Recurrent Laryngeal Nerve Invasion Research Articles

The Effect of Hemithyroidectomy in Papillary Thyroid Carcinoma with an Exclusive Involvement of the Recurrent Laryngeal Nerve: A Retrospective Study with a Propensity Score-Matched Analysis.

Involvement of the recurrent laryngeal nerve (RLN) in papillary thyroid carcinoma (PTC) is an important prognostic factor and is associated with a higher risk of recurrence. This study aimed to retrospectively analyze the outcomes of patients treated with hemithyroidectomy (HT) in PTC patients with an exclusive RLN invasion who could not tolerate staged surgery, did not wish to undergo another operation, or had other reasons. A retrospective review was conducted on 163 patients with PTC and exclusive RLN involvement at our institution between 2013 and 2019. Patients were divided into a total thyroidectomy (TT) group and HT group. The clinicopathologic factors and prognostic outcomes were compared between the two groups. A propensity score-matched analysis was carried out to reduce selection bias, with the following covariates: gender, age, tumor size, multifocality, central lymph node metastasis (CLNM), and RLN resection. The Kaplan-Meier method was used for a comparison of recurrence outcomes. In the baseline data of the 163 PTC patients, tumor size (p < 0.001), multifocality (p = 0.011), CLNM (p < 0.001), and RLN resection (p < 0.008) in the TT and HT groups differed significantly, whereas age and gender did not differ between the two groups. The TT group reported significantly higher temporary and permanent hypoparathyroidism than the HT group (p < 0.001 and p = 0.042, respectively). With 72-month median follow-up, 11 (6.7%) patients developed recurrence. After propensity score matching, 24 patients with HT and 43 patients with TT were included. Recurrence-free survival (RFS) in the matched samples showed no difference between the TT and HT groups (p = 0.092). Our results indicate that HT may be a feasible treatment for PTC patients with exclusive RLN involvement in specific circumstances without significantly increasing the risk of recurrence. Performing a thorough preoperative examination is crucial to exclude multifocal tumors and lymph node metastasis before undergoing HT.

Comparison of pembrolizumab plus chemotherapy versus concurrent or sequential radiochemotherapy in patients with driver mutation-lacking lung adenocarcinoma presenting with recurrent laryngeal nerve invasion leading to hoarseness.

e14635 Background: For patients with advanced non-small cell lung cancer (NSCLC), particularly those with adenocarcinoma lacking a driver mutation, the encroachment upon the recurrent laryngeal nerve causing hoarseness presents a substantial challenge in treatment. Such patients, at TNM stage IIIB or higher, may undergo platinum-based doublet chemotherapy combined with concurrent or sequential radiotherapy. Despite these treatments, survival rates remain modest, and quality of life is significantly impaired by symptoms such as hoarseness, dysphagia, and coughing. Recently, pembrolizumab combined with chemotherapy has emerged as a frontline treatment for adenocarcinoma patients, showing promising outcomes in unresectable, advanced stages of the disease. However, its efficacy in patients experiencing hoarseness due to recurrent laryngeal nerve involvement has not been previously investigated. Methods: Between September 2018 and October 2022, Jiangmen Central Hospital admitted 71 patients with advanced adenocarcinoma and hoarseness, who lacked a driver mutation as confirmed by NGS testing. After excluding patients who did not complete the treatment plan, the remaining subjects were randomly divided into two groups. The treatment group, consisting of 21 patients, received pembrolizumab, pemetrexed, and platinum-based doublet chemotherapy. The control group, also comprising 21 patients, underwent concurrent or sequential radiotherapy alongside pemetrexed and platinum-based chemotherapy. Results: Among the treatment group, hoarseness was reversed in 13 out of 21 patients, with a return to normal vocal function. In the control group, 5 out of 21 patients experienced a reversal of hoarseness. The treatment group showed superior outcomes in reversing hoarseness caused by recurrent laryngeal nerve involvement (p=0.013). The objective response rate (ORR) in the treatment group was 28.57%, with a disease control rate (DCR) of 66.67%. In contrast, the control group had an ORR of 9.52% and a DCR of 28.57% (p&lt;0.05). The Progression-Free Survival (PFS), as calculated by the Kaplan-Meier survival curve method, was 11.77 months (95% CI: 11.19-12.35) in the treatment group and 7.53 months (95% CI: 6.73-8.33) in the control group, indicating a significantly higher survival rate in the treatment group (p&lt;0.05). Conclusions: In patients with advanced lung adenocarcinoma, pembrolizumab combined with chemotherapy appears to effectively reverse hoarseness caused by recurrent laryngeal nerve involvement, higher objective response rates, and increased PFS. This suggests the necessity for multicentric, prospective, evidence-based studies in the treatment of lung adenocarcinoma patients with hoarseness due to recurrent laryngeal nerve invasion.

