectomies were attempted in the time period considered. Conversion to the conventional procedure was necessary in 7 cases. Thyroid lobectomy was successfully performed in 157 cases, total thyroidectomy in 1175, and completion thyroidectomy in 24. In 126 patients, the central neck nodes were removed through the same access. Simultaneous video-assisted parathyroidectomy, for a parathyroid adenoma, was performed in 42 patients. Pathological studies showed benign disease in 986 cases, papillary thyroid carcinoma in 368 cases, C-cells hyperplasia in 1 case, and medullary microcarcinoma in 1 patients with RET germline mutation. Post-operative complications included 27 transient and 1 definitive recurrent laryngeal nerve palsy, 230 transient hypocalcemia, 10 definitive hypoparathyroidism, 4 postoperative hematoma and 5 wound infection.
PMCID: PMC2868209  PMID: 20463836
Thyroidectomy; Minimally invasive thyroidectomy; Endoscopic thyroidectomy
8.  Risk factors of central lymph node metastasis in cN0 papillary thyroid carcinoma: A study of 529 patients 
Background
Lymph node metastasis in papillary thyroid carcinoma (PTC) is common; however, the need for prophylactic central lymph node dissection (CLND) in PTC is still controversial. The objective of this study was to investigate the risk factors of central lymph node metastasis (CLNM) in clinically lymph node-negative (cN0) PTC patients.
Material/Methods
A total of 529 cN0 PTC patients who underwent lobectomy plus isthmusectomy or total thyroidectomy with unilateral or bilateral CLND between 2010 and 2012 were enrolled in this study. Clinicopathologic risk factors for CLNM were studied using univariate and multivariate analysis.
Results
CLNM was found in 238 (45.0%) cases. In univariate analysis, male sex, age <45 years, tumor size >2 cm, tumor located in the middle/lower third of lobe, and multifocality were significantly associated with CLNM (P<0.05); extrathyroid extension, Hashimoto’s thyroiditis, and TSH value were not associated with CLNM. In multivariate analysis, tumor size >2 cm, age <45 years, multifocality, and tumor located in the middle/lower third of the lobe were independent predictors for CLNM.
Conclusions
Prophylactic CLND should be considered in cN0 PTC patients with the following risk factors: tumor size >2 cm, age <45 years, multifocality, or tumor located in the middle/lower third of the lobe. However, further long-term follow-up studies and multicenter research are needed to better understand these risk factors and the significance of prophylactic CLND.
doi:10.12659/MSM.890182
PMCID: PMC4031227  PMID: 24831428
CLND; CLNM; Prophylactic; cN0; Lymph Nodes; Thyroid Neoplasms; Risk Factors
9.  Papillary thyroid carcinoma with thyroiditis: lymph node metastasis, complications 
Purpose
The aim of this study was to evaluate the clinicopathologic characteristics of papillary thyroid cancer with thyroiditis, and to determine the rate of its complications for it.
Methods
A retrospective review of 1,247 patients with papillary thyroid cancer who underwent primary thyroidectomy was performed. Among them, 316 patients had thyroiditis (group I) while 931 patients had no thyroiditis (group II), as reflected in the final pathologic reports. The two groups' clinicopathologic results and rate of complications were compared.
Results
Female gender, preoperative hypothyroidism, total thyroidectomy, no extrathyroid extension, no lymphovascular invasion, and no perineural invasion were associated with group I. More central lymph nodes were removed in group I than in group II, but there were fewer central lymph nodes with metastasis in group I than in group II. For the lateral lymph nodes, the two groups had the same numbers of removed nodes and nodes with metastatic tumor. Multivariate analysis revealed female predominance, more cases of preoperative hypothyroidism, more dissected lymph nodes, and fewer lymph nodes with metastasis in group I. Among the patients who underwent lobectomy, postoperative hypothyroidism occurred more in group I than in group II (P < 0.001). There was no difference in postoperative complications between the two groups.
