Resonance of fatty acid metabolism and immune infiltration in anti-PD-1 monotherapy for breast cancer.

The interaction between tumor fatty acid metabolism and immune microenvironment is a novel topic in oncology research, and the relationship of lipid-derived factors with immune editing in tumor is unclear. The breast cancer samples from the TCGA database were used as the training set, and samples from GSE42568 were employed as the validation set for constructing a model to identify a signature associated with fatty acid metabolism through Lasso Cox regression. And the changes in immune related signatures and risk score before and after anti-PD-1 monotherapy were caught by the differential analysis in GSE225078. A 14-gene prognostic risk scoring model identifying by fatty acid metabolism relevant signature was conducted, and the high risk group had shorter overall survival and progression free survival than low risk group. Many metabolism-related pathways were enriched in the high risk group, and many immune-related pathways were enriched in low risk group. The crucial differentially expressed genes between the high/low risk groups, CYP4F8 and CD52, were found to be strongly associated with SUCLA2 and ACOT4 of 14-gene model, and strongly related to immune infiltration. Immune related signatures, fatty acid metabolism-risk score and the expression level of ALDH1A1 (in 14-gene-model) changed after anti-PD-1 monotherapy. And the mice model results also showed anti-PD-1 mAb could significantly reduce the expression level of ALDH1A1 (p < 0.01). These results brought up the crosstalk between immune components and fatty acid metabolism in breast cancer microenvironment, which provided a new possibility of targeting fatty acid metabolism for combination therapy in breast cancer immunotherapy.

Circ_0053943 complexed with IGF2BP3 drives uveal melanoma progression via regulating N6-methyladenosine modification of Epidermal growth factor receptor.

Numerous studies have characterized the critical role of circular RNAs (circRNAs) as regulatory factors in the progression of multiple cancers. However, the biological functions of circRNAs and their underlying molecular mechanisms in the progression of uveal melanoma (UM) remain enigmatic. In this study, we identified a novel circRNA, circ_0053943, through re-analysis of UM microarray data and quantitative RT-PCR. Circ_0053943 was found to be upregulated in UM and to promote the proliferation and metastatic ability of UM cells in both in vitro and in vivo settings. Mechanistically, circ_0053943 was observed to bind to the KH1 and KH2 domains of insulin-like growth factor 2 mRNA-binding protein 3 (IGF2BP3), thereby enhancing the function of IGF2BP3 by stabilizing its target mRNA. RNA sequencing assays identified epidermal growth factor receptor (EGFR) as a target gene of circ_0053943 and IGF2BP3 at the transcriptional level. Rescue assays demonstrated that circ_0053943 exerts its biological function by stabilizing EGFR mRNA and regulating the downstream mitogen-activated protein kinase/extracellular signal-regulated kinase (MAPK/ERK) signaling pathway. Collectively, circ_0053943 may promote UM progression by stabilizing EGFR mRNA and activating the MAPK/ERK signaling pathway through the formation of a circ_0053943/IGF2BP3/EGFR RNA-protein ternary complex, thus providing a potential biomarker and therapeutic target for UM.

Weak acid-initiated slow release of Dexamethasone from hydrogel to treat orbital inflammation.

Rationale: Orbital inflammation is a prevalent and prolonged ocular disease that poses a significant challenge to clinicians. Glucocorticoid Dexamethasone sodium phosphate (Dex) has demonstrated efficacy in the clinical treatment of nonspecific orbital inflammation. However, frequent administration is required due to the short half-life of Dex, which may lead to drug waste and adverse side effects. Methods: In this study, we co-assembled Dex with a weak acid responsive hydrogelator Py-Phe-Phe-Lys-Lys-OH (K) to obtain a novel supramolecular hydrogel Dex/K that could release Dex in a slow manner to treat orbital inflammation. The therapeutic effect of Gel Dex/K on orbital inflammation was verified by in vitro and in vivo experiments. Results: In vitro experiments indicated that co-assembly of Dex with K significantly increased mechanic strength of the hydrogel, enabling a continuous release of 40% of total Dex within 7 days. In vivo experiments further demonstrated that sustained release of Dex from Gel Dex/K could effectively alleviate the infiltration of inflammatory cells and the release of inflammatory factors in the orbit of mice, improving symptoms such as increased intraocular pressure and proptosis. Additionally, Gel Dex/K mitigated the degree of tissue fibrosis and fatty infiltration by reducing the development of local inflammation in the orbit. Conclusions: Our research results indicate that Gel Dex/K could more efficiently achieve responsive drug release in orbit, providing an innovative method for treating orbital inflammation.

