Prophylactic Central Neck Dissection Research Articles

Long-term impact of prophylactic central neck dissection in non-invasive classic papillary thyroid carcinoma

BackgroundThe utilization of prophylactic central neck dissection (pCND) in cases of non-invasive clinical node-negative (cN0) papillary thyroid carcinoma (PTC) remains a topic of debate, with a dearth of long-term evidence. Materials and methodsWe retrospectively reviewed 1181 cN0 PTC patients from 1997 to 2011. Of these, 641 underwent pCND (pCND + group) and 540 did not (pCND-group). Propensity score matching (PSM) was used to identify similar patients. Event-free survival and long-term complications including permanent hyperparathyroidism and permanent recurrent laryngeal nerve (RLN) paralysis were analyzed after PSM. ResultsThe pCND + group had more aggressive characteristics. In the matched cohort after PSM, the 5-year, 10-year, and 15-year EFS rates were 98.9 %, 98.2 %, and 97.1 % for the pCND + group, and 97.7 %, 97.1 %, and 97.1 % for the pCND-group, respectively. There was no statistically significant difference in EFS rates between the two groups (Log Rank P = 0.38). There was no statistically significant difference in the incidence of permanent hyperparathyroidism (3.3 % vs. 1.5 %, P = 0.08) and permanent RLN paralysis (1.7 % vs. 0.9 %, P = 0.13) between the pCND+ and pCND– groups. ConclusionOur study, with a median follow-up duration of 107 months, indicates that pCND does not lead to a significant reduction in nodal recurrence among non-invasive cN0 PTC patients.

Risk factors for central lymph node metastasis in patients with papillary thyroid carcinoma: a retrospective study.

Thyroid cancer is the most prevalent endocrine malignancy, with its global incidence increasing annually in recent years. Papillary carcinoma is the most common subtype, frequently accompanied by cervical lymph node metastasis early on. Central lymph node metastasis (CLNM) is particularly the common metastasis form in this subtype, and the presence of lymph node metastasis correlates strongly with tumor recurrence. However, effective preoperative assessment methods for CLNM in patients with papillary thyroid carcinoma (PTC) remain lacking. Data from 400 patients diagnosed with PTC between January 1, 2018, and January 1, 2022, at the Shandong Provincial Hospital were retrospectively analyzed. This data included clinicopathological information of the patients, such as thyroid function, BRAF V600E mutation, whether complicated with Hashimoto's thyroiditis, and the presence of capsular invasion. Univariate and multivariate logistic regression analyses were performed to assess the risk factors associated with cervical CLNM in patients with PTC. Subsequently, a clinical prediction model was constructed, and prognostic risk factors were identified based on univariate and multivariate Cox regression analyses. Univariate and multivariate analyses identified that age >45 years (P=0.014), body mass index ≥25 (P=0.008), tumor size ≥1 cm (P=0.001), capsular invasion (P=0.001), and the presence of BRAF V600E mutation (P<0.001) were significantly associated with an increased risk of CLNM. Integrating these factors into the nomogram revealed an area-under-the-curve of 0.791 (95% confidence interval 0.735-0.846) and 0.765 (95% confidence interval: 0.677-0.852) for the training and validation sets, respectively, indicating strong discriminative abilities. Subgroup analysis further confirmed that patients with papillary thyroid microcarcinoma and BRAF V600E mutations who underwent therapeutic central compartment neck dissection had significantly better 3-year disease-free survival than those who had prophylactic central compartment neck dissection (P<0.001). The study revealed that age >45 years, body mass index ≥25, tumor size ≥1 cm, BRAF V600E mutation, and capsular invasion are the related risk factors for CLNM in patients with PTC. For patients with clinically nodal-negative (cN0) papillary thyroid microcarcinoma, accurately identifying the BRAF V600E mutation is essential for guiding the central lymph node dissection approach and subsequent treatments.

Central node dissection from the perspective of lateral neck node metastasis in papillary thyroid carcinoma

