Thyroidectomy without lymph node dissection should be considered for stage T1 medullary thyroid carcinoma: a population-based cohort study.

Background: The necessity and therapeutic value of lymph node dissection (LND) in early stage T1 MTC patients remain controversial. Methods: Patients with T1MTC were identified from the Surveillance, Epidemiology, and End Results (SEER) database. Poisson regression analysis was utilized to investigate promotive factors for lymph node metastasis in T1MTC patients. Fisher's exact test was employed to calculate baseline differences between non-LND and LND groups. Propensity score match (PSM) was used to control baseline bias. Survival outcomes were calculated by Kaplan-Meier method and log-rank test. Multivariable Cox regression assessed the prognostic impact of LND across subgroups. Results: Of 3298 MTC cases, 50.4% were T1MTC. The lymph node metastasis rate increased along with the T stage (from 22.2% to 90.5%). Among 1231 T1MTC patients included after exclusion criteria, 72.0% underwent LND and 22.0% had lymph node metastasis. Patients aged younger than 44 years (RR=1.700, p<0.001), male (RR=1.832, p<0.001), and with tumor larger than 10mm (RR=2.361, p<0.001) were more likely to have lymph node metastasis, while elderly patients (p<0.001) and those with microcarcinoma (p<0.001) were more likely to undergo non-LND procedures. LND provided no OS or DSS benefit over non-LND before and after propensity score match (matched 10-year OS/DSS: LND 83.8/96.2% vs non-LND 81.9/99.3%, p>0.05). Subgroup analyses revealed no prognostic gain with LND in any subgroup (p>0.05). Conclusion: Nearly half of MTC patients were diagnosed at T1 stage and had low lymph node risk. Different from ATA guidelines, avoiding routine LND conferred similar prognosis to standard procedures while potentially improving quality of life. Large-scale prospective multi-center studies should be conducted to further validate these findings.

Improved survival after primary tumor resection in distant metastasis medullary thyroid carcinoma: a population-based cohort study with propensity score matching.

Few studies have investigated the impact of primary tumor resection (PTR) on patients with distant metastasis medullary thyroid carcinoma (DMMTC). This population-based study aims to assess the application of PTR in DMMTC patients, ascertain its benefits, and identify optimal surgical indications. DMMTC Patients diagnosed between 2010 and 2020 were included through the Surveillance, Epidemiology, and End Results (SEER) program. Logistic regression analysis identified driving factors of surgical decision-making. Propensity score matching (PSM), Kaplan-Meier method, and Cox regression were utilized to compare overall survival (OS) and disease-specific survival (DSS) between surgical and non-surgical groups. Subgroup analyses were performed to determine optimal surgical indications. Of 238 DMMTC patients included, 122 (51.3%) patients underwent PTR. Extrathyroidal extension and N1 stage emerged as independent factors promoting the surgical decision. PSM-adjusted survival analyses revealed significant advantages in both OS and DSS for the surgical group. Moreover, subgroup analyses indicated that except for patients aged ≥ 65 years, tumors ≤ 20 mm, or with multiple metastasized sites (> 1), the others significantly benefit from PTR. PTR significantly improves prognosis in selected DMMTC patients. The decision to undergo PTR in other patients should be based on a comprehensive assessment of the disease, surgeon's experience, and family discussions for potential survival benefits.

The Predictive Factors of Combined Implant Application for Breast Cancer Patients Receiving Immediate Breast Reconstruction with a Pedicled Omental Flap.

BACKGROUND: Whether a laparoscopically harvested omental flap is adequate for total breast reconstruction could not be determined preoperativaly due to lack of reliable assessment methods. This study aimed to establish a statistical model to predict the probability of omental flap insufficiency. METHODS: In this study, 200 female patients with breast cancer receiving immediate breast reconstruction with pure pedicled omental flaps or pedicled omental flaps combined with implants after nipple-areolar complex-sparing mastectomy were divided into two groups depending on whether implants were needed or not. The clinical characteristics of these two groups were compared. Correlation of body mass index (BMI) and omental volume was analyzed. Binary logistic regression was performed to predict the probability of implant requirement based on clinical parameters, showing significant differences between the two groups. RESULTS: The patients who needed implants in adjunct treatment were younger. In addition, they had larger breast specimens and smaller omental volumes than the others whose omental flaps were sufficient for total breast reconstruction. Body mass index and omental volume showed a moderately positive correlation. Age, specimen volume, and BMI all were entered into the logistic regression equation. For the patients with a BMI lower than 24.0 kg/m2, the probability of requiring implants was 5.467 times that of comparable patients with a BMI of 24.0 kg/m2 or higher. At the cutoff of 0.61, the regression equation yielded a sensitivity of 84.2% and a specificity of 72.1% in recognizing subjects with the necessity of implant application. CONCLUSION: The combination of BMI, age, and volume of breast specimen could predict with high accuracy whether implants are required for breast cancer patients receiving pedicled omental flap-based breast reconstruction.

