Risk of second primary thyroid cancer in cancer survivors.

A risk factor for thyroid cancer (TC) may be a history of former cancer and cancer therapy. The precise risk of a second primary thyroid carcinoma has not yet been revealed. In this study, we evaluated standardized incidence ratios (SIRs) of second primary thyroid cancer (SPTC) with consideration of different conditions and further analyzed the clinicopathological characteristics and survival of these patients. The cohort was selected from the US Surveillance, Epidemiology, and End Results (SEER) Program between 1975 and 2019. The standardized incidence ratios, morbidity risk, clinicopathological features, and survival of second primary thyroid carcinoma were analyzed. Propensity score matching (PSM) was used to balance covariates. Kaplan-Meier method was performed to assess the survival outcomes. Overall, 7066 patients with SPTC and 83,113 patients with primary TC were identified. The SIR of TC in tumor patients was 1.51/10,000, statistically higher than the natural population (0.94/10,000, P < 0.05). The most significant tumors contributing to the increased SIRs of SPTC were acute lymphocytic leukemia (3.49/10,000), Hodgkin's lymphoma-nodal (3.29/10,000), salivary gland cancer (3.23/10,000), and kidney and renal pelvis cancer (3.05/10,000). The incidence of TC increased significantly in tumor patients who received radiotherapy/chemotherapy before age 35. The age at diagnosis of the SPTC was much older than the primary TC (64.01 vs. 49.55 years, p < 0.001). The SPTC had a higher percentage of histological grades 3/4 (23.14% vs. 15.19%, p < 0.001). Survival analyses demonstrated a worse prognosis for the SPTC group compared to the primary TC group. But after PSM, the survival outcomes of the two groups tended to be equivalent (P = 0.584). The SIRs of TC are higher in tumor patients. The most significant factors contributing to the increased risk of SPTC were some specific former tumors and acceptance of radiotherapy/ chemotherapy before age 35. There was no significant difference in survival between SPTC and primary TC.

The survival after thyroidectomy versus lobectomy in multifocal papillary thyroid microcarcinoma patients.

BACKGROUND: The extent of thyroid surgery for multifocal papillary thyroid microcarcinoma (PTMC) remains controversial. Studies on the optimal surgical approach for a multifocal PTMC are scarce. This study aimed to compare the effectiveness of thyroidectomy and lobectomy for the treatment of multifocal PTMC. METHODS: A population-based retrospective cohort of patients with multifocal PTMC was analyzed using the Surveillance, Epidemiology, and End Results (SEER) database between 2004 and 2017, and divided into two groups (thyroidectomy, lobectomy) based on the surgical approach. The clinicopathologic features and survival outcomes were compared between the two groups. Cox proportional hazards regression analysis to explore prognostic factors of survival. Propensity score matching (PSM) was used to balance covariates. RESULTS: Overall, a total of 9387 multifocal PTMC patients were included in the study. Among them, 8,107 (86.36%) patients received thyroidectomy, and 1280 (13.64%) patients underwent lobectomy. Compared to patients in the thyroidectomy group, patients in the lobectomy group were diagnosed with older age (50.47 years vs. 49.32 years, p = 0.003), a higher proportion of males (20.47% vs. 14.99%, p < 0.001), larger tumors (6.22 mm vs. 4.97 mm, p < 0.001), and more frequently underwent radiotherapy (35.40% vs. 10.16%, p < 0.001). Multivariate Cox regression analysis revealed that age was the only independent prognostic factor for thyroid cancer-specific survival (TCSS), and the determinants of overall survival (OS) were age and gender. Unadjusted survival analysis revealed no difference between the two treatment groups in TCSS (p = 0.598) and OS (p = 0.126). After 1:1 Propensity Score Matching (PSM), there was still no difference in TCSS (p = 0.368) or OS (p = 0.388). The stratified analysis revealed that for patients aged under or above 55, thyroidectomy was not associated with superior BCSS or OS (p > 0.05). CONCLUSIONS: Thyroidectomy was not associated with improved survival compared to thyroid lobectomy for patients with multifocal PTMC.