ObjectivesControversy exists on how to handle central lymph nodes in papillary thyroid carcinoma, particularly regarding indications for prophylactic central neck dissection (CND). Central node metastases are more difficult to diagnose preoperatively than lateral node metastases. MethodsWe enrolled 493 patients with papillary thyroid carcinoma treated at our department in the past 22 years. Metastatic lymph nodes were diagnosed preoperatively mainly by ultrasonography. In principle, CND was performed for all cases; ipsilateral CND was performed for hemithyroidectomy, and bilateral CND was performed for total thyroidectomy. Lateral neck dissection (levels II to V; LND) was performed for metastases to lateral neck lymph nodes (clinical node (cN) 1b). ResultsThe cN stage was cN0 in 365 patients, cN1a in 10, and cN1b in 118. Of the 357 patients with stage cN0 who underwent CND, 42.9 % had pathologically positive nodes (pN+) in level VI, and of the 118 with stage cN1b who underwent CND, 78.0 % had pN+ in level VI. Cases with advanced T stage were significantly more common with pN+ in level VI. Level VI metastases were significantly associated with pN+ in level IV. As the total number of pN+ at each level of the lateral neck increased, the rate of patients with pN+ in level VI increased, and in patients with 3 or more pN+, about 85 % had level VI metastases. ConclusionBecause about half of the patients with cN0 patients had pN+ in level VI, and the rate of pN+ in level VI in each clinical T stage was 46 to 65 %, prophylactic CND should be performed, considering the various clinical benefits. Central nodes will have metastases in about 80 % of cases with lateral node metastases, requiring more accurate dissection. In lateral node metastases, there is a significant association between metastases in levels IV and VI.

Predictive Factors of Lymph Nodes Recurrence in Patients with Differentiated Thyroid Carcinoma Post Thyroidectomy in Clinically Node Negative Patients: A Systematic Review and Meta-Analysis Study

Abstract Background Differentiated thyroid cancer (DTC), a term used to describe papillary thyroid cancer (PTC), follicular thyroid cancer (FTC), and Hürthle cell thyroid cancer (HTC), accounts for approximately 95% of all thyroid malignancies. The expression clinically lymph node-negative (cN0)‘ was used to describe the patients that did not show the clinical evidence of CLNM on US or other imaging modalities preoperatively. Objective To assess the incidence of recurrence after surgery for DTC and to identify predictive factors of recurrence. Patients and Methods The search was conducted through PubMed, Web of science, Scopes, and the Cochrane Library for data from inception to November 1, 2021 with a combination of the following terms: "clinically node negative", "Risk Factors" and "Thyroid Neoplasms". All the studies were reviewed according to the eligible criteria. Abstract-based eligibility studies were obtained, and the manuscripts were fully reviewed. Results There was no evidence of publication bias. The funnel plot analysis demonstrated a symmetrical appearance, and the P values were greater than 0.05 for all comparisons according to the Begg-Mazumdar test and eggers test. Data Sources Medline databases (PubMed, Medscape, ScienceDirect. EMF-Portal) and all materials available in the Internet till 2021. Data Extraction If the studies did not fulfill the inclusion criteria, they were excluded. Study quality assessment included whether ethical approval was gained, eligibility criteria specified, appropriate controls, and adequate information and defined assessment meas ures. Conclusion Young age (&amp;lt;45 years), male gender, Bilaterality, multifocality, capsular invasion, lymphovascular invasion and ETE were significantly associated with LNM in clinically N0 DTC patients and Prophylactic central neck dissection would be expected to have higher yield in patients with these factors.

Comparative Study between Total Thyroidectomy with Ipsilateral versus Bilateral Prophylactic Central Neck Dissection in Patients with Clinically Node – Negative Papillary Thyroid Carcinoma. A Meta-Analysis

Abstract Background Papillary thyroid carcinoma (PTC) accounts for &amp;gt; 80% of all thyroid malignancies. It is generally slow-growing and the overall prognosis is excellent, with 5-year, 10-year, and 20-year survival rates of 94%, 89%, and 87%, respectively. Aim of the Work The aim of this study is to compare between unilateral PCND and bilateral PCND in patients with clinically unifocal cN0 PTC using meta-analysis approach Methodology A Systemic review and meta-analysis Study was performed after the data extraction process. Five studies comparing the out-comes of unilateral PCND and bilateral PCND procedures in adult patients with PTC CN0 were included in this study. The publicly available literature on PubMed, and, the Web of Knowledge, and the China Journal Net, EMBASE, Cochrane Library, and Scopus databases and the ClinicalTrials.gov registry. Published from January 2005 to December 2020 concerning TT plus ipsilateral PCND versus TT plus bilateral PCND for PTC CN0 will be retrieved by searching the national and international online databases. Results The result of our study revealed that: Bilateral central neck dissection had higher insignificant operative time than ipsilateral one, bilateral central neck dissection had higher overall significant complications rate than ipsilateral one, bilateral central neck dissection had higher significant permanent hypo PTH and insignificant hematoma, seroma, and transient hypo PTH rate than ipsilateral one, ipsilateral central neck dissection had higher insignificant PRLNP, TRLNP rate nearly equal with bilateral one, ipsilateral CND appears to be sufficient in patients with tumors&amp;lt;1 cm as bilateral central neck dissection had higher insignificant tumor size than ipsilateral one, there was no statistically significant difference found between unilateral PCND and bilateral PCND regarding rate of recurrence. Conclusion We suggest that, ipsilateral central neck dissection may be a reasonable surgical option for prophylactic CND in unilateral PTC with clinically negative lymph nodes because of its lower rates of contralateral paratracheal node metastasis and transient hypoparathyroidism and lower complications than bilateral pCND. and effective for selected patients undergoing a total thyroidecto- my for cN0 unilateral PTC.