Prognostic values of Annexins and validation of the influence on cell proliferation, migration, and invasion in uveal melanoma.

OBJECTIVES: Uveal melanoma (UVM), the leading type of intraocular malignant tumor in adults, has an aggressive course with poor prognoses, high mortality, and lacking effective therapeutic targets and prognostic markers. Annexins are well known as dysregulated and correlated with aggressiveness and prognosis of various cancers. However, little is known about the expression pattern of Annexins in UVM and their prognostic value. This study aimed to investigate and verify the role of Annexins in the pathogenesis of metastatic UVM. METHODS: The mRNA expression of Annexins in UVM was analyzed from The Cancer Genome Atlas (TCGA) database and validated in three independent datasets (GSE22138, GSE27831, and GSE156877). The bioinformatics analysis and experimental verification of ANXA2 expression in UVM were performed to evaluate its influence on clinical prognosis, cell proliferation, migration, and invasion. RESULTS: Prognostic analysis suggested that high ANXA2/4 expression levels were significantly correlated with worse overall survival (OS), progress-free interval (PFI), and metastasis-free survival (MFS) prognoses. Meanwhile, the prognostic model (ANXA2/4) was built using the PFI-based LASSO analysis in TCGA-UVM and validated in GSE22138 and GSE27831. Multivariate Cox regression analyses indicated that the ANXA2/4 model is an independent prognostic factor associated with UVM. The expression analysis confirmed that ANXA2 was upregulated in metastatic patients. Then, ANXA2 mRNA was confirmed positive and expressed higher in four human UVM cell lines compared with ARPE19 cells, especially in two highly invasive metastatic types (C918 and MUM2B). Moreover, silencing ANXA2 blocked cell proliferation, migration, and invasion abilities of C918 and MUM2B while upregulating ANXA2 enhanced these cell functions remarkably in vitro, suggesting that ANXA2 had a positive effect on malignant biological properties of UVM cells. In addition, flow cytometry analysis showed that the knockdown of ANXA2 had a higher apoptotic rate than the control groups in C918 and MUM2B cells. ANXA2 overexpression had a lower apoptotic rate than those in the control group in OCM-1. In addition, ANXA2 expression had significant correlations with the tumor microenvironment and multiple tumor-infiltrating immune cells. CONCLUSIONS: ANXA2 is a novel potential prognostic biomarker for the metastatic diagnosis of UVM.

Association of different digital media experiences with paediatric dry eye in China: a population-based study.

OBJECTIVE: To investigate the ocular surface effects of different digital media experiences in Chinese elementary school students. DESIGN: Population-based cross-sectional study was used. SETTING: 14 randomly selected primary schools in Yuhuatai District, Nanjing, China PARTICIPANTS: 2,694 students between 7 and 8-year-old. OUTCOME MEASURES: Prevalence of and risk factors for different types of dry eye disease，and different digital media experience with different ocular signs. RESULTS: The prevalence of 'symptomatic DED' was 8.7% (95% CI 7.6% to 9.8%) and 'definite DED' prevalence rate was 5.5% (95% CI 4.7% to 6.4%). In multivariable logistic regression model, allergic conjunctivitis (OR=4.33, 95% CI (3.01 to 6.23), p<0.001), more than 1 hour per day on outdoor activity (OR=0.69, 95% CI (0.49 to 0.99), p=0.043), smartphone (OR=2.73, 95% CI (1.51 to 4.91), p=0.001), tablet (OR=2.09, 95% CI (1.07 to 4.07), p=0.030) and homework (OR=1.86, 95% CI (1.22 to 2.83), p=0.004) were independently associated with 'definite DED', while allergic conjunctivitis (OR=5.58, 95% CI (4.12 to 7.55), p<0.001), more than 1 hour per day on outdoor activity (OR=0.72, 95% CI (0.53 to 0.97), p=0.028), smartphone (OR=2.60, 95% CI (1.55 to 4.35), p<0.001), tablet (OR=1.84, 95% CI (1.02 to 3.34), p=0.044) and homework (OR=2.57, 95% CI (1.84 to 3.60), p<0.001) were independently associated with 'symptomatic DED'. CONCLUSIONS: Using smartphones or tablets for an average of more than 1 hour per day through the course of a year is independently associated with paediatric DED.

