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.

BACKGROUND: 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. METHODS: 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. RESULTS: 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). CONCLUSION: 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.

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

PURPOSE: 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. METHODS: 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. RESULTS: 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). CONCLUSION: 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.

Sternomastoid intermuscular approach has better postoperative cosmesis and less neck discomfort than linea alba cervicalis approach in hemithyroidectomy: a randomized clinical trial.

BACKGROUND: Surgery is still the most important treatment method for thyroid cancer. The classic linea alba cervicalis approach caused obvious neck scarring. This study explored an alternative open operative approach with concealed incision for hemithyroidectomy, and demonstrated whether it was non-inferior to traditional approach in postoperative complications and operation efficiency. METHODS: Patients ( n =220) from November 2019 to November 2020 willing to undergo hemithyroidectomy because of differentiated thyroid cancer were randomly divided into the sternocleidomastoid intermuscular approach (SMIA) group ( n =110), and the linea alba cervicalis approach (LACA) group ( n =110). The incidence of postoperative complications within 3 months and operation efficiency indicator R0 resection rate were recorded as primary endpoint, while scar apperance was assessed as secondary endpoint. The data were statistically analyzed. RESULTS: The baseline data of these two groups were comparable, with no significant difference ( P >0.05). As primary endpoint, R0 resection rate was 100% in both groups. In the 1-month follow-up period, the SMIA group had a lower score for neck discomfort compared with that of the LACA group (1.01±0.1648 vs. 0.5657±0.0976, P =0.0217). The SMIA group's scar had better results from the observer scar assessment compared to that of the LACA group as secondary endpoint. Within the 3-month follow-up, the total complications were calculated, and it was demonstrated that SMIA was non-inferior to traditional LACA operation ( P of non-inferiority=0.0048). CONCLUSIONS: Compared with LACA group, surgery through the SMIA is safe, effective, and has non-inferior postoperative complications. SMIA can be considered an alternative approach to classic LACA in hemithyroidectomy.

Differences in the clinical characteristics of papillary thyroid microcarcinoma located in the isthmus ≤5 mm and >5mm in diameter.

Background: The optimal treatment of papillary thyroid microcarcinomas (PTMCs) located in the isthmus (iPTMCs) is still controversial. The purpose of this study was to compare the clinicopathologic features of patients with iPTMCs ≤5 mm and >5 mm in diameter after total thyroidectomy, and to identify the risk factors for recurrence in patients with iPTMCs. Methods: A total of 102 iPTMC patients who underwent total thyroidectomy were reviewed retrospectively. The clinicopathologic characteristics of iPTMCs ≤5 mm group (n = 29) have been compared with a group >5 mm (n = 73). Univariate and multivariate Cox proportional hazard models served to identify risk factors associated with recurrence-free survival (RFS). Results: Gender (p = 0.033), multifocality (p = 0.041), and central lymph node metastasis (CLNM) (p = 0.009) of patients in the ≤5 mm and >5 mm groups differed significantly. iPTMC patients with age <55 years, male, multiple tumor, and extrathyroidal extension showed comparatively more frequent of CLNM in >5 mm groups. Of the 102 patients, nine (8.8%) developed recurrence during follow-up (median: 49.5 months). The patients with recurrences had comparatively high rates of CLNM (p = 0.038), extranodal invasion (p = 0.018), and more MNCND (Metastasis Nodes for Central Neck dissection) (p = 0.020). A cutoff of MNCND >2.46 was established as the most sensitive and specific level for the prediction of recurrence based on receiver operating characteristic (ROC) curve analyses. Multivariate analysis showed that the number of MNCND ≥3 was an independent predictor of poor RFS (p = 0.028). Conclusion: We have found that the recurrence rates are similar in patients with iPTMCs ≤5 mm and >5 mm. The iPTMCs >5 mm were more likely to be associated with pathological features such as multifocality and CLNM. The male gender, extrathyroidal extension, and CLNM were associated with recurrence of iPTMCs except for tumor size and multifocality. Higher risk of CLNM should be considered in iPTMC >5 mm when it reaches some risk factors. The numbers of MNCND ≥3 may be an independent predictor for recurrence, which could help clinicians for the decision of radioiodine administration and the modulation of follow-up modalities.