Surgical management of low-risk papillary thyroid cancer in real life in Spain: a nationwide survey of endocrine neck surgeons and endocrinologists.

The extent of surgery in patients with papillary thyroid cancer (PTC) is a subject of ongoing debate. We aimed to explore the attitude of Spanish specialists (endocrinologists, surgeons, and otolaryngologists) in real life on the surgical management of low-risk PTC. We designed an anonymous, web-based survey to inquire information regarding the preferences of interviewees for hemithyroidectomy (Hem), total thyroidectomy (TT) and prophylactic central neck dissection (pCND) in one standard patient with PTC and six clinical variants. We differentiated between small (1.1-2.5 cm) and large (2.6-4.0 cm) tumors. A total of 278 valid responses were received and divided into two groups: group END (n = 135) and group SUR (n = 143, 101 general surgeons and 42 otolaryngologists). The preference for Hem was low in the standard patient and similar between both groups (40.6 vs 49.0%, NS). This preference decreased for tumors measuring 2.6-4.0 cm, multifocal, with risk location, family history of thyroid cancer, or history of irradiation, and increased in patients older than 65 years or with comorbidity. Preference for pCND ranged from 12.6-71.1% in the group END and from 22.4-65.0% in the group SUR, with few differences between the two. In multivariate analysis, being a high-volume specialist was associated with a lower preference for Hem, while having private practice was associated with a more favorable opinion of Hem. The real clinical practice of Spanish specialists is far from what is recommended by the clinical guidelines in patients with low-risk PTC, especially among high-volume professionals.

Evolving variation in the extent of surgery for low-risk papillary thyroid cancer in the United States

BackgroundThe continued debate over total thyroidectomy versus lobectomy and declining favor for prophylactic central neck dissection for patients with clinically node-negative papillary thyroid cancer ≤4 cm is ongoing after the 2015 guideline updates from the American Thyroid Association. This study aimed to evaluate contemporary trends in the extent of surgery in this low-risk cohort. MethodsRetrospective data from the National Cancer Database were used to identify adult patients with clinically node-negative papillary thyroid cancer ≤4 cm who underwent resection from 2012 to 2020. The primary outcome was the extent of surgery (lobectomy or total thyroidectomy, with or without prophylactic central neck dissection). Multivariable regression was performed to identify characteristics associated with variation in the extent of surgery. ResultsOf 83,464 included patients, 79.3% were female patients with a median age of 51 years. The majority underwent total thyroidectomy either with prophylactic central neck dissection (39.1%) or without (37.5%) versus lobectomy with prophylactic central neck dissection (7.2%) or without (16.2%). Lobectomy rates increased from 18.3% in 2012 to 29.9% in 2020. Prophylactic central neck dissection rates also increased (42.9% to 52.1%). Patients who were male sex, Asian American, had smaller tumors or were treated at community cancer programs had a decreased likelihood of total thyroidectomy. Patients who were older, male sex, Black race, with smaller tumors, or were treated at community cancer programs or mid- or low-volume facilities had decreased likelihood of prophylactic central neck dissection. ConclusionProportional use rates of operative approaches for low-risk, clinically node-negative papillary thyroid cancer have changed in recent years after the American Thyroid Association guideline changes, including increasing overall rates of lobectomy as well as prophylactic central neck dissection, with differences noted based on patient- and facility-level factors.

Prevalence of Occult Central Lymph Node Metastasis by Tumor Size in Papillary Thyroid Carcinoma: A Systematic Review and Meta-Analysis.

While papillary thyroid carcinoma (PTC) is associated with high occult central neck metastasis (CNM) rates, prophylactic central neck dissection (pCND) is controversial. This meta-analysis aims to look at the occult CNM rate according to tumor size. A literature search was conducted in PubMed from inception to April 2023. Inclusion criteria were primary studies that determined occult CNM rates in cN0 PTC by tumor size. Heterogeneity, influential case diagnostics, and proportion data were evaluated with Cochran's Q-test, Baujat plots and Forest plots, respectively. Fifty-two studies were included in this meta-analysis. The findings demonstrated an occult CNM rate of 30.3% for tumors ≤ 5 mm, 32.7% for tumors ≤ 1 cm, 46.0% for tumors between 1 and 2 cm, 43.1% for tumors between 2 and 4 cm, and 61.2% for tumors > 4 cm. The heterogeneity of each study group was high, though no publication bias was noted. While there was a trend towards increased occult CNM rates with larger tumors, comparisons between different size cutoffs varied in significance. This comprehensive review affirms that occult CNM is high and that an ipsilateral pCND can be justified in all PTC patients for accurate differentiation between Stage I and Stage II disease and its clinical implications.

