Elucidating the role of Pyroptosis in papillary thyroid cancer: prognostic, immunological, and therapeutic perspectives.

BACKGROUND: Pyroptosis, an inflammatory form of programmed cell death, has been implicated in the pathogenesis and progression of several cancers. However, the significance of pyroptosis-related genes (PRGs) in papillary thyroid cancer (PTC) remains unclear. METHODS: Transcriptome and clinical data of PTC patients were obtained from The Cancer Genome Atlas. The expression patterns of PRGs were identified by consensus clustering. A prognostic model for predicting the thyroid cancer-free interval (TCFi) employed five machine learning methods. Enrichment and immune-related analyses were performed to elucidate the role of pyroptosis. The responses to radioactive iodine (RAI), immune checkpoint inhibitors (ICIs), molecular targeted therapy (MTT), and chemotherapy (CTx) were predicted based on pyroptosis-derived features. Additionally, the expression of prognostic PRGs was validated via six external datasets, 16 cell lines, and 20 pairs of clinical samples. RESULTS: PTC patients were classified into three PyroClusters, C1 exhibited BRFA-like tumors with the highest invasiveness and the worst prognosis, C2 presented RAS-like tumors, and C3 was characterized by gene fusion. Nine PRGs (CXCL8, GJA1, H2BC8, IFI27, PRDM1, PYCARD, SEZ6L2, SIGLEC15, TRAF6) were filtered out to construct a PyroScore prognostic model. A derived nomogram demonstrated superior predictive performance than four clinical staging systems. A strong correlation between pyroptosis and tumor immune microenvironment (TIME) remodeling was observed in mechanistic analyses. Patients with a high PyroScore exhibited "hot" tumor immunophenotypes and had a poorer prognosis but could benefit more from ICIs and CTx (such as paclitaxel). Patients with a low PyroScore were more sensitive to RAI and MTT (such as pazopanib and sorafenib). CONCLUSIONS: PyroScore model can effectively predict TCFi in patients with PTC. Dysregulated expression of PRGs is associated with the TIME modeling. Pyroptosis features have potential significance for developing novel therapeutic strategies for PTC patients.

The risk factors for postoperative temporary vocal cord paralysis after thyroid cancer surgery: an observational retrospective cohort study.

OBJECTIVE: To analyze the potential factors influencing new-onset postoperative transient vocal cord paralysis (VCP) in thyroid cancer patients. METHODS: Case information of 8340 thyroid cancer patients hospitalized at China-Japan Union Hospital of Jilin University, Jilin Province, China, in the Thyroid Surgery Department from January 2018 to December 2020 was collected retrospectively and analyzed. The possible influencing factors were analyzed using a χ2 test, rank-sum test, and multiple logistic regression analysis. A nomogram was used to construct the clinical prediction model that was validated in the validation set by receiver operating characteristic, calibration curves, and Decision curve analysis. RESULTS: The strengthening the reporting of cohort, cross-sectional, and case-control studies in surgery (STROCSS) guideline was followed to conduct a retrospective cohort study. A total of 8340 patients, including 1817 (21.8%) men and 6523 (78.2%) women, were enrolled in this study. The rate of temporary VCP was 3.6% (308/8340). Based on the results of postoperative laryngoscopy, the patients were divided into VCP group and non-VCP group. Comparative analysis between the groups revealed that potential factors associated with postoperative transient VCP were tumor location on the dorsal side of the gland ( P =0.042), ultrasound showing a maximum nodal diameter >1 cm ( P =0.002), multifocal carcinoma ( P <0.001), invasion of surrounding tissue ( P =0.005), lymph node metastases in the central compartment ( P =0.034), lateral cervical lymph node metastasis ( P <0.001), and prolonged operation ( P <0.001). A multiple logistic regression analysis showed that the independent risk factors in postoperative transient VCP were T stage (OR=1.411, P =0.013, 95% CI: 1.075-1.853), multifocal carcinoma (OR=1.532, P =0.013, 95% CI: 1.095-2.144), and duration of surgery (OR=1.009, P <0.001, 95% CI: 1.006-1.012). Finally, a clinical prediction model was established via a nomogram and was validated in the validation set, although its diagnostic efficacy needs to be improved further. CONCLUSION: High T stage, multifocal carcinoma, and prolonged operation time may be independent risk factors for the occurrence of postoperative transient VCP in patients undergoing initial surgery for thyroid cancer.