Comparative Efficacy and Acceptability of 12 Phosphorus-Lowering Drugs in Adults with Hyperphosphatemia and Chronic Kidney Disease: A Systematic Review and Network Meta-Analysis.

BACKGROUND: Hyperphosphatemia is associated with cardiovascular morbidity and mortality in adults with chronic kidney disease (CKD). Drug therapy has an irreplaceable role in the management of hyperphosphatemia. OBJECTIVES: We aimed to compare and rank phosphorus-lowering drugs, including phosphate binder and nonphosphate binder, in hyperphosphatemia adults with CKD. METHODS: We did a systematic review and frequentist random-effect network meta-analysis. We searched in PubMed, Cochrane Library, Web of Science, and Embase from inception to February 1, 2023, for randomized controlled trials of 12 phosphorus-lowering drugs in adults with hyperphosphatemia and CKD. Primary outcomes were efficacy (changes in serum phosphorus) and acceptability (treatment withdrawals due to any cause). We ranked each drug according to the value of surface under the cumulative ranking curve. We applied the Confidence in Network Meta-Analysis frameworks to rate the certainty of evidence. This study was registered with PROSPERO, number CRD42022322270. RESULTS: We identified 2,174 citations, and of these, we included 94 trials comprising 14,459 participants and comparing 13 drugs or placebo. In terms of efficacy, except for niacinamide, all drugs lowered the level of serum phosphorus compared with placebo, with mean difference ranging between -1.61 (95% credible interval [CrI], -2.60 to -0.62) mg/dL for magnesium carbonate and -0.85 (-1.66 to -0.05) mg/dL for bixalomer. Only ferric citrate with odds ratios 0.56 (95% CrI: 0.36-0.89) was significantly associated with fewer dropouts for acceptability. Of the 94 trials, 43 (46%), 7 (7%), and 44 (47%) trials were rated as high, moderate, and low risk of bias, respectively, the certainty of the evidence was moderate to very low. CONCLUSIONS: Magnesium carbonate has the best phosphorus-lowering effect in hyperphosphatemia adults with CKD; considering efficacy and acceptability, ferric citrate shows evidence to be the most appropriate drug with or without dialysis.

Efficacy and safety of tenapanor in hemodialysis patients with hyperphosphatemia: A systematic review and meta-analysis of randomized placebo-controlled trials.

BACKGROUND: The effects of tenapanor in reducing serum phosphorus in hemodialysis patients with hyperphosphatemia are uncertain and no relevant meta-analysis has been conducted. We performed a meta-analysis of randomized placebo-controlled trials to evaluate the efficacy and safety of tenapanor. METHODS: All randomized controlled trials of tenapanor were searched up to 1 August 2022. The primary endpoint was the change in serum phosphorus level from baseline with tenapanor and placebo. Data on drug-related adverse events (AEs), gastrointestinal AEs and diarrhea were collected to determine the safety of tenapanor. RESULTS: There were 533 patients throughout five trials that were eligible. Tenapanor significantly lowered blood phosphorus level by 1.79 mg/dl in the mean difference than the placebo. Diarrhea, gastrointestinal AEs, and drug-related AEs were more severe than placebo. CONCLUSIONS: This meta-analysis showed that although drug side effects were common, tenapanor significantly reduced serum phosphorus level in hemodialysis patients.

Insight into the Experimental Error in the Mapping of Electrical Properties with Electrostatic Force Microscopy.

Electrostatic force microscopy (EFM) is an emergent, powerful technique for nanoscale detection of electrical properties such as permittivity and charge distribution. However, the surface irregularity of samples has been unfortunately overlooked in most EFM studies. Herein, we use a polymer nanocomposite dielectric (PND) as the showcase and demonstrate that the morphological discontinuity at the matrix/particle interface can lead to major discrepancies or even incorrect results in the EFM study. First, the influence of the morphology, permittivity, and charge density of the interface is quantitively analyzed with a numerical method, proving that linking EFM results directly to sample properties is impracticable in the research based on classical interface configuration. Then, two methods are proposed to address the issue. The first method is numerical inversion, which takes heterogeneous materials and irregular surfaces into consideration. In this method, the influence of several experimental uncertainties, such as the radius of the nanoparticle and the permittivity of the matrix, is estimated. It is shown that the uncertainties related to geometry have a great impact on inversion and should be determined preferentially. In the second method, two standard configurations of the interface are recommended and compared for the interface study to bypass the morphological issue. This work provides quantitative results regarding the long-overlooked error in the EFM detection of the microregion with heterogeneous composition and surface irregularities and offers methods to tackle this issue.

