N1b Papillary Thyroid Carcinoma Patients Research Articles

Level IIb neck dissection guided by fine-needle aspiration for N1b papillary thyroid carcinoma

BackgroundThe extent of neck dissection for patients with papillary thyroid carcinoma (PTC) metastasis in lateral cervical lymph nodes is still debated. Studies aiming to omit level IIb were generally based on postoperative histopathologic information. The purpose of this study was to evaluate the predictive value of fine-needle aspiration (FNA) for level II lymph nodes in identifying candidates for neck dissection sparing level IIb before surgery. MethodsWe prospectively enrolled 156 consecutive previously untreated PTC patients with lateral neck metastases who were subjected to 178 therapeutic lateral neck dissections (including level IIa, IIb, III, IV, and Vb) between June 2018 and August 2021. Ultrasound-guided FNA of suspicious lymph nodes at level II was preoperatively performed. The cytology of FNA and thyroglobulin (Tg) washout concentration with other clinical predictors was analyzed for lymph node metastases at level IIb. ResultsPreoperative ultrasonography revealed suspicious lymph nodes at level II in 118 cases, and fifty were positive on FNA results. Metastasis at level IIb was seen in 17 (9.6%) of the postoperative specimens. By univariate analysis, the rate of level IIb metastasis was significantly higher in patients with FNA-positive lymph nodes at level II (P<0.001, odds ratio = 16.899). The tumor sizes of the two FNA-negative level IIb metastatic lymph nodes were 0.4 mm and 3 mm. ConclusionsLevel IIb lymph node dissection may be omitted in the treatment of N1b PTC patients if FNA to level II lymph nodes is negative.

Clinical Outcomes of N1b Papillary Thyroid Cancer Patients Treated with Two Different Doses of Radioiodine Ablation Therapy.

BackgroundThe optimal dose of radioactive iodine (RAI) therapy for N1b papillary thyroid carcinoma (PTC) is controversial. We evaluated the clinical outcome of N1b PTC patients treated with either 100 or 150 mCi of RAI.MethodsWe retrospectively analyzed N1b PTC patients who underwent total thyroidectomy and postoperative RAI therapy at a tertiary referral center between 2012 and 2017. As the baseline characteristics differed between treatment groups, we performed exact matching for various pathological factors according to RAI dose. We evaluated the response to therapy and recurrence-free survival (RFS) in the matched patients. Structural recurrent/persistent disease was defined as new structural disease detected after initial therapy, which was confirmed by cytology or pathology.ResultsOf the total 436 patients, 37 (8.5%) received 100 mCi of RAI and 399 (91.5%) received 150 mCi of RAI. After an exact 1:3 matching, 34 patients in the 100 mCi group and 100 patients in the 150 mCi group remained. There was no significant difference in response to therapy between the groups in the matched population (P=0.63). An excellent response was achieved in 70.6% (n=24) of patients in the 100 mCi group and 76.0% (n=76) in the 150 mCi group. Two (5.9%) patients in the 100 mCi group and four (4.0%) in the 150 mCi group had recurrence and there was no significant difference in RFS between the groups in the matched population (P=0.351).ConclusionThere were no differences in response to therapy and RFS in N1b PTC patients according to RAI dose.

ROLE OF LEVEL V LYMPH NODE DISSECTION IN N1b PAPILLARY THYROID CARCINOMA

Background: For the N1b papillary thyroid carcinoma (PTC) patients, modified radical neck dissection (MRND) encompassing levels II – V is generally recommended. However, routine level V dissection is controversial because of the low incidence of metastasis/recurrence in level V and the increased morbidities associated with level V dissection. Objective: This study was designed to determine the clinical risks and benefits of routine level V dissection in N1b PTC patients with clinical negative level V. Patients and Methods: This study was a prospective, comparative, randomized and descriptive study of 40 patients suffering N1b papillary thyroid carcinoma. The patients were divided into two equal groups: Group 1 subjected to MRND, and Group 2 subjected to SND. Both groups were compared for age, sex, intraoperative (duration of surgery and complications) and postoperative results (complications and distribution of lateral nodal recurrence). Results: Under a matched condition, occult level V metastasis was observed in 5.0%. The MRND group exhibited a significantly longer operation time compared with the SND group. The amount of drainage was significantly more in the MRND group compared with the SND group. Time of drain removal was significantly less in the SND group compared to MRND group. Chyle leak was more frequent in the MRND group compared with the SND group but not statically significant. Level V recurrences did not occur in 3 recurred N1b PTC patients who underwent unilateral MRND and SND. Shoulder syndrome encompassing shoulder dysfunction and pain was significantly more frequent in the MRND group than in the SND group. There were no statistically difference between the groups according to infection, transient hypocalcaemia, transient RLN palsy and nodal recurrence. Conclusion: Because of the low incidence of metastasis/recurrence in level V and the clear evidence of increased morbidities, level V dissection in N1b PTC patients may be reserved for those clinically/radiologically evident metastasis in level V.