An automatic parathyroid recognition and segmentation model based on deep learning of near-infrared autofluorescence imaging.

INTRODUCTION: Near-infrared autofluorescence imaging (NIFI) can be used to identify parathyroid gland (PG) during surgery. The purpose of the study is to establish a new model, help surgeons better identify, and protect PGs. METHODS: Five hundred and twenty three NIFI images were selected. The PGs were recorded by NIFI and marked with artificial intelligence (AI) model. The recognition rate for PGs was calculated. Analyze the differences between surgeons of different years of experience and AI recognition, and evaluate the diagnostic and therapeutic efficacy of AI model. RESULTS: Our model achieved 83.5% precision and 57.8% recall in the internal validation set. The visual recognition rate of AI model was 85.2% and 82.4% on internal and external sets. The PG recognition rate of AI model is higher than that of junior surgeons (p < 0.05). CONCLUSIONS: This AI model will help surgeons identify PGs, and develop their learning ability and self-confidence.

Subgroup analysis of steadily increased trends in medullary thyroid carcinoma incidence and mortality in the USA, 2000-2020: a population-based retrospective cohort study.

The incidence rate of medullary thyroid carcinoma (MTC) continues to grow, along with its mortality rate in the USA. However, the subgroup trends in MTC have not yet been established. This population-based retrospective cohort study was based on the Surveillance, Epidemiology, and End Results (SEER) 17/12 registry database. Subgroup analysis was performed through clinicopathological and treatment-related characteristics. Annual average percentage change (AAPC) was calculated using joinpoint regression analysis. A total of 3833 MTC patients and 536 death cases were diagnosed in the SEER database. Between 2000 and 2019, the incidence (AAPC = 1.64) and mortality (AAPC = 3.46) rates of MTC continued to rise. Subgroup analysis showed the proportion of elderly patients (65-84 years) gradually increased in incidence between 2000 and 2020. Patients with early-stage tumors, such as tumors ≤20 mm, showed the same trends. Aspects of treatment, the implementation rate of total thyroidectomy (AAPC = 0.38) and lymph node dissection (AAPC = 1.06) also increased persistently in almost all of the age subgroups. The incidence and mortality of MTC consistently increased from 2000 to 2019. Subgroup analysis indicated a significant increase in elderly patients and early-stage patients, and more attention should be paid to the management of these increased subgroups.

Surgery is a Viable Treatment Option for Stage IE Primary Thyroid Lymphoma.

BACKGROUND: Stage IE primary thyroid lymphoma (PTL) has been diagnosed in approximately half of patients with PTL; however, the optimal treatment for stage IE PTL has not yet been established. METHODS: Stage IE PTL patients were identified from the Surveillance, Epidemiology, and End Results (SEER) database between 1998 and 2019. Thereafter, the disease-specific survival (DSS) and treatment modalities (surgery alone, surgery + radiotherapy (RT) and/or chemotherapy (CT), and RT and/or CT) of these patients were compared by Kaplan-Meier curves and log-rank test after propensity score matching (PSM). Additionally, patients with PTL from the Affiliated Sixth People's Hospital of the Shanghai Jiao Tong University and School of Medicine (Shanghai, China) between 2007 and 2022 were retrospectively analyzed as an external cohort. RESULTS: Among the 1596 patients with PTL from the SEER database, 842 were identified as patients with stage IE PTL, with an average follow-up period of 7.8 years. Pairwise analysis after PSM revealed no significant difference between the DSS of the three treatment groups. A total of 38 patients with PTL were identified in the external cohort, with an average follow-up period of 3.4 years. Compared with the RT and/or CT group, the surgery-alone group showed no significant difference in the incidence of hypothyroidism (p = 0.161) but had significantly fewer treatment-related complications (p = 0.021), shorter treatment duration (p < 0.001), and lower treatment costs (p = 0.025). CONCLUSIONS: The results of our study demonstrate that surgery is a viable treatment option for patients with stage IE PTL.