Noticeable effect of lower baseline amplitude on the predictive accuracy of intraoperative amplitude changes for postoperative vocal cord palsy: a prospective cohort study.

BACKGROUND: To explore the effect of lower baseline amplitude on its predictive accuracy of postoperative vocal cord paralysis (VCP) in monitored thyroid surgery. MATERIALS AND METHODS: Clinical and electrophysiological data were collected during thyroid surgeries performed between November and December 2021 at China-Japan Union Hospital. Univariate/multivariate regression analysis were applied to these data to examine a possible correlation. A receiver operating characteristic curve was used to evaluate predictive efficacy. RESULTS: A total of 631 nerves-at-risk (NAR) were identified in 460 patients who were divided into two groups according to postoperative development of VCP. The VCP group included a higher percentage of NAR with V1<1000 (68.2 vs. 40.7%, respectively; P =0.014) and NAR with R1<1400 (77.3 vs. 47.0%, respectively; P =0.005) compared with the non-VCP group. Multivariate regression analysis further identified V1<1000 [odds ratio (OR)=2.688, P =0.038], R1<1400 (OR=3.484, P =0.018) as independent risk factors for postoperative temporary VCP. The receiver operating characteristic curve showed the AUC value of V signal decline for predicting VCP was 0.87. The diagnostic efficiency of R signal decline reached as high as 0.973. A multivariate logistic regression analysis identified independent risk factors for V1<1000 and these included: higher BMI (OR=1.072, P =0.013), hypertension (OR=1.816, P =0.015), smoking (OR=1.814, P =0.031), and male sex (OR=2.016, P =0.027). CONCLUSION: In our cohort, lower baseline amplitude was an independent risk factor for developing transient postoperative VCP. It also affected the predictive efficacy of intraoperative amplitude changes on VCP. Higher BMI, hypertension, smoking, and male sex may also be closely associated with lower initial amplitude. Thus, maintaining a higher initial amplitude is critical for patient safety during thyroid surgery.

Utilization of recurrent laryngeal nerve monitoring during thyroid surgery in china: a point prevalence survey (2015-2023).

BACKGROUND: The survey aimed to elucidate the complete range of national practices, including all technical and non-technical aspects, as well as surgical stratification and maturation, of the use of intraoperative neuromonitoring (IONM) during thyroid surgery in China. MATERIALS AND METHODS: Six national questionnaires, developed by the Chinese Neural Monitoring Study Group (CNMSG) between 2015 and 2023, were used to collect and analyze data regarding the clinical application, education, and scientific research related to IONM in Chinese medical institutions. RESULTS: Among the surveyed hospitals, 45% reported an average annual surgical volume exceeding 3,000 cases, with 82.5% performing more than 80% of the surgeries for malignant thyroid tumors. Additionally, 97.5% of the hospitals reported a<3% incidence of postoperative hoarseness with IONM. Statistical analysis from 2011 to 2015 found that the incidence of postoperative hoarseness decreased by 30% in 2013 compared with 2011, when the technology was introduced. Preoperative and postoperative laryngoscopies were routinely performed by 82.5% and 15% of the hospitals, respectively. For 65% of the hospitals, the publication of the Chinese edition of neuromonitoring guidelines in 2013 prompted the utilization of IONM technology. An average annual number of IONM applications exceeding 500 cases (18.5% the average volume) was reported by 80% of the hospitals, while 62.5% reported a cumulative number of applications greater than 5,000 cases (47.1% the average cumulative volume). Regarding technical parameters, 75% of the hospitals reported an intraoperative V1 amplitude of >500 µV, and 70% reported an intraoperative loss of signal (LOS) rate of<3%. 92.5% of the surveyed hospitals believed that IONM could help identify dissociated nerves, and 95% of the surveyed hospitals believed that IONM could reduce nerve damage. However, 72.5% of the respondents thought that cost was the main limitation. Furthermore, 67.5% of the hospitals reported that half of their thyroid surgical team members were trained in IONM, with 17.5% reporting that all team members were trained. Areas for reinforced training included IONM research methods and directions (72.5%), and analysis and treatment of abnormal EMG signals (72.5%). Research projects related to IONM were conducted by 42.5% of the hospitals, while 52.5% had published papers on neuromonitoring. CONCLUSIONS: IONM was independently and incrementally associated with the annual surgical volume. This survey emphasized the importance of national collaboration and/or a registry for the uptake, consolidation, and development of CNMSG consensus.

