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.

Incidentally discovered parathyroid lipoadenoma in thyroid surgery: A case report and review of the literature.

Parathyroid lipoadenoma is a rare type of parathyroid adenoma, described as a single parathyroid adenoma with more than 50% fat on histologic examination and an unknown etiology, which is one of the rare causes of primary hyperparathyroidism. The difficulty of parathyroid lipoadenoma is mainly diagnosed by preoperative imaging localization. We hope to arouse attention to the parathyroid adenoma which is difficult to locate through our case report. The patient was a middle-aged male with a body mass index of 38.4 kg/m2 who admitted to our hospital with a 40-day history of an untreated thyroid nodule. We incidentally discovered parathyroid lipoadenoma in his thyroid surgery. His prognosis was good, and there were no signs of recurrence at his 12-month follow-up appointment. We believe that parathyroid lipoadenoma needs to rely on paraffin pathology to make a final diagnosis. This case report serves as a reminder that parathyroid lipoadenomas are also possible in patients who do not have primary hyperparathyroidism preoperatively and who have negative imaging. Clinicians must carefully examine the adipose tissue for the presence of parathyroid lipoadenomas during thyroid surgery to avoid postoperative hypoparathyroidism and persistent hypocalcaemia.

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.

Meta-analysis of the effect and clinical significance of Delphian lymph node metastasis in papillary thyroid cancer.

Objective: To investigate the effect and clinical significance of Delphian lymph nodes (DLN) on the factors influencing papillary thyroid cancer (PTC) to provide individualized guidance for the surgical treatment of thyroid cancer. Methods: Relevant studies from PubMed, Web of Science, the Cochrane Library, Embase, and China National Knowledge Infrastructure databases were searched until February 13, 2023. Stringent selection parameters were used to obtain included data and homogeneous articles. Analyses were performed using Revman 5.4 and SPSS software. A P-value of < 0.05 was considered statistically significant. Results: Five studies were finally included in this study. The results revealed a higher risk of DLN metastasis (DLNM) in patients with tumor size >1cm, multifocality, and extrathyroidal extension (ETE) of the thyroid. The risk of central lymph node metastasis (CLNM) was 11.25 times higher in DLN-positive patients with PTC than in DLN-negative (OR = 11.25, 95% CI: 8.64-14.64, P < 0.05) patients. The risk of LLNM was 5.57 times higher in DLN-positive patients with PTC than in DLN-negative (OR = 5.57, 95% CI: 4.57-6.78, P < 0.001) patients. The risk of postoperative recurrence in DLN-positive patients with PTC was 3.49 times higher (OR = 3.49, 95% CI: 1.91-6.38, P < 0.001) than in DLN-negative patients with PTC. Conclusion: Patients with tumor size >1 cm in diameter, multifocality, and ETE have an increased risk for DLN development. DLN-positive patients with central and lateral cervical lymph node metastasis and postoperative recurrence are at higher risk than DLN-negative patients.

Preparing Thick Gradient Surface Layer in Cu-Zn Alloy via Ultrasonic Severe Surface Rolling for Strength-Ductility Balance.

A gradient structure (GS) design is a prominent strategy for strength-ductility balance in metallic materials, including Cu alloys. However, producing a thick GS surface layer without surface damage is still a challenging task limited by the available processing technology. In this work, a gradient structure (GS) surface layer with a thickness at the millimeter scale is produced in the Cu-38 wt.% Zn alloy using ultrasonic severe surface rolling technology at room temperature. The GS surface layer is as thick as 1.1 mm and involves the gradient distribution of grain size and dislocation density. The grain size is refined to 153.5 nm in the topmost surface layer and gradually increases with increasing depth. Tensile tests indicate that the single-sided USSR processed alloy exhibits balanced strength (467.5 MPa in yield strength) and ductility (10.7% in uniform elongation). Tailoring the volume fraction of the GS surface layer can tune the combination of strength and ductility in a certain range. The high strength of GS surface layer mainly stems from the high density of grain boundaries, dislocations and dislocation structures, deformation twins, and GS-induced synergistic strengthening effect. Our study elucidates the effect of the thick GS surface layer on strength and ductility, and provides a novel pathway for optimizing the strength-ductility combination of Cu alloys.