Prophylactic central neck dissection for cN0 papillary thyroid carcinoma: is there any difference between western countries and China? A systematic review and meta-analysis.

Recommendations for the performance of prophylactic central neck dissection (pCND) in patients with clinically node-uninvolved (cN0) papillary thyroid carcinoma (PTC) are not the same. This meta-analysis set out to compare the effectiveness of pCND with total thyroidectomy (TT) in different countries and regions, mainly between western countries and China. The electronic databases PubMed, EMBASE, and Cochrane Library were searched for studies published until August 2022. The incidence rate of cervical lymph node metastases (LNMs), locoregional recurrences (LRRs), and postoperative complications were pooled by a random-effects model. Subgroup analyses based on different countries and regions were performed. Eighteen studies involving 5,346 patients were analyzed. In the subgroup of western countries, patients undergoing pCND with TT had a significantly lower LRR rate [69/1,804, 3.82% vs. 139/2,541, 5.47%; odds ratio (OR) = 0.56; 95% CI 0.37-0.85] and a higher rate of temporary hypoparathyroidism (HPT) (316/1,279, 24.71% vs. 194/1,467, 13.22%; OR = 2.23; 95% CI 1.61-3.08) than that of the TT alone group, while no statistically significant difference was found in the rate of permanent HPT and temporary and permanent recurrent laryngeal nerve (RLN) injury. In the Chinese subgroup, the pCND with TT group had a significantly higher incidence rate of both temporary HPT (87/374, 23.26% vs. 36/324, 11.11%; OR = 2.24; 95% CI 1.32-3.81) and permanent HPT (21/374, 5.61% vs. 4/324, 1.23%; OR = 3.58; 95% CI = 1.24-10.37) than that of the TT alone group, while no significant difference was detected in the rate of LRR and temporary and permanent RLN injury. Compared with the TT alone for cN0 PTC patients, pCND with TT had a significantly lower LRR rate while having a higher temporary HPT rate in Europe, America, and Australia; however, it showed no significant difference in decreasing LRR rate while having a significantly raised rate of temporary and permanent HPT in China. More population-based results are required to advocate precision medicine in PTC. https://www.crd.york.ac.uk/PROSPERO/, identifier CRD42022358546.

Application of carbon nanoparticles combined with refined extracapsular anatomy in endoscopic thyroidectomy.

To evaluate the value of refined extracapsular anatomy combined with carbon nanoparticle suspension tracing technology for protecting parathyroid function and the thoroughness of lymph node dissection in the central region during endoscopic thyroid cancer surgery. Retrospective clinical data analysis was performed on 108 patients who underwent endoscopic thyroid cancer surgery at the First Affiliated Hospital of Wannan Medical College (Yijishan Hospital) from November 2019 to November 2022. Before surgery, thyroid function tests, color Doppler ultrasounds and neck-enhanced CT scans were performed on all patients. Cytopathological diagnosis obtained via ultrasound-guided fine-needle aspiration served as confirmation for the primary diagnosis. It was determined whether to perform a total thyroidectomy or a hemithyroidectomy (HT) together with preventive unilateral (ipsilateral) central neck dissection. Follow-up times were 1 to 34 months. Transient neuromuscular symptoms were present in 3.70% (4/108) cases, with no permanent neuromuscular symptoms or permanent hypoparathyroidism. Regarding transient hypoparathyroidism, the patients recovered after three months and did not need long-term calcium supplementation. The number of harvested LNs (mean± SD) was 5.54 ± 3.84, with ≤5 in 57.41% (62/108) and >5 in 42.59% (46/108) cases. The number of patients with metastatic LNs was 37.96% (41/108), with ≤2 in 65.85% (27/41) and >2 in 34.15% (14/41) cases. Fine extracapsular anatomy combined with carbon nanoparticle suspension tracing is effective in endoscopic thyroid cancer surgery. It can improve the thoroughness of prophylactic central neck dissection and recognition of the parathyroid gland and avoid parathyroid injury and other complications to effectively protect parathyroid function.

