Comparative long-term outcomes of airway resection and functional reconstruction for papillary thyroid cancer.

INTRODUCTION: The surgical management of patients diagnosed with papillary thyroid carcinoma (PTC) and tracheal invasion has been a subject of ongoing discussion, particularly regarding the approach to tracheal functional reconstruction. The objective of this study was to examine the surgical technique and prognosis of PTC patients with tracheal invasion. MATERIALS AND METHODS: This study employed both univariate and multivariate Cox proportional hazard models to determine predictive factors that affect the progression-free survival (PFS) of PTC patients with tracheal invasion. Cox regression analysis was conducted by using R software version 4.3.1. RESULTS: In our study, we included 247 patients with T4a PTC. Among them, 146 patients (59.1 %) were classified as Shin I, 57 patients (23.1 %) as Shin II-III, and 44 patients (17.8 %) as Shin IV. Patients in the Shin I group underwent shaving of the tumours in the airway. The preferred surgical methods in the Shin II, III and IV groups were window resection (66.7 %), sleeve resection (34.8 %) and partial tracheal resection and skin fistula (61.8 %), respectively. Multivariate analysis demonstrated that neither tracheal surgery nor reconstruction procedures had an impact on PFS in T4a PTC patients with tracheal invasion. The 5-year DSS rate for patients receiving radioiodine (RAI) therapy was 87.3 % (p = 0.033). CONCLUSION: This study confirmed that tracheal surgery and reconstruction methods had no impact on PFS in T4a PTC patients with tracheal invasion in different Shin groups. Furthermore, RAI therapy has the potential to increase the survival rate of patients with preoperative distant metastasis of T4a PTC.

Extent of surgery for unilateral papillary thyroid cancer with nonsuspicious contralateral nodules by ultrasound.

BACKGROUND: The discussion about surgical treatment of patients with papillary thyroid cancer(PTC) has been an ongoing issue, which is mainly focused on characteristics of tumor, but rarely on nonsuspicious contralateral nodules. We aimed to compare recurrence-free survival(RFS)/progression-free survival(PFS) of unilateral PTC patients with nonsuspicious contralateral nodules after different extents of surgery. METHODS: Unilateral PTC patients with nonsuspicious contralateral nodules underwent surgery from 2015 to 2017 were enrolled. The association between surgical extent and RFS/PFS was analyzed by Kaplan-Meier method and Cox proportional hazards model. RESULTS: A total of 1293 PTC patients (595[46.0%]TT,523[40.4%]lobectomy+nodule enucleation(LNE),175[13.5%]lobectomy) were analyzed. Patients with a greater surgical extent were more likely to be older, have a greater multifocality of the tumor and contralateral nodules, larger contralateral nodules and primary tumors, and more micro extrathyroidal extension (P < 0.05). After a median follow-up of 45 months, significant growth(>3 mm) was identified in 24 (4.6%) and 19 (10.9%) patients in the LNE and lobectomy group, 7 (1.2%), 14 (2.7%) and 11 (6.3%) structural recurrences and 7 (1.2%), 11 (2.1%) and 7 (4.0%) progression in disease were identified in the TT, LNE and lobectomy groups, respectively. Unadjusted and adjusted RFS/PFS were significantly worse for patients treated with lobectomy than for those who underwent LNE or TT(3-year RFS, 95.5%, 98.2% vs. 99.0%; 3-year PFS, 97.9%, 98.9% vs. 99.0%, P < 0.05), but difference in PFS between LNE and TT lost statistical significance (unadjusted P = 0.226, adjusted P = 0.150). CONCLUSIONS: Due to subtle changes in nodules and acceptable prognosis, lobectomy is a considerable option for unilateral PTC patients with nonsuspicious nodules, when a similar prognosis to TT is expected, LNE may be an effective alternative to optimize quality of life.

Stimulated Raman Scattering Microscopy Reveals Aberrant Triglyceride Accumulation in Lymphatic Metastasis of Papillary Thyroid Carcinoma.