Does pretreatment elevated calcitonin level cause the poor prognosis in patients with medullary thyroid cancer?

Background: Medullary thyroid carcinoma (MTC) patients have poor survival, tumor/node/metastasis (TNM) stage and biochemical prognosis are the most important factors. We investigated the clinical significance of calcitonin (Ctn) to assess the biochemical prognosis of MTC. Methods: This retrospective observational study enrolled 77 MTC patients with complete information and primary surgery at the Department of Thyroid Surgery, China-Japan Union Hospital of Jilin University between 2009 and 2020. Patient and MTC characteristics were recorded. All patients were divided into remission, stable, and progression according to biochemical prognosis. We analyzed the correlation between preoperative serum Ctn, TNM stage and biochemical prognosis. Results: Elevated preoperative serum Ctn was positively correlated with TNM stage. Patients with higher Ctn, multifocality, and bilateral tumors were associated with a higher TNM stage. Multivariate logistic regression analysis showed that preoperative serum Ctn level was an independent risk factor for TNM stage. Receiver operating characteristic (ROC) analysis found the best Ctn cut-off value for predicting TNM III was 45.88 pg/mL, which had a sensitivity of 87.2% and a specificity of 65.8%. The best Ctn cut-off value for predicting TNM IV was 167.00 pg/mL, with a sensitivity of 92.9% and a specificity of 77.6%. In univariate analysis, patients with higher preoperative serum Ctn, multifocality, bilateral tumors, and higher TNM stage were more likely to progress. The optimal cut-off value for progression was 195.5 pg/mL, which had a sensitivity of 80.0% and a specificity of 70.2%. For every 1-unit increase in preoperative serum Ctn levels, the risk of progression increased by 1.004 times (P=0.008), and patients with TNM stage III [hazard ratio (HR) =9.663; 95% confidence interval (CI): 1.411, 66.156] were nearly 9.7-fold more likely to progress than those in TNM stage I/II. Conclusions: Elevated preoperative serum Ctn predicted poor clinical outcomes in MTC.

Metastasis to lymph nodes at the contralateral entrance point to the recurrent laryngeal nerve in unilateral thyroid papillary carcinoma: a case report and literature review.

Background: Papillary thyroid carcinoma (PTC) is the most common type of thyroid cancer. PTC is slow growing, and prognosis after surgery is excellent. However, PTC is associated with a high incidence of cervical lymph node metastasis, and usually metastasizes from the central lymph nodes to the ipsilateral cervical and mediastinal lymph nodes. Anatomic studies have shown that the thyroid gland and surrounding tissue have an abundant lymphatic network that facilitates tumor dissemination and lymph node metastasis, there may be many ways to connect lymph nodes on both sides of the neck of patients, which needs further research and discussion. Case Description: We report the case of a 45-year-old female who was diagnosed with thyroid cancer of the right lobe and right lateral lymph node metastasis by fine-needle aspiration (FNA). During surgery, 0.2 mL of carbon nanoparticle (CN) suspension was injected into the right lobe of the thyroid gland, which resulted in black staining of a lymph node at the contralateral entrance point to the recurrent laryngeal nerve (LN-epRLN). The black-stained lymph node was resected, and the pathology results revealed lymph node metastasis from thyroid cancer. The left lobe of the thyroid was benign. Conclusions: Retro-tracheal periesophageal lymph node metastasis may be a rare metastatic pathway in thyroid cancer.

Advances in the Study of Acute Acalculous Cholecystitis: A Comprehensive Review.

BACKGROUND: Acute acalculous cholecystitis (AAC) is characterized by acute necrotizing inflammation with no calculi and is diagnosed based on imaging, intraoperative, and pathological examinations. KEY MESSAGE: Although AAC has been studied clinically for a long time, it remains difficult to diagnose and treat. The pathogenesis of AAC is still not fully understood, and it is often regarded as a relatively independent clinical disease that is different from acute calculous cholecystitis (ACC). Pathological studies suggest that AAC is the manifestation of a critical systemic disease, while ACC is a local disease of the gallbladder. SUMMARY: Concerning the pathogenesis, diagnosis, and treatment of AAC, we reviewed the research progress of AAC, which will enhance the understanding of the early diagnosis and treatment of AAC.