Conclusion
Papillary thyroid cancer with thyroiditis showed less aggressive features. Postoperative hypothyroidism occurred more in the patients with thyroiditis.
doi:10.4174/jkss.2013.85.1.20
PMCID: PMC3699683  PMID: 23833756
Thyroiditis; Papillary thyroid cancer; Hypothyroidism
10.  Risk factors for central lymph node metastasis of patients with papillary thyroid microcarcinoma: a meta-analysis 
Objective: To evaluate the risk factors of central lymph node metastasis of papillary thyroid microcarcinoma. Method: Published articles about papillary thyroid microcarcinoma were searched in PubMed, MEDLINE and EMBASE until October 2013 to examine the risky factors of central lymph node metastasis. Software RevMan 5.0 was used for meta-analysis. Results: Within the patients suffering papillary thyroid microcarcinoma underwent thyroidectomy plus prophylactic central lymph node dissection, tumor size, multifocality and capsular invasion have statistically relevant association with central lymph node metastasis, but no relation was observed associated with sex and age. Conclusion: The papillary thyroid microcarcinoma should be considered central lymph node metastasis when tumor size ≥0.5 cm, multifocality and have capsular invasion.
PMCID: PMC3971295  PMID: 24696711
Risk factors; central lymph node metastasis; papillary thyroid carcinoma
11.  Prognostic parameters for recurrence of papillary thyroid microcarcinoma 
BMC Cancer  2008;8:296.
Background
Papillary thyroid microcarcinoma (PTMC) is defined as a papillary thyroid carcinoma less than or equal to 1.0 cm in size. Independent prognostic factors for clinical recurrence of PTMC have not been clearly delineated.
Methods
Clinicopathological parameters predicting PTMC recurrence were determined by retrospective analysis of 307 patients.
Results
Of the 293 patients eligible for analysis, 14 (5%) had recurrence during a median follow-up time of 65 months. Recurrence was observed in 8 of 166 patients (0.5%) treated with total or near-total thyroidectomy; gender (P = 0.02) and presence of lateral cervical node metastases at initial surgery (P = 0.01) were associated with recurrence. Six of the 127 patients (0.5%) treated with hemi- or subtotal thyroidectomy experience recurrences, but no significant prognostic factor for recurrence was identified. Multivariate Cox-regression analysis showed that gender and cervical lymph node metastasis were significant variables
Conclusion
PTMC showed very diverse disease extent and could not be regarded as indolent, relatively benign disease based on the primary tumor size. The extent of surgery should be based on prognostic parameters, such as gender and lateral neck node metastasis, in patients with PTMC.
doi:10.1186/1471-2407-8-296
PMCID: PMC2576338  PMID: 18851763
12.  Comparative study comparing endoscopic thyroidectomy using the axillary approach and open thyroidectomy for papillary thyroid microcarcinoma 
Background
Endoscopic thyroidectomy has been applied prudently to malignant thyroid tumors. The purpose of our study was to compare the surgical outcomes of endoscopic thyroidectomy (ET) and conventional open thyroidectomy (COT) for micropapillary thyroid carcinoma.
Methods
From October 2002 to December 2008, 78 patients underwent unilateral lobectomy and isthmectomy with central lymph node dissection for papillary thyroid microcarcinoma. Of these, 37 patients underwent ET and 41patients COT. Surgical outcomes, including operation time, number of retrieved lymph nodes, postoperative complication rate and patients’ satisfaction with the cosmetic results, were analyzed.
Results
The mean age of the patients was 42.3 ± 7.6 years in the ET group and 49.0 ± 10.8 years in the OT group (P = 0.003). The operation time was shorter in the COT group (112.3 ± 14min) than in the ET group (138.4 ± 36.9 min, P< 0.01). However, there were no significant differences in tumor size (0.5 ± 0.231vs. 0.41 ± 0.264cm, P = 0.116), number of retrieved lymph nodes (3.63 ± 2.1vs. 3.82 ± 3.28, P = 0.78) or postoperative hospital stay (3.35 ± 0.94vs. 3.17 ± 1.16 days, P = 0.457). Patients in the ET group experienced more pain than those in the COT group at 1 and 7 days after the operation as evaluated by a visual analog scale (P = 0.037, 0.026). Cosmetically, patients in the ET group were very satisfied with the operative procedure according to the questionnaire we used (1.43 ± 0.55vs. 3.21 ± 0.72, P< 0.001). The mean follow-up period was 54.3 months in the ET group and 47.4 months in the COT group, and each group exhibited one case of tumor recurrence detected at the other thyroid lobe within 2 years.
