Routine Central Lymph Node Dissection Research Articles

The prognostic value of lymph node dissection in patients with parathyroid carcinoma.

Surgery is the only curative treatment strategy for parathyroid carcinoma (PC). However, the optimal extent of surgery remains uncertain, particularly regarding whether routine central lymph node dissection (LND) confers a survival advantage to patients with PC. This study aimed to evaluate the prognostic value of LND in PC patients. Patients diagnosed with PC between 2004 and 2018 were identified in the Surveillance, Epidemiology, and End Results (SEER)-18 registries. With inclusion and exclusion criteria, a total of 338 patients were included as cohort 1 to describe the characteristics of PC, while 215 patients were selected as cohort 2 to assess the effect of LND on cancer-specific survival (CSS). Univariate and multivariate Cox proportional hazards regression models were used to identify independent risk factors associated with CSS. Propensity score matching (PSM) was performed to adjust for potential confounding variables. The prognostic value of LND was further analyzed in subgroups stratified by predictors associated with CSS. The 5- and 10-year CSS were 94.4% and 87.9% respectively in cohort 1. LND failed to significantly improve CSS in the entire cohort 2 and the PSM cohort 2. Large tumor size (>40 mm) and distant metastasis were independently associated with poor CSS. Subgroup analyses revealed that LND was not significantly associated with improved CSS in patients with aggressive PC, such as those with a tumor size greater than 40 mm. Unexpectedly, LND may compromise CSS in patients with distant disease (P=0.03). PC is a rare and indolent endocrine malignancy. The presence of large tumors and distant metastases are independent predictors of poor CSS. Routine central LND as part of initial surgery does not significantly improve CSS in PC patients, even for those with large tumors, lymph node metastasis, or distant disease.

Nomogram for predicting central lymph node metastasis in T1-T2 papillary thyroid cancer with no lateral lymph node metastasis.

Whether routine central lymph node dissection (CLND) is necessary for T1-T2 papillary thyroid carcinoma (PTC) patients without certain lateral lymph node metastases (LLNM) remains controversial. This study aims to construct a nomogram that predicts central lymph node metastasis (CLNM) for T1-T2 PTC patients without LLNM. We retrospectively reviewed adult T1-T2 PTC patients with no LLNM retrieved from the Surveillance, Epidemiology, and End Results (SEER) database from 2010 to 2015. We also collected data from patients treated at the First Hospital of China Medical University between February and April 2021 for external validation. Logistic regression model was used to construct a risk prediction model nomogram. The receiver-operating characteristic (ROC) curve, calibration plot, and decision curve analyses (DCA) were used for assessing the nomogram. 5,094 patients from the SEER database and 300 patients from our department were finally included in this study. Variables such as age, gender, race, tumor size, multifocality, and minimal extrathyroidal extension (mETE) were found to be associated with CLNM and were subsequently incorporated into our nomogram. The C-index of our constructed model was 0.704, while the internal and external validation C-indexes were 0.693 and 0.745, respectively. The nomogram was then evaluated using calibration and decision curve analyses. A visualized nomogram was successfully developed to predict CLNM in T1-T2 PTC patients without LLNM and assist clinicians in making personalized clinical decisions.

Lymph node metastasis around the entrance point to recurrent laryngeal nerve in papillary thyroid carcinoma

There are few reports on the lymph nodes of entrance point to recurrent laryngeal nerve (LN-epRLN) in patients with papillary thyroid carcinoma (PTC). Thus, we investigated the clinical significance of LN-epRLN and implications it may have. An observational analysis of 878 consecutive patients with PTC who underwent thyroidectomy from April 2016 to March 2017 was conducted. We explored the surrounding tissue of laryngeal entry point, during routine central lymph node dissection (CLND). The lymph node specimens were sent separately for routine histopathological examination. Thereafter, complications and follow-ups were recorded. LN-epRLNs were found in 73 of the 878 patients, with the metastatic rate of 3.76%. Univariate and multivariate analysis showed central lymph node metastases can serve as independent predictors for LN-epRLN metastasis. In summary, we confirmed the significance of LN-epRLN in metastasis and recurrence, which required precise anatomy and thorough CLND. In PTC patients, especially in suspicious presence of central cervical lymph node metastasis, attention should be given to excising the nodal tissue at the laryngeal entry point.