Corneal endothelial cell density and its correlation with birth weight, anthropometric parameters, and ocular biometric parameters in Chinese school children.

BACKGROUND: To describe the distribution of corneal endothelial cell density (ECD), and to explore its correlation with birth weight (BW), anthropometric parameters, and ocular biometric parameters in Chinese school children. METHODS: In the population-based cross-sectional Nanjing Eye Study, children were measured for anthropometric information, for ECD by the noncontact specular microscope and for ocular biometric parameters by the optic low-coherent reflectometer. Data from right eyes were analyzed to illustrate the distribution of ECD and for determining correlated factors with ECD using univariate and multiple linear regression analysis. Comparisons among three different BW groups were performed using a one-way ANOVA analysis followed by the Bonferroni correction for pairwise comparisons. RESULTS: Of 1171 children, the mean (± standard deviation) ECD was 2875.34 ± 195.00 cells/mm2. In the Multiple Linear Regression analysis, BW, gender and central corneal thickness were significantly associated with ECD. The ECD increased by 36.16 cells/mm2 with BW increasing by 1 kg (P = 0.001) and increased by 0.44 cells/mm2 for every additional 1 mm in central corneal thickness (P = 0.01). The ECD of girls was 54.41 cells/mm2 higher than boys (P < 0.001). Children born with low BW presented significantly lower ECD than those born with normal BW (P < 0.05) and high BW (P < 0.05). Age and axial length were not significantly associated with ECD (P = 0.06 and P = 0.21, respectively). CONCLUSIONS: In Chinese school children aged 82 to 94 months, the ECD is positively correlated with BW and central corneal thickness, in which BW is a newly identified associated factor. It is like that gender plays an important role in ECD distribution while girls have relatively greater ECD than boys.

Analysis of Genetic Alterations in Ocular Adnexal Mucosa-Associated Lymphoid Tissue Lymphoma With Whole-Exome Sequencing.

Next-generation sequencing studies on ocular adnexal marginal zone lymphoma of mucosa-associated lymphoid tissue (OAML) have to date revealed several targets of genetic aberrations. However, most of our current understanding of the pathogenesis and prognosis of OAML is primarily based on studies conducted in populations from Europe and the US. Furthermore, the majority were based on formalin-fixed paraffin-embedded (FFPE) tissue, which generally has poor integrity and creates many sequencing artifacts. To better investigate the coding genome landscapes of OAML, especially in the Chinese population, we performed whole-exome sequencing of 21 OAML cases with fresh frozen tumor tissue and matched peripheral blood samples. IGLL5, as a novel recurrently mutated gene, was found in 24% (5/21) of patients, with a higher relapse rate (P=0.032). In addition, mutations of MSH6, DIS3, FAT1, and TMEM127 were found in 10% of cases. These novel somatic mutations indicate the existence of additional/alternative lymphomagenesis pathways in OAML. Moreover, the difference between our and previous studies suggests genetic heterogeneity of OAML between Asian and Western individuals.

A Composite of Two Dimensional GeSe2 /Nitrogen-Doped Reduced Graphene Oxide for Enhanced Capacitive Lithium-Ion Storage.

A composite of two-dimensional (2D) GeSe2 nanosheets dispersed on N-doped reduced graphene oxide (GeSe2 /N-rGO) is fabricated via a simple hydrothermal method combined with post-selenization process. The high electronic conductivity and the substantial void spaces of the wrinkled N-rGO can improve the electrical conductivity of the active material and accommodate the volume evolution of GeSe2 nanosheets during the (de)lithiation processes, while GeSe2 nanosheets can reduce ion diffusion length effectively. Meanwhile, the unique layered structure is beneficial to the contact of the active material and electrolyte, and the reversibility of conversion reaction has also been improved. Furthermore, kinetics analysis reveals a pseudocapacitance-dominated Li+ -storage mechanism at high rates. In-situ X-ray diffraction analysis discloses that the conversion reaction has played a certain part in Li+ -storage. Thus, the GeSe2 /N-rGO composite delivers excellent rate capability and good long-term stability with a high reversible capacity of 711.0 mA h g-1 after 2000 cycles at 1 A g-1 .