Conclusions
Large series of prospective studies and long-term follow-up are needed, but the results of ET using the axillary approach for micropapillary thyroid carcinoma were not inferiortothose using COT, and it might be a safe and feasible procedure with good cosmetic results.
doi:10.1186/1477-7819-10-269
PMCID: PMC3544716  PMID: 23234462
Endoscopic thyroidectomy; Conventional open thyroidectomy; Micropapillary thyroid carcinoma
13.  Hybrid-type endoscopic thyroidectomy (HET: Tori’s method) for differentiated thyroid carcinoma including invasion to the trachea 
Surgical Endoscopy  2013;28:902-909.
Background
Endoscopic thyroidectomy (ET) or robotic thyroidectomy is yet to be applied to thyroid carcinoma invasive to the trachea and to wide lymph node node metastasis. On the other hand, small-incision thyroidectomy lacks sufficient working space and clear vision. The author has newly developed hybrid-type endoscopic thyroidectomy (HET) to overcome these problems.
Methods
From March 2011 to February 2012, HET was performed for 85 patients. Clinicopathologic characteristics were analyzed. To evaluate the superiority of HET for malignancy representatively, conventional lobectomy with central compartment node dissection (CCND) performed 1 year previously was compared with HET. In lobectomy and node dissection, a single skin incision (1.5 cm) is made above the clavicle, with a port incision (5 mm) made 3 cm below the clavicle. Then CCND is performed directly through the incision by lifting up the isthmus. To obtain sufficient working space for the lobectomy, the strap muscles are taped and pulled toward the head, then hung by the cradle. The thyroid lobe is retracted to the midline with a retractor, followed by isolation of the inferior laryngeal nerve and transection of the inferior thyroid vessels with the monitor of the scope. Lateral lymph nodes dissection can be performed at the same time, if necessary. In total thyroidectomy, the same procedure is performed at the opposite side. The scalpel can be used to shave through each incision in case of tracheal invasion.
Results
Of the 85 cases, 62 were malignant, involving papillary thyroid carcinoma (PTC), and 23 were benign. Total thyroidectomy was performed for 22 of the PTC cases and CCND for 49 of the cases. Shaving for tracheal invasion was performed for eight patients. No mortality, complications, recurrence, or metastasis was found 1–2 years after the operation. Compared with conventional thyroidectomy, HET was superior in blood loss, visual analog scale, and postoperative hospital stay.
Conclusion
The author’s method (Tori’s method) might be less invasive, cosmetically excellent, and moreover, safe and feasible for differentiated thyroid carcinoma including invasion to the trachea.
doi:10.1007/s00464-013-3245-4
PMCID: PMC3931932  PMID: 24263457
Endoscopic thyroidectomy; Thyroid cancer; Tracheal invasion; Hybrid-type operation; HET (Tori’s method)
14.  Pattern, predictors, and recurrence of cervical lymph node metastases in papillary thyroid cancer 
Contemporary Oncology  2013;17(6):504-509.
Aim of the study
This study investigated the pattern, predictors, and recurrence of node metastasis in papillary thyroid cancer patients.
Material and methods
One hundred and 65 papillary thyroid cancer (PTC) patients who underwent total thyroidectomy and cervical lymph node (LN) dissection (LND), in which more than 12 lymph nodes were dissected, were examined. The nodes were classified from levels I to VI. Final pathologic diagnosis of positive lymph node metastases in the differential node levels was determined.
Results
Cervical metastases of PTC were most commonly encountered in level VI, followed by levels III and IV, and then levels II and V. Metastases in level I seldom occurred. Skip metastases occurred in nine patients. Univariate analysis suggested that multifocality and extracapsular invasion were associated with LN metastases. The metastatic ratio for micro PTC and local canceration derived from benign lesions and encapsulation was low. Multivariate analysis showed that LN metastases were closely related to invasion of the thyroid capsule and primary PTC. Standardized estimation showed that the encapsulating pattern had the greatest impact on developing cervical LN metastases. Lymph node recurrence was observed in 11 patients.
Conclusions
The metastatic pattern of PTC assists in delineating the extent of selective LND. Routine bilateral central node dissection at the time of thyroidectomy is recommended. Comprehensive selective LND is recommended in multifocal PTC and with capsular invasion.
doi:10.5114/wo.2013.38910
PMCID: PMC3934041  PMID: 24592137
papillary thyroid cancer (PTC); cervical lymph node metastases; lymph node dissection (LND)
15.  Risk of lymph node metastases in multifocal papillary thyroid cancer associated with Hashimoto's thyroiditis 
Aims
The aim of this study was to evaluate the risk factors of lymph nodes metastases (LNM) in patients with papillary thyroid cancer (PTC) and coexisting Hashimoto’s thyroiditis (HT).