Identifying risk factors of lateral lymph node recurrence in clinically node-negative papillary thyroid cancer.

There is still debate regarding the role of routine central lymph node (LN) dissection in treating clinically node-negative papillary thyroid cancer (PTC). The aim of this study was to investigate the risk factors for lateral recurrence after total thyroidectomy and prophylactic bilateral central LN dissection in clinically node-negative PTC patients.We retrospectively collected the medical records of 1406 PTC patients who underwent total thyroidectomy and prophylactic bilateral central LN dissection between January 2004 and December 2008. We used Cox- proportional hazards regression analyses to inspect the predictive factors for recurrence.During a median follow-up of 107 months (range, 13–164 months), 68 (4.8%) and 37 (2.6%) patients experienced recurrence in any lesion and in lateral neck LN, respectively. Male, main tumor size >1 cm, nodal factors (pathologic N1a, positive delphian LN, and LN ratio >0.15), lymphovascular invasion, and extrathyroidal extension (ETE) were significantly associated with lateral neck LN recurrence in univariate analysis. Multivariate analysis showed that male (hazard ratio [HR], 2.217; 95% confidence interval [CI], 1.057–4.647; P = .035), main tumor size >1 cm (HR, 2.257; 95% CI, 1.138–4.476; P = .020), pathologic N1a (HR, 5.957; 95% CI, 2.573–13.789; P < .002), minor ETE (vs no ETE; HR, 3.027; 95% CI, 1.315–6.966; P = .009), and gross ETE (vs no ETE; HR, 4.058; 95% CI, 1.685–9.774; P = .002) were independent predictors for lateral neck LN recurrence.Among patients with pathologic N1a, those with LN ratio of more than 0.55 had worse lateral neck LN recurrence-free survival. Lateral neck LN recurrence in clinically node-negative PTC patients is predicted by the factors of male, main tumor size >1 cm, ETE, and pathologic N1a.

Correlation analysis and clinical significance of lymph node metastasis in right recurrent laryngeal nerve of papillary thyroid carcinoma

Objective To explore the correlation factors and clinical significance of lymph node metastasis in right recurrent laryngeal nerve of thyroid papillary carcinoma (PTC). Methods Ninty-eight consecutive patients with PTC who were underwent total thyroidectomy with routine central lymph node dissection in the Second People′s Hospital of Hefei from January 2015 to August 2017 were analyzed. The right paratracheal lymph nodes in the central compartment lymph nodes were divided into the level Ⅵ-A (anterior) and level Ⅵ-B (posterior, that was lymph node posterior to recurrent laryngeal nerve) compartments by recurrent laryngeal nerve. The lymph node metastasis of Ⅵ-B area during central compartment lymph node dissection was analyzed. We drew the receiver-operating characteristic curve (ROC) for right neck Ⅵ-A number of lymph node metastasis, and calculated the area under the curve (AUC) and Youden index. Results Among 98 cases, 16 cases occurred Ⅵ-B district lymph node metastasis (16.33%). Single factor analysis results showed that lymph node metastasis in Ⅵ-B area of PTC patients were related to the tumor size (χ2=12.864, P 0.05). Lymph node metastasis in Ⅵ-B area of PTC patients were related to the number of right neck Ⅵ-A area lymph node metastasis. When the number of right neck Ⅵ-A metastatic lymph nodes was 2.5, the sensitivity and specificity were 70.60% and 70.00% respectively, AUC was 0.754, and Youden index was 0.406. Conclusion For patients with PTC, primary tumor diameter >1 cm, tumor extracapsular invasion, Ⅵ-A area lymph node metastasis, multiple tumor and lateral cervical lymph node metastasis were the predictive factors for the lymph node metastasis in Ⅵ-B area. When the number of right neck Ⅵ-A area metastatic lymph nodes was greater than 3, we should dissect Ⅵ-B area. Key words: Thyroid neoplasms; Papilloma; Lymphatic metastasis; Lymph node posterior to right recurrent laryngeal nerve