Prophylactic Central Neck Dissection Based on Preoperative Imaging and Intraoperative Surgeon's Palpation Versus Total Thyroidectomy Alone for Papillary Thyroid Cancer

IntroductionTo compare the overall morbidity and recurrence of papillary thyroid cancer (PTC) after total thyroidectomy (TT) with or without prophylactic central compartment neck dissection (CCND) in cases of both preoperative and intraoperative nonsuspicious central lymph nodes (CLNs). MethodsA total of 570 PTC patients who harbored no preoperative and intraoperative suspicious CLNs at two institutions were enrolled. They were randomly assigned to TT alone or TT with prophylactic CCND (pCCND) after intraoperative assessment of CLNs during the surgery. Lymph nodes that were hard or large enough to be palpated were regarded as suspicious metastatic lymph nodes during the surgery. The characteristics, postoperative complications, and locoregional recurrence of the two groups were recorded and compared. ResultsWith a median follow-up of 5 y, the rates of lymph node recurrence in the TT alone and TT with pCCND groups were similar (7.3% versus 4.6%, P = 0.247), but there were significantly higher rates of overall morbidity (6.6% versus 19.1%, P < 0.001) when pCCND was performed. ConclusionspCCND is not recommended for patients with clinically node-negative PTC preoperatively and intraoperatively because of the high complication rate and lack of benefit of reducing recurrence.

Prediction of Cervical Lymph Node Metastasis in Clinically Node-Negative T1 and T2 Papillary Thyroid Carcinoma Using Supervised Machine Learning Approach.

Papillary thyroid carcinoma (PTC) is generally considered an indolent cancer. However, patients with cervical lymph node metastasis (LNM) have a higher risk of local recurrence. This study evaluated and compared four machine learning (ML)-based classifiers to predict the presence of cervical LNM in clinically node-negative (cN0) T1 and T2 PTC patients. The algorithm was developed using clinicopathological data from 288 patients who underwent total thyroidectomy and prophylactic central neck dissection, with sentinel lymph node biopsy performed to identify lateral LNM. The final ML classifier was selected based on the highest specificity and the lowest degree of overfitting while maintaining a sensitivity of 95%. Among the models evaluated, the k-Nearest Neighbor (k-NN) classifier was found to be the best fit, with an area under the receiver operating characteristic curve of 0.72, and sensitivity, specificity, positive and negative predictive values, F1 and F2 scores of 98%, 27%, 56%, 93%, 72%, and 85%, respectively. A web application based on a sensitivity-optimized kNN classifier was also created to predict the potential of cervical LNM, allowing users to explore and potentially build upon the model. These findings suggest that ML can improve the prediction of LNM in cN0 T1 and T2 PTC patients, thereby aiding in individual treatment planning.

ESTIMation of the ABiLity of prophylactic central compartment neck dissection to modify outcomes in low-risk differentiated thyroid cancer: a prospective randomized trial

BackgroundProphylactic central neck dissection in clinically low-risk cT1bT2N0 papillary thyroid carcinoma is controversial, due to a large number of conflicting retrospective studies, some showing an advantage in terms of locoregional recurrence, others showing no advantage. These previous studies all show high rates of excellent response. We aim to demonstrate the non-inferiority of thyroidectomy alone as compared to total thyroidectomy with prophylactic central neck dissection in conjunction with adjuvant RAI 30 mCi with rTSH stimulation in terms of excellent response at 1 year.Trial design and methodsProspective randomized open multicenter phase III trial including patients with 11–40-mm papillary thyroid carcinoma (Bethesda VI) or suspicious cytology (Bethesda V) confirmed malignant on intra-operative frozen section analysis, with no suspicious lymph nodes on a specialized preoperative ultrasound examination. Patients will be randomized 1:1 into two groups: the reference group total thyroidectomy with bilateral prophylactic central neck dissection, and the comparator group total thyroidectomy alone. All patients will receive an ablative dose of 30mCi of radioactive iodine (RAI) within 4 months of surgery. The primary outcome is to compare the rate of excellent response at 1 year after surgery between the groups, as defined by an unstimulated serum thyroglobulin (Tg) level ≤ 0.2 ng/mL with no anti-Tg antibodies, an normal neck ultrasound and no ectopic uptake on the post-RAI scintiscan. Non-inferiority will be demonstrated if the rate of patients with excellent response at 1 year after randomization does not differ by more than 5%. Setting the significance level at 0.025 (one-sided) and a power of 80% requires a sample size of 598 patients (299 per group). Secondary outcomes are to compare Tg levels at 8 +/− 2 postoperative weeks, before RAI ablation, the rate of excellent response at 3 and 5 years, the rate of other responses at 1, 3, and 5 years (biochemical incomplete, indeterminate, and structurally incomplete responses), complications, quality of life, and cost-utility.Discussion (potential implications)If non-inferiority is demonstrated with this high-level evidence, prophylactic neck dissection will have been shown to not be necessary in clinically low-risk papillary thyroid carcinoma.Trial registrationNCT 03570021. June 26,2018

Application of decision tree algorithms to predict central lymph node metastasis in well-differentiated papillary thyroid carcinoma based on multimodal ultrasound parameters: a retrospective study.