Lipid metabolic alterations are known to play a crucial role in cancer metastasis. As a key hub in lipid metabolism, intracellular neutral lipid accumulation in lipid droplets (LDs) has become a signature of aggressive human cancers. Nevertheless, it remains unclear whether lipid accumulation displays distinctive features in metastatic lesions compared to the primary ones. Here, we integrated multicolor stimulated Raman scattering (SRS) imaging with confocal Raman spectroscopy on the same platform to quantitatively analyze the amount and composition of LDs in intact human thyroid tissues in situ without any processing or labeling. Inspiringly, we found aberrant accumulation of triglycerides (TGs) in lymphatic metastases but not in normal thyroid, primary papillary thyroid carcinoma (PTC), or normal lymph node. In addition, the unsaturation degree of unsaturated TGs was significantly higher in the lymphatic metastases from patients diagnosed with late-stage (T3/T4) PTC compared to those of patients diagnosed with early-stage (T1/T2) PTC. Furthermore, both public sequencing data analysis and our RNA-seq transcriptomic experiment showed significantly higher expression of alcohol dehydrogenase-1B (ADH1B), which is critical to lipid uptake and transport, in lymphatic metastases relative to the primary ones. In summary, these findings unravel the lipid accumulation as a novel marker and therapeutic target for PTC lymphatic metastasis that has a poor response to the regular radioactive iodine therapy.

PAX2 is regulated by estrogen/progesterone through promoter methylation in endometrioid adenocarcinoma and has an important role in carcinogenesis via the AKT/mTOR signaling pathway.

Endometrioid adenocarcinoma (EEC) is one of the most common cancers of the female reproductive system. In recent years, much emphasis has been placed on early diagnosis and treatment. PAX2 (Paired box 2) inactivation is reportedly an important biomarker for endometrioid intraepithelial neoplasia (EIN) and EEC. However, the role of PAX2 in EEC carcinogenesis remains unclear. PAX2 expression and associated clinical characteristics were analyzed via The Cancer Genome Atlas, Gene Expression Omnibus, and Cancer Cell Line Encyclopedia databases and clinical paired EIN/EEC tissue samples. Bioinformatic analysis was conducted to identify the putative molecular function and mechanism of PAX2. Cell proliferation, colony formation, cell migration, and invasion assays in vitro, and mouse xenograft models were utilized to study the biological functions of PAX2 in vivo. Pyrosequencing and the demethylating drug 5-Aza-dc were used to verify promoter methylation in clinical tissues and cell lines, respectively. The mechanism underlying the regulatory effect of estrogen (E2) and progesterone (P4) on PAX2 expression was investigated by receptor block assay and double luciferase reporter assay. PAX2 expression was found to be significantly downregulated in EIN and EEC tissues, its overexpression inhibited EEC cell malignant behaviors in vivo and in vitro and inhibited the AKT/mTOR signaling pathway. PAX2 inactivation in EEC was related to promoter methylation, and its expression was regulated by E2 and P4 through their receptors via promoter methylation. Our findings elucidated the expression and function of PAX2 in EEC and have provided hitherto undocumented evidence of the underlying molecular mechanisms. PAX2 expression is suppressed by estrogen prompting its methylation through estrogen receptor. Furthermore, PAX2 regulates the AKT/mTOR signaling pathway to influence EEC progression. © 2024 The Pathological Society of Great Britain and Ireland.

The U-Shaped association between age and distant metastasis in patients with papillary thyroid carcinoma.

PURPOSE: To investigate the association between age distribution and synchronous distant metastasis of papillary thyroid carcinoma. METHOD: Patients with PTC who were treated from January 2013 to December 2018 at a single institute in a cancer referral center in China were retrospectively reviewed. A logistic regression model with restricted cubic splines (RCS) was used to examine the association between age at diagnosis and synchronous distant metastasis. RESULTS: A total of 111 patients (0.7%) were diagnosed with distant metastasis. The logistic regression model with RCS revealed a "U-shape" association between age and distant metastasis. The RCS curve suggested a U-shaped pattern. The multivariable regression analysis showed that patients in the age groups ≤21 years (OR 2.33, 95% CI 1.09-4.68, P = 0.022) and >55 years (OR 3.32, 95% CI 1.99-5.46, P < 0.001) had a significantly higher incidence of distant metastasis than patients in the age group of 22 to 55 years. CONCLUSIONS: A U-shaped association was observed between age at diagnosis and synchronous distant metastasis in papillary thyroid carcinoma patients.

Impact of lateral cervical lymph node metastasis on lung metastasis in pediatric thyroid cancer: A correlation study.