Application of mesangial thyroid resection in papillary thyroid carcinoma with central lymph node dissection and its influence on postoperative recurrence

Objective To explore the application of mesangial thyroid resection in papillary thyroid carcinoma(PTC) with central lymph node dissection, and its influence on postoperative recurrence. Methods 76 cases with PTC were divided into two groups according to random number table, each group in 38cases.The control group was given primary lesions radical prostatectomy and routine central lymph node dissection, the treatment group was given primary lesions radical prostatectomy and central lymph node dissection by thyroid mesangial resection.The parathyroid function, injury of recurrent laryngeal nerve and local recurrence were compared between the two groups. Results Compared with before surgery, the levels of serum PTH and blood calcium were significantly decreased at the 1st, 3rd day after surgery (all P 0.05). The levels of serum PTH and blood calcium at the 1st, 3rd, 7th day after surgery between the two groups had no statistically significant differences(all P<0.05). The incidence rate of injury of recurrent laryngeal nerve in the treatment group was significantly lower than that in the control group (5.3% vs.21.1%, χ2=4.15, P<0.05). The secondary surgery rate and local recurrence within 2 years in the treatment group were significantly lower than those in the control group(0% vs.15.8%, 2.6% vs.18.4%, χ2=6.51, 4.69, all P<0.05). Conclusion Primary lesions radical prostatectomy and central lymph node dissection by thyroid mesangial resection can be used as the routine operation for PTC, which can effectively produce complete dissection, reduce injury of recurrent laryngeal nerve and local recurrence. Key words: Thyroid neoplasms; Neck dissection; Recurrence

Clinical significance of prophylactic central compartment neck dissection in the treatment of clinically node-negative papillary thyroid cancer patients.

BackgroundLymph nodal involvement is very common in differentiated thyroid cancer, and in addition, cervical lymph node micrometastases are observed in up to 80 % of papillary thyroid cancers. During the last decades, the role of routine central lymph node dissection (RCLD) in the treatment of papillary thyroid cancer (PTC) has been an object of research, and it is now still controversial. Nevertheless, many scientific societies and referral authors have definitely stated that even if in expert hands, RCLD is not associated to higher morbidity; it should be indicated only in selected cases.Main bodyIn order to better analyze the current role of prophylactic neck dissection in the surgical treatment of papillary thyroid cancers, an analysis of the most recent literature data was performed. Prophylactic or therapeutic lymph node dissection, selective, lateral or central lymph node dissection, modified radical neck dissection, and papillary thyroid cancer were used by the authors as keywords performing a PubMed database research. Literature reviews, PTCs large clinical series and the most recent guidelines of different referral endocrine societies, inhering neck dissection for papillary thyroid cancers, were also specifically evaluated. A higher PTC incidence was nowadays reported in differentiated thyroid cancer (DTC) clinical series. In addition, ultrasound guided fine-needle aspiration citology allowed a more precocious diagnosis in the early phases of disease. The role of prophylactic neck dissection in papillary thyroid cancer management remains controversial especially regarding indications, approach, and surgical extension. Even if morbidity rates seem to be similar to those reported after total thyroidectomy alone, RCLD impact on local recurrence and long-term survival is still a matter of research. Nevertheless, only a selective use in high-risk cases is supported by more and more scientific data.ConclusionsIn the last years, higher papillary thyroid cancer incidence and more precocious diagnoses were worldwide reported. Among endocrine and neck surgeons, there is agreement about indications to prophylactic treatment of node-negative “high-risk” patients. A recent trend toward RCLD avoiding radioactive treatment is still debated, but nevertheless, prophylactic dissections in low-risk cases should be avoided. Prospective randomized trials are needed to evaluate the benefits of different approaches and allow to drawn definitive conclusions.