Patients and methods
This was a retrospective cohort study of patients with PTC and HT who had undergone total thyroidectomy (TT) with central neck dissection (CND) over an 11-year period (between 2002 and 2012). Pathological reports of all eligible patients were reviewed. Multivariable analysis was performed to identify risk factors of LNM.
Results
During the study period, PTC was diagnosed in 130 patients with HT who had undergone TT with CND (F/M ratio = 110:20; median age, 52.4 ± 12.7 years). Multifocal lesions were observed in 28 (21.5 %) patients. LNM were identified in 25 of 28 (89.3 %) patients with multifocal PTC and HT versus 69 of 102 (67.5 %) patients with a solitary focus of PTC and HT (p = 0.023). In multivariable analysis, multifocal disease was identified as an independent risk factor for LNM (odds ratio, 3.99; 95 % confidence interval, 1.12 to 14.15; p = 0.033).
Conclusions
Multifocal PTC in patients with HT is associated with an increased risk of LNM. Nevertheless, the clinical importance of this finding needs to be validated in well-designed prospective studies.
doi:10.1007/s00423-013-1158-2
PMCID: PMC3916705  PMID: 24407910
Hashimoto’s thyroiditis; Multifocal papillary thyroid cancer; Benign thyroid disease
16.  Impact of Iymph node metastases identified on central neck dissection (CND) on the recurrence of papillary thyroid cancer: potential role of BRAFV600E mutation in defining CND 
Endocrine-related cancer  2013;20(1):13-22.
The impact of metastasized cervical lymph nodes (CLN) identified on central neck dissection (CND) on the recurrence/persistence of papillary thyroid cancer (PTC) and the extent of CND needed to reduce recurrence/persistence have not been firmly established. To assess the impact of CLN metastasis and BRAF mutation on the recurrence/persistence of PTC and the potential of BRAF mutation in assisting CND, we analysed data of 379 consecutive patients with PTC who underwent thyroidectomy with (n=243) or without CND (n=136) at a tertiary-care academic hospital during the period 2001–2010 for their clinicopathological outcomes and BRAF mutation status. Increasingly aggressive tumor characteristics were found as the extent of CND was advanced following conventional risk criteria from non-CND to limited CND to formal CND. Disease recurrence/persistence rate also sharply rose from 4.7% to 15.7% and 40.5% in these CND settings respectively (P<0.0001). CLN metastasis rate rose from 18.0 to 77.3% from limited CND to formal CND (P<0.0001). An increasing rate of BRAF mutation was also found from less to more extensive CND. A strong association of CLN metastasis and BRAF mutation with disease recurrence/persistence was revealed on Kaplan– Meier analysis and BRAF mutation strongly predicted CLN metastasis. CLN metastases found on CND are closely associated with disease recurrence/persistence of PTC, which are both strongly predicted by BRAF mutation. Current selection of PTC patients for CND is appropriate but higher extent of the procedure, once selected, is needed to reduce disease recurrence, which may be defined by combination use of preoperative BRAF mutation testing and conventional risk factors of PTC.
doi:10.1530/ERC-12-0309
PMCID: PMC3779438  PMID: 23132792
papillary thyroid cancer; neck dissection; BRAF mutation; lymph node metastasis; thyroid cancer recurrence
17.  Optimal surgical extent of lateral and central neck dissection for papillary thyroid carcinoma located in one lobe with clinical lateral lymph node metastasis 
Background
The indications and extent of cervical lymph node dissection in papillary thyroid carcinoma (PTC) are still being debated. The aim of this study was to analyze the patterns of cervical lymph node metastasis in the lateral and central compartment and related factors and suggest the optimal extent of lateral and central neck dissection for PTC patients with clinical lateral lymph node metastasis.
Methods
We retrospectively analyzed 72 patients with unilateral PTC who underwent therapeutic lateral neck dissections with concomitant total thyroidectomy and central neck dissection between January 2001 and December 2009.
Results
The 72 patients underwent 79 sides of therapeutic lateral neck dissection. The most frequent metastatic level in the ipsilateral lateral compartment was level IV (75.0%), followed by level III (69.4%), level II (56.9%) and level V (20.8%). Multiple level metastases were common (77.8%) and were correlated with tumor size (≥ 10 mm). The central compartment lymph node metastasis rate was 87.5%, including 26.4% of contralateral central compartment metastases.