Prediction of Recurrent Laryngeal Nerve Invasion in Thyroid Cancer by Ultrasound

Prediction of Recurrent Laryngeal Nerve Invasion in Thyroid Cancer by Ultrasound

Impact of thyroid carcinoma invasion of recurrent laryngeal nerve on cervical lymph node metastasis.

Papillary thyroid carcinoma (PTC) has a favorable prognosis. However, involvement of the recurrent laryngeal nerve (RLN) significantly increases the risk of recurrence. RLN invasion was an important factor in determining the extent of thyroid surgery. The purpose of this study was to compare clinicopathologic features and characterize risk factors of central and lateral lymph node metastasis (LLNM) of RLN invasion in patients with PTC. A retrospective review was conducted of 130 patients with PTCs who had exclusive tumor involvement of the RLN at our institution between January 2014 and February 2019. All patients underwent total thyroidectomy and high-dose radioactive iodine (RAI) therapy. The clinicopathologic factors and prognostic outcomes of the patients with solitary and multiple RLN involvements were compared. Kaplan-Meier method was performed to compare the outcomes of tumor recurrence. Univariate and multivariate logistic regression analyses were used to identify risk factors associated with LLNM. The invasion of the RLN was similar on both sides, with 58.5% on the right, 40.0% on the left, and 1.5% on both sides. Significant differences were observed in tumor size (p < 0.001), lymph node metastasis classification (p = 0.002), RLN resection (p < 0.001), and thyroglobulin (p = 0.010) in the solitary and multiple groups. During the median follow-up of 67 months, 9 (6.9%) patients developed recurrence. There were no statistical differences in recurrence for age, tumor size, gender, multifocality, lymph node metastasis (LNM), and RLN resection. According to receiver operating characteristic (ROC) curve analyses, a cut-off of tumor size > 1.7 cm was identified as the most sensitive and specific predictor of RLN with multiple involvements or LNM invasion. Univariate and multivariate analyses revealed that central lymph node metastasis (CLNM) and RLN invasion by LNM can serve as independent risk factors for LLNM (p = 0.006 and p < 0.001, respectively). Our results indicate that recurrence was comparable in patients with solitary and multiple RLN involvements. Multiple RLN involvement was associated with pathological features such as larger tumors, RLN resection, and LLNM. The presence of LNM invading RLN and multiple nerve involvement increases the risk of intraoperative RLN resection. A higher risk of multiple invasion or LNM invasion should be considered when tumor size > 1.7 cm. The presence of CLNM and RLN invaded by LNM were independent predictors for LLNM, which could aid surgeons in deciding on lateral lymph node dissection.

Predicting recurrent laryngeal nerve invasion by preoperative ultrasonography in patients with thyroid carcinoma.

For thyroid cancer staging, evaluation of extent of local invasion, including recurrent laryngeal nerve (RLN), may assist surgical decision-making. This prospective study evaluated patients who underwent thyroidectomy at a single tertiary-level academic institution. Patients with complete clinical information and ultrasound imaging of thyroid carcinoma and RLN were enrolled. Those who had thyroidectomy before or did not fit the above conditions were excluded. Patients were assigned to either a development or validation cohort. Development of models was constructed in a primary cohort based on preoperative ultrasound features and clinicodemographic data from August 2020 to December 2021. Validation of the models was then performed on an independent cohort between January and March of 2022. Multivariate logistic regression and nomograms were mainly used for statistical analysis. Using data from 816 patients (80 RLN invasion), we built nomogram 1 based on age [95% confidence interval (CI): 1.315 to 145.933, P=0.029], body mass index (BMI; 95% CI: 1.228 to 10.874, P=0.020), tumor size (95% CI: 4.677 to 1,373.1, P=0.002), tumor adjacent to medial (95% CI: 1.816 to 26.713, P=0.005) and posterior thyroid capsules (95% CI: 5.567 to 756.583, P=0.001), and distance <1 mm between tumor and the RLN (95% CI: 10.389 to 826.746, P<0.001). Nomogram 2 was built based on tumor adjacent to the posterior thyroid capsule (95% CI: 2.922 to 53,074.51, P=0.017), distance <1 mm between tumor and the RLN (95% CI: 1.478 to 1,241.646, P=0.029), and loss of typical fascicular echotexture of the RLN along the long axis (95% CI: 35.11 to 53,272.81, P<0.001). In the validation cohort, nomogram 1 and 2 showed sensitivities of 94.74% and 57.89%, specificities of 74.12% and 95.29%, positive predictive values (PPV) of 45.00% and 73.26%, negative predictive values (NPV) of 98.43% and 91.03%, accuracies of 76.92% and 88.46%, and C-indices of 0.86 and 0.89. Preoperative ultrasound is a feasible approach to evaluate RLN invasion in patients with thyroid carcinoma. Nomogram 1 may sensitively identify the risk of RLN invasion, and it may be checked using the more specific and accurate nomogram 2 to reduce false positives.