Inhibition of MAC30 exerts antitumor effects in nasopharyngeal carcinoma via affecting the Akt/GSK-3ß/ß-catenin pathway.

Meningioma-associated protein 30 (MAC30) is a vital modulator of malignant transformation in numerous cancers. Yet, the involvement of MAC30 in nasopharyngeal carcinoma (NPC) is undetermined. This study was devoted to the study of the function of MAC30 in NPC, along with the molecular mechanism of its involvement in disease progression. This study showed an elevated level of MAC30 in NPC tissues and cell lines. MAC30 silencing impeded the proliferation, colony formation, and invasion of NPC cells, while MAC30 upregulation had the opposite effects. MAC30 regulated the Wnt/ß-catenin pathway via affecting the protein kinase B (Akt)/glycogen synthase kinase-3ß axis. Akt inhibition markedly abrogated the MAC30-mediated activation of the Wnt/ß-catenin pathway. Restoration of ß-catenin reversed MAC30 silencing-induced tumor-inhibiting effects. Knockdown of MAC30 weakened the tumorigenic potential of NPC cells in vivo. This study elucidates the fact that inhibition of MAC30 produces antitumor effects in NPC via affecting the Akt/Wnt/ß-catenin pathway.

Longitudinal change in components of astigmatism and its association with axial length-corneal radius ratio in Chinese young children: the Nanjing Eye Study.

PURPOSE: To assess the longitudinal change in components of astigmatism from age 4 to 7 years and its association with axial length-corneal radius ratio (AL/CR). METHODS: Children born between September 2011 and August 2012 in Yuhuatai District of Nanjing were invited to participate in the Nanjing Eye Study for a comprehensive eye examination annually since 2015. The data presented in this paper were obtained in 2016, 2017, and 2019. At each study encounter, noncycloplegic autorefraction and ocular biometric parameters were measured. Changes of total astigmatism (TA), corneal astigmatism (CA), anterior corneal astigmatism (ACA), residual astigmatism (RA), and internal astigmatism (IA) were analyzed in clinical notation (Cyl) and vector notation (J0, J45). RESULTS: Nine hundred fifty-four children (mean ± standard deviation of baseline age: 4.63 ± 0.29 years, 53.7% boys) had complete data and were included in this study. Mean slopes of longitudinal changes in Cyl notation were significantly negative for TA, CA, and ACA, but positive for IA. TA, CA, ACA, and RA of J0 notation had a shift toward increasing with-the-rule (WTR) astigmatism and/or decreasing against-the-rule (ATR) astigmatism. TA of J45 notation showed an increase in astigmatism at axis 135° and/or a decrease in astigmatism at axis 45°, while CA and ACA of J45 notation showed an opposite change. Longitudinal changes in ACA and IA were negatively correlated in J0 notation, but not in J45 notation. Based on compensation factor (CF, defined as the minus ratio of IA and ACA), the compensation proportions for J0 in varying degrees (CF: 0.1-2) in 2016, 2017, and 2019 were 91.3%, 93.5%, and 90.0%, respectively, while these for J45 were 74.9%, 76.5%, and 34.6%, respectively. Higher AL/CR increase was associated with less decrease or more increase in CA and ACA of Cyl notation, and a shift toward increasing WTR and/or decreasing ATR in these of J0 notation. CONCLUSIONS: The compensatory role of IA was persistent and prominent from 4 to 7 years old for J0 notation in Chinese young children. The progression of AL/CR was correlated with astigmatism originated from the cornea.

Expanding the phenotypic spectrum of mutations in LRP2: a novel candidate gene of non-syndromic familial comitant strabismus.