BACKGROUND: Thyroid cancer (TC) frequently manifests with lung metastases in the pediatric population, occurring at a significant rate of 30 %. This study aims to evaluate the impact of regional patterns of cervical lymph node metastases on lung metastases in pediatric TC. METHODS: Retrospective analysis was conducted on data from pediatric TC patients spanning the years 2000 to 2018. We compared the rates of lymph node metastasis (LNR), the number of lymph node metastases, and the number of dissected lymph nodes in the central and lateral cervical regions between patients with and without lung metastases. Statistical methods were employed to adjust for confounders during hypothesis testing. RESULTS: A total of 227 pediatric patients, with a median age of 15.12 ± 2.84 years, were included in the study. Of these, 202 (89 %) exhibited LN metastasis, with 40(17.62 %) patients presenting with lung metastasis. Patients with lung metastases were found to be younger (13.40 ± 3.11 vs. 15.50 ± 2.64, p < 0.001), had larger primary tumor diameters (3.49 ± 1.98 vs. 2.31 ± 1.45, p < 0.001), and exhibited a higher number of lymph node metastases (23.40 ± 10.75 vs. 14.65 ± 13.16, p < 0.001). Notably, in patients with LN metastases, the presence of >12 lateral cervical lymph node metastases emerged as a significant risk factor for lung metastases. Among children with metachronous lung metastases, the median time to detection of lung metastases was 43 (12-132) months, and they appeared to receive a greater proportion of radioactive iodine (RAI) treatment compared to those with synchronous lung metastases. CONCLUSION: Lateral cervical lymph node metastasis independently predicts the likelihood of lung metastases in pediatric TC. Furthermore, our findings emphasize the importance of thorough examination of the lungs during follow-up, particularly when the number of metastatic lateral cervical lymph nodes exceeds 12.

The frequency of risk pathological characteristics in clinically low-risk papillary thyroid microcarcinoma suitable for active surveillance.

PURPOSE: Active surveillance has emerged as an initial management strategy for patients with low-risk papillary thyroid microcarcinoma (PTMC). The main objective of this research was to investigate the frequency of risk pathological characteristics among patients with clinically low-risk PTMC who are suitable for Active Surveillance. METHODS: A retrospective review was conducted on patients who underwent lobectomy for PTMC between January 2013 and December 2018. Patients with bilateral tumors, macroscopic multifocal tumors, macroscopic extrathyroidal extension (ETE), clinical lymph node metastases, macroscopic extranodal extension (ENE), distant metastases, a history of neck radiation or familial thyroid cancer were excluded. Pathological characteristics were collected from the postoperative pathological results. Aggressive variants, multifocality, ETE, lymphovascular invasion (LVI), perineural invasion (PNI), metastatic lymph nodes (LNs) ≥ 5, and ENE were defined as risk characteristics. RESULTS: The study included 4923 patients, of whom 1229 (25.0%) were male. The mean age was 43 years. A total of 2250 patients (45.7%) exhibited risk characteristics. Among them, 15 patients presented with aggressive variants, and 1813 patients (36.8%) had ETE. Multifocality, LVI, and PNI were observed in 551 (11.2%), 21 (0.4%), and 40 (0.8%) patients, respectively. A total of 139 patients (2.8%) had five or more metastatic LNs, and ENE was identified in 140 patients. Notably, 172 patients (3.5%) fulfilled the criteria for completion thyroidectomy, as they had aggressive variants, LVI, or five or more metastatic LNs. CONCLUSIONS: Nearly half of the patients diagnosed with clinically low-risk PTMC exhibited risk pathological characteristics, and a small proportion of patients met the criteria for completion thyroidectomy.

The role of targeted therapy and/or immunotherapy therapy in anaplastic thyroid carcinoma.

BACKGROUND: Anaplastic thyroid carcinoma (ATC) is a highly invasive malignant tumor with a poor prognosis. Traditional treatment methods have not been effective. However, advancements in targeted therapy and immunotherapy in recent years have shed new light on the management of ATC. The aim of this study was to examine the treatment plan and prognostic factors of ATC. METHODS: This study conducted a retrospective analysis of ATC patients who received treatment at our institution between 2000 and 2023 to evaluate the clinical characteristics, treatment methods, and factors influencing survival. Survival analysis was performed by the Kaplan‒Meier method and log-rank test, and multivariate analysis was performed using the Cox proportional hazard model. RESULTS: The 6-month and 1-year disease-specific OS rates were 49% and 29%, respectively. The presence of clinical symptoms and the timing of treatment significantly impacted patient prognosis (P < 0.05). Compared with surgery + radiotherapy/chemotherapy and only surgery, targeted therapy and targeted + immunotherapy represented an improved overall survival, The 6-month/1-year survival rates of which were 81%/61% and 91%/73% (P < 0.05), respectively. Multivariate analysis indicated that the symptoms at initial diagnosis, year of presentation, performance status and treatment plan were independent factors affecting the prognosis. The year of presentation (P = 0.048) and the treatment plan (P = 0.038) were significantly meaningful in predicting prognosis. CONCLUSION: Targeted therapy and targeted+immune therapy can effectively prolong the survival period of ATC patients. Symptoms at initial diagnosis and treatment plan have a significant impact on the prognosis.