Clinical classification of recurrent laryngeal nerve palsy.

The application of intraoperative neurophysiological monitoring (IONM) has been accepted to avoid injury of a recurrent laryngeal nerve (RLN). Loss of the neuromonitoring signal indicates nerve injury and is subdivided into segmental type and global type nerve paralysis. This study aimed to determine the course of vocal cord function recovery after definitive loss of signal (LOS) types. This retrospective study included 1,442 patients (with 2,752 nerves at risk) who had thyroidectomies between January 2018 and December 2021. Preoperative and postoperative vocal cord functions were evaluated by laryngoscopic examination. LOS occurred in 168 of 1,442 (11.7%) patients and 171 of 2,748 (6.2%) nerves at risk during surgery. Of LOS nerves of benign tumors, 74.2% showed global type. In cancer cases, segmental paralysis was more common, accounting for 51.3% of LOS nerves. Of nerves with segmental LOS in cancer patients, 55.3% needed partial layer resection for RLN invasion. Intraoperative recovery was seen in 9 of 62 nerves (14.5%) with segmental LOS and 32 of 109 (29.4%) nerves with global type LOS. The vocal cord palsy rate on postoperative days (PODs) 2-3 was lower after global type nerve paralysis (63.6%) than after segmental loss (84.9%). At 6 months postoperatively, the rate of vocal cord paralysis in benign tumors was not significantly different between segmental type and global type (P=0.586). However, cancer patients with segmental LOS significantly more often had vocal cord dysfunction than those with global LOS at 6 months postoperatively (rate of nerve palsy: segmental 40.0% vs. global 3.4%) (P<0.001). The intraoperative recovery rate and early nerve recovery rate are significantly higher for patients with global LOS than for patients with segmental LOS. Cancer patients with segmental LOS significantly more often had vocal cord dysfunction than those with global LOS at 6 months postoperatively.

Complications of Thyroid Cancer Surgery in Pediatric Patients at a Tertiary Cancer Center.

The incidence of complications and risk factors for hypocalcemia after pediatric thyroid cancer surgery has not been clearly defined in the literature because most reports fail to distinguish between benign and malignant disease. The trend away from total thyroidectomy (TT) to thyroid lobectomy in low-risk disease means there is a need to clearly define the complication profile of malignant disease. After institutional review board (IRB) approval, a retrospective chart review was undertaken at Memorial Sloan Kettering Cancer Center for pediatric patients undergoing surgery for well-differentiated thyroid cancer from 1986 to 2021. Clinicopathologic characteristics and complications were evaluated. Multivariable analysis was performed to identify factors independently associated with postoperative hypocalcemia. The study identified 307 pediatric patients with well-differentiated thyroid carcinoma (median follow-up period, 61 months). Of these patients, 69% underwent TT and 31% received a partial thyroidectomy. Among them, 40% had N0 disease, 28% had N1a disease, and 33% had N1b disease. Postoperatively, no patients experienced a neck hematoma, 1.6% had temporary unilateral vocal cord palsy (VCP), and 0.7% had permanent VCP due to recurrent laryngeal nerve (RLN) invasion. Temporary and permanent hypocalcemia occurred in respectively 32.6 % and 5.2 % of the patients. Multivariable analysis identified central neck dissection (CND) (odds ratio [OR] 3.30; p < 0.001) and N1 disease (OR 2.51; p = 0.036) as independent risk factors for temporary hypocalcemia and N stage (OR 3.64; p = 0.018) as a risk factor for permanent hypocalcemia. Pediatric thyroid cancer surgery results in low complication rates despite nodal metastases. Vocal cord paralysis is rare unless disease is found to be invading the RLN intraoperatively. Both N stage and CND are independent risk factors for hypocalcemia, helping to identify high-risk patients.