Single-Cell Transcriptomic Atlas of Parathyroid Adenoma and Parathyroid Carcinoma.

Primary hyperparathyroidism is typically characterized by monoclonal parathyroid tumors that secrete an excessive amount of parathyroid hormone (PTH). However, the underlying pathogenesis of tumorigenesis remains unclear. We performed single-cell transcriptomic analysis on five parathyroid adenoma (PA) and two parathyroid carcinoma (PC) samples. A total of 63,909 cells were divided into 11 different cell categories; endocrine cells accounted for the largest proportion of cells in both PA and PC, and patients with PC had larger populations of endocrine cells. Our results revealed significant heterogeneity in PA and PC. We identified cell cycle regulators that may play a critical role in the tumorigenesis of PC. Furthermore, we found that the tumor microenvironment in PC was immunosuppressive, and endothelial cells had the highest interactions with other cell types, such as fibroblast-musculature cells and endocrine cells. PC development may be stimulated by fibroblast-endothelial cell interactions. Our study clarifies the transcriptional signatures that underlie parathyroid tumors and offer a potential significant contribution in the study of pathogenesis of PC. © 2023 American Society for Bone and Mineral Research (ASBMR).

Clinical efficacy and inflammatory reaction of submental endoscopic thyroidectomy versus conventional thyroidectomy: A prospective randomized study.

OBJECTIVES: This prospective study aimed to explore the clinical efficacy and inflammatory reaction of submental endoscopic thyroidectomy versus conventional thyroidectomy. METHODS: We prospectively recruited 45 patients (total 90 patients) who met the eligibility criteria to undergo conventional open thyroidectomy or submental endoscopic thyroidectomy from January 2021 to July 2022 in the Shanghai Sixth People's Hospital Affiliated to Shanghai Jiao Tong University School of Medicine. These patients were evaluated using the following indices: number of lymph nodes dissected, complications, pain severity, inflammatory indicators, cosmetic satisfaction, and economic cost. All data were analyzed by the t-test or chi-squared test. RESULTS: Ninety patients were enrolled. The two groups did not significantly differ regarding baseline characteristics. All patients who underwent thyroidectomy had a similar trauma index and increased level of inflammation. There were no significant differences between the open thyroidectomy and submental endoscopic thyroidectomy groups in the total number of lymph nodes dissected, number of positive lymph nodes, drainage volume, and complications. The Vancouver scar score and cosmetic satisfaction score were significantly better in the submental endoscopic thyroidectomy group than the open thyroidectomy group. The submental endoscopic thyroidectomy group had a significantly lower pain scores on postoperative days 1 and 2, less downtime, and cheaper medical and esthetic costs than the open thyroidectomy group. CONCLUSION: Compared with conventional open thyroidectomy, submental endoscopic thyroidectomy did not increase the degree of trauma, had superior clinical efficacy, caused less pain, required a shorter downtime, achieved a better cosmetic effect, and was associated with lower healthcare costs.

Clinical characteristics and long-term outcomes for parapharyngeal metastases of well-differentiated thyroid cancer during 131 I therapy and follow-up.