Routine central lymph node dissection with total thyroidectomy for papillary thyroid cancer potentially minimizes level VI recurrence

Treatment strategies for papillary thyroid cancer remain controversial due to the lack of large, randomized controlled trials. The purpose of this study was to review the benefit of routine bilateral central lymph node dissection (CLND) by analyzing local recurrence and complication rates from a single institution over a 15-year period. A retrospective, institutional review board-approved review of the Baylor Scott & White Tumor Registry was performed on all patients who underwent operation for papillary thyroid cancer between 2000 and 2015. Patients were evaluated by age, sex, tumor size, operation performed, pathologic findings, adjuvant therapy, and date of recurrence. Primary outcomes were cancer recurrence, recurrent laryngeal nerve injury, and hypoparathyroidism. Total thyroidectomy with CLND was performed in 266 patients. Metastases to level VI lymph nodes were present in 106/266 (39.8%) patients. Average follow-up after thyroidectomy was 46months (range 1-125months). Papillary thyroid cancer recurred in 4 patients after thyroidectomy with CLND for primary tumors with mean size of 1.6cm (range 1.0-2.0cm). Two patients with T4 tumors had local recurrence in the paratracheal soft tissues, and 2 patients presented with recurrence in the lateral neck. Temporary nerve injuries occurred in 9/266 (3.4%) and permanent nerve injuries in 1/266 (0.4%) of CLND. Permanent hypoparathyroidism occurred in 4/266 (1.5%) patients. Total thyroidectomy with CLND can safely be performed routinely for treatment of papillary thyroid cancer in the hands of experienced endocrine surgeons. Dissection of level VI lymph nodes does not increase the risk of recurrent laryngeal nerve injury when performed routinely. Bilateral CLND with total thyroidectomy for papillary thyroid cancer potentially minimizes recurrence in the level VI compartment.

A Study on Central Lymph Node Metastasis in 543 cN0 Papillary Thyroid Carcinoma Patients

Background. Papillary thyroid carcinoma (PTC) with central lymph node metastases (CLNMs) is common. The objective of this study was to investigate the incidence and risk factors of lymph node metastasis patients with PTC. Patients and Methods. Between January 2013 and February 2015, a retrospective study of 543 patients with PTC undergoing hemithyroidectomy or total thyroidectomy with routine central lymph node dissection (CLND) was analyzed. Clinicopathologic risk factors for CLNM were studied using univariate and multivariate analysis by SPSS 22.0 software. Results. The incidence of CLNMs in PTC patients was 38.1% (207/543). In the multivariate analysis, male gender (p < 0.001, OR: 1.984), age <45 years (p < 0.001, OR: 1.934), bilaterality (p = 0.006, OR: 1.585), tumor size ≥0.25 cm (p = 0.001, OR: 7.655), and external extension (p = 0.001, OR: 7.579) were independent risk factors of CLNMs. Furthermore, in PTC patients with tumor size <0.25 cm, all 7 males and 21 patients with unilaterality were not found to have CLNMs. Conclusions. CLNMs are prevalent in the PTC patients with the following risk factors: male gender, age <45 years, bilaterality, tumor size ≥0.25 cm, and external extension. PTC patients with tumor size <0.25 cm, male patients, and patients with unilateral lesion could be considered safe from CLNMs.

MicroRNA Expression and Association with Clinicopathologic Features in Papillary Thyroid Cancer: A Systematic Review.

Studies have suggested that microRNAs (miR) may be useful prognostic markers and are associated with aggressive clinicopathologic features in papillary thyroid cancer (PTC). This systematic review examined associations between miRs and aggressive clinicopathologic features in PTC. A literature search was performed within the PubMed, Embase, Cochrane, Web of Science, and Scopus databases for papers published prior to November 24, 2014. The search was performed by combining the concepts "thyroid tumor" with "microRNA" and by using "and" as the Boolean operator. Upon retrieval of candidate studies, full-text publications were reviewed in their entirety and selected if they examined the prognostic significance between miR expression and established aggressive clinicopathologic features of PTC. Fifteen studies from 13 unique groups that included 807 patients were reviewed. Most of the studies were retrospective, and none included patients who had undergone routine central lymph node dissection. Expression levels of miRs-21, -34b, -130b, -135b, -146b, -151, -181b, -199b-5p, -221, -222, -451, -623, -1271, -2861, and let-7e showed significant association with at least one aggressive feature, such as large tumor size, extrathyroidal extension, multifocality, lymphovascular invasion, lymph node metastases, distant metastasis, advanced American Joint Cancer Committee stage, and presence of the BRAF(V600E) mutation. Herein we summarize the literature with regard to these associations. Further studies are needed to investigate whether miRs are independent predictors of aggressive clinicopathologic features before it can be recommended that miR expression levels should be incorporated into the management algorithm for patients with PTC. A well-designed prospective study is needed to assess these potential associations.