Conversion surgery after lenvatinib treatment for anaplastic thyroid carcinoma: a case report

BackgroundAnaplastic thyroid carcinoma (ATC) is the most aggressive form of thyroid carcinoma. Lenvatinib, a multikinase inhibitor, is rarely used in preoperative settings due to adverse effects including delayed wound healing and fistula formation. Herein, we report the use of lenvatinib treatment prior to conversion surgery for the treatment of ATC.Case presentationA 71-year-old woman was referred to our hospital with suspected thyroid cancer with recurrent laryngeal nerve invasion and cervical lymph node metastasis based on the results of ultrasonography. Computed tomography demonstrated the presence of a thyroid tumor invading the trachea and esophagus with no evidence of distant metastasis. Fine needle aspiration of the left cervical lymph node indicated the lymph node metastasis of ATC. As the tumor had widely invaded the trachea and esophagus, unresectable ATC was diagnosed and treatment with lenvatinib was initiated at a dose of 24 mg/day. On day 13 of lenvatinib treatment, the primary tumor and lymph node metastases demonstrated a partial response to therapy. As the tumor was now considered resectable, the decision was made to perform conversion surgery. Total thyroidectomy and left lateral neck node dissection were performed 7 days after the withdrawal of lenvatinib. The patient was discharged on postoperative day 5 with no complications. Histopathological examination demonstrated that the tumor contained the component of papillary thyroid carcinoma, squamoid ATC cells, and granulation tissue. In areas of granulation tissue, atypical cells with spindle-shaped or polygonal morphology, pyknotic nuclei, and scant cytoplasm were observed. Immunohistochemically, these cells were positive for cytokeratin AE1/AE3, TTF-1, and p53 and negative for thyroglobulin and PAX8. Therefore, the areas of granulation tissue observed within tumor samples were also considered ATC that were affected by lenvatinib treatment. In total, approximately 50% of resected tumor comprised ATC, and 70% of them had been changed to granulation tissue.ConclusionsThe findings in the present case indicate that lenvatinib may have significant antitumor effects in preoperative settings. Lenvatinib may represent a promising candidate therapy for unresectable ATC by increasing tumor resectability.

Clinical characteristics and prognosis of anaplastic thyroid carcinoma: a 20-year single-center retrospective study

Objectives: To investigate the clinical characteristics and prognoses of patients with anaplastic thyroid carcinoma(ATC), and to explore the value of multi-modality treatment in improving overall survival(OS) of ATC patients. Methods: Medical records including clinicopathological data of patients diagnosed with ATC at Cancer Hospital, Chinese Academy of Medical Sciences between 2001 and 2020 were retrospectively analyzed. The cohort were divided into surgery-only and multi-modality subgroups, and the latter included patients treated with surgery plus radiotherapy and/or medical therapy(including chemotherapy, target therapy and immunotherapy). Univariate survival analysis was conducted through Kaplan-Meier method, and multivariate survival analysis was performed using Cox proportional hazard model. Results: A total of 47 patients were included in the study, including 24 males and 23 females, with a median age of 63 years. After a median follow-up duration of 3.37 months, 42 patients died due to tumor recurrence or progression. The median OS of the cohort was 4.33 months. Univariate survival analysis demonstrated that symptoms of recurrent laryngeal nerve(RLN) involvement, distant metastasis, leukocyte elevation, and treatment modality were significantly associated with OS (P values all<0.05). Multivariate analysis showed that symptoms of RLN involvement(HR=2.49, 95%CI: 1.16-5.32, P=0.019), distant metastasis(HR=2.33, 95%CI: 1.06-5.16, P=0.036), and leukocyte elevation(HR=2.50, 95%CI: 1.16-5.40, P=0.020) were all independent risk factors for OS, while multi-modality therapy significantly prolonged OS compared with surgery alone(HR=0.22, 95%CI: 0.10-0.47, P<0.001). Conclusions: Among ATC patients, absence of symptoms of RLN invasion, normal leukocyte level and absence of distant metastasis at initial diagnosis are all independent protective factors for OS and multi-modality treatment can help to improve the prognosis.

Predictive factors and risk analysis of recurrent laryngeal nerve invasion in papillary thyroid carcinoma ≤ 1 cm.