Factors Influencing Delayed Treatment in Patients With Breast Cancer During COVID-19 Pandemic.

Background: The outbreak of coronavirus disease 2019 (COVID-19) has endangered human health and life. This pandemic has changed people's lifestyle and affected the regular delivery of standard cancer treatment. In the present study, we aimed to explore the influencing factors of delayed treatment in patients with breast cancer during COVID-19 pandemic. Methods: This study was a cross-sectional investigation, and the subjects were patients who were discharged from the department of burn and plastic surgery after February 2020. All participants completed this study's online questionnaire based on the WeChat and Wenjuanxing platforms. Levels of anxiety and depression were measured by the Hospital Anxiety and Depression Scale (HADS). Patients were divided into a delay group and non-delay group according to the occurrence of delayed treatment. Univariate analysis was performed by using the t test or chi-square test. A logistic regression model was employed to determine factors associated with delayed treatment. Results: The present study included a total of 397 patients with breast cancer, among whom delayed treatment occurred in 76 patients, accounting for 19.1%. Scores on both the anxiety subscale and depression subscale in delay group were significantly higher than those in non-delay group. Compared with non-delay group, we found that patients in delay group usually had a higher level of education (P = 0.020), worse self-feeling (P = 0.030), poor compliance of medical order (P = 0.042), and a higher prevalence of anxiety (P = 0.004) and depression (P = 0.012). Traffic inconvenience was also an important relevant factor for delayed treatment (P = 0.001). The prevalence of recurrence in delay group was higher than that in non-delay group (P = 0.018). By using logistic multivariate regression analysis, the results revealed that level of education and traffic inconvenience were independent factors influencing delayed treatment in patients with breast cancer during COVID-19 pandemic. Conclusion: The prevalence of delayed treatment in patients with breast cancer during COVID-19 pandemic is relatively high. Our findings reveal several influencing factors closely associated with delayed treatment, which is useful information that will be beneficial for patients to receive standardized therapy by taking targeted measures.

Preoperative prediction of central lymph node metastasis in cN0T1/T2 papillary thyroid carcinoma: A nomogram based on clinical and ultrasound characteristics.

BACKGROUND: Preoperative status of central lymph nodes is a key determinant of the initial surgical extent for papillary thyroid carcinoma (PTC). We aimed to develop and validate a nomogram based on preoperative clinical characteristics and ultrasound features to predict central lymph node status in patients with clinically lymph node-negative (cN0) T1/T2 PTC. METHODS: This retrospective study included 729 patients with cN0T1/T2 PTC who were treated between January 2015 and March 2020. Based on the ratio of 6:4, 431 patients who underwent surgeries relatively earlier comprised the training set to develop the nomogram, while the other 298 who underwent surgeries relatively later comprised validation set to validate the performance of nomogram. Least absolute shrinkage and selection operator (LASSO) regression and multivariate logistic regression were used to identify predictors of central lymph node metastasis (CLNM). These variables were used to construct a nomogram for predicting the risk of CLNM. The predictive performance, discriminative ability, calibration, and clinical utility of the nomogram model were evaluated in both sets. RESULTS: A total of 313 (42.9%) PTC patients were identified with CLNM. On multivariate logistic regression analyses, malegender, younger age, larger maximum diameter, multifocality, capsular invasion, infiltrative margins, intra-nodular vascularity, and aspect ratio >1 were independent risk factors for CLNM. Nomogram integrating these 8 factors showed excellent discrimination in the training [area under the curve (AUC): 0.788] and validation (AUC: 0.829) sets, and obtained well-fitted calibration curves. The cut-off value of this nomogram was 0.410 (∼245 points). Decision curve analysis confirmed the clinical utility of the nomogram. CONCLUSION: The CLNM-predicting nomogram can facilitate stratification of cN0T1/T2 PTC patients. Prophylactic central neck lymph node dissection can be considered for those with high nomogram scores.