Factors influencing serum calcium levels and the incidence of hypocalcemia after parathyroidectomy in primary hyperparathyroidism patients.

Background: Parathyroidectomy (PTX) is an effective treatment for primary hyperparathyroidism (PHPT) patients. Postoperative hypocalcemia is a common complication after PTX. This study aimed to analyze the factors influencing serum calcium levels and the incidence of hypocalcemia after parathyroidectomy in primary hyperparathyroidism patients. Methods: The retrospective study included 270 PHPT patients treated with PTX and collected their demographic and clinical information and their laboratory indices. Factors influencing serum calcium levels and hypocalcemia after PTX in PHPT patients were analyzed using univariate and multifactorial analyses. Results: First, in patients with normal preoperative serum calcium levels (2.20-2.74 mmol/L), the higher the preoperative alkaline phosphatase and serum phosphorus levels, the lower the postoperative serum calcium levels. Furthermore, the higher the preoperative serum calcium levels and the accompanying clinical symptoms, the higher the postoperative serum calcium levels. Low preoperative serum calcium levels were shown to be a risk factor for postoperative hypocalcemia (OR=0.022), and the optimal preoperative serum calcium threshold was 2.625 mmol/L (sensitivity and specificity were 0.587 and 0.712, respectively). Second, in the mild preoperative hypercalcemia group (2.75-3.00 mmol/L), the older the patient, the higher the preoperative and postoperative serum calcium levels, the higher the postoperative serum calcium; the lower the alkaline phosphatase and calcitonin levels, the higher the postoperative serum calcium levels. On the other hand, the younger the patient was, the more likely hypocalcemia blood was (OR=0.947), with an optimal age threshold of 47.5 years (sensitivity and specificity were 0.543 and 0.754, respectively). Third, in the preoperative moderate to severe hypercalcemia group (>3.0mmol/L), patients undergoing a combined contralateral thyroidectomy and a total thyroidectomy had low postoperative serum calcium levels. Conclusion: Patients with different preoperative serum calcium levels had various factors influencing their postoperative serum calcium levels and postoperative hypocalcemia, which facilitated the assessment of their prognosis.

A novel risk stratification model based on tumor size and multifocality to predict recurrence in pediatric PTC: comparison with adult PTC.

Background: Pediatric papillary thyroid cancer presents with a more advanced stage of disease than adult PTC; and it is more likely to be aggresive and distant metastases, although the survival rate is high. Methods: A retrospective observational study was performed in children and adults with PTC. Fisher's exact, chi-square, and rank-sum tests were used to examine the differences. Univariate and multivariate Cox regression analyses were applied to determine the possible risk factors for prognosis. A Kaplan-Meier curve analysis was performed to investigate the relationship between the clinicopathological characteristics and recurrence rate. Results: The study involved 156 children and 1,244 adults with PTC. Compared to the group without recurrence, proportions of tumors measuring > 1 cm (48.3% vs. 90.9%) and multifocality (30.3% vs. 63.6%) were higher, N1b stage occurred more frequently (33.8% vs. 100%). However, among adult PTC patients, those with recurrence were older (76.1% vs. 59.4%) than those without recurrence. Risk factors for pediatric PTC recurrence included tumor size and multifocality. However, in adult PTC, the risk factor was LLNM. The newly constructed Stratification.N showed better performance, as illustrated by the fact that patients who were classified into Stratification.N 3 showed an obviously poorer prognosis (P=0.01 and P=0.00062), especially in those aged >14 years (P=0.0052). Conclusion: Compared with adult PTC, pediatric PTC showed unique characteristics in terms of clinical pathology and recurrence. Tumor size and multifocality were strong risk factors for pediatric PTC. Accordingly, the novel proposed risk stratification method could effectively predict the recurrence of pediatric PTC.