The recurrent laryngeal nerve (RLN) may be involved by papillary thyroid carcinoma ≤ 1 centimeter (PTC ≤ 1 cm). Current study investigated the predictive factors of RLN invasion in PTC ≤ 1 cm, the risk factors of disease recurrence in RLN invaded cases and the results of surgical management for RLN invasion. Data of 374 PTC ≤ 1 cm patients were retrospectively collected. We performed univariate and multivariate analysis to identify predictive factors of RLN invasion and risk factors of disease recurrence. The abilities of factors in predicting RLN invasion were evaluated. Surgical outcomes and recurrence free survival (RFS) of patients were analyzed. A total of 28 patients suffered RLN invasion, among which seven had disease recurrence. Preoperative vocal cord palsy (VCP), gross extrathyroidal extension, larger tumor size and tumor on the dorsal side of thyroid were verified as predictive factors of RLN invasion. RLN involved patients had poorer RFS, but better than those who also had upper-aerodigestive tract invasion. Upper-aerodigestive tract invasion, lateral neck lymph nodes metastasis (LNM) and BRAF V600E mutation were independent risk factors of disease recurrence in RLN invaded cases. Tumor shaving showed better RLN function preservation without increasing recurrent risk. Current study confirmed the rarity of RLN invasion in PTC ≤ 1 cm. Various aggressive features were verified as predictive factors of RLN invasion. Tumor shaving showed superiority in preserving nerve function without increasing recurrent risk. Special attentions should be paid for disease recurrence when RLN invasion accompanied by upper-aerodigestive tract invasion, lateral neck LNM or BRAF V600E mutation.

Outcomes of immediate surgery for low-risk papillary thyroid microcarcinoma in patients with or without risky features at surgery.

Active surveillance (AS) is an accepted management option for patients with low-risk papillary thyroid microcarcinoma (PTMC), although some patients undergo immediate surgery (IS). At surgery, patients may have risky features such as adhesion or invasion to the adjacent organs. The surgical outcomes of this subset of patients are unknown. Here, we investigated the surgical and oncological outcomes of these patients in comparison with others. Between 2005 and 2019, 4,635 patients were diagnosed with low-risk PTMC at our institute. Of these, 1,739 patients underwent IS. In total, 114 patients had risky features at surgery (risky feature group), while the remaining 1,625 did not (no-risky feature group). The median follow-up periods in the risky and no-risky feature groups were 8.5 and 7.6 years, respectively. The risky feature group had higher incidences of tracheal invasion (8.8%), recurrent laryngeal nerve invasion (RLN) (7.9%), and permanent vocal cord paralysis postoperatively (10.0%) and higher frequency of pathological lateral lymph node metastasis (6.1%) than the no-risky feature group (0%, 0%, and 0.2%, and 0%, respectively [p < 0.01]). However, unexpectedly, the former had a lower incidence of high Ki-67 labeling index (1.1%) and lower locoregional recurrence rate (0%) than the latter (8.3% and 0.7, respectively [p < 0.01], not calculable). None of the groups developed distant metastasis or died of the disease. The risky feature group required resection of the trachea and/or the RLN more often than the no-risky feature group. However, unexpectedly, the tumor growth activity in the risky feature group was low, and their oncological outcome was excellent.

Clinical characteristics and prognosis in papillary thyroid carcinoma patients with recurrent laryngeal nerve invasion

Objective: To investigate the clinical characteristics and risk factors of postoperative recurrence in papillary thyroid carcinoma (PTC) patients with recurrent laryngeal nerve (RLN) invasion. Methods: The data of PTC patients with recurrent laryngeal nerve invasion treated in Beijing Tongren Hospital, Capital Medical University from January 2006 to December 2019 were retrospectively analyzed. The acoustic parameters were compared between different subgroups. Kaplan-Meier method was used to calculate the overall survival (OS) and the recurrence-free rate (RFS), and univariate and multivariate Cox regression analyses were performed to determine the risk factors for postoperative recurrence. Results: A total of 150 PTC patients were enrolled in the final analysis, including 102 females and 48 males, with an average age of (53.5±13.7) years, and 62 patients (41.3%) aged over 55 years. There were 88 cases with stage Ⅰ, and 62 cases with stage Ⅲ. Fifty-five patients presented with preoperative vocal cord paralysis. There were 75 cases appearing adhesion between tumor or lymph node and recurrent laryngeal nerve while 75 cases presented with direct invasion. The comparisons of acoustic parameters showed that patients with RLN invasion had higher jitter compared with patients without RLN invasion [2.3% (1.4%, 3.2%) vs 1.8% (0.8%, 2.6%), P<0.001]. Moreover, patients with preoperative vocal cord paralysis (VCP) had higher jitter[3.1% (2.2%, 4.6%) vs 2.0% (1.1%, 2.8%), P<0.001] and shimmer [7.1% (4.9%, 9.9%) vs 5.5% (4.2%, 7.3%), P<0.001] and shorter maximum phonation time (MPT) [8.0 (6.0, 10.0) s vs 12.0 (10.0, 15.3) s, P<0.001] compared with patients without preoperative VCP. However, there was no statistical difference in acoustic parameters between cases with RLN adhesion and RLN invasion (all P>0.05). Postoperative follow-up time ranged between 12-196 months, with an average of (65.0±35.9) months. Sixteen patients (10.7%) had recurrence or metastasis, and 8 cases (5.3%) died of recurrence or metastasis. The 5-year OS rate was 95.1%, and the 10-year OS rate was 92.8%. The 5-year RFS rate was 88.9%, and the 10-year RFS rate was 86.2%. Univariate Cox analysis showed that age of onset ≥ 55 years, preoperative recurrent laryngeal nerve palsy, laryngeal, trachea or esophageal invasion were the risk factors for postoperative recurrence of PTC with RLN invasion (all P<0.05). Multivariate Cox analysis showed that age of onset ≥ 55 years (OR=1.060, 95%CI: 1.011-1.110, P=0.015) was an independent risk factor. Conclusions: Age of onset ≥ 55 years is an independent risk factor for postoperative recurrence in PTC patients with RLN invasion. Preoperative acoustic parameters may provide reference for evaluation of RLN function.