A prediction model for identifying high-risk lymph node metastasis in clinical low-risk papillary thyroid microcarcinoma.

BACKGROUND: The presence of high-volume lymph node metastasis (LNM) and extranodal extension (ENE) greatly increases the risk of recurrence in patients with low-risk papillary thyroid microcarcinoma (PTMC). The goal of this research was to analyze the factors that contribute to high-risk lymph node metastasis in patients with low-risk PTMC. METHODS: We analyzed the records of 7344 patients who were diagnosed with low-risk PTMC and treated at our center from January 2013 to June 2018.LNM with a high volume or ENE was classified as high-risk lymph node metastasis (hr-LNM). A logistic regression analysis was conducted to identify the risk factors associated with hr-LNM. A nomogram was created and verified using risk factors obtained from LASSO regression analysis, to predict the likelihood of hr-LNM. RESULTS: The rate of hr-LNM was 6.5%. LASSO regression revealed six variables that independently contribute to hr-LNM: sex, age, tumor size, tumor location, Hashimoto's thyroiditis (HT), and microscopic capsular invasion. A predictive nomogram was developed by integrating these risk factors, demonstrating its excellent performance. Upon analyzing the receiver operating characteristic (ROC) curve for predicting hr-LNM, it was observed that the area under the curve (AUC) had a value of 0.745 and 0.730 in the training and testing groups showed strong agreement, affirming great reliability. CONCLUSION: Sex, age, tumor size, tumor location, HT, and microscopic capsular invasion were determined to be key factors associated with hr-LNM in low-risk PTMC. Utilizing these factors, a nomogram was developed to evaluate the risk of hr-LNM in patients with low-risk PTMC.

CT-based quantification of trachea shape to detect invasion by thyroid cancer.

OBJECTIVE: This study aims to develop a CT-based method for quantifying tracheal shape and evaluating its ability to distinguish between cases with or without tracheal invasion in patients with thyroid carcinoma. METHODS: A total of 116 quantitative shape features, including 56 geometric moments and 60 bounding shape features, were defined. The tracheal lumen was semi-automatically defined with a CT threshold of less than - 500 HU. Three contiguous slices with the 1st, 2nd, and 3rd smallest trachea lumen areas were contiguously selected, and the appropriate number of slices to be included was determined. Fifty-six patients with differentiated thyroid carcinoma (DTC) invading the trachea and 22 patients with DTC but without invasion were retrospectively included. A receiver operating characteristic (ROC) curve was applied to select the representative shape features and determine the optimal threshold. RESULTS: 23.3%, 25.9%, and 24.1% of the features displayed an area under the ROC curve (AUC) ≥ 0.800 when derived from 1, 2, and 3 slices, respectively. Calculating feature values from two slices with the 1st and 2nd smallest tracheal lumen area were considered appropriate. Six final features, including 3 geometric moments and 3 bounding shape features, were selected to determine the tracheal invasion status of DTC and displayed AUCs of 0.875-0.918, accuracies of 0.821-0.891, sensitivities of 0.813-0.893, and specificities of 0.818-0.932, outperforming the visual evaluation results. CONCLUSIONS: Geometric moments and bounding shape features can quantify the tracheal shape and are reliable for identifying DTC tracheal invasion. The selected features quantified the extent of tracheal deformity in DTC patients with and without tracheal invasion. CLINICAL RELEVANCE STATEMENT: Six geometric features provide a non-invasive, semi-automated evaluation of the tracheal invasion status of thyroid cancer. KEY POINTS: • A novel method for quantifying tracheal shape using 56 geometric moments and 60 bounding shape features was developed. • Six features identify tracheal invasion by thyroid carcinoma. • The selected features quantified the extent of tracheal deformity in differentiated thyroid carcinoma patients with and without tracheal invasion.

Clinical factors associated with severe surgical complications in patients with hypopharyngeal cancer: a single-center case-cohort study.