Conclusion
In PTC patients with clinical lateral lymph node metastasis, the optimal extent of lateral and central neck dissection should include levels II, III, IV and V as well as the bilateral central compartment.
doi:10.1186/1477-7819-10-221
PMCID: PMC3544686  PMID: 23098385
Papillary thyroid carcinoma; Lateral neck dissection; Lymph node metastasis; Central neck dissection
18.  Thymectomy in central lymph node dissection for papillary thyroid cancer 
Background: Central lymph node dissection (CND) has been proposed in the treatment of patients affected by papillary thyroid cancer (PTC) with clinically negative neck lymph nodes. The procedure allows pathologic staging of lymph nodes of the central compartment and treatment of the micrometastases. By comparing bilateral and unilateral thymectomy during total thyroidectomy with central lymph node dissection for postoperative complications in sonographically node-negative papillary thyroid carcinomas, we aimed to determine the optimal extent of prophylactic central lymph node dissection. Methods: Patients were divided into two study groups: Group 1, total thyroidectomy plus unilateral thymectomy during the CND; Group 2, total thyroidectomy associated with bilateral thymectomy (both upper poles) during the CND. Primary endpoints of the study were evaluated by comparing the postoperative complications between the two groups. Results: The only significant result found when comparing the two groups was the rate of transient hypocalcemia. (Group 1: 13.7%, Group 2: 52.4%, p<0.01). A total of five cases of papillary thymic metastases were found in this study. And final pathology confirmed that all cases of thymic metastases were lymph node micrometastases of PTC, only situated in the ipsilateral thymus upper pole. Conclusions: Bilateral thymectomy during the CND did not provide a better carcinologic resection, as no contralateral thymic metastases were found. The unilateral thymectomy with total thyroidectomy during the CND may represent an effective strategy for reducing the rate of postoperative hypocalcemia.
PMCID: PMC4057874  PMID: 24955195
Thymectomy; papillary thyroid cancer; lymph node dissection
19.  Metastatic papillary thyroid carcinoma with absence of tumor focus in thyroid gland 
Summary
Background:
Papillary thyroid carcinoma presenting as isolated cervical lymphadenopathy with clinically and histologically normal thyroid gland is rarely reported.
Case Report:
We report a case of 31 years old female who presented with a left cervical mass and clinically normal thyroid gland. After inconclusive FANC, excision biopsy of her cervical lymph nodes revealed metastatic papillary thyroid carcinoma. The patient subsequently underwent total thyroidectomy with bilateral lymph node dissection. Interestingly pathological examination showed no primary carcinoma in the gland. Postoperative radioactive iodine scan revealed no other metastasis.
Conclusions:
Total thyroidectomy is the next best step despite clinically and radiologically normal appearing thyroid gland once cervical lymph nodes are proven to be metastatic in nature followed by a RAI therapy to treat occult foci of PTC.
doi:10.12659/AJCR.883834
PMCID: PMC3619041  PMID: 23569568
papillary thyroid micro carcinoma (PTMC); fine needle aspiration cytology (FNAC); computed tomography (CT); papillary thyroid carcinoma (PTC)
20.  Role of prophylactic central neck dissection in cN0 papillary thyroid cancer 
Summary
Prophylactic central neck dissection in papillary thyroid cancer is controversial. In this retrospective cohort study, the aim was to assess possible advantages of prophylactic central neck dissection with total thyroidectomy in cN0 papillary thyroid cancer. A total of 244 consecutive patients with papillary thyroid cancer, without clinical and ultrasound nodal metastases (cN0), were evaluated out of 1373 patients operated for a thyroid disease at the Istituto Europeo di Oncologia, Milan, Italy from 1994 to 2006. Of these 244 patients, 126 (Group A) underwent thyroidectomy with central neck dissection, while 118 (Group B) underwent thyroidectomy alone. Demographic, clinical and pathological features were analysed. Overall recurrence rate was 6.3% (8/126) in Group A and 7.7% (9/118) in Group B, with a mean follow-up of 47 (Group A) and 64 (Group B) months. In Group A patients, 47% were pN1a and all patients with recurrence had nodal involvement (p = 0.002). Survival rate did not differ in the two groups. Nine patients were lost to follow-up. Group A patients were older and their tumours were larger in size; according to the pT distribution, a higher extra-capsular invasion rate was observed. The two groups were equivalent as far as concerns histological high risk variants and multifocality. Nodal metastases correlated with stage: pT1-2 vs. pT3-T4a, p = 0.0036. A lower risk of nodal metastases was related to thyroiditis (p = 0.0034). In conclusion, central neck metastases were predictive of recurrence without influencing prognosis. From data obtained, possible greatest efficacy of central neck dissection in pT3-4 papillary thyroid cancer without thyroiditis is suggested.