Surgical treatment and prognosis values of extranodal extension to recurrent laryngeal nerve in papillary thyroid carcinoma.

Recurrent laryngeal nerve (RLN) invasion by extranodal extension (ENE) is a rare condition that may occur in papillary thyroid cancer (PTC), and it has never been characterised in the literature.Our research aims to investigate the clinical significance of ENE to RLN including its effect on vocal cord function, relationship with the aggressive behaviour of PTC, and optimal surgical methods. A total of 3119 patients, including 2868 patients without RLN invasion, 251 patients with RLN invasion [categorised into the ENE invasion group (n = 55) and extrathyroidal extension (ETE) invasion group (n = 196)] were analyzed retrospectively. Data on clinicopathological characteristics, vocal cord paralysis (VCP), postoperative complications, surgical methods, rates of recurrence and metastasis were collected. Predictive disease-free survival (DFS) was analysed using the Kaplan-Meier method. The ENE invasion group showed a similar rate of VCP and DFS compared with the ETE invasion group (P = 0.15, P = 0.38, respectively). Sharp separation applied on the invaded nerves preserves the visual integrity of the RLN without significantly reducing the DFS (P > 0.05). ETE or ENE to RLN, lymph nodes metastasis (LNM), and T4 stage were independent factors for total recurrence [P = 0.04, hazard ratio (HR), 1.97 (1.04-3.75); P = 0.00, HR, 4.63 (2.24-9.54); P = 0.00, HR, 3.63 (1.94-6.77); P = 0.00, HR, 6.1 (3.24-11.50)]. RLN invasion, both by ETE or ENE, was significantly associated with reduced DFS (P = 0.00; P = 0.00, respectively). ENE to RLN, while rare, has not previously been well-studied. Our interesting premise and important findings including ENE to RLN has the same poor prognostic impact on recurrence as does invasion of the RLN by ETE and surgical management for the invaded RLN that preserves its visual integrity without compromising DFS. Those novel findings indicate that ENE to RLN could be considered as an additional factor beyond post-operative disease status and risk stratification, and it would be a valuable addition to further individualise treatment/surveillance for PTC.

Preoperative voice analysis and survival outcomes in papillary thyroid cancer with recurrent laryngeal nerve invasion.

To investigate the clinicopathological characteristics of papillary thyroid cancer (PTC) and identify risk factors for postoperative recurrence of PTC with recurrent laryngeal nerve (RLN) involvement. In total, 171 patients (112 women and 59 men, age: 18-80 years, and 65 patients aged ≥ 55) with T4a PTC with RLN involvement, treated at Beijing Tongren Hospital, Capital Medical University, from January 2006 to December 2020, were retrospectively examined. Clinicopathological characteristics, including voice analysis results, and survival outcomes were assessed. The Mann-Whitney U and Kruskal-Wallis H tests were used to analyze differences in acoustic parameters. The Kaplan-Meier method was used to calculate the overall survival (OS) and recurrence-free (RFS) rates. Univariate and multivariate Cox regression analyses were performed of the clinical data. The postoperative follow-up period ranged from 12 to 196 months (mean: 66.18 months). Of the 171 patients, 16 had recurrence and 8 died of thyroid-related diseases. The 5-year OS rate was 95.22%. The 5-year RFS rate was 89.38%. Jitter and shimmer were higher and maximum phonation time was shorter in patients with preoperative vocal cord paralysis (VCP) than in those without RLN involvement, and in those with RLN involvement but without preoperative VCP. Acoustic parameters were similar in patients with no preoperative VCP and those without RLN involvement. Voice analysis results did not differ between cases with RLN adhesion and RLN invasion. Univariate analysis showed that age at onset ≥ 55 years, preoperative RLN palsy, and esophageal invasion were risk factors for postoperative recurrence of PTC with RLN involvement. Multivariate analysis showed that onset age ≥ 55 years (OR 4.52, 95% confidence interval: 1.44-14.19, P = 0.010) was an independent risk factor for recurrence. PTC patients with RLN invasion can achieve good outcomes. Preoperative voice analysis may offer insights into RLN function. Age of onset ≥ 55 years is an independent risk factor for postoperative recurrence in T4a PTC patients.