ROLE OF LEVEL V LYMPH NODE DISSECTION IN N1b PAPILLARY THYROID CARCINOMA

Background: For the N1b papillary thyroid carcinoma (PTC) patients, modified radical neck dissection (MRND) encompassing levels II – V is generally recommended. However, routine level V dissection is controversial because of the low incidence of metastasis/recurrence in level V and the increased morbidities associated with level V dissection. Objective: This study was designed to determine the clinical risks and benefits of routine level V dissection in N1b PTC patients with clinical negative level V. Patients and Methods: This study was a prospective, comparative, randomized and descriptive study of 40 patients suffering N1b papillary thyroid carcinoma. The patients were divided into two equal groups: Group 1 subjected to MRND, and Group 2 subjected to SND. Both groups were compared for age, sex, intraoperative (duration of surgery and complications) and postoperative results (complications and distribution of lateral nodal recurrence). Results: Under a matched condition, occult level V metastasis was observed in 5.0%. The MRND group exhibited a significantly longer operation time compared with the SND group. The amount of drainage was significantly more in the MRND group compared with the SND group. Time of drain removal was significantly less in the SND group compared to MRND group. Chyle leak was more frequent in the MRND group compared with the SND group but not statically significant. Level V recurrences did not occur in 3 recurred N1b PTC patients who underwent unilateral MRND and SND. Shoulder syndrome encompassing shoulder dysfunction and pain was significantly more frequent in the MRND group than in the SND group. There were no statistically difference between the groups according to infection, transient hypocalcaemia, transient RLN palsy and nodal recurrence. Conclusion: Because of the low incidence of metastasis/recurrence in level V and the clear evidence of increased morbidities, level V dissection in N1b PTC patients may be reserved for those clinically/radiologically evident metastasis in level V.

Level V lymph node metastasis in N1b papillary thyroid carcinoma patients: contributing factors and pattern of metastasis

Level V lymph node metastasis in N1b papillary thyroid carcinoma patients: contributing factors and pattern of metastasis

Nomogram for predicting level V lymph node metastases in papillary thyroid carcinoma with clinically lateral lymph node metastases: A large retrospective cohort study of 1037 patients from FDUSCC.

Objective: Extensive lateral neck dissection (LND), especially routine level V dissection, may potentially increase morbidity and have no significant benefit to survival in patients with papillary thyroid carcinoma (PTC). Our study aimed to determine the pattern and risk factors for level V lymph node metastasis (LNM) and to develop an assessment model based on a nomogram for predicting whether level V dissection is necessary.Methods: A total of 1037 PTC patients with clinically suspected LNM (N1b) who underwent total thyroidectomy (TT) with central LND and unilateral LND from 2011 to 2015 were retrospectively retrieved. Univariate and multivariate analyses were performed to examine risk factors associated with level V metastasis. A nomogram for predicting level V metastasis was established and internally validated.Results: The overall rate of level V metastasis was 21.3% (221/1037). Unilateral central LNM (CLNM), level II/III/IV metastasis, extra nodal extension (ENE) and lymph node (LN) size ≥2 cm were found to be independent predictive factors for level V metastasis (P<0.05). In the nomogram, ENE was confirmed as the largest contributor to scores, followed by LN size, unilateral CLNM and level IV/III/II metastasis. The discrimination of the prediction model was 0.738 (95% confidence interval (CI): 0.703-0.773, P<0.001).Conclusions: The rate of level V metastasis in N1b PTC patients was apparently lower than that of other levels. With the help of our nomogram, a modified lateral neck dissection encompassing levels II-V and a strictly postoperative evaluation may be indicated when the patient has a high score.

Level V Metastasis, a Novel Predicative Factor for Recurrence in N1b Papillary Thyroid Carcinoma.