PMCID: PMC2808683  PMID: 20111614
Thyroid; Papillary thyroid cancer; Nodal metastases; Central neck dissection
21.  Cerebellar mass as a primary presentation of papillary thyroid carcinoma: case report and literature review 
Head & Neck Oncology  2009;1:23.
Background
Papillary carcinoma is the most common differentiated malignant thyroid neoplasm. The biological course of this cancer is typically indolent with a protracted clinical course. Metastases commonly occur in regional lymph nodes, and distant metastasis is a late and rare occurrence. We report a patient who presented with cerebellar metastasis prior to the diagnosis of papillary thyroid carcinoma and review the literature of brain metastasis from papillary thyroid carcinoma.
Results
A 75-year old female presented at the emergency room with progressive dizziness, headache and vomiting, where a brain CT and MRI showed a posterior cerebellar tumor. Surgical resection revealed papillary carcinoma consistent with thyroid origin. Subsequent ultrasound and CT-scan revealed a thyroid nodule, after which the patient underwent total thyroidectomy. Pathologic evaluation was consistent with papillary thyroid carcinoma.
Conclusion
Brain metastasis may rarely be the initial presentation of papillary thyroid carcinoma. Solitary brain metastasis can completely be resected with better prognosis.
doi:10.1186/1758-3284-1-23
PMCID: PMC2712461  PMID: 19558727
22.  Predictive value of nodal metastases on local recurrence in the management of differentiated thyroid cancer. Retrospective clinical study 
BMC Surgery  2013;13(Suppl 2):S3.
Background
The significance of nodal metastases, very common in papillary thyroid cancer, and the role of lymph node dissection in the neoplasm management, are still controversial. The impact of lymph node involvement on local recurrence and long-term survival remains subject of active research. With the aim to better analyze the predictive value of lymph node involvement on recurrence and survival, we investigated the clinico-pathological patterns of local relapse following total thyroidectomy associated with lymph node dissection, for clinical nodal metastases papillary thyroid cancer, in order to identify the preferred surgical treatment.
Methods
Clinical records, between January 2000 and December 2006, of 69 patients undergoing total thyroidectomy associated with selective lymph node dissection for clinical nodal metastases papillary thyroid cancer, were retrospectively evaluated. Radioiodine ablation, followed by Thyroid Stimulating Hormone suppression therapy was recommended in every case. In patients with loco regional lymph nodal recurrence, a repeated lymph node dissection was carried out. The data were compared with those following total thyroidectomy not associated with lymph node dissection in 210 papillary thyroid cancer patients without lymph node involvement, at preoperative ultrasonography and intra operative inspection.
Results
Incidence of permanent hypoparathyroidism (iPTH < 10 pg/ml) and permanent monolateral vocal fold paralysis were respectively 1.4 % (1/69) and 1.4% (1/69), similar to those reported after total thyroidectomy "alone". The rate of loco regional recurrence, with positive cervical lymph nodes, following 8 year follow-up, was 34.7% (24/69), higher than that reported in patients without nodal metastases (4.2%). A repeated lymph node dissection was carried out without significant complications.
Conclusions
Nodal metastases are a predictor of local recurrence, and a higher rate of lymph node involvement is expected after therapeutic lymph node dissection associated with total thyroidectomy. The prognostic significance of nodal metastases on long-term survival remains unclear, and more prospective randomized trials are requested to better evaluate the benefits of different therapeutic approaches.
doi:10.1186/1471-2482-13-S2-S3
PMCID: PMC3851192  PMID: 24267409
Total thyroidectomy; Papillary thyroid cancer; Lymph node recurrence; Lymph node neck dissection; Radio active iodine ablation
23.  Solitary lateral neck node metastasis in papillary thyroid carcinoma 
Background
Papillary thyroid carcinoma (PTC) is associated with a high incidence of regional node metastasis, but the patterns of lateral neck node metastasis (LNM) vary. Occasionally, a solitary LNM (SLNM) is seen in PTC patients. We therefore assessed whether selective single level node dissection is appropriate in PTC patients with SLNM.