BACKGROUND: Comitant strabismus (CS) is a heterogeneous disorder that is a major contributing factor to unilateral childhood-onset visual impairment. Studies have confirmed that genetic factors play an important role in the development of CS. The aim of this study was to identify the genetic cause of non-syndromic familial CS. METHODS: Fourteen unrelated CS families were recruited for the study. Twelve affected and 2 unaffected individuals from a large four-generation family (CS08) were selected to perform whole genome-wide linkage analysis. Parallel whole-exome sequencing (WES) was conducted in the same family (9 patients and 1 unaffected member) and 31 additional CS cases from 13 other unrelated families. Sanger sequencing was used to determine whether any of the remaining variants co-segregated with the disease phenotype in the corresponding family. RESULTS: Based on linkage analysis, CS in family CS08 mapped to a novel region of 34.17 centimorgan (cM) on chromosome 2q22.3-2q32.1 between markers D2S151 and D2S364, with a maximum log odds (LOD) score of 3.54 (theta = 0) at D2S142. Parallel WES identified a heterozygous variant, LRP2 c.335 A > G (p.Q112R), located in such a linkage interval that completely co-segregated with the disease in the family. Furthermore, another novel heterozygous variant (c.7274A > G, p.D2425G) in LRP2 that co-segregated was detected in 2 additional affected individuals from another unrelated family by WES. Both variants are predicted to be damaging by PolyPhen-2, SIFT and MutationTaster, and were absent in 100 ethnically matched normal controls. CONCLUSION: LRP2 is a novel candidate genetic cause of non-syndromic familial CS.

Variants identified by next-generation sequencing cause endoplasmic reticulum stress in Rhodopsin-associated retinitis pigmentosa.

BACKGROUND: Rhodopsin (RHO) is the most well-known genetic cause of autosomal dominant retinitis pigmentosa (adRP). This study aimed to investigate the genetic cause of a large Chinese adRP family and assess the pathogenicity of the detected RHO mutant. METHODS: Routine ocular examinations were conducted on all participants. Next-generation sequencing with targeted capture was performed to screen mutations in 179 genes associated with hereditary retinal diseases and 10 candidate genes. Variants detected by NGS were validated by Sanger sequencing and evaluated for pathogenicity. Fragments of mutant and wild-type RHO were cloned into the pEGFP-N1 vector and were transfected into different cell lines to observe the cellular localization of the Rhodopsin-GFP fusion protein and evaluate the expression of endoplasmic reticulum (ER) stress markers. RT-PCR analysis was used to detect transfected the splicing of X box-binding protein 1 (XBP1) mRNA, which is a critical factor affecting ER stress. RESULTS: Genetic analysis identified a heterozygous missense variant, RHO, c.284 T > C (p.L95P) in this adRP family. Another RHO variant (p.P53R) that we reported previously was also included in further functional assessment. Both misfolded mutant proteins accumulated in the ER in a manner similar to that noted for the classic mutant P23H. Spliced XBP1 was observed in cells transfected with mutants, indicating an increase in ER stress. CONCLUSIONS: Although the p.L95P variant is not a novel change, it was the first variant to be functionally evaluated and reported in Chinese RP patients. The results in our study provide significant evidence to classify the p.L95P mutation as a class II mutation.

Prevalence of strabismus among preschool children in eastern China and comparison at a 5-year interval: a population-based cross-sectional study.

OBJECTIVE: To update data on strabismus and evaluate the changes in prevalence and patterns among preschoolers in eastern China over a period of 5 years. DESIGN: Nanjing Eye Study, a longitudinal population-based study. SETTING: Recruitment and testing in kindergartens in Yuhuatai District, Nanjing. PARTICIPANTS: 2300 eligible children. MAIN OUTCOME MEASURES: Comprehensive ocular examinations were conducted in 1986 children aged 48-<60 months in Nanjing Eye Study (NES, 2016-2017), including visual acuity, ocular alignment, refractive error and ocular structures evaluation. The prevalence rate and pattern of strabismus were calculated and compared with those from the Nanjing Pediatric Vision Project (NPVP, 2011-2012) in children of the same age, of the same area and using the same diagnostic criteria. RESULTS: The overall prevalence rate of strabismus in NES was 5.56% (95% CI 4.54% to 6.57%), which was not significantly different from that in NPVP (4.99%, 95% CI 4.13% to 5.84%, p=0.40). The prevalence of subtypes of strabismus underwent significant changes, with significant increase in intermittent exotropia (IXT) in NES (2.78% vs 4.69%, p=0.001) and significant decrease in constant exotropia (1.17% vs 0.15%, p<0.001). Significant change in pattern was observed in IXT, where the proportion of the convergence insufficiency type (2.90% vs 27.17%) increased and exceeded the divergence excess type (20.29% vs 11.96%) to be the second common type (p<0.001). CONCLUSION: The prevalence of strabismus appeared stable in children aged 48-<60 months in eastern China at a 5-year interval. The prevalence of IXT increased significantly, and the convergence insufficiency type became more prevalent in patients with IXT. Timely detection and intervention of IXT are important among preschoolers.