Prophylactic central neck dissection (pCND) in patients with well-differentiated primary papillary thyroid carcinoma (PTC) has become controversial. Several attempts have been made to predict central compartment lymph node metastasis (CLNM) based on clinical and conventional ultrasonic parameters. This study aimed to develop a decision tree (DT) model for predicting the risk of CLNM in patients with PTC based on clinical and preoperative multimodal ultrasound (US) characteristics. A total of 148 PTC nodules confirmed by surgical pathology at Beijing Tiantan Hospital were retrospectively analyzed. All nodules underwent multimodal US examinations preoperatively from January 2020 to September 2021. Correlation analysis of CLNM with clinical characteristics as well as multimodal US parameters of PTC lesions based on gray-scale US, color Doppler flow imaging (CDFI), superb microvascular imaging (SMI), contrast-enhanced ultrasound (CEUS), and shear wave elastography (SWE) technology was carried out. Finally, the chi-squared automatic interaction detector (CHAID) with a 10-fold cross-validation was used to establish DTs for CLNM prediction. The area under the curve was calculated to compare the predictive performance. Univariate analysis indicated that CLNM was positively correlated with thyroglobulin level, maximum size, taller-than-wide, the number of microcalcifications greater than or equal to 5, contact capsule, abnormal cervical lymph node on conventional US, noncentripetal perfusion, delayed clearance, the average shear wave velocity (SWV mean), and the SWV ratio (P<0.05). The multimodal US DT based on taller-than-wide, contact capsule, abnormal cervical lymph node on conventional US, and centripetal enhancement as independent variables showed good discrimination: the sensitivity, specificity, accuracy, and area under the receiver operating characteristic curve were 80.0%, 76.7%, 78.4%, and 0.837 [95% confidence interval (CI): 0.771-0.902]. There was a significant difference between the multimodal and conventional US DTs (P=0.009). Our results indicated that the DT based on the preoperative multimodal US characteristics of PTCs has a reasonable predictive ability for CLNM and can be conveniently used for clinical decision-making of individualized treatment in patients with well-differentiated PTC.

The Effect of Prophylactic Central Neck Dissection during Total Thyroidectomy on Locoregional Recurrence in Patients with Papillary Thyroid Carcinoma: An Updated Meta-Analysis

AIM: The current systematic review was conducted to update the existing evidence regarding the association between prophylactic central neck dissection (pCND) and locoregional recurrence (LRR) in patients undergoing total thyroidectomy (TT). METHODS: Studies were identified through systematic searches of electronic databases (PubMed, Scopus, Cochrane Library, and Clinical Trials.gov) between November and December 2022. The primary outcome was the unadjusted pooled estimate for LRR using an inverse variance – a weighted random-effects meta-analysis of odds ratios (ORs). RESULTS: Twenty-two studies comparing pCND + TT and TT alone in cN0 PTC patients were analyzed. The meta- analysis included 6918 patients, 2796 cases in the combined group, and 3402 controls in the TT-alone group. The summary OR for overall LRR was not statistically significant, indicating a lack of additional benefit for pCND (OR = 0.76 95% CI [0.5–1.14], p = 0.18). Results were consistent for studies with an experimental or nonexperimental design. The rates of transient (OR = 1.81, 95% CI [1.36–2.41], p &lt; 0.001) and permanent (OR = 2.56, 95% CI [1.72–3.8], p &lt; 0.001) hypoparathyroidism were significantly higher in patients who underwent pCND. The rates of transient (OR = 1.71, 95% CI 1.24–2.35, p &lt; 0.001) and permanent (OR = 2.12, 95% CI 1.29–3.45, p &lt; 0.001) RLN nerve injury were also higher in patients who underwent pCND. Contradictory results were observed for adjuvant RAI with RCTs suggesting a lower need for postoperative RAI therapy. CONCLUSION: The meta-analysis and the systematic review suggest that pCND was not associated with lower odds of LRR in patients with N0 PTC. Moreover, transient and permanent hypoparathyroidism and RLN injury were higher in patients undergoing TT + PCND. TT + pCND should not be routinely recommended except in high-risk patients due to the lack of benefit and lower safety profile than TT only.