Papillary thyroid carcinoma with rare lymph node metastasis between the non-ipsilateral sternocleidomastoid and striate muscles: two case reports and literature review.

Background: Differentiated thyroid cancer (DTC) has a high incidence but a generally good prognosis. However, lymph node metastasis is likely to occur. It usually metastasizes from the central group lymph nodes to the deep cervical lymph nodes and less frequently to the sternocleidomastoid-sternohyoid muscle. The lymph nodes between the sternocleidomastoid and sternohyoid muscles (LNSS) is easily overlook. Ignoring the preoperative assessment and dissection of level LNSS, especially in the contralateral neck level LNSS, may lead to incomplete surgery and thus require reoperation. The metastatic relevant factors and pathway for LNSS remains inconclusive require further investigation. There is a lack of reports of contralateral or bilateral cervical level LNSS metastasis in thyroid cancer. We hope to arouse attention to the level LNSS through our two case reports. Case Description: We report two cases of non-ipsilateral LNSS metastases. The patients were diagnosed with thyroid cancer by fine-needle aspiration (FNA), and ultrasound examination showed enlarged lymph nodes at the LNSS level. After surgical treatment and postoperative paraffin pathology, both patients were diagnosed with papillary thyroid carcinoma (PTC) and LNSS-level lymph node metastasis. Case 1 was a 63-year-old woman admitted to our hospital with a 15-day history of an untreated thyroid nodule and preoperative euthyroidism. This patient underwent total thyroidectomy, central and left neck LNSS dissection. Her prognosis was good, and there were no signs of recurrence at her 6-month follow-up appointment; Case 2 was a 24-year-old woman admitted to our hospital for a physical examination of an anterior cervical mass that had been present for 1 year and preoperative euthyroidism. This patient underwent total thyroidectomy, central and bilateral neck LNSS dissection. Her prognosis was good, and there were no signs of recurrence at her 12-month follow-up appointment. Conclusions: The occurrence of contralateral and bilateral simultaneous LNSS metastasis in thyroid cancer is relatively rare. However, in clinical practice, surgeons should focus on the evaluation and clearance of LNSS, especially in patients with cancer foci located in the lower pole, cancer foci invading the anterior cervical band muscle, extensive metastasis in the lateral cervical lymph nodes or stages T3/4 and to reduce postoperative recurrence.

Diagnostic performance of Midkine ratios in fine-needle aspirates for evaluation of Cytologically indeterminate thyroid nodules.

BACKGROUND: Fine-needle aspiration cytology (FNAC) is a basic diagnostic tool for thyroid nodules. However, 15-30% of nodules are cytologically indeterminate. Midkine (MK), a pleiotropic growth factor, is often upregulated in patients with cancers. This study aimed to evaluate the role of MK and its ratios in fine-needle aspirates (FNA) for predicting thyroid malignancy. METHODS: This retrospective study included patients with thyroid nodules who underwent preoperative FNA and/or thyroidectomy between April 2017 and September 2017. MK levels in FNA washout were measured by enzyme-linked immunosorbent assay, and thyroglobulin (TG) and free thyroxine (FT4) levels in FNA washout were measured by chemiluminescent immunometric assays. RESULTS: A total of 217 patients with 242 nodules were included in this study. The concentrations of TG, FT4, MK/TG, MK/FT4, and FT4/MK were significantly different between papillary thyroid carcinomas and benign thyroid nodules. Both MK/TG and MK/FT4 ratios were positively correlated with maximum tumor diameter, extrathyroidal extension, and T and N stages. The area under the curve for MK/TG was 0.719 with a cutoff value of 55.57 ng/mg, while the area under the curve for MK/FT4 was 0.677 with a cutoff value of 0.11 µg/pmol. FNAC in combination with MK/FT4 had a higher sensitivity (95% vs. 91%) and accuracy (96% vs. 92%) than FNAC alone for cytologically indeterminate specimens, those of unknown significance, or those suspected of malignancy. CONCLUSIONS: MK/FT4 and MK/TG may have diagnostic utility for evaluation of papillary thyroid carcinomas, particularly for cytologically indeterminate thyroid nodules.