Poor prognosis of male triple-positive breast Cancer patients: a propensity score matched SEER analysis and molecular portraits.

BACKGROUND: The purpose of this study was to explore clinicalpathology features, molecular features and outcome of male breast cancer patients who expressed ER, PR as well as HER-2, namely triple-positive male breast cancer (TP-MBC), and compared them with triple-positive female breast cancer patients (TP-FBC). METHODS: TP-MBC and TP-FBC from 2010 to 2017 were selected from the Surveillance, Epidemiology, and End Results database (SEER). Kaplan-Meier plotter and multivariable Cox regression model were applied to analyse the difference between TP-MBC and TP-FBC on cancer-specific survival (CSS) and overall survival (OS). Propensity score matched (PSM) analysis was used to ensure well-balanced characteristics. 7 cases TP-MBC and 174 cases TP-FBC patients with the genomic and clinical information were identified from the cohort of The Cancer Genome Atlas (TCGA) and the Memorial Sloan Kettering (MSK). RESULT: 336 TP-MBC and 33,339 TP-FBC patients were taken into the study. The percentages of TP-MBC in MBC patients were higher than the rates of TP-FBC in FBC patients from 2010 to 2017 except 2012. Compared with TP-FBC, more TP-MBC were staged III (17.9% vs. 13.5%) or stage IV (11.0% vs. 6.9%). TP-MBC were more frequently to be older than 65-years-old (47.0% vs. 29.3%), Balck (15.2% vs. 10.8%), ductal carcinoma (91.7% vs. 84.4%) and metastases to lung (4.5% vs. 2.1%) or bone (8.6% vs. 4.7%). TP-MBC had worse OS and CSS than TP-FBC in all stages (P < 0.001). In multivariable prediction model of TPBC, male patients had a higher risk than female. Lastly, the worse OS (P < 0.001) and CSS (P = 0.013) were seen in the 1:3 PSM analysis between TP-MBC and TP-FBC. Genomic analysis revealed that TP-MBCs have some notable rare mutations, like ERBB2, ERBB3, RB1, CDK12, FGFR2, IDH1, AGO2, GATA3, and some of them are not discovered in TP-FBC. CONCLUSION: TP-MBC had a worse survival than TP-FBC, and there were different genomic features between two groups. Current knowledge and treatment to TP-MBC maybe inadequate and remain to be explored.

Nomogram for predicting preoperative regional lymph nodes metastasis in patients with metaplastic breast cancer: a SEER population-based study.

BACKGROUND: Metaplastic breast cancer (MBC) is a rare subtype of breast cancer, and generally associated with poor outcomes. Lymph nodes metastasis (LNM) is confirmed as a critical independent prognostic factor and determine the optimal treatment strategies in MBC patients. We aimed to develop and validate a nomogram to predict the possibility of preoperative regional LNM in MBC patients. METHODS: MBC patients diagnosed between 1990 and 2016 in the Surveillance, Epidemiology, and End Results (SEER) database were included and stochastically divided into a training set and validation set at a ratio of 7:3. The risk variables of regional LNM in the training set were determined by univariate and multivariate logistic regression analyses. And then we integrated those risk factors to construct the nomogram. The prediction nomogram was further verified in the verification set. The discrimination, calibration and clinical utility of the nomogram were evaluated by the area under the receiver operating characteristic (ROC) curve (AUC), calibration plots and decision curve analysis (DCA), respectively. RESULTS: A total of 2205 female MBC patients were included in the study. Among the 2205 patients, 24.8% (546/2205) had positive regional lymph nodes. The nomogram for predicting the risk of regional LNM contained predictors of grade, estrogen receptor (ER) status and tumor size, with AUC of 0.683 (95% confidence interval (CI): 0.653-0.713) and 0.667 (95% CI: 0.621-0.712) in the training and validation sets, respectively. Calibration plots showed perfect agreement between actual and predicted regional LNM risks. At the same time, DCA of the nomogram demonstrated good clinical utilities. CONCLUSIONS: The nomogram established in this study showed excellent prediction ability, and could be used to preoperatively estimate the regional LNM risk in MBC.