OBJECTIVE: Parapharyngeal metastases (PPM) are rarely observed in patients with well-differentiated thyroid cancer (WDTC). Radioiodine (131 I) therapy has been the main treatment for metastatic and recurrent DTC after thyroidectomy. This study was performed to evaluate the clinicopathological features and long-term outcomes associated with survival of patients with PPM at the end of follow-up. DESIGN: In total, 14,984 consecutive patients with DTC who underwent 131 I therapy after total or near-total thyroidectomy from 2004 to 2021 were retrospectively reviewed. Therapeutic efficacy was evaluated using the Response Evaluation Criteria in Solid Tumours v1.1 and logistic regression analysis. The disease status was determined using dynamic risk stratification. Disease-specific survival (DSS) was assessed using the Kaplan-Meier method and a Cox proportional hazards model. PATIENTS: Seventy-five patients with PPM from WDTC were enroled in this study. Their median age at the initial diagnosis of PPM was 40.2 ± 14.1 years, and the patients comprised 32 men and 43 women (male:female ratio, 1.00:1.34). Of the 75 patients, 43 (57.33%) presented with combined distant metastases. Fifty-seven (76.00%) patients had 131 I avidity and 18 had non-131 I avidity. At the end of follow-up, 22 (29.33%) patients showed progressive disease. Sixteen of the 75 patients died; of the remaining 59 patients, 6 (8.00%) had an excellent response, 6 (8.00%) had an indeterminate response, 10 (13.33%) had an biochemical incomplete response, and 37 (49.33%) had a structural incomplete response. Multivariate analysis confirmed that age at initial PPM diagnosis, the maximal size of PPM, and 131 I avidity had significant effects on progressive disease of PPM lesions (p = .03, p= .02, and p < .01, respectively). The 5- and 10-year DSS rates were 98.49% and 62.10%, respectively. Age of ≥55 years at initial diagnosis of PPM and the presence of concomitant distant metastasis were independently associated with a poor prognosis (p = .03 and p = .04, respectively). CONCLUSION: The therapeutic effect for PPM was closely associated with 131 I avidity, age at initial PPM diagnosis, and maximal size of PPM at the end of follow-up. Age of ≥55 years at initial diagnosis of PPM and the presence of concomitant distant metastasis were independently associated with poor survival.

FAK-mediated phosphorylation at Y464 regulates p85ß nuclear translocation to promote tumorigenesis of ccRCC by repressing RB1 expression.

PI3K regulatory subunit p85s normally stabilizes and regulates catalytic subunit p110s in the cytoplasm. Recent studies show that p110-free p85s in the nucleus plays important roles in biological processes. However, the mechanisms by which p85s translocate into the nucleus remain elusive. Here, we describe the mechanism by which p85ß translocates into the nucleus to promote ccRCC tumorigenesis. Phosphorylation of p85ß at the Y464 by FAK facilitates its nuclear translocation in the kidney through enhancing the binding of p85ß to KPNA1. PIK3R2/p85ß is highly expressed in ccRCC samples and associated with overall survival of ccRCC patients. Nuclear but not cytoplasmic p85ß performs oncogenic functions by repressing RB1 expression and regulating the G1/S cell cycle transition. Nuclear p85ß represses RB1 expression by stabilizing histone methyltransferase EZH1/EZH2 proteins. Last, the FAK inhibitor defactinib significantly suppresses the tumor growth of ccRCC with high p85ß Y464 levels.

Genetic analysis and clinicopathologic features of locally advanced papillary thyroid cancers: a prospective observational study.

PURPOSE: Locally advanced papillary thyroid cancer (LAPTC) has poor prognosis. Large-scale genomic testing has revealed multiple oncogenic drivers which may be essential for understanding tumor progression. However, the accurate identification of high recurrence risk and poor prognosis in thyroid carcinoma remains unclear. The objective of this study was to analyze genetic profile and clinicopathologic features of locally advanced papillary thyroid cancers. METHODS: An observational cohort study was performed to identify molecular characteristics of LAPTC and a prognosis comparison of LAPTC with different genetic mutations. ThyroSeq v2 next-generation sequencing (57-gene panel) was performed on fresh tumor tissue. Then, the clinicopathological features between tumors with different genetic mutations were compared. Additionally, correlations of tumor recurrence and disease free survival with different genetic alterations were analyzed. RESULTS: This study showed that the main mutation is common BRAFV600E (66.2%, 43/65) in LAPTC, followed by the TERT promoter mutations (38.5%, 25/65). Synergetic mutations of BRAFV600E and TERT promoters (B&T) were identified in 26.2% LAPTC (17/65), which is associated with tall-cell variant, extrathyroidal invasion and advanced tumor stage (III/IV). The synergetic mutations of B&T are also significantly associated with higher risk of recurrence (hazard ratio [HR], 6.0; 95% confidence interval, CI 1.26-28.55, P = 0.02) and mortality (17.6%, 3/17). CONCLUSIONS: Synergetic mutations of B&T are common in LAPTC, which is associated with the aggressive clinicopathologic features and an increased risk of recurrence and mortality. This finding may help to predict aggressive behavior of LAPTC and to assist in clinical decision-making.