Lymph nodal (LN) metastasis, classified as pN1b, is considered as an independent poor prognostic factor for Papillary thyroid carcinoma (PTC) patients. However, whether LN metastasis can serve as a predictive factor for recurrence or disease-free survival of N1b PTC is still plagued by controversy. The N1b PTC patients who underwent total thyroidectomy and unilateral modified radical neck dissection (MRND) by the same surgical team in Ningbo NO.2 Hospital from March, 1998 to March, 2015 were included in this study. The clinical and pathological characteristics of each patient were recorded in detail. Univariate and multivariate Cox proportional hazards regression models were performed to analyze the associations between clinicopathological characteristics with recurrence. Kaplan-Meier analysis and log-rank test were used for the analysis of overall RFS and level V metastasis. A total of 214 patients were eligible for the final analyses. Of the 214 finally included patients with N1b PTC, 39 patients were classified with recurrence and 175 without recurrence. The final univariate and multiple Cox proportional hazards analysis only suggested level V metastasis as the independent predictive factor of N1b PTC recurrence (HR: 4.11; 95% CI:1.22-11.05, P=0.028). The patients with level V metastasis showed a significantly lower 10-year RFS rate (P=0.031) as illustrated by Kaplan-Meier analysis and log-rank test. Level V metastasis is a novel indicator for tumor recurrence and 10-year RFS in patients with N1b PTC.

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

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

Level I lymph node involvement in patients with N1b papillary thyroid carcinoma: a prospective study.

Most of the studies on the incidence, pattern, and predictive factors of lymph node (LN) metastasis with papillary thyroid carcinoma (PTC) have been performed retrospectively and no common consensus has been reached regarding the predictors for the involvement of level I LNs. This study was conducted prospectively to determine the incidence and the possible predictors of level I involvement in N1b PTC patients. The study included 30 consecutive patients with N1b stage of PTC. All the patients underwent neck dissection (ND) including level I. The relation between involvement of level I LNs and various clinicopathological variables was studied. Unilateral neck dissection was performed in 24 patients and bilateral neck dissection in six patients leading to 36 NDs. Level I was excised in all patients, with five specimens (14%) positive for metastasis. Levels II, III, IV, V, VI, and VII werepositivein52.8,58.3, 58.3, 33.3, 63, and 22.2%, respectively. Level I involvement was significantly related to the number of lymph node levels affected (p=0.003) and macroscopic extranodal invasion (p=0.04). It was not related to the involvement of other individual levels, gender, age, size of the largest thyroid nodule, size of the largest LN involved, or histo-pathological variant of the tumor. This study suggests that including level I in therapeutic neck dissection for N1b PTC patients might be recommended in selected cases of multiple level involvement and macroscopic extranodal invasion requiring sacrifice of internal jugular vein, spinal accessory nerve, or sternomastoid muscle.

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

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

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

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

Recurrence of papillary thyroid carcinoma with lateral cervical node metastases: Predictive factors and operative management

Lateral neck lymph node (LN) metastases (N1b) have been identified as independent risk factors of recurrence in patients with papillary thyroid carcinoma (PTC). This study aimed to determine the predictive factors of recurrence in N1b PTC patients and to clarify the postoperative event patterns. All patients who underwent operation for N1b PTC between 1978 and 2012 were reviewed. The median follow-up period was 6.5 years. In total, 344 N1b patients were included. Twenty-four patients (7%) were lost to long-term follow-up. Among the remaining 320 patients, the mean (± SD) follow-up time was 8.9 ± 8.8 years (median, 6.5; range, 2-36.4). Eighty-two patients (26%) presented with lymph node recurrence (LR). Multivariate analyses showed that LN metastases with extracapsular extension and the LN ratio (ratio between the number of N1 and number of resected LN) in the lateral compartment were independent predictors of recurrent disease. The median time to reoperation was 19 months (range, 3-173), with 79% of reoperations occurring within 2 years after the initial thyroidectomy. Reoperations for LR (75 patients) were performed in 76% of the patients with a focused minimal access approach or selective LN dissection. After curative reoperative surgery for recurrence, complications occurred in 6 patients (8%), including a 1% permanent complication rate. Extranodal extension of LN metastases and the LN ratio in the lateral compartment are prognostic factors for recurrence. In most cases, reoperation for LR can be performed with a focused minimal access approach, with a low morbidity rate.

Sub-Classification of Lateral Cervical Lymph Node Metastasis in Papillary Thyroid Carcinoma by Pathologic Criteria.