Risk factors for recurrence and survival analysis in locally advanced T4a papillary thyroid carcinoma after R0 resection

Objective: To investigate the treatment outcomes and risk factors of postoperative recurrence in T4a papillary thyroid carcinoma (PTC). Methods: A total of 185 patients with locally advanced T4a PTC treated in Beijing Tongren Hospital, Capital Medical University from January 2006 to December 2019 were retrospectively analyzed, including 127 females and 58 males, aged between 18 and 80 years, with 74 patients aged over 55 years. According to AJCC thyroid tumor staging, 111 cases were stage I (T4aN0M0 26 cases, T4aN1aM0 35 cases, and T4aN1bM0 50 cases) and 74 cases were stage Ⅲ (T4aN0M0 29 cases, T4aN1aM0 19 cases, and T4aN1bM0 26 cases). Kaplan-Meier method was used to calculate the overall survival and the recurrence-free rate, and univariate and multivariate logistic regression analyses on the clinical data were performed. Results: Recurrent laryngeal nerve invasion was observed in 150 cases, trachea invasion in 61 cases, esophagus invasion in 30 cases, and laryngeal structure invasion in 10 cases. Postoperative follow-up periods were 24-144 months, with an average of 68.29 months. Of the 185 patients, 18 (9.73%) had recurrences or metastases, including 9 cases (4.86%) died of recurrences or metastases. The 5-year and 10-year overall survival rates were respectively 95.21% and 93.10%. The 5-year and 10-year disease-free survival rates were respectively 89.65% and 86.85%. Univariate analysis showed that age of onset, tumor diameter, preoperative recurrent laryngeal nerve palsy, esophageal invasion and cervical lymph node metastasis were the risk factors for postoperative recurrence of T4a PTC(all P<0.05). Multivariate analysis showed that preoperative recurrent laryngeal nerve palsy (OR=3.27, 95%CI: 1.11-9.61, P=0.032) and lateral cervical lymph node metastasis (OR=4.71, 95%CI: 1.19-18.71, P=0.027) were independent risk factors for T4a PTC recurrence. Survival rate of patients with T4a PTC involving only the recurrent laryngeal nerve or the outer tracheal membrane was significantly better than that of patients with tracheal invasion (P<0.05). Conclusions: T4a PTC patients with R0 resection can still achieve good efficacy. Preoperative recurrent laryngeal nerve palsy and lateral cervical lymph node metastasis are independent risk factor for postoperative recurrence in the patients.

Recurrent Laryngeal Nerve Invasion by Thyroid Cancer: Laryngeal Function and Survival Outcomes.

Recurrent laryngeal nerve (RLN) invasion by thyroid carcinoma represents an advanced disease status with potentially significant co-morbidity. In a retrospective single-center study, we included patients with invaded RLNs operated on while using nerve monitoring techniques. We studied pre-, intra-, and postoperative parameters associated with postoperative vocal cord paralysis (VCP); 5-year recurrence-free survival (RFS); and 5-year overall survival (OS) in addition to two subgroup analyses of postoperative VCP in patients without preoperative VCP and based on source of RLN invasion. Of 65 patients with 66 nerves-at-risk, 39.3% reported preoperative voice complaints. Preoperative VCP was documented in 43.5%. The RLN was invaded by primary tumor in 59.3% and nodal metastasis in 30.5%. Papillary thyroid carcinoma was the most common pathologic subtype (80%). After 6 months, 81.8% had VCP. Complete tumor resection of the RLN was not associated with 5-year RFS (p=0.24) or 5-year OS (p=0.9). Resecting the RLN did not offer statistically significant benefit on 5-year RFS (p=0.5) or 5-year OS (p=0.38). Radioactive Iodine (RAI) administration was associated with improvement in 5-year RFS (p=0.006) and 5-year OS (p=0.004). Patients without preoperative VCP had higher IONM amplitude compared with patients with VCP. After a mean follow-up of 65.8 months, 35.9% of patients had distant metastases, whereas 36.4% had recurrence. Preoperative VCP accompanies less than half of patients with RLN invasion. Invaded RLNs may have existent electrophysiologic stimulability. Complete tumor resection and RLN resection were not associated with better 5-year RFS or OS, but postoperative RAI was. 4 Laryngoscope, 132:2285-2292, 2022.