Genomic Profiling Reveals the Variant Landscape of Sporadic Parathyroid Adenomas in Chinese Population.

OBJECTIVE: To define somatic variants of parathyroid adenoma (PA) and to provide novel insights into the underlying molecular mechanism of sporadic PA. METHODS: Basic clinical characteristics and biochemical indices of 73 patients with PA were collected. Whole-exome sequencing was performed on matched tumor-constitutional DNA pairs to detect somatic alterations. Functional annotation was carried out by ingenuity pathway analysis afterward. The protein expression of the variant gene was confirmed by immunohistochemistry, and the relationship between genotype and phenotype was analyzed. RESULTS: Somatic variants were identified in 1549 genes, with an average of 69 variants per tumor (range, 13-2109; total, 9083). Several novel recurrent somatic variants were detected, such as KMT2D (15/73), MUC4 (14/73), POTEH (13/73), CD22 (12/73), HSPA2 (12/73), HCFC1 (11/73), MAGEA1 (11/73), and SLC4A3 (11/73), besides the previously reported PA-related genes, including MEN1 (11/73), CASR (6/73), MTOR (4/73), ASXL3 (3/73), FAT1 (3/73), ZFX (5/73), EZH1 (2/73), POT1 (2/73), and EZH2 (1/73). Among them, KMT2D might be the candidate driver gene of PA. Crucially, 5 patients carried somatic mutations in CDC73, showed an aggressive phenotype similar to that of parathyroid carcinoma (PC), and had a decreased expression of parafibromin. Pathway analysis of recurrent potential PA-associated driver variant genes revealed functional enrichments in the signaling pathway of Notch. CONCLUSION: Our study expanded the pathogenic variant spectrum of PA and indicated that KMT2D might be a novel candidate driver gene and be considered as a diagnostic biomarker for PA. Meanwhile, CDC73 mutations might be an early developmental event from PA to PC. The results provided insights into elucidating the pathogenesis of parathyroid tumorigenesis and a certain basis for clinical diagnosis and treatment.

The Prognostic Implication of the BRAF V600E Mutation in Papillary Thyroid Cancer in a Chinese Population.

Background: The BRAF V600E mutation is an important genetic event in papillary thyroid cancer (PTC). This study aimed to provide additional information regarding the association of the BRAF V600E mutation with PTC prognosis. Methods: A retrospective single-center study based on a Chinese population was performed to analyze the association of the BRAF V600E mutation with several clinicopathological features. Kaplan-Meier survival curves and Cox proportional hazards regression analysis were applied to implement the survival analysis. Results: The BRAF V600E mutation was present in 1102 (87.7%) of the 1257 patients and was significantly associated with older age, conventional subtype, multifocality, advanced TNM stage, and a reduced prevalence of Hashimoto's thyroiditis. The Kaplan-Meier survival curves demonstrated that the difference between the BRAF V600E-positive and BRAF V600E-negative groups was significant with a log-rank P-value of 0.048. The Cox proportional hazards regression analysis adjusted HR was 3.731 (95% CI, 1.457 to 9.554). We further demonstrated that larger tumor size (>1 cm), extrathyroidal extension (ETE), and lateral lymph node metastasis (LNM) were associated with a higher probability of PTC recurrence in patients harboring the BRAF V600E mutation. Conclusions: The BRAF V600E mutation remains an independent risk factor for PTC recurrence and may be useful for clinical decisions when it combines with some pathological factors.

Correction: MicroRNA-613 inhibits cell growth, migration and invasion of papillary thyroid carcinoma by regulating SphK2.

[This corrects the article DOI: 10.18632/oncotarget.9530.].

Tumor microenvironment remodeling modulates macrophage phenotype in breast cancer lymphangiogenesis.