BACKGROUND: Surgical complications are a major concern in the surgical treatment of hypopharyngeal cancer. OBJECTIVE: To identify clinical factors that predispose patients with hypopharyngeal cancer to severe surgical complications. MATERIALS AND METHODS: The data of 449 patients who were underwent surgery as a part of the initial treatment with curative intent or as salvage treatment were retrospectively reviewed. The Chi-square test and logistic regression were used to evaluate the association of different factors with severe surgical complications. RESULTS: The incidence of severe complications was 22% (99/449), and 10 patients (2.2%) experienced rupture of the carotid artery. Multivariate analysis identified T3/4 stage (p = .002, odds ratio (OR) = 1.58, 95% confidence interval (CI) 1.177-2.122), radiotherapy (RT) (p < .001, OR = 2.744, 95% CI 1.680-4.482), diabetes mellitus (DM) (p = .007, OR = 2.697, 95% CI 1.308-5.56), and nonprimary closure (p = .008, OR = 1.992, 95% CI 1.193-3.327) as significant risk factors for severe surgical complications. CONCLUSIONS AND SIGNIFICANCE: T3/4 stage, RT, nonprimary closure, and DM were independent predisposing factors for severe surgical complications in our study population of hypopharyngeal cancer patients. Taking measures to lower the tumor stage and simplify the surgical procedure may be crucial in reducing the incidence of severe surgical complications among these patients.

Prognostic Significance of Primary Tumor Surgery in Adenoid Cystic Carcinoma Patients With Distant Metastases at Diagnosis: A Population-Based Database Analysis in Head and Neck Region.

Purpose: Adenoid cystic carcinoma (ACC) is an aggressive cancer that often leads to poor prognosis, especially when it has metastasized. The prognostic significance of primary tumor surgery (PTS) for ACC with distant metastasis (DM) at the time of diagnosis has not been extensively studied. Methods: Using data from the surveillance, epidemiology, and end results (SEER) database from 2010 to 2019, we identified patients with ACC in head and neck region and synchronous DM. We evaluated the effect of PTS on different patterns of metastasis using Kaplan-Meier analysis, log-rank tests, and multivariate Cox regression analysis to assess the therapeutic benefit of PTS in the overall cohort and various subgroups. Results: Of the 192 identified patients with synchronous metastatic ACC of head and neck, 91 (47.4%) underwent PTS. Patients who received PTS had significantly better survival than nonsurgical patients (median overall survival: 19 vs 43 months, P = .006). Cox regression analysis also showed that PTS was associated with improved survival (HR = .46, 95% CI: 0.42-0.88; P = .028). In sub-analyses, except for patients with liver metastases [overall survival (OS), P = .107, cancer-specific survival (CSS), P = .153], PTS consistently conferred significant survival benefits in patients with bone metastases (OS, P = .041, CSS, P = .065) and lung metastases (OS, P = .016, CSS, P = .027). PTS also led to better survival in patients who did not receive radiotherapy (median OS: 13 vs 52 months, P = .007). Conclusion: Our study suggests that PTS in metastatic ACC patients of head and neck improved overall and CSS, particularly in those with bone or lung metastases and those who did not receive radiotherapy. However, further prospective studies are needed to confirm these findings, and the indications for PTS in metastatic ACC should be carefully evaluated by a multidisciplinary board.

Kruppel-like factor 13 acts as a tumor suppressor in thyroid carcinoma by downregulating IFIT1.

BACKGROUND: Kruppel-like factor 13 (KLF13) is a transcription factor and plays an important role in carcinogenesis. However, the significance of KLF13 in thyroid carcinoma (THCA) is underdetermined. In this study, we aimed to explore the clinical relevance and function of KLF13 in the progress of THCA. METHODS: The expression of KLF13 in thyroid carcinoma and normal tissue was investigated by qPCR and IHC assay. The expression of KLF13 and IFIT1 in cell samples was investigated with Western blot assay. Cell proliferation ability was detected with CCK8 and colony formation assay. Cell growth in vivo with or without KLF13 overexpression was evaluated on a xenograft model. Cell migration ability was measured with Transwell assay. Cell cycle was detected with flow cytometer. The downstream genes of KLF13 were screened using RNA-seq assay. Luciferase activity was employed to assess the transcriptional regulation of KLF13 on IFIT1 promoter. RESULTS: KLF13 expression was downregulated in THCA samples. KLF13 knockdown and overexpression promoted and inhibited the proliferation and migration of THCA cells, respectively. The RNA-seq, RT-qPCR and immunoblotting data showed that KLF13 knockdown significantly potentiated IFIT1 expression at both mRNA and protein levels. Luciferase assays showed that KLF13 suppressed the transcription activity of IFIT1 promoter. Besides, IFIT1 upregulation was critical for the proliferation and migration of THCA cell lines. Lastly, silencing of IFIT1 greatly reversed the proliferation and migration induced by KLF13 knockdown. CONCLUSIONS: In conclusion, KLF13 may function as an anti-tumor protein in THCA by regulating the expression of IFIT1 and offer a theoretical foundation for treating thyroid carcinoma.