Circ_0079558 promotes papillary thyroid cancer progression by binding to miR-26b-5p to activate MET/AKT signaling.

Circular RNAs (circRNAs) are a group of non-coding RNAs featured by covalently closed circular structure. CircRNA_0079558 (circ_0079558) is derived from RAPGEF5 gene, and it has been found to be significantly up-regulated in papillary thyroid carcinoma (PTC). However, the role and working mechanism of circ_0079558 in PTC progression have never been illustrated. The levels of circ_0079558 and MET proto-oncogene, receptor tyrosine kinase (MET) were up-regulated in PTC tissues and cell lines, as evidenced by reverse transcription-quantitative polymerase chain reaction (RT-qPCR) and Western blot assay. The silencing of circ_0079558 or MET restrained cell proliferation, migration and invasion whereas triggered cell apoptosis in PTC cells, as verified by Cell Counting Kit-8 (CCK8) assay, plate colony formation assay, transwell invasion assay, wound healing assay and flow cytometry. Through using MET specific inhibitor PHA665752, we found that circ_0079558 overexpression enhanced the malignant behaviors of PTC cells through activating MET/AKT pathway. Through dual-luciferase reporter assay and RNA immunoprecipitation (RIP) assay, microRNA-26b-5p (miR-26b-5p) was identified to be the intermediary molecular between circ_0079558 and MET, and circ_0079558 knockdown reduced the expression of MET partly through elevating miR-26b-5p in PTC cells. The miR-198/FGFR1 pathway was identified as another signal axis downstream of circ_0079558, and the co-overexpression of FGFR1 and MET largely rescued the proliferation ability of circ_0079558-silenced PTC cells. Through xenograft tumor model, we found that circ_0079558 silencing restrained xenograft tumor growth in vivo. In conclusion, circ_0079558 facilitated the proliferation and motility whereas inhibited the apoptosis of PTC cells largely through mediating miR-26b-5p/MET/AKT signaling.

[Retracted] Function of miR­212 as a tumor suppressor in thyroid cancer by targeting SIRT1.

Following the publication of this paper, it was drawn to the Editors' attention by a concerned reader that the tumor images shown in Fig. 6B bore unexpected similarities to data appearing in different form in other articles by different authors. In addition, there were potential anomalies associated with the cell migration assay data shown in Fig. 2E. Owing to the fact that some of the contentious data in the above article had already been published elsewhere, or were already under consideration for publication, prior to its submission to Oncology Reports, the Editor has decided that this paper should be retracted from the Journal. The authors agree with the decision to retract the paper. The Editor apologizes to the readership for any inconvenience caused. [the original article was published in Oncology Reports 39: 695-702, 2018; DOI: 10.3892/or.2017.6119].

Bilateral axillo-breast approach robotic thyroidectomy: review of a single surgeon's consecutive 317 cases.