Hyaluronan (HA) is dynamically remodeled in tumor microenvironment (TME) and is reported to be closely related to tumor lymphatic metastasis by inducing lymphangiogenesis. Macrophages are known to be involved in neo-lymphatic vessels formation. However, few studies have investigated the role of HA-mediated TME remodeling on macrophages-dependent lymphangiogenesis. We previously showed that HA could drive macrophages to acquire the M2 phenotype. In this study, we attempt to study the crosstalk between HA in TME and macrophages dependent lymphangiogenesis. First, we found that the abundant assembly of HA in breast cancer tissue was accompanied by increased infiltration of macrophages featured by expressing lymphatic endothelial markers. Then, to further identify the remodeling of HA in regulating macrophage phenotype, we used HA fragments which are usually enriched in TME for this purpose. Our results showed that the reconstructed HA could induce bone marrow-derived macrophages (BMDMs) to express markers of lymphatic endothelium and form tube-like structures, suggesting a novel function of HA from TME on macrophages-dependent lymphangiogenesis. Finally, we found that inhibition of the HA-TLR4 pathway could reduce the ability of BMDMs to exhibit lymphatic endothelial phenotype. Our results provide new insight into tumor microenvironment remodeling and macrophages in breast cancer lymphangiogenesis.

The Prognosis of Skip Metastasis in Papillary Thyroid Microcarcinoma Is Better Than That of Continuous Metastasis.

CONTEXT: A few papillary thyroid microcarcinomas (PTMCs) may have skip metastasis (SLNM), but the risk factors remain controversial and the prognosis is unclear. OBJECTIVES: To investigate the incidence, lymph node metastasis (LNM) patterns, risk factors, and prognosis of SLNM in PTMCs. METHODS: We reviewed the medical records of PTMC patients who underwent thyroid surgery in our institution. Analyses of risk factors were performed for SLNM. Recurrence-free survival (RFS) of SLNM, central lymph node metastasis (CLNM), and continuous metastasis (CLNM and lateral lymph node metastasis [CLNM + LLNM]) were compared after propensity score matching (PSM). RESULTS: SLNM was detected in 1.7% (50/3923) and frequently involved level III (66.7%). Compared with CLNM + LLNM, SLNM had more LNM at a single level (P < 0.01) and less LNM at 2 levels (P < 0.05). A tumor size of 0.5 to 1 cm (odds ratio [OR], 2.26; 95% CI, 1.27-4.00) and location in the upper pole (OR, 3.30; 95% CI, 2.02-5.40) were independent risk factors for SLNM. A total of 910 (23.2%) PTMCs with LNM were included in the prognostic analysis. At a median follow-up of 60 months, the RFS of SLNM did not differ from that of CLNM (P = 0.10) but was significantly higher than that of CLNM + LLNM (P < 0.01) after using PSM. CONCLUSIONS: When the tumor size is 0.5 to 1 cm or its location is in the upper pole, we must remain vigilant to SLNM in PTMC. Because its prognosis is comparable to that of only CLNM and better than that of CLNM + LLNM, less intensive treatment should be considered.

Single-Cell Transcriptomic Analysis of Ecosystems in Papillary Thyroid Carcinoma Progression.

Background: Despite extensive research, the papillary thyroid carcinoma (PTC) ecosystem is poorly characterized and, in particular, locoregional progression. Available evidence supports that single-cell transcriptome sequencing (Sc-RNA seq) can dissect tumor ecosystems. Methods: Tissue samples from one PTC patient, including matched primary tumor (Ca), lymph node (LN) metastasis, and paracancerous tissue (PCa), were subjected to Sc-RNA seq with 10×Genomics. Dual-label immunofluorescence and immunohistochemistry were used to confirm the existence of cell subtypes in a separate cohort. Results: 11,805 cell transcriptomes were profiled, cell landscapes of PTC were composed of malignant follicular epithelial cells (MFECs), CD8+ and CD4+ T cells, B cells, vascular endothelial cells, fibroblasts and cancer-associated fibroblasts (CAFs). Between Ca and LN ecosystems, the proportions of MFEC and interstitial cells were similar, less than 1/25(229/6,694, 361/3,895), while the proportion of normal follicular epithelial cells (NFECs) and interstitial cells was > 2 in PCa (455/171). NFECs in PCa formed a separate cluster, while MFECs in Ca and LN exhibited a profound transcriptional overlap, and the interstitial cells among these samples had an overall concordance in their identity and representation, albeit with some distinctions in terms of the cell percentage per subset. A fraction of the B cell subpopulation in Ca expressed inhibitory receptors, while their respective ligand genes were clearly transcribed in T cell and malignant epithelial cell clusters, while some CD8+ T cells in both Ca and LN produced high levels of inhibitory receptors whose respective ligands were overexpressed in some CD4+ T cells. Three CAF subtypes in Ca and LN were identified, which may be due to mutual transitions. Conclusions: Our data provide new insights into the PTC ecosystem and highlight the differences in ecosystems in PTC progression, which updates our understanding of PTC biology and will improve individualized patient treatment.