SYT7 plays a role in promoting thyroid cancer by mediating HMGB3 ubiquitination.

Thyroid cancer is one of the most common endocrine malignancies. It is necessary to discover more effective molecular targets for the treatment of thyroid cancer. The results of immunohistochemical staining, qPCR and Western blot indicated that the expression of SYT7 in thyroid cancer tissues and cells was higher than that in paracarcinoma tissues and normal thyroid cells. Through cell function testing experiments, it was found that SYT7 knockdown inhibited the proliferation and migration of thyroid cancer cells and promoted cell apoptosis, while SYT7 overexpression had the opposite effect. Similarly, SYT7 downregulation also suppressed tumor growth in vivo. HMGB3 was confirmed to be the downstream gene of SYT7 by GeneChip and Ingenuity Pathway Analysis. Besides, through UbiBrowser database predictions and Co-IP assays, we found that SYT7 interacted with BRCA1 to inhibit HMGB3 ubiquitination and thus upregulated the protein level of HMGB3. Similar to SYT7, HMGB3 was significantly upregulated in thyroid cancer. HMGB3 knockdown inhibited the proliferation and migration of thyroid cancer cells and promoted cell apoptosis. Furthermore, HMGB3 knockdown restored the promotion of cell proliferation and migration caused by SYT7 overexpression. SYT7 and HMGB3 were upregulated in thyroid cancer, and SYT7 regulated the expression of HMGB3 through BRCA1-mediated ubiquitination of HMGB3 to promote thyroid cancer progression.

Papillary Thyroid Carcinoma Landscape and Its Immunological Link With Hashimoto Thyroiditis at Single-Cell Resolution.

The tumor microenvironment heterogeneity of papillary thyroid cancer (PTC) is poorly characterized. The relationship between PTC and Hashimoto thyroiditis (HT) is also in doubt. Here, we used single-cell RNA sequencing to map the transcriptome landscape of PTC from eight PTC patients, of which three were concurrent with HT. Predicted copy number variation in epithelial cells and mesenchymal cells revealed the distinct molecular signatures of carcinoma cells. Carcinoma cells demonstrated intertumoral heterogeneity based on BRAF V600E mutation or lymph node metastasis, and some altered genes were identified to be correlated with disease-free survival in The Cancer Genome Atlas datasets. In addition, transcription factor regulons of follicular epithelial cells unveil the different transcription activation state in PTC patients with or without concurrent HT. The immune cells in tumors exhibited distinct transcriptional states, and the presence of tumor-infiltrating B lymphocytes was predominantly linked to concurrent HT origin. Trajectory analysis of B cells and plasma cells suggested their migration potential from HT adjacent tissues to tumor tissues. Furthermore, we revealed diverse ligand-receptor pairs between non-immune cells, infiltrating myeloid cells, and lymphocytes. Our results provided a single-cell landscape of human PTC. These data would deepen the understanding of PTC, as well as the immunological link between PTC and HT.

Factors Associated with Malignancy in Patients with Maximal Thyroid Nodules ≥2 Cm.