BACKGROUND: Bilateral axillo-breast approach robotic thyroidectomy (BABA RT) is one of the most popular remote-access approaches for thyroid surgery. This study aimed to evaluate the surgical outcomes of BABA RT. METHODS: Medical records of patients who underwent BABA RT between July 2008 and July 2016 were retrospectively reviewed. Surgeries were performed by one surgeon at one institution. Clinicopathological features and postoperative surgical outcomes were evaluated. RESULTS: A total of 317 patients were enrolled. The mean age was 40.0±9.7 years, and 287 (90.5%) were female. The mean tumor size was 1.02 cm. Papillary thyroid carcinoma (PTC) was most commonly seen (n=282, 88.8%), followed by benign nodules (n=33, 10.5%) and follicular thyroid carcinoma (n=2, 0.6%). Total thyroidectomy was performed in 202 (63.7%) patients, while unilateral lobectomy was performed in 113 (35.6%). Two patients (0.6%) had transient vocal cord palsy, but none showed permanent vocal cord palsy. Thirty-four (16.8%) patients developed hypoparathyroidism, 33 (16.3%) were transient and 1 (0.5%) was permanent. The mean operation time for total thyroidectomy and lobectomy was 264.9±52.4 and 203.4±47.6 min, respectively. A decrease in operation time in total thyroidectomy was observed in 49-51 cases (P=0.015). Four patients (1.4%) had local recurrence during the median follow-up of 61±23 months. CONCLUSIONS: BABA RT can be performed safely in selected patients with thyroid nodules. The learning curve duration for BABA RT was 49-51 cases of total thyroidectomy.

Pictorial essay of vestibular incision outcomes from transoral endoscopic thyroidectomy.

PURPOSE: The transoral endoscopic thyroidectomy vestibular approach (TOETVA) has emerged as a new treatment option for patients with selected thyroid disease requiring surgery. The aim of this pictorial essay is to illustrate the healing outcomes of the vestibular incisions. METHODS: TOETVA patients were recruited at two Centers in China and Italy. TOETVA is initiated with one 10-20-mm median incision in the center of the oral vestibule 10 mm above the inferior labial frenulum, and two 5-mm lateral incisions, just below the lower lip near the labial commissure. Healing of the vestibular incision was monitored through serial photographs 1, 3, 7, 30, and 90 days after surgery. Outcomes were evaluated by Landry's score, time to healing, issues affecting wound outcomes, scar, fibrin, granulation, necrotic tissue formation, and infections. RESULTS: Results of TOETVA were monitored in 52 patients. There were no postoperative infections. All lateral incisions demonstrated favorable surgical outcomes. Landry's criteria scores indicated worse outcomes for the median incisions vs. the lateral ones (p<0.05). Median incisions healed well in 65.4% of patients, but 34.6% of patients had visible scars from the median incision 90 days after surgery. Eight (15.4%) had cicatricial diathesis, seven (13.5%) experienced displacement of the stitches, and three (5.8%) developed synechia with gingiva. When the central vestibular incision was <10mm from the gingiva, patients tended to form synechia (60%). There were no significant differences in wound healing between the Chinese and Italian patients. CONCLUSIONS: Knowledge of vestibular incision healing is essential to provide practical TOETVA clinical guide and to define optimal outcomes evaluation for transoral surgeons. Vestibular wound problems were confined only to the central incision.

Prevention of non-recurrent laryngeal nerve injury in robotic thyroidectomy: imaging and technique.

INTRODUCTION: The aim of this report was to summarize observations, evaluate the feasibility, provide detailed information concerning proper techniques, and address limitations for non-recurrent laryngeal nerve (NRLN) dissection and release during the robotic bilateral axillo-breast approach (BABA) for thyroidectomy. MATERIALS AND METHODS: The BABA approach was used in two cases of thyroidectomy in the setting of NRLN. Preoperative CT imaging findings suggesting the aberrant anatomy are reviewed and technical planning, inclusive of intraoperative nerve monitoring, was employed. Intraoperative videos with narrative discussion of technique for safe dissection are provided, along with supplementary video of additional technical guidance. RESULTS: In both cases, the NRLNs were identified, dissected, and preserved. We dissected the proximal segment of each NRLN to its origin. We determined that the use of only the NRLN proximal to distal robotic dissection jeopardized the nerve. The BABA approach with the Type I NRLN is similar to the dissection of the recurrent laryngeal nerve (RLN) in transoral thyroidectomy. Due to interference with endoscopic viewing caused by the thyroid cartilage, the Type I NRLN is more challenging to manage both at the laryngeal entry point and its origin from the vagus nerve (VN). For the Type II NRLN, it is essential to identify its point of origin and the reflection of the nerve from the VN. Therefore, modification of nerve dissection to mirror open surgery with bidirectional nerve dissection assisted in avoidance of traction injury to the nerve. CONCLUSIONS: We presented a video, a detailed description of methods, and discussed limits for NRLN management in robotic BABA. This report included (i) a description of the aberrant anatomy and CT scans to inform surgeons of the possible NRLN locations, (ii) a description of a technique for using the nerve monitor in the robotic surgeries, and (iii) a description of the techniques used to isolate and protect the NRLN during the robotic surgery. In robotic BABA, our NRLN-sparing technique and degree included mainly a multi-directional nerve dissection (i.e., medial-grade, later-grade approach together with proximal to/from distal) using athermal technique. The NRLN-sparing technique is predominantly carried out in an anterior dissection plane.