Analysis of the patterns of cervical lymph node recurrence in patients with cN0 papillary thyroid carcinoma after central neck lymph node dissection

To retrospectively analyze the long-term results of prophylactic central lymph node dissection in cN0 papillary thyroid carcinoma (PTC), and investigate the treatment method of the cervical lymph nodes for cN0 PTC. One hundred and thirty-six patients with cN0 PTC were treated by surgery at the Cancer Hospital of Chinese Academy of Medical Sciences from 2000 to 2006. Their clinicopathological characteristics, surgical procedures and survival outcomes were collected and analyzed. The occult lymph node metastasis rate in central compartment was 61.0%. The average number of positive lymph nodes was 2.47 (1-13), in which 54 patients had 1-2 and 29 patients had ≥ 3 positive lymph nodes. Multiple logistic regression analysis showed that age less than 45 (P=0.001, OR 3.571, 95% CI 1.681-7.587)and extracapsular spread (ECS) (P=0.015, OR 2.99, 95% CI 1.241-7.202)were independent risk factors for lymph node metastasis in the central compartment. The ten-year cumulative overall survival rate was 98.3% and cumulative lateral neck metastasis rate was 25.2%. Multivariate analysis with Cox regression model showed that ECS (P=0.001, OR 5.211, 95% CI1.884-14.411) and positive lymph nodes in the central compartment ≥ 3 (P=0.009, OR 4.005, 95% CI 1.419-11.307) were independent risk factors for lymph node recurrence in the lateral neck region. The distribution of recurrent lymph nodes: level IV (82.4%), level III (64.7%), level II (29.4%) and level V (11.8%). Routine central lymph node dissection, at least unilateral, should be conducted for cN0 papillary thyroid carcinoma. Attention should be paid to the treatment of lateral neck region in patients with cN0 papillary thyroid carcinoma. Selective neck dissection is suggested for cN0 PTC with ECS or positive central lymph nodes ≥ 3, or both. The range of dissection should include level III and IV at least.

Should central lymph node dissection be considered for all papillary thyroid microcarcinoma?

Central lymph node dissection (CLND) in patients with papillary thyroid microcarcinoma (PTMC) is still controversial. The aim of this study was to examine the risk factors and the incidence of central lymph node metastases (CLNMs) in patients with PTMC who underwent thyroidectomy and CLND. Between 2002 and 2013, 613 patients were enrolled who underwent thyroidectomy with routine CLND for PTMC at the Korea University Medical Center, Ansan Hospital and risk factors and the incidence of CLNM were analyzed. In addition, we also evaluated the complications after thyroidectomy with CLND. Out of 613 patients, 239 (39.0%) were found to have CLNM. Male sex (p=0.012), tumor size ≥ 0.5cm (p=0.001), capsular invasion or extrathyroidal extension (p=0.029), and multifocality (p=0.004) were independent risk factors for CLNM. Among the 69 patients who had PTMC without these risk factors, CLNM was identified in 12 (17.4%). In this study group, two (0.3%) had permanent recurrent laryngeal nerve injury, two (0.3%) had persistent hypocalcemia, and two (0.3%) developed postoperative hemorrhage. CLNM in PTMC is highly prevalent in male sex, tumor size ≥ 0.5cm, extrathyroidal extension, and multifocality. Even in PTMC patients without these risk factors, the incidence of CLNM is rather higher than expected, and the complication rate of thyroidectomy with CLND is acceptable. Thus, CLND should be considered in all patients with PTMC.