The role of adjuvant radiotherapy in patients with malignant phyllodes tumor of the breast: a propensity-score matching analysis.

BACKGROUND AND OBJECTIVES: Malignant phyllodes tumor of the breast (MPTB) is a kind of rare tumor. Our objective was to investigate the role of adjuvant radiotherapy (RT) in MPTB patients. METHODS: MPTB patients were identified in the Surveillance, Epidemiology and End Results (SEER) database. Kaplan-Meier curves and multivariable Cox proportional hazards analyses were conducted to determine the effect of adjuvant RT on MPTB patients. Propensity-score matching (PSM) method was used to balance the clinicopathological characteristics. RESULTS: A total of 1353 MPTB patients were included in our study and the median follow-up time was 99 months (range: 0-331 months). 16.7% (226) MPTB patients received adjuvant RT, of which 49.1% (111) received mastectomy and 50.9% (115) underwent breast conservation surgery (BCS). Patients receiving adjuvant RT were more likely to be white, with better differentiation and larger tumors (p < 0.05). Multivariate analysis showed that poorer tumor differentiation grade, larger tumor size, and lymph node metastasis were associated with reduced survival while BCS was a protective factor of disease-specific survival (DSS) (HR 0.297; 95% CI 0.184-0.480) and overall survival (OS) (HR 0.445; 95% CI 0.321-0.616). After PSM, survival curves showed patients did not achieve an improved OS or DSS from adjuvant RT (p > 0.05). In subgroup analysis, no subgroup benefited from adjuvant RT. Exploratory analysis showed a survival benefit trend from adjuvant RT in patients with tumor larger than 50 mm and undergoing BCS. CONCLUSIONS: Among MPTB patients, adjuvant RT did not improve OS or DSS. In patients with tumor larger than 50 mm and receiving BCS, a survival benefit trend from adjuvant RT existed.

A nomogram for predicting survival in patients with de novo metastatic breast cancer: a population-based study.

BACKGROUND: 5-10% of patients are diagnosed with metastatic breast cancer (MBC) at the initial diagnosis. This study aimed to develop a nomogram to predict the overall survival (OS) of these patients. METHODS: de novo MBC patients diagnosed in 2010-2016 were identified from the Surveillance, Epidemiology, and End Results (SEER) database. They were randomly divided into a training and a validation cohort with a ratio of 2:1. The best subsets of covariates were identified to develop a nomogram predicting OS based on the smallest Akaike Information Criterion (AIC) value in the multivariate Cox models. The discrimination and calibration of the nomogram were evaluated using the Concordance index, the area under the time-dependent receiver operating characteristic curve (AUC) and calibration curves. RESULTS: In this study, we included 7986 patients with de novo MBC. The median follow-up time was 36 months (range: 0-83 months). Five thousand three-hundred twenty four patients were allocated into the training cohort while 2662 were allocated into the validation cohort. In the training cohort, age at diagnosis, race, marital status, differentiation grade, subtype, T stage, bone metastasis, brain metastasis, liver metastasis, lung metastasis, surgery and chemotherapy were selected to create the nomogram estimating the 1-, 3- and 5- year OS based on the smallest AIC value in the multivariate Cox models. The nomogram achieved a Concordance index of 0.723 (95% CI, 0.713-0.733) in the training cohort and 0.719 (95% CI, 0.705-0.734) in the validation cohort. AUC values of the nomogram indicated good specificity and sensitivity in the training and validation cohort. Calibration curves showed a favorable consistency between the predicted and actual survival probabilities. CONCLUSION: The developed nomogram reliably predicted OS in patients with de novo MBC and presented a favorable discrimination ability. While further validation is needed, this may be a useful tool in clinical practice.

Comparative Analysis of Outcomes and Clinicopathological Characteristics of Synchronous and Metachronous Contralateral Breast Cancer: A Study of the SEER Database.