Methods
We retrospectively reviewed the medical records of 241 PTC patients who underwent total thyroidectomy with central neck dissection plus ipsilateral internal jugular node dissection (level II to IV) between January 2010 and December 2011. Of these patients, 51 had SLNM and 190 had multiple LNM (MLNM). The clinicopathologic characteristics of the two groups were compared.
Results
Age, gender ratio, and numbers of lateral neck nodes harvested (29.4 ± 11.0 versus 30.3 ± 9.5; P = 0.574) were similar in the SLNM and MLNM groups. Mean primary tumor size was significantly smaller in the SLNM than in the MNLM group (1.03 cm versus 1.35 cm; P = 0.037). The proportion of patients with primary tumor ≤ 1 cm was significantly greater in the SLNM group (60.8% versus 38.4%; P = 0.006), whereas the proportion with maximal node size ≤ 0.7 cm (28.9% versus 73.3%; P <0.001) and the proportion with capsular invasion (62.7% versus 83.7%, P = 0.002) were significantly lower in the SLNM than in the MLNM group.
Conclusions
Selective single level neck dissection can be considered as an alternative to systemic lateral neck dissection in PTC patients with SLNM, maximal metastatic node size ≤ 0.7 cm, and no extrathyroidal invasion.
doi:10.1186/1477-7819-12-109
PMCID: PMC4016639  PMID: 24755464
thyroid; papillary; solitary; metastasis
24.  Contralateral papillary thyroid cancer: Does size matter? 
American journal of surgery  2009;197(3):342-347.
Background
The optimal extent of thyroidectomy for papillary thyroid cancers (PTCs) < 1 cm is controversial. Our aim was to identify the rate and factors predictive of contralateral PTC in these patients.
Methods
We examined 228 patients with PTC who underwent either completion or total thyroidectomy and analyzed the predictive value of tumor size, histology, margin status, capsular invasion, extrathyroid extension, multifocality, and node metastases.
Results
We observed no differences in the rate of contralateral disease in patients with primary PTC ≥ 1 cm compared to those < 1 cm, 30% vs. 24% respectively (P=0.43). Multifocality was the only factor predictive of contralateral PTC in patients with tumors < 1 cm (P=0.02). Patients with tumors < 0.5 cm also had a comparable rate of contralateral disease (27%).
Conclusion
The presence of contralateral PTC appears to be unrelated to the size of the primary tumor. Furthermore, in patients with PTCs < 1 cm, multifocality is a risk factor for PTC in the contralateral lobe.
doi:10.1016/j.amjsurg.2008.09.011
PMCID: PMC2679519  PMID: 19245912
Papillary thyroid cancer; Contralateral; Size; Risk factors; Microcarcinoma
25.  Clinical analysis of prophylactic central neck dissection for papillary thyroid carcinoma 
Purpose
The need of prophylactic central neck dissection (PCND) in patients with papillary thyroid carcinoma (PTC) is still controversial. The major restriction of PCND is the potential complications. We undertook a retrospective study to discuss its necessity in PTC patients.
Methods
A total of 188 patients with PTC who underwent total thyroidectomy and PCND were involved. In all of these, central lymph nodes were pathologic examined. Univariate and multivariate analyses were performed based on tumor location and size, etc.
Results
Overall, node metastases were found in 44.1 % (83/188) of patients. Tumor size was the independent positive predictor for lymph node metastasis, while gender, age, tumor multifocality, tumor location, and capsular infiltration were not independent predictors of central lymph node metastases. Postoperative complications happened in 5.3 % (10/188) of patients, which 4.8 % (9/188) had temporary hypocalcemia and 0 % (0/188) had permanent hypocalcemia. Rates of temporary and permanent recurrent laryngeal nerve injury were 0.5 % (1/188) and 0 % (0/188), respectively.
Conclusions
PCND is recommended in all patients with PTC.
doi:10.1007/s12094-013-1038-9
PMCID: PMC3884135  PMID: 23606353
Thyroid carcinoma; Papillary; cN0; Central lymph node; Prophylactic; Central neck dissection

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