Should multifocality be an indication for prophylactic central neck dissection in papillary thyroid cancer?

Although multifocality is common in patients with papillary thyroid cancer, its effects on lymphatic metastasis and the necessity of central dissection in the presence of multifocality are still controversial. In our clinic, 258 patients who underwent thyroidectomy between 2015 and 2020 and were found to have papillary thyroid cancer in postoperative pathology reports were analyzed. The tumor characteristics contributing to central lymph node metastasis positivity were evaluated. Lymph node metastases were not significantly increased in the presence of multifocality. In cases with bilateral multifocal tumors, compared to cases with unilateral multifocal tumors, capsular invasion (p = 0.02), vascular invasion (p = 0.01) and cervical lymphatic metastasis (p = 0.004) were observed to increase. Bilateral multifocal tumors have more aggressive clinicopathological features than unilateral tumors. We found that the risk of central lymph node metastasis increased significantly in bilateral multifocal tumors in our study. Prophylactic central lymph node dissection may be considered in patients with no preoperative or intraoperative lymph node metastasis but thought to have a multifocal tumor.

The role of prophylactic central compartment neck dissection in patients with T1-T2 cN0 papillary thyroid carcinoma.

It remains controversial whether prophylactic central compartment neck dissection (pCCND) is necessary in cases of stage T1-T2 cN0 papillary thyroid carcinoma (PTC). Some studies have demonstrated the benefits of pCCND on oncologic outcomes, whereas others reported that any advantages were insignificant. The purpose of this study was to investigate the effects of pCCND on cancer recurrence and its pattern in patients with T1-T2 cN0 PTC. We retrospectively reviewed 2,902 patients with PTC who had undergone thyroidectomy between 2006 and 2012 at Seoul St. Mary's Hospital: 2,099 patients had undergone pCCND and thyroidectomy (pCCND group), whereas 803 did not undergo pCCND (non-pCCND group). We investigated the effects of pCCND on cancer recurrence by comparing these two groups. Recurrence was classified according to the location of the recurrence. The mean follow-up period was 112 months. The mean patient age was significantly younger in the pCCND group than in the non-pCCND group. There were no statistically significant differences in the distribution of sex, tumor size, or thyroidectomy extension between the groups. In the pCCND group, 883 (42%) patients showed evidence of N1a disease, and the mean number of metastatic lymph nodes was 1.26±2.2. Recurrence occurred in 67 (2.3%) patients in the total cohort. Recurrence was observed in 20 (2.5%) and 47 (2.2%) patients in the non-pCCND and pCCND groups, respectively, but there were no significant differences between the groups (P=0.687). When analyzed by the site of recurrence, 50% and 4.3% of recurrent disease in the non-pCCND and pCCND groups, respectively, occurred in the central compartment (P<0.001). There were no differences between the two groups in recurrent disease at other sites. The 15-year cumulative central compartment recurrence-free survival (RFS) rates of patients in the non-pCCND and pCCND groups were 99% and 100%, respectively (P<0.001). In the multivariate analysis, not performing pCCND was the only independent risk factor related to central compartment RFS, and the hazard ratio was 13.362 [95% confidence interval (CI): 2.928-60.986; P<0.001]. The omission of pCCND was found to be an independent risk factor for recurrence in the central compartment in patients with T1-T2 cN0 PTC.

Endoscopic hemithyroidectomy plus prophylactic central neck dissection via breast approach versus gasless transaxillary approach in treating low-risk papillary thyroid cancer: a retrospective series.

Hemithyroidectomy plus prophylactic central neck dissection (pCND) has been adopted as a de-escalating surgical strategy for low-risk papillary thyroid cancer (PTC). This study aimed to evaluate and compare the outcomes of these two different endoscopic approaches in the treatment of PTC with hemithyroidectomy plus pCND. This retrospective study reviewed medical records of 545 patients receiving breast approach (ETBA) (n = 263) or gasless transaxillary approach (ETGTA) (n = 282) in treating PTC. Demographics and outcomes were compared between the two groups. Preoperatively, the two groups were similar in demographics. Regarding surgical outcomes, no differences were found in terms of intraoperative bleeding, total amount of drainage, duration of drainage, postoperative pain, hospital stay, vocal cord palsy, hypoparathyroidism, hemorrhage, wound infection, chyle leakage, or subcutaneous ecchymosis. Conversely, ETBA recorded fewer skin paresthesia (1.5% vs. 5.0%, respectively) but longer operative times (138.1 ± 27.0 vs. 130.9 ± 30.8min,) and more swallowing disturbances (3.4% vs. 0.7%) compared to ETGTA (p < 0.05). No difference in scar cosmetic results, but ETBA had lower neck assessment score than ETGTA (2.6 ± 1.2 vs. 3.2 ± 2.0, p < 0.05). For low-risk PTC, endoscopic hemithyroidectomy plus pCND using either ETBA or ETGTA is both feasible and safe. Although the two approaches are comparable in terms of most surgical and oncological outcomes, ETBA is superior to ETGTA in terms of neck cosmetic results and skin paresthesia but is associated with more swallowing disturbances and requires a longer operative time.