The role of surgery in the current management of differentiated thyroid cancer

In the last decades, a surprising increased incidence of differentiated thyroid cancer (DTC), along with a precocious diagnosis of "small" tumors and microcarcinomas have been observed. In these cases, better oncological outcomes are expected, and a "tailored" and "less aggressive" multimodal therapeutic protocol should be considered, avoiding an unfavorable even if minimal morbidity following an "overtreatment." In order to better define the most suitable surgical approach, its benefits and risks, we discuss the role of surgery in the current management of DTCs in the light of data appeared in the literature. Even if lymph node metastases are commonly observed, and in up to 90 % of DTC cases micrometastases are reported, the impact of lymphatic involvement on long-term survival is still argument of intensive research, and indications and extension of lymph node dissection (LD) are still under debate. In particular, endocrine and neck surgeons are still divided between proponents and opponents of routine central LD (RCLD). Considering the available evidence, there is agreement about total thyroidectomy, therapeutic LD in clinically node-positive DTC patients, and RCLD in "high risk" cases. Nevertheless, indications to the best surgical treatment of clinically node-negative "low risk" patients are still subject of research. Considering on the one hand, the recent trend toward routine central lymphadenectomy, avoiding radioactive treatment, and on the other hand, the satisfactory results obtained reserving prophylactic LD to "high risk" patients, we think that further prospective randomized trials are needed to evaluate the best choice between the different surgical approaches.

Impact of prophylactic central compartment neck dissection on locoregional recurrence of differentiated thyroid cancer in clinically node-negative patients: A retrospective study of a large clinical series

In clinically node-negative patients with differentiated thyroid cancer (DTC), indications for routine central lymph node dissection (RCLD) are the subject of intensive research, and surgeons are divided between the pros and cons of this surgery. To better define the role of neck dissection in the treatment of DTC, we analyzed retrospectively the results in three centers in Italy. The clinical records of 752 clinically node-negative patients with DTC who underwent operative treatment between January 1998 and December 2005 in three endocrine surgery referral units were evaluated retrospectively. The complications and medium- and long-term outcomes of total thyroidectomy (TT) alone (performed in 390 patients: group A) and TT combined with bilateral RCLD (362 patients: group B) were analyzed and compared. The incidence of permanent hypoparathyroidism and permanent unilateral vocal folds was 1% and 0.8% in group A and 3.6% and 1.7% in the group B, respectively. Bilateral temporary recurrent nerve palsy was observed in one of the 362 patients in group B. After a follow-up of 9.5 ± 3.5 years (mean ± SD), the locoregional recurrence rate with positive cervical lymph nodes was not substantially significantly different between the two groups. In our series, TT combined with bilateral RCLD was associated with a greater rate of transient and permanent complications. Similar incidences of locoregional recurrence were reported in the two groups of patients. Considering the recent trend toward routine central lymphadenectomy, further studies are needed to evaluate the benefits of these different approaches.

Prospective analysis of the risk factors and clinical indications of dissection of lymph node posterior to right recurrent laryngeal nerve in 283 cases of papillary thyroid carcinoma

To investigate the risk factors for metastasis and clinical indications for dissection of lymph node posterior to right recurrent laryngeal nerve (LN-prRLN) in papillary thyroid carcinoma (PTC). A prospective analysis including 283 consecutive patients with PTC who underwent total thyroidectomy with routine central lymph node dissection (CLND) in our hospital from Jan. 2010 to Jan. 2012 was performed. The right paratracheal lymph nodes in the central compartment lymph nodes (CCLN) were divided into the anterior (level VIa) and posterior (level VIb) compartments by recurrent laryngeal nerve (RLN), and were removed respectively. The complications and recurrences were recorded with a follow-up of 3 months to 3 years. CCLN metastases were present in 47.7% (135/283) of the patients, and level VIb metastases were present in 27.2% (77/283) of the patients. The incidence of level VIb metastasis was 20.5% (58/283) in level VIa-positive patients, while 6.7% (19/283) in level VIa-negative patients. Complications of level VIb dissection were found in 4.9% (14/283) of all patients. 2.1% (6/283) of all patients were diagnosed with regional recurrence during the 3-year follow-up. Univariate analysis revealed that level VIb metastasis was significantly associated with tumor size, number, extrathyroidal invasion, clinical nodal stage, level VIa and lateral lymph node metastases. Multivariate analysis revealed that tumor larger than 1 cm, multifocality, extrathyroidal invasion, level VIa and lateral lymph node metastases were independent risk factors for level VIb metastasis. Lymph node posterior to right recurrent laryngeal nerve can be the only site of metastasis from PTC without other cervical compartment involvements. Therefore, routine intraoperative detection of these nodes may be necessary for patients with right PTC, and dissection should be considered when a right-side PTC tumor is larger than 1 cm, multifocality, with extrathyroidal invasion or cervical nodal metastases.