The role of multifocality in predicting central lymph node metastasis in initially treated 18-55 years old female patients with unilateral papillary thyroid microcarcinoma.

Objective: To determine the predictive ability of multifocality for central lymph node metastasis in initially treated 18-55 years old female patients with unilateral papillary thyroid microcarcinoma. Study design: Retrospective review. Setting: Tertiary medical center. Methods: We retrospectively collected clinical data from initially treated papillary thyroid microcarcinoma (PTMC) patients at Cancer Hospital Chinese Academy of Medical and sciences between January 1st, 2018, and December 31st, 2018. Data from 975 initially treated 18-55 years old female patients with unilateral PTMC was collected. We also collected data from 340 initially treated 18-55 years old male patients with unilateral PTMC patients to compare the results between genders. Clinicopathological factors associated with central lymph node metastasis (CLNM) were investigated by univariate and multivariate analysis. Results: (1) In the female group, there were 196 (20.1%) cases that had tumor multifocality, including 126 (12.9%) with 2 foci and 70 (7.2%) with >2 foci. The risk of CLNM in patients with 2 foci was not significantly higher than patients with 1 focus (37.3% vs 38.6%, P=0.775). However, diagnosed with >2 foci were independently and positively correlated with CLNM (OR=2.708, 95%CI=1.592-4.607, P<0.001), as was tumor diameter >0.55cm (OR=2.047, 95%CI=1.535-2.730, P<0.001). (2) In the male group, the risk of CLNM with 2 foci was significantly higher than 1 focus (P=0.008). Compared to female patients, the risk of CLNM was significantly higher in patients with 1 focus (P<0.001) or 2 foci (P<0.001). Conclusion: In summary, the risk of CLNM in patients with 2 foci was not significantly higher than patients with 1 focus, while multifocality with over 2 foci was an independent risk factor of CLNM. Therefore, multifocality in this subgroup should not be simply defined as "more than 1 focus". Future models that include multifocality as a predictive factor for cervical lymph node metastasis could consider stratifying the cohort into smaller subgroups for more accurate conclusions.

Association between surgical extent and recurrence in unilateral intermediate- to high-risk papillary thyroid cancer.

BACKGROUND: Guidelines recommend total thyroidectomy (TT) to facilitate radioactive ablation and serological follow-up for intermediate- to high-risk papillary thyroid carcinoma (PTC). However, the association between surgical extent and tumor recurrence in these patients has not been well validated. We aimed to examine the association between the extent of surgery and recurrence in patients with completely resected unilateral intermediate- to high-risk PTC. METHODS: Patients with completely resected unilateral PTC from 2000 to 2017 in a single institute were reviewed. Those who had extrathyroidal extension (ETE) or lymph node metastasis (LNM, cN1 or pN1 > 5 lymph nodes involved) were included for analysis. Cox proportional hazards models were applied to measure the association between surgical extent and recurrence-free survival (RFS) while adjusting for patient demographic, clinicopathological and treatment variables. RESULTS: A total of 4550 patients (mean[SD] age, 43.0[11.7] years; 3379 women[74.3%]) were included. Of these patients, 2262(49.7%), 656(14.4%), 1032(22.7%), and 600 (13.2%) underwent lobectomy, TT, lobectomy + neck dissection (ND) and TT + ND, respectively. With a median follow-up period of 68 months, after multivariate adjustment, lobectomy was associated with a compromised RFS compared with other surgical extents (HR[95%CI], TT 0.537[0.333-0.866], P = 0.011, lobectomy + ND 0.531[0.392-0.720] P < 0.0001, TT + ND 0.446[0.286-0.697] P < 0.0001). RFS was similar between the two extents with ND (lobectomy + ND, HR [95%CI], 1.196 [0.759-1.885], P = 0.440). CONCLUSION: Lobectomy alone is associated with an elevated recurrence risk in patients with unilateral intermediate- to high-risk PTC compared with larger surgical extents. However, lobectomy and ND may provide similar tumor control compared with the conventional approach of TT and ND.