Invasion of a Recurrent Laryngeal Nerve from Small Well-Differentiated Papillary Thyroid Cancers: Patient Selection Implications for Active Surveillance.

Background: The success of an active surveillance management approach to low-risk papillary thyroid cancer (PTC) is heavily dependent on proper patient selection. For example, primary tumors located in a subcapsular position immediately adjacent to the trachea or a recurrent laryngeal nerve (RLN) are considered to be inappropriate for active surveillance. Since preoperative imaging cannot reliably rule out extrathyroidal extension or reveal the full course of the RLN relative to the thyroid gland, it is important for clinicians to understand subcapsular tumor locations and minimum tumor sizes that are most likely to be associated with gross invasion of the RLNs. Methods: We assessed the medical records of 123 patients treated at Memorial Sloan Kettering Cancer Center (MSK) between 1986 and 2015 who had a primary PTC tumor demonstrating gross extrathyroidal extension to either the right or left RLN. Thirty patients with a primary tumor ≤2 cm in diameter demonstrating extrathyroidal extension into an RLN were included in the analysis. Results: Gross invasion of an RLN by tumors ≤2 cm is a rare event that was seen in only 0.8% (35/4334) of patients with PTC who underwent initial thyroid surgery at MSK between 1986 and 2015. Gross RLN invasion was associated with subcapsular PTC tumors located in either the right paratracheal area (60%), left paratracheal area (36.7%), or right lateral posterior lobe area not adjacent to the trachea (3.3%). Only a quarter of the patients had imaging findings suggestive of extrathyroidal extension and only 30% had clinically apparent vocal paresis/paralysis on preoperative examination. Invasion of the RLN was not observed for primary tumors <0.9 cm in diameter, regardless of tumor location. Conclusions: Well-differentiated PTC tumors ≥0.9 cm in maximal diameter that are located in the right paratracheal, left paratracheal, and right lateral posterior lobe subcapsular positions are usually not appropriate for active surveillance even in the absence of definitive evidence for nerve invasion on preoperative imaging or vocal cord examination. Patient selection for active surveillance management should take into account not only the size and growth rate of a tumor but also its location in relation to the expected course of RLNs.

Good News for Active Surveillance: Recurrent Laryngeal Nerve Invasion by Small Papillary Thyroid Carcinomas Is Rare and May Only Occur in Subcapsular Tumors

Good News for Active Surveillance: Recurrent Laryngeal Nerve Invasion by Small Papillary Thyroid Carcinomas Is Rare and May Only Occur in Subcapsular Tumors

P-207 Recurrent Laryngeal Nerve Invasion as an Independent Determinant of Complications and Outcome in Papillary Thyroid Cancer

P-207 Recurrent Laryngeal Nerve Invasion as an Independent Determinant of Complications and Outcome in Papillary Thyroid Cancer

Clinical outcomes of T4a papillary thyroid cancer with recurrent laryngeal nerve involvement: a retrospective analysis

Preoperative vocal cord palsy (VCP) may indicate locally invasive papillary thyroid cancer (PTC); using this relationship, we evaluated the clinical outcomes and risk factors for recurrence in post-thyroidectomy T4a PTC patients with recurrent laryngeal nerve (RLN) involvement. We retrospectively investigated thyroidectomy patients, recorded their clinical factors, recurrence rate, and pathological findings, and analysed the relationship between recurrence rate and clinical factors. Of 72 patients, 37 (51%) had preoperative VCP and 35 (49%) had normal preoperative vocal cord movement with confirmed intraoperative RLN invasion. Tracheal and esophageal invasion was observed in 13 (18%) and 15 (21%) patients, respectively. Thyroid cancer recurred in 18 (25%) patients over 58 months, resulting in 2 (3%) deaths. Recurrence was not associated with surgical extent, organ invasion, enlarged tumour size, or lymph node infiltration (p > 0.05). The recurrence rate was significantly higher in patients with positive resection margins (p < 0.05). T4a PTC patients with RLN involvement showed a poor prognosis. The recurrence rate was not affected by preoperative VCP, intraoperative detection of RLN invasion, nerve resection, nerve preservation by shaving, lymph node metastasis, or tracheal or esophageal invasion. The most important prognostic factor for recurrence was a positive resection margin.