Predictive Factors Affecting the Development of Lateral Lymph Node Metastasis in Papillary Thyroid Cancer.

Lateral lymph node metastasis (LLNM) in papillary thyroid cancer (PTC) determines the extent of surgery to be performed and the prognosis of the disease. In this study, we aimed to evaluate the clinicopathological risk factors affecting the development of LLNM. We retrospectively evaluated the demographic and clinicopathological data of 346 cases with PTC who were operated in our clinic between May 2012 and September 2020. The patients were divided into 2 groups as patients with LLNM (Group 1) and without LLNM (Group 2). Thirty-six (10.4%) patients out of 346 patients with PTC had LLNM. A statistically significant difference was found between Group 1 and Group 2 regarding the male gender (M/F: 38.9% vs. 21.6%; p=0.020), tumor size (2.30±1.99 cm vs. 1.31±1.40 cm; p=0.000), lymphovascular invasion (69.4 vs. 20.6%; p=0.000), multicentricity (69.4% vs. 35.5%; p=0.000), multifocality (p=0.000), aggressive variant (22.2% vs. 9.4%; p=0.000), extrathyroidal extension (50% vs. 16.1% p=0.000), central lymph node metastasis (CLNM) rates (75% vs. 6.5%; p=0.000), and ≥3 cm lymph node metastasis (48.5% vs. 0%, p=0.000), distant metastasis (2.1% vs. 0%, p=0.000), respectively. Multivariance analysis determined the presence of CLNM as an independent risk factor for the development of LLNM. The presence of CLNM in patients with PTC was determined as an independent risk factor for the development of LLNM. Although there has been increasing debate about prophylactic central neck dissection (pCND) in LLNM, pCND should still be considered in these patients as the rate of CLNM is high in patients with LLNM. CLNM might be a reference for surgeons to determine the extent of surgery. In addition, the presence of CLNM is important for close follow-up for the early detection of LLNM recurrence.

Survey of Korean head and neck surgeons and endocrinologists for the surgical extent of 1.5 and 2.5 cm papillary thyroid carcinoma

The surgical extent of 1-4 cm papillary thyroid carcinoma (PTC) is controversial. We aimed to determine the current trend in the extent of thyroidectomy and prophylactic central neck dissection (pCND) for 1.5 and 2.5 cm PTC, which are the most clinically controversial sizes. The questionnaire was sent to 342 Korean Society of Head and Neck Surgery and 160 one branch of Korean Endocrine Society members from June to July 2021 by e-mail. A questionnaire included extent of thyroidectomy [hemithyroidectomy (Hemi) vs. total thyroidectomy (TT)] and pCND according to the tumor location and degree of extrathyroidal extension (ETE) at 1.5 or 2.5 cm PTC. We compared the proportion of respondents' preference for each scenario. Fifty-seven of 342 surgeons and twenty-seven of 160 endocrinologists responded to the questionnaire. At 1.5 and 2.5 cm PTC without ETE, both groups preferred Hemi, and there was no difference between the groups. When 1.5 or 2.5 cm PTC with anterior minimal ETE was suspected, the preference for Hemi by endocrinologists was significantly lower than that by surgeons (P<0.05). When anterior and posterior gross ETE were suspected, TT was preferred in both groups. When anterior gross ETE was suspected, the preference for Hemi by endocrinologists was significantly lower than that by surgeons (P<0.05). There was no difference between the groups in the posterior gross ETE. Surgeons preferred Hemi and endocrinologists preferred TT for a 1.5 cm PTC located in the isthmus. The pCND showed a similar pattern in both groups according to the size and location of the tumor and the degree of ETE. The proportion of Hemi did not differ between high-experience and low-experience endocrinologists. Also, there was no significant difference in preference for surgical extent between low-volume and high-volume surgeons. TT was frequently preferred in tumors with a large size or gross ETE, and pCND was frequently preferred in cases of suspected gross ETE. This study shows as the extent of thyroid surgery may differ between endocrinologists and surgeons and this could be confusing to patient and affect the patient outcomes. Therefore, multidisciplinary approach considering the extent of surgery for thyroid cancer is recommended.