Usefulness of PET-CT scan in recurrent thyroid cancer.

The aim of this paper is to discuss the risk of recurrence in patients with differentiated thyroid cancer and emphasize the importance of risk-group stratification, early recurrence identification and application of new imaging modalities, what is the PET-CT. Moreover, follow-up of patients with thyroid carcinoma should be carried out by specialized teams throughout life. Therefore, interdisciplinary case discussions in tumor conferences may improve the use of multimodal therapy especially in patients with poorly differentiated thyroid carcinomas. After baseline follow-up, if there is a suspicion of thyroid carcinoma, early PET-CT should be used for early detection and appropriate planning. Fortunately, due to the good localization possibility, the PET-CT enables a focused surgical procedure with avoidance of an unnecessary tumor search and thereby a reduction of the risk of injury of neighboring structures which is a concern with reoperative neck surgery.

Recent developments in electrochemiluminescence nanosensors for cancer diagnosis applications.

In recent years, electrochemiluminescence (ECL) nanosensing systems have undergone rapid development and made significant progress in ultrasensitive analysis and cell imaging. Because of the unique advantages of high selectivity, ultra-sensitivity, and good reproducibility, ECL nanosensors can open new paths for cancer diagnosis. With the development of ECL nanosensors, high-throughput analysis, visual detection and spatially resolved ECL imaging of single cells are being realized. The innovations of ECL nanosensors consist of electrochemical excitation, coreactant catalysis, light radiation and luminescence signal amplification, which involve several fields such as nanotechnology, catalysis, optics, and electrochemistry. The developments of ECL instruments also relate to imaging technology. Herein, we review the construction modes, sensing strategies and cancer diagnosis applications of ECL nanosenors. Firstly, the nano-components of the ECL sensing system are discussed. The construction and signal amplification methods of the nanosensing system are emphasized. Secondly, the high-efficiency cancer identification strategies are presented, including protein tumor marker detection, nucleic acid assay, cancer cell identification and exosome detection. The recent advances in representative examples of ECL nanosenors in cancer diagnosis are highlighted, including high-throughput ECL analysis, in situ assay, visual ECL detection, single-cell imaging diagnosis, and so on. Finally, the challenges are featured based on the recent development of the ECL nanosensing system in the clinical diagnosis. The ECL nanosensors provide effective and reliable analytical methods and open new paths for cancer diagnosis. It is noteworthy that the prospects of the ECL nanosensing system in clinical diagnosis are instructive to the developments of other nanosensor research.

A Randomized Comparison of Carbon Nanoparticles in Endoscopic Lymph Node Dissection Via the Bilateral Areola Approach for Papillary Thyroid Cancer.