Preoperative neoadjuvant targeted therapy with apatinib for inoperable differentiated thyroid cancer: A case report.

RATIONALE: Though the majority of differentiated thyroid cancer (DTC) patients have a good prognosis after careful and standardized therapy, approximately 13% to 15% of DTC cases show surprisingly aggressive behavior and invasion of the surrounding structures, and a few progress to unresectable diseases. In this study, we report a case of an inoperable locally advanced DTC patient who underwent a curative operation after treatment of preoperative monotherapy of apatinib in a short time. PATIENT CONCERNS: A 64-year-old woman complained of dysphagia due to large cervical mass, which severely invaded the left esophagus at the junction of the neck and thorax. DIAGNOSES: The female patient was diagnosed with locally advanced papillary thyroid cancer (PTC) by cytopathology and it was difficult to perform a safe and complete removal. INTERVENTIONS: Apatinib (500 mg orally once a day) was initially used to treat this patient as a neoadjuvant therapy. OUTCOMES: Six weeks later, the tumor dramatically shrunk from 56 × 37 mm to 29 × 26 mm with well-controlled mild hypertension. After a 10-day interval of apatinib withdrawal, complete tumor excision was accomplished through cervical incision without esophageal fistula. Postoperative thyroid stimulating hormone suppression and radioiodine 131I ablation therapy were performed. At the 1-year follow-up evaluation, no tumor recurrence or metastasis was observed. LESSONS: Preoperative short term targeted treatment with apatinib for locally advanced inoperable DTC may become a promising neoadjuvant therapy that, can reduce the tumor size and decrease stage, thus making the complete and safe removal of the lesion feasible.

Clinical Characteristics of Primary Hyperparathyroidism: 15-Year Experience of 457 Patients in a Single Center in China.

Objective: Primary hyperparathyroidism (PHPT) is a common endocrine disorder of calcium metabolism. However, data concerning a large cohort of PHPT patients in the Chinese population are scarce. Thus, the objective of this study was to determine the general clinical signatures of 457 Chinese PHPT patients and explore the clinical characteristic differences between benign and malignant PHPT. Methods: A single-center retrospective study was designed. Medical records between preoperation and postoperative follow-up, were assessed and statistical analysis of the clinical data was performed. Results: Patients with PHPT aged 12-87 years, with a mean onset age of 56.16 ± 14.60 years, were included. Most patients (68.7%) in our center had symptomatic patterns described as bone pain (74.8%), urolithiasis (25.5%), fatigue (17.5%), and pathological fracture (13.1%), but an increasing tendency has been established in the proportion of patients with asymptomatic forms. Correlation analysis revealed that patients with higher serum levels of parathyroid hormone (PTH) and calcium presented higher serum levels of bone turnover markers (BTMs) and lower 25-hydroxy-vitamin D (25OHD) values (P<0.001). Gains in bone mineral density (BMD) at L1-4, the femoral neck and the total hip were observed 1-2 years after parathyroidectomy (9.6, 5.9, and 6.8%). Parathyroid carcinoma patients presented prominently higher serum PTH and calcium levels and BTMs and lower BMD at femoral neck and total hip than benign PHPT patients (P<0.05), while no significant differences in age, sex, and serum 25OHD concentration were observed between benign and malignant PHPT patients. Conclusions: PHPT should be paid attention to in the patients with bone pain. While, BMD and BTMs can differentiate parathyroid carcinoma from parathyroid adenoma and hyperplasia to some extent. In addition, anti-osteoporosis drugs could be used when necessary to avoid hip fractures in patients with parathyroid carcinoma.