DoesBRAFV600E Mutation Predict Aggressive Features in Papillary Thyroid Cancer? Results From Four Endocrine Surgery Centers

Existing evidence is controversial regarding the association between BRAF mutation status and aggressive features of papillary thyroid cancer (PTC). Specifically, no study has incorporated multiple surgical practices performing routine central lymph node dissection (CLND) and thus has patients who are truly evaluable for the presence or absence of central lymph node metastases (CLNMs). Consecutive patients who underwent total thyroidectomy and routine CLND at 4 tertiary endocrine surgery centers were retrospectively reviewed. Descriptive and bivariable analyses examined demographic, patient, and tumor-related factors. Multivariable analyses examined the odds of CLNM associated with positive BRAF status. In patients with classical variant PTC, bivariate analysis found no significant associations between BRAF mutation and aggressive clinicopathologic features; multivariate analysis demonstrated that BRAF status was not an independent predictor of CLNM. When all patients with PTC were analyzed, including those with aggressive or follicular subtypes, bivariate analysis showed BRAF mutation to be associated with LNM, advanced American Joint Committee on Cancer (AJCC) stage, and histologic subtype. Multivariable analyses showed BRAF, age, size, and extrathyroidal extension to be associated with CLNM. Although BRAF mutation was found to be an independent predictor of central LNM in the overall cohort of patients with PTC, this relationship lost significance when only classical variant PTC was included in the analysis. The usefulness of BRAF in predicting the presence of LNM remains questionable. Prospective studies are needed before BRAF mutation can be considered a reliable factor to guide the treatment of patients with PTC, specifically whether to perform prophylactic CLND.

Is BRAF mutation associated with lymph node metastasis in patients with papillary thyroid cancer?

Some have proposed using V600E BRAF mutation status to dictate the surgical management of patients with papillary thyroid cancer (PTC). However, well-designed studies examining BRAF association with aggressive clinicopathologic features of PTC, including the presence of lymph node metastases (LNM), in patients who have undergone routine central lymph node dissection (CLND), are lacking. Under institutional review board approval, 63 patients diagnosed with PTC on fine-needle aspiration who underwent total thyroidectomy and CLND were included. BRAF mutation status was determined in fresh frozen or intraoperative fine-needle aspiration samples with a colorimetric assay. Associations between BRAF mutation status and clinicopathologic features of PTC were examined using Chi-square and multivariate logistic regression analyses. BRAF mutation was found to be significantly associated with race only on Chi-square analysis. BRAF mutation was not found to be significantly associated with the presence of LNM (P = .167). On multivariate analysis, only size and venous/lymphatic invasion were significantly associated with LNM. This small series underscores the prematurity in utilizing BRAF mutation status to determine the surgical management of patients with PTC, specifically whether or not to perform a CLND.

BRAFV600E mutation and Its Association with Clinicopathological Features of Papillary Thyroid Cancer: A Meta-Analysis