PURPOSE: Numerous previous studies have reported inconsistent results about the differences between synchronous contralateral breast cancer (sCBC) and metachronous contralateral breast cancer (mCBC). This study aimed to compare the clinical characteristics and outcomes between sCBC and mCBC and determine predictive factors for the survival of sCBC and mCBC patients. METHODS: Using the Surveillance, Epidemiology, and End Results Program database, we identified sCBC or mCBC patients from 2000 to 2010. The Kaplan-Meier method and Cox proportional hazards regression analysis were used to analyze overall survival and breast cancer-specific survival (BCSS) rates of sCBCs and mCBCs, respectively. RESULTS: Overall, 14,057 sCBC (n = 8,139, 57.9%) and mCBC (n = 5,918, 42.1%) patients were included. The first tumors of sCBC were more likely to have higher stage and more lymph and distant metastases, whereas those of mCBC were more often infiltrating ductal carcinoma (IDC), had localized stage, were estrogen receptor (ER) and progesterone receptor (PR) negative, and had less axillary nodal involvement. The second tumors of mCBC tended to be IDC and have higher grade, adverse stage, ER and PR-negativity; and more axillary nodal involvement, compared to the second tumors of sCBC. mCBC patients had significantly favorable 5-year BCSS but worse long-term BCSS compared with sCBC patients. Moreover, subgroup analysis revealed no significant difference of BCSS between sCBC and mCBC among patients aged 18-60 years. Multivariate analysis indicated that age, grade, and stage of 2 tumors; surgery for second tumor; and ER status of the second tumor were independent prognostic factors for BCSS of contralateral breast cancer (CBC). CONCLUSION: The characteristics and outcomes of sCBCs and mCBCs were substantially different. sCBC and mCBC patients may have different prognosis, and the prognosis of CBC depends on the first and second tumors.

The role of radiotherapy in patients with resected ampullary carcinoma: findings based on the SEER database.

BACKGROUND: The role of adjuvant radiotherapy for resected ampullary carcinoma (AC) remains controversial. The aim of this study was to assess the effect of adjuvant radiotherapy on survival in patients who underwent resection for AC. METHODS: The Surveillance, Epidemiology and End Results (SEER) database was used to identify patients diagnosed with AC from 2004 to 2012. Kaplan-Meier survival curve and multivariable Cox proportional hazards analyses were conducted to determine the effect of adjuvant radiotherapy on overall survival (OS) and disease-specific survival (DSS). Propensity score matching (PSM) method was used to balance the differences of clinicopathological characteristics between groups. RESULTS: A total of 1227 patients were included. Patients who received adjuvant radiotherapy were younger, had more advanced T stage and N stage tumors and were more likely to receive chemotherapy (p < 0.001). Adjuvant radiotherapy failed to improve either OS (p = 0.119) or DSS (p = 0.188) in PSM cohorts. In subgroup analysis, no subgroup benefited from adjuvant radiotherapy and in patients older than 70 years, radiotherapy was associated with a worse OS and DSS. CONCLUSION: Patients with resected AC do not benefit from adjuvant radiotherapy.

Intracardiac echogenic focus and its location: association with congenital heart defects.

Purpose: Significance of intracardiac echogenic focus (ICEF) in the fetal heart remains controversial. We aimed to investigate whether the location of ICEF is associated with fetal cardiac structure defects (CSDs) in low-risk pregnant women. Materials and Methods: A retrospective cohort study was conducted. Singleton pregnancies with normal values of triple fetal serum markers were included. 758 of 9782 fetuses with ICEF were reviewed for involvement of three ICEF locations (left, right, and bilateral ventricles (BVs)) in CSDs. χ2 or Fisher's exact test was performed for statistical analysis. Results: ICEF prevalence was 7.7% and its location was most frequently in the left ventricle (LV) (84.8%), followed by the BV (11.6%) and the right ventricle (RV) (3.6%). No statistically significant difference was found between the ICEF location and maternal age (χ2 = 3.92, p-value = .1409). There were cardiac defects with an isolated echogenic focus in 24 of 758 fetuses (3.2%). Significant difference for CSDs was observed among groups of RV, LV, and BV (p-fisher = .0146). Conclusions: Significantly more CSDs cases were identified in fetuses with ICEF in RV. Further investigation is warranted to examine the histological characteristics of fetal echogenic focus in the RV.