Efficacy and safety of pembrolizumab with preoperative neoadjuvant chemotherapy in patients with resectable locally advanced head and neck squamous cell carcinomas.

Background: This study aimed to explore the efficacy and safety of pembrolizumab combined with chemotherapy as neoadjuvant therapy in patients with resectable locally advanced head and neck squamous cell carcinomas (LA-HNSCCs). Methods: In this prospective, single-arm, single-centre clinical trial, patients meeting the inclusion criteria were treated with preoperative neoadjuvant therapy with 200 mg pembrolizumab combined with 75 mg/m2 cisplatin and 175 mg/m2 paclitaxel. This was followed by surgery and postoperative adjuvant therapy. The primary endpoint was the postoperative pathological complete response (pCR) rate. All statistical analyses were performed using SPSS 26. Results: A total of 22 patients were enrolled. The location of primary lesion showed: hypopharynx were 15 (68.2%), oropharynx were 6 (27.3%) and oral cavity was 1 (4.5%). The postoperative pCR rate, was 36.4% (8/22), and there was no delay to surgery due to adverse drug reactions. The rate of laryngeal function preservation was 90.9% (20/22). Delayed wound healing was the main surgical complication, with an incidence of 22.7% (5/22). The median follow-up time was 9.5 months, and only 1 patient (4.55%) suffered a regional recurrence. Conclusion: Preoperative treatment with pembrolizumab and chemotherapy in resectable LA-HNSCC has a high pCR rate with no significant impact on surgical safety. This treatment was found to increase the rate of laryngeal function preservation. However, the effects of neoadjuvant immunotherapy on long-term prognosis in LA-HNSCCs require further study.

A nomogram for predicting lateral lymph node metastasis in cN0 unifocal papillary thyroid microcarcinoma.

BACKGROUND: Identifying risk factors for occult lateral lymph node metastasis (LLNM) in papillary thyroid microcarcinoma (PTMC) can provide valuable insights into the necessity of lateral neck dissection (LND). The objective of this study was to develop a nomogram for predicting the probability of LLNM in patients with cN0 unifocal PTMC. METHODS: We conducted a retrospective analyzed a total of 4872 patients with cN0 unifocal PTMC who were treated at our center from January 2013 to June 2018. Logistic regression analysis was used to determine the risk factors for LLNM, and a nomogram was constructed based on these risk factors. RESULTS: The rate of LLNM was 3.2%. Tumors located in the upper lobe(odds ratio [OR] = 2.56, 95% confidence interval [CI] 1.80-3.62; p < 0.001) and size greater than 7 mm (OR = 2.59, 95% CI 1.85-3.62; p < 0.001) had a significantly higher risk of LLNM compared to tumors in the lower or middle lobe and size less than or equal to 7 mm. Tumors with extrathyroidal extension (ETE) had a significantly higher risk of LLNM (OR = 1.41, 95% CI 1.01-1.99; p = 0.044). The presence of three or more central lymph node metastases (CLNMs) (OR = 5.84, 95% CI 3.83-8.93; p < 0.001) or one or two CLNMs (OR = 2.91, 95% CI 1.93-4.42; p < 0.001) also increased the risk of LLNM compared to having no CLNMs. A nomogram incorporating these risk factors was developed, and the receiver operating characteristic (ROC) curve demonstrated an area under the curve (AUC) of 0.777, indicating a high degree of predictive accuracy. CONCLUSION: Tumor location in the upper lobe, greater than 7 mm in size, ETE, and CLNMs, especially three or more, were independent risk factors for LLNM in cN0 unifocal PTMC. The nomogram based on these factors exhibited favorable predictive value and consistency.

Hashimoto's thyroiditis is negatively associated with lymph node metastasis in PTMC.