BackgroundLateral cervical lymph node (LCLN) metastasis, or pathologic N1b disease, is an important risk factor in papillary thyroid carcinoma (PTC). However, many patients have favorable prognosis even with pathologic N1b patients in clinical practice. The study aims to identify high- and intermediate-risk groups based on initial pathologic characteristics in these patients.PatientsThis study included 518 classical PTC patients confirmed as pathologic N1b at initial surgery between 2001 and 2010. All patients underwent a single fixed activity (5.6 GBq) of radioactive I-131 remnant ablation.ResultsPatients with a primary tumor larger than 4 cm, gross extrathyroidal extension, metastatic LN larger than 3 cm, or greater than 10 metastatic LCLN were classified as high-risk group. These comprehensive pathologic criteria were retrieved from cox proportional hazard models. Twenty two percent of patients (n = 113) were classified as high-risk and 78% (n = 405) as intermediate-risk group. Successful ablation was identified in only 32% of the patients in the high-risk group and 61% in the intermediate-risk group (p < 0.001). The difference between the two risk groups was independent to gender. There was a significant difference in disease-free survival between the high- and intermediate- risk N1b groups during 5.1 years of median follow-up (84% vs. 59%, p < 0.001). Distant metastasis was more prevalent in the high-risk group (20%) than in the intermediate-risk group (4%, p < 0.001).ConclusionsThe prognosis of PTC patients with LCLN metastasis varies depending on initial pathologic characteristics. We proposed the comprehensive pathologic criteria for sub-classification of N1b into high- and intermediate-risk groups and this sub-classification may permit personalized management of N1b PTC patients.

Lymph Node Recurrence in Patients With N1b Papillary Thyroid Carcinoma Who Underwent Unilateral Therapeutic Modified Radical Neck Dissection

Therapeutic modified radical neck dissection (MND) is a mandatory surgical procedure for patients with papillary thyroid carcinoma (PTC) having clinical lateral node metastasis (N1b). However, N1b PTC is still likely to recur in regional lymph nodes after surgery. We investigated the clinicopathological features predicting recurrence in nodes in previously dissected compartments (ipsilateral lateral compartment or central compartment) and nodes in the contralateral lateral compartment for N1b patients who underwent unilateral therapeutic MND. A total of 744 N1b PTC patients who underwent thyroidectomy with unilateral therapeutic MND between 1987 and 2004 were enrolled in the study. The patient ages ranged from 12 to 88 years (average 50.2 years). The average postoperative follow-up period was 113 months. To date, 87 (12%) and 49 (7%) patients showed recurrence in previously dissected compartments and the contralateral lateral compartment, respectively. On univariate analysis, age >55 years, node metastasis >3 cm, extranodal tumor extension, and extrathyroid extension affected recurrence in previously dissected compartments. Also, the former two were independent predictors on multivariate analysis (P = 0.0170 and <0.0001, respectively). In contrast, only extrathyroid extension and tumor size >4 cm influenced recurrence in the contralateral lateral compartment on univariate analysis. On multivariate analysis, the former was an independent predictor (P = 0.0015), and the latter was of marginal significance (P = 0.0909). To date, 13% of patients having both of these characteristics showed recurrence in the contralateral lateral compartment. Extremely careful therapeutic MND is required for N1b patients with age >55 years or node metastasis >3 cm because of the likelihood of recurrence in previously dissected compartments. Bilateral MND (therapeutic for ipsilateral side and prophylactic for contralateral side) may be a therapy option for N1b PTC >4 cm and having extrathyroid extension.

Is Level IIb Lymph Node Dissection Always Necessary in N1b Papillary Thyroid Carcinoma Patients?

Papillary thyroid carcinoma (PTC) patients show a high rate of cervical lymphatic metastasis. However, there are no universal binding guidelines for the extent of lateral cervical lymph node dissection (LND) in such cases. In particular, the need for LND above the spinal accessory nerve (SAN) remains controversial. The present study examined whether level IIb lymph node (LN) dissection is always necessary in PTC patients with lateral cervical LN metastasis. The study prospectively examined 167 PTC patients with lateral cervical LN metastasis who underwent modified radical neck dissection (MRND) in our institution from November 2005 to March 2007. The MRND was bilateral in 24 cases. All patients underwent level II, III, IV, and V LND. Levels IIa and IIb LNs were individually dissected in all cases. All LND was performed using strict leveling criteria by a single operating team. The patterns of lymphatic metastasis and potential risk factors for level IIb LN involvement were evaluated. The most common site of metastasis was level III (80.6% of cases), followed by level IV (74.9%) and II (55.5%). The metastasis rates in level IIa and IIb were 55.5% and 6.8%, respectively; all level IIb LN metastasis was accompanied by level IIa metastasis (p=0.001). In addition, level IIb LN metastasis was found to be associated with the aggressiveness of lymphatic metastasis (i.e., the total number of metastatic LNs) (p<0.0001). A level IIb LND should be performed when there is clinical or radiological evidence of lymphatic metastasis. In the absence of such evidence, the findings suggest that level IIb LND is not necessary in N1b PTC patients when there is no level IIa LN metastasis, or when the metastasis is not aggressive.