OBJECTIVE: We assess the value of carbon nanoparticles (CNP) staining in patients undergoing endoscopic thyroidectomy and central compartment lymph node (CLN) dissection via the bilateral areola approach [endoscopic thyroidectomy via bilateral areola approach (ETBAA)]. METHODS: This was a prospective randomized study. Three hundred two consecutive early-stage thyroid cancer patients eligible for ETBAA were recruited at the Division of Thyroid Surgery, China-Japan Union Hospital, Jilin University, China. CLN were mapped and retrieved under the guidance of stained or unstained CNP. The location, detection rates, positive nodes, and number of stained lymph nodes were compared. RESULTS: ETBAA patients were randomly divided into a CNP group (n=152) and a control group (n=150). In the CNP group, the imaging of lymphatic flow could be observed in 1016 (95.9%) lymph nodes, whereas 43 (4.1%) were unstained. The mean number of stained lymph nodes in each procedure was 6.68 (range, 3 to 12). The total number of dissected lymph nodes was 1059 in the CNP group and 872 in the control group (P=0.00). There was a significant difference of inadvertent parathyroidectomy between the 2 groups: 0.5% versus 3.9% in lobectomy (P=0.035) and 0.6% versus 5.2% in total thyroidectomy (P=0.012). However, the rates of hypoparathyroidism were not significantly different (P>0.05). There were no cases of CNP-related adverse effects. CONCLUSIONS: The lymphatic navigation by CNP increases the number of detected CLN without the involvement of radioactive isotopes. However, CNP did not lower hypocalcemia, did not improve parathyroid hormone range, and there was no significant difference in the percentage of metastatic lymph nodes between the 2 groups.

Time trend analysis of thyroid cancer surgery in China: single institutional database analysis of 15,000 patients.

PURPOSE: The institutional database of the Thyroid Surgery Division in China-Japan Union Hospital of Jilin University was queried to audit time trend patterns in thyroid cancer (TC) management between 2008 and 2017. METHODS: Retrospective longitudinal analysis. Clinicopathological features and treatment strategies were analyzed. Frequencies and multivariate tests were used to detect correlations. RESULTS: Clinical data were obtained from 15,000 TC patients (i.e., 71.3% of 21,044 operations). Papillary was the most common histological subtype (n = 14,916, 99%), and 76% were microcarcinomas. Stage I (95%) and low-risk patients (58%) were prevalent throughout the 10-year period. The trend for total thyroidectomy increased from 29.1% (2008-2012) to 67.9% (2013-2015), and then dropped to 48.6% (2016-2017). A total of 8827 (52%) patients received central lymph node dissection (CLND). The tendency for CLND increased from 15.7 to 86.4% during the 10-year period. While the trend of lateral lymph node dissection decreased from 71.3 to 13.3%. Radioactive iodine therapy was offered to 10% of patients (2008-2012), except for a low value (5.4%) in 2009, and then increased from 12.3% (2012) to 41.3% (2015), while decreased to 32.4% (2017). CONCLUSION: The surgical management of TC patients has undergone continuous changes over the past 10 years. The evolution from aggressive treatment to a more conservative approach has been constant. Our results suggest that the current surgical management approach for TC is adequate and in support of the published guidelines. Our findings warrant further investigation to determine the clinical implications of decision making for TC.

Long Non-Coding RNA MAPK8IP1P2 Inhibits Lymphatic Metastasis of Thyroid Cancer by Activating Hippo Signaling via Sponging miR-146b-3p.

The principal issue derived from thyroid cancer is its high propensity to metastasize to the lymph node. Aberrant exprssion of long non-coding RNAs have been extensively reported to be significantly correlated with lymphatic metastasis of thyroid cancer. However, the clinical significance and functional role of lncRNA-MAPK8IP1P2 in lymphatic metastasis of thyroid cancer remain unclear. Here, we reported that MAPK8IP1P2 was downregulated in thyroid cancer tissues with lymphatic metastasis. Upregulating MAPK8IP1P2 inhibited, while silencing MAPK8IP1P2 enhanced anoikis resistance in vitro and lymphatic metastasis of thyroid cancer cells in vivo. Mechanistically, MAPK8IP1P2 activated Hippo signaling by sponging miR-146b-3p to disrupt the inhibitory effect of miR-146b-3p on NF2, RASSF1, and RASSF5 expression, which further inhibited anoikis resistance and lymphatic metastasis in thyroid cancer. Importantly, miR-146b-3p mimics reversed the inhibitory effect of MAPK8IP1P2 overexpression on anoikis resistance of thyroid cancer cells. In conclusion, our findings suggest that MAPK8IP1P2 may serve as a potential biomarker to predict lymphatic metastasis in thyroid cancer, or a potential therapeutic target in lymphatic metastatic thyroid cancer.