PURPOSE: The relationship between large thyroid nodules and the risk of malignancy is controversial. This study aimed to examine the relationship between thyroid nodule size and the risk of malignancy of maximal thyroid nodules ≥2 cm and the risk of accompanied by occult thyroid carcinoma. METHODS: This was a retrospective study of patients who underwent near-total or total thyroidectomy for thyroid nodules from January 2016 to January 2019 at the First Affiliated Hospital,Zhejiang University School of Medicine. Clinical, biochemical, and pathological characteristics were examined for association with malignancy using univariable, multivariable, and receiver operating characteristic curve analyses. RESULTS: Finally, 367 patients (277 females (75.5%) and 90 males (24.5%)) with a mean age of 49.0±13.5 years were included. Multivariable logistic regression analysis showed that age (OR=0.959, 95% CI: 0.939-0.979, P<0.001), Hashimoto's thyroiditis (OR=2.437, 95% CI: 1.162-5.112, P=0.018), the diameter of maximal nodule (small) (OR=0.706, 95% CI: 0.541-0.919, P=0.010), and punctate echogenic foci (OR=2.837, 95% CI: 1.598-5.286, P<0.001) were independently associated with malignancy. Of 223 patients who had non-suspicious malignant nodules (TI-RADS <4), 12.7% (n=29) patients showed malignancy at postoperative pathology. Only age was associated with occult PTC in the univariable analyses (OR=0.962, 95% CI: 0.934-0.991, P=0.011). When TPOAb was used as a continuous variable for statistical analysis, it showed a significant difference in the ROC curve, and the results showed TPOAb >31.4 mIU/L was more associated with occult PTC (P=0.006). A predictive model including four independent risk factors of malignancy showed an optimal discriminatory accuracy (area under the curve, AUC) of 0.783 (95% CI=0.732-0.833). CONCLUSION: Relatively young age (<54.5 years), Hashimoto's thyroiditis, the diameter of the maximal nodule, and punctate echogenic foci were independently associated with thyroid malignancy in patients with maximal thyroid nodules ≥2 cm. Young age (<54.5 years) and TPOAb >31.4 mIU/L were associated with occult PTC.

The steps and key points of thyroid surgery with lateral cervical incision.

The thyroid surgery with lateral cervical incision uses the sternocleidomastoid intermuscular approach through the gap between band muscles and carotid sheath to reach the surgical field. The recurrent laryngeal nerve and upper and lower parathyroid glands are first identified, the upper pole vessels are severed; then the Berry ligament is separated; the isthmus is severed, and the thyroid gland is finally removed. This approach can avoid the trauma of the skin and muscle tissue in the anterior neck region, to relieve the pressure on the neck and swallowing stretch feeling for patients after surgery. The surgical modality is effective and less time-consuming. This article gives a detailed introduction to the standardized procedures and some key points of thyroid surgery with lateral cervical incision.

Regeneration of a Bioengineered Thyroid Using Decellularized Thyroid Matrix.

BACKGROUND: Hypothyroidism is a common hormone deficiency condition. Regenerative medicine approaches, such as a bioengineered thyroid, have been proposed as potential therapeutic alternatives for patients with hypothyroidism. This study demonstrates a novel approach to generate thyroid grafts using decellularized rat thyroid matrix. METHODS: Isolated rat thyroid glands were perfused with 1% sodium dodecyl sulfate to generate a decellularized thyroid scaffold. The rat thyroid scaffold was then recellularized with rat thyroid cell line to reconstruct the thyroid by perfusion seeding technique. As a pilot study, the decellularized rat thyroid scaffold was perfused with human-derived thyrocytes and parathyroid cells. RESULTS: The decellularization process retained the intricate three-dimensional microarchitecture with a perfusable vascular network and native extracellular matrix components, allowing efficient reseeding of the thyroid matrix with the FRTL-5 rat thyroid cell line generating three-dimensional follicular structures in vitro. In addition, the recellularized thyroid showed successful cellular engraftment and thyroid-specific function, including synthesis of thyroglobulin and thyroid peroxidase. Moreover, the decellularized rat thyroid scaffold could further be recellularized with human-derived thyroid cells and parathyroid cells to reconstruct a humanized bioartificial endocrine organ, which maintained expression of critical genes such as thyroglobulin, thyroid peroxidase, and parathyroid hormone. CONCLUSION: These findings demonstrate the utility of a decellularized thyroid extracellular matrix scaffold system for the development of functional, bioengineered thyroid tissue, which could potentially be used to treat hypothyroidism.