Extensive analysis of the molecular biomarkers excision repair cross complementing 1, ribonucleotide reductase M1, ß-tubulin III, thymidylate synthetase, and topoisomerase IIα in breast cancer: Association with clinicopathological characteristics.

ABSTRACT: Excision repair cross complementing 1 (ERCC1), ribonucleotide reductase M1 (RRM1), ß-tubulin III (TUBB3), thymidylate synthetase (TYMS), and topoisomerase IIα (TOP2A) genes have been shown to be associated with the pathogenesis and prognosis of various types of carcinomas; however, their roles in breast cancer have not been fully validated. In this study, we evaluated the correlations among these biomarkers and the associations between their expression intensity and the clinicopathological characteristics to investigate whether the above genes are underlying biomarkers for patients with breast cancer.Ninety-seven tissue specimens collected from breast cancer patients. The expression levels of these biomarkers were measured by the multiplex branched DNA liquidchip (MBL) technology and clinicopathological characteristics were collected simultaneously.The expression levels of ERCC1, TUBB3, TYMS, and TOP2A were significantly associated with the characteristics of menopausal status, tumor size, lymph node metastasis, hormone receptor status, triple-negative status, Ki-67 index, and epidermal growth factor receptor. The expression intensity of ERCC1 negatively associated with that of TUBB3 and TYMS, and positively associated with that of RRM1. The expression intensity of TOP2A positively associated with that of TYMS. Hierarchical clustering analysis and difference test indicated that breast cancer with higher levels of TUBB3, TYMS, and TOP2A, as well as lower levels of ERCC1 and RRM1 tended to have higher histological grade and Ki-67 index.Our studies showed that ERCC1, TYMS, TUBB3, and TOP2A may be potential biomarkers for prognosis and individualized chemotherapy guidance, while there may be interactions between ERCC1 and RRM1, or TUBB3, or TYMS, as well as between TOP2A and TYMS in pathogenesis and development of breast cancer.

Individualized chemotherapy guided by the expression of ERCC1, RRM1, TUBB3, TYMS and TOP2A genes versus classic chemotherapy in the treatment of breast cancer: A comparative effectiveness study.

ERCC1, RRM1, TUBB3, TYMS and TOP2A genes have been shown to be associated with drug resistance in various types of tumors; however, their roles in breast cancer chemotherapy have not been fully validated. In the present study, 140 well-matched patients with breast cancer, comprising 70 patients receiving individualized chemotherapy and 70 receiving classic chemotherapy, were analyzed. In the individualized chemotherapy group, the mRNA expression levels of ERCC1, RRM1, TUBB3, TYMS and TOP2A in breast cancer tissues were measured using multiplex branched DNA liquidchip technology prior to chemotherapy; an individualized chemotherapy regimen was developed for each patient according to the results. As a control, patients in the classic chemotherapy group received a docetaxel + epirubicin + cyclophosphamide regimen. Survival analyses were performed using the Kaplan-Meier method. The prognostic factors for disease-free survival (DFS) and overall survival (OS) in the patients were identified via Cox's proportional hazards regression model. Adverse reactions were evaluated according to the National Cancer Institute Common Toxicity Criteria 4. Compared with the classic chemotherapy group, the DFS and OS of the individualized chemotherapy group were significantly longer (DFS, 77.4 vs. 67.1 months, P=0.039; OS, 81.4 vs. 75.4 months, P=0.031), and the incidence of grade 2 or 3 palpitations and chest tightness was lower (12.9 vs. 27.1%, P=0.035). The chemotherapy strategy guided by genetic detection was an independent protection factor for DFS [hazard ratio (HR)=0.389, 95% confidence interval (CI): 0.153, 0.989, P=0.047], but not an independent protection factor for OS (HR=0.340, 95% CI: 0.107, 1.078, P=0.067). The results indicate that the combined detection of ERCC1, RRM1, TUBB3, TYMS and TOP2A gene expression and use of the results to guide individualized chemotherapy can improve treatment efficacy and reduce unnecessary toxicity.