There is conflicting literature regarding the association of the BRAF V600E mutation and aggressive clinicopathological features of papillary thyroid cancer (PTC). Nevertheless, some propose that BRAF status be incorporated into the management of patients with PTC, specifically recommendations regarding lymph node dissection. We therefore performed a meta-analysis to examine the relationship between BRAF and clinicopathological features of PTC. A literature search was performed within PubMed and EMBASE databases using the following Medical Subject Headings (MeSH) and keywords: "braf," "mutation," "thyroid," "neoplasm(s)," "tumor," "cancer," and "carcinoma." Individual study-specific odds ratios and confidence intervals were calculated, as were Mantel-Haenszel pooled odds ratios for the combined studies. Thirty-two studies including 6372 patients were reviewed. BRAF mutation was associated with lymph node metastases (LNM), advanced stage, extrathyroidal extension, tumor size, male gender, multifocality, absence of capsule, classic PTC, and tall-cell variant PTC. There was no association with age or vascular invasion. Only two studies were prospective; nine included consecutive patients, whereas one included randomly selected patients; and only two included patients who had undergone routine central lymph node dissection and were thus evaluable for the presence of LNM. Meta-analysis found that BRAF mutation is associated with LNM, stage, extrathyroidal extension, tumor size, male gender, multifocality, absence of capsule, classic PTC, and tall-cell variant PTC in PTC. However, almost all studies were retrospective and only two of 32 included patients who had undergone routine central lymph node dissection, emphasizing the need for well-designed studies to appropriately examine this association before making important clinical decisions.

BRAF V600E Mutation Independently Predicts Central Compartment Lymph Node Metastasis in Patients with Papillary Thyroid Cancer

Howell et al. examine a very timely question regarding the utility of measuring BRAF mutation status in papillary thyroid cancer (PTC) specimens to determine if it can be used to predict the presence or absence of lymph node metastases. The premise is that its measurement could potentially guide the surgical management of patients with PTC; i.e., to determine whether a prophylactic central lymph node dissection (CLND) should be performed. This is a very well-written study that nicely captures the common clinical dilemma faced by endocrine surgeons and also is comprehensive in the interpretation of its results. It is generally accepted that patients with PTC who have clinically detectable lymph node metastases either on physical examination or by ultrasound should undergo a lymph node dissection. Whether to perform a prophylactic CLND for PTC remains debatable; some authors claim that there is no advantage in terms of decreased local recurrence and improved survival, whereas others claim advantages regarding both. Because of this controversy, some authors have proposed that BRAF may confer a more aggressive phenotype and its measurement could then help to guide the surgeon in terms of whether or not to perform a prophylactic CLND. Conversely, other authors have documented no correlation with BRAF mutation and aggressive features of PTC, including the case in point, namely, the presence of lymph node metastases. The literature is replete with studies that include only patients who had therapeutic and not routine prophylactic CLND, patients who had lymph nodes removed only incidentally, or patients who had no lymph nodes removed; none of these groups of patients would therefore be evaluable in terms of determining whether BRAF status is truly associated with CLN metastases. Two studies have included only patients who have undergone routine CLND and both found that BRAF mutation predicted metastatic disease only in patients who had a PTC that was less than 1 cm in size; there was no association for larger tumors. Howell et al. initially identified 274 patients who were operated on for PTC at the University of Pittsburgh in 2010 and from this group studied 156 (57 %) patients who had both lymph nodes resected and BRAF testing. In their study, therapeutic CLND was performed for patients who had evidence of metastatic disease either on ultrasonography or at the time of surgery. A prophylactic CLND was performed for patients who had a diagnosis of PTC or a positive BRAF mutation. If PTC was not diagnosed preoperatively, the lymph nodes were assessed with visual and tactile inspection and patients ‘‘had nonanatomic resection of immediate perithyroidal central compartment lymph nodes if no suspicious lymphadenopathy was identified.’’ Incidentally, we know from others’ work that intraoperative assessment of lymph nodes is generally unreliable. In the study by Howell et al. 29 (19 %) had a therapeutic CLND, 85 (54 %) had a prophylactic CLND, and 42 (27 %) had incidental central lymph nodes resected. In the entire group of 156, 37 % had evidence of metastatic disease and 46 % were BRAF mutation-positive. They found that BRAF mutation was associated with lymph node metastases both in univariate analysis and multivariable logistic regression. The sensitivity was noted to be 62 % and the specificity was 63 %; the positive and negative predictive values were 50 and 74 %, respectively. The study by Howell et al. includes patients who have undergone some sort of lymph node removal. It excludes, however, more than 40 %, because they did not have a Society of Surgical Oncology 2012

A multicenter cohort study of total thyroidectomy and routine central lymph node dissection for cN0 papillary thyroid cancer

A multicenter cohort study of total thyroidectomy and routine central lymph node dissection for cN0 papillary thyroid cancer