PURPOSE: The association between Hashimoto's thyroiditis (HT) and lymph node metastasis (LNM) of papillary thyroid microcarcinoma (PTMC) remains poorly understood. We aimed to elucidate the impact of HT on PTMC and its association with LNM. METHODS: A retrospective cohort study was conducted at a single cancer referral center. Patients diagnosed with PTMC and complete clinicopathological results between January 2013 and June 2018 were included. Propensity score matching (PSM) and logistic regression analysis were performed to evaluate the difference in LNM characteristics between patients with and without HT. RESULTS: Among the 9929 PTMC patients, 2389 (24.1%) were pathologically diagnosed with HT. After PSM using variables including age, sex, primary tumor size, central neck dissection, extrathyroidal extension (ETE), gross ETE, multifocality and bilaterality, we identified 2324 pairs of patients for analysis. Patients with HT had a significantly lower incidence of LNM in the central neck (40.9% vs 56.2%, P < 0.001) and lateral neck (11.6% vs 14.2%, P = 0.016), a lower incidence of extranodal extension (ENE) (10.1% vs 17.0%, P < 0.001), fewer positive lymph nodes (median [IQR], 0 [0 to 2] vs 1 [0 to 3], P < 0.001), and a lower lymph node ratio (median [IQR], 0.00 [0.00 to 0.15] vs 0.12 [0.00 to 0.33], P < 0.001) than those without HT. Logistic regression analysis indicated that patients with HT had a significantly reduced risk of CLNM and LLNM compared to those without HT. CONCLUSIONS: Our study indicated a negative association between HT and LNM in PTMC.

Involvement of KLRK1 in immune infiltration of head and neck squamous cell carcinoma correlates with favorable prognosis.

Head and neck squamous cell carcinoma (HNSCC) is a malignancy commonly found in the head and neck region, with a low 5-year survival rate. Although immunotherapy has made significant progress, its efficacy in HNSCC treatment remains unsatisfactory. Killer cell lectin-like receptor K1 (KLRK1), a marker highly expressed in immune cells, can bind to its ligands expressed by cancer cells to exert its antitumor effect. However, the role of KLRK1 in HNSCC has yet to be studied extensively. This study aimed to explore the involvement of KLRK1 in immune infiltration of HNSCC and its correlation with prognosis. We analyzed KLRK1 expression data from the Cancer Genome Atlas database. The relationship between KLRK1 and immune cell infiltration has also been investigated. Finally, we analyzed the association between the expression of KLRK1 and its ligands and the prognosis of patients with HNSCC. We found that KLRK1 was highly expressed in HNSCC and correlated with better prognosis. KLRK1 expression was correlated with age, histological grade, HPV infection, pT, pN, pTNM stage, primary site, and survival status. High expression levels of KLRK1 have been linked to high levels of immune cell infiltration, particularly CD4/8 (+) T lymphocytes. Among the ligands of KLRK1, UL16 binding protein (ULBP) 1-3 showed high expression, which was associated with an increased risk of death. Notably, the expression of KLRK1 was negatively correlated with ULBP1-3. Patients with high levels of ULBP2/3 expression in tonsil carcinoma had poorer prognosis than those with low levels (P < .01), whereas ULBP1 expression levels had no significant effect on tonsil carcinoma prognosis (P = .770). The expression levels of ULBP1/3 were correlated with worse prognosis in patients with laryngeal cancer (P < .05), whereas there was no significant correlation between ULBP2 expression levels and overall survival (P = .269). Our study revealed that KLRK1 is highly expressed in HNSCC and is associated with a better prognosis and immune infiltration. Patients with high expression of KLRK1 ligands exhibited worse prognoses, possibly because of the expression of more soluble ligands.

Intraparotid node metastasis affects the long-term survival of patients with resectable recurrent parotid gland carcinoma.

PURPOSE: The recurrence rate of parotid gland cancer is high, but research on the prognosis of recurrent parotid gland cancer (RPC) is relatively limited. We aim to determine the potential prognosis factors of RPC. STUDY DESIGN: Retrospective cohort analysis. SETTING: Tertiary cancer center. METHODS: We conducted a retrospective review from 2012 to 2021 on RPC patients treated at the China National Cancer Center (CNCC). To analyze the impact of various variables on overall survival (OS) after recurrence, a univariate and multivariate Cox proportional hazard model was employed. RESULTS: A total of 50/218 (23.0%) patients diagnosed with RPC and underwent surgery. The 5-year OS of all RPC patients in this cohort was 61.9%. 5 of 50 patients (10%) exhibited intraparotid node (IPN) metastasis. By univariate and multivariate analyses, we found that IPN metastasis was one of the prognostic factors of OS (p = 0.039) in RPC patients. The presence of IPN metastasis was also related to poor survival in individuals with negative cervical lymph nodes (CN0) (p = 0.011). In terms of the influence of surgical margins on prognosis, our findings revealed that RPC patients with negative margins exhibited a higher survival result than those with positive margins (p = 0.002). CONCLUSION: According to this study, IPN metastasis indicate a high incidence of mortality in recurrent parotid cancer patients. Particularly, in CN0 patients, the presence of IPN metastasis was associated with poor survival in CN0 patients.