Trends of incidence and mortality in metaplastic breast cancer and the effect of contralateral prophylactic mastectomy: A population-based study.

INTRODUCTION: Metaplastic breast cancer (MBC) is considered rare and aggressive. We examined the epidemiology of and prognostic factors for MBC and investigated the effect of contralateral prophylactic mastectomy (CPM), because neither had been thoroughly examined previously. METHODS: We obtained data from the Surveillance, Epidemiology, and End Results (SEER)-18(2000-2018) for epidemiological and survival analysis. RESULTS: The age-adjusted incidence per 100,000 persons of MBC increased significantly from 0.12 to 0.35 [annual percent change (APC):2.95%, 95% confidence interval [CI], 1.73-4.19]. The incidence-based mortality increased from 0.01 to 0.12 (APC: 5.01%, 95% CI: 2.50-7.58). The incidence of MBC patients who underwent CPM significantly increased from 0.003 to 0.039 with an APC of 10.96% (95%CI, 7.26-14.78). Older patients and those with higher T classification were less likely to receive CPM. The multivariate Cox model showed that CPM was not an independent predictor of good prognosis for both overall survival (OS) and breast cancer-specific survival (BCSS) (pre-propensity score matching (PSM): OS: P = 0.331; BCSS: P = 0.462. post-PSM: OS: P = 0.916; BCSS: P = 0.967). Subgroup analysis showed that CPM still did not provide a survival benefit to any risk groups. CONCLUSION: In this study, we demonstrated that the incidence and incidence-based mortality of MBC have increased over the past decades. Although the number of MBC patients who underwent CPM has significantly increased recently, CPM did not confer a survival benefit compared with unilateral mastectomy, indicating that the decision to undergo CPM should be considered carefully.

Ligustilide enhances pregnancy outcomes via improvement of endometrial receptivity and promotion of endometrial angiogenesis in rats.

Ligustilide (LIG) is the main active ingredient of Angelica sinensis (Oliv.) Diels, which could promote focal angiogenesis to exert neuroprotection. However, there was no report that verified the exact effects of LIG on endometrial angiogenesis and the pregnancy outcomes. To explore the effects of LIG on low endometrial receptivity (LER) and angiogenesis, pregnancy rats were assigned into Control (saline treatment), LER (hydroxyurea-adrenaline treatment), LIG 20 mg/kg and LIG 40 mg/kg groups. Hematoxylin and eosin (H&E) staining was performed to evaluate endometrial morphology. Quantitative real-time PCR, immunofluorescence staining, western blot and immunohistochemistry staining were employed to assess the expression of endometrial receptivity factors and angiogenesis-related gene/protein, respectively. RNA sequencing was used to analyze the effects of LIG on LER caused by Kidney deficiency and blood stasis. We found that endometrial thickness and the implanted embryo number were substantially reduced in the hydroxyurea-adrenaline-treated pregnancy rats. At the same time, the gene and protein expressions of ERα, LIF, VEGFA and CD31 in the endometrium were markedly reduced, while the expressions of MUC1, E-cadherin were increased in the LER group. Administration of LIG raised the endometrial thickness and implanted embryos, as well as reversed the expressions of these factors. Collectively, our findings revealed that LIG could facilitate embryo implantation via recovery of the endometrium receptivity and promotion of endometrial angiogenesis.

Epidemiologic trends of and factors associated with overall survival in patients with neuroendocrine tumors over the last two decades in the USA.

Background: Updated epidemiological data of neuroendocrine tumors are currently lacking. Thus, we performed epidemiological and survival analyses on a large cohort of patients with neuroendocrine tumors and developed a new nomogram to predict survival. Methods: This population-based study examined 112,256 patients with neuroendocrine tumors between 2000 and 2018 using data from the Surveillance, Epidemiology, and End Results program. Results: The age-adjusted incidence per 100,000 persons of neuroendocrine tumors increased from 4.90 in 2000 to 8.19 in 2018 (annual percentage change, 3.40; 95% confidence interval, 3.13-3.67), with the most significant increases in grade 1, localized stage, and appendix neuroendocrine tumors. The age-adjusted mortality rate increased 3.1-fold from 2000 to 2018 (annual percentage change, 4.14; 95% confidence interval, 3.14-5.15). The 1-, 5-, and 10-year relative survival rates for all neuroendocrine tumors were 80.5%, 68.4%, and 63.5%, respectively. Multivariate analyses showed that male sex; older age; Black, American Indian, and Alaska Native populations; earlier year of diagnosis; lung neuroendocrine tumors; higher grades; and later stage were associated with a worse prognosis and that disease stage and grade were the most important risk factors for prognosis. Furthermore, we established a nomogram to predict the 3-, 5-, and 10-year survival rates, and its discrimination ability was better than that of the TNM classification. Conclusions: The incidence, prevalence, and mortality rate of neuroendocrine tumors continued to increase over the last two decades. Additionally, the nomogram could accurately quantify the risk of death in patients with neuroendocrine tumors and had good clinical practicability.

Effect of open versus video-assisted thoracoscopy on perioperative outcomes and survival for cases of thymic carcinomas and thymic neuroendocrine tumors.

BACKGROUND: The oncology-related indices between open and video-assisted thoracoscopic surgery (VATS) procedures for thymic carcinomas (TCs) and thymic neuroendocrine tumors (TNETs) remain unclear. METHODS: Propensity score matching (PSM) and multivariate Cox proportional risk models were used to evaluate the perioperative outcomes and survival rates of patients undergoing open and VATS for TCs and TNETs at the Second Affiliated Hospital of Air Force Military Medical University Hospital, between 2009 and 2018. RESULTS: Of the total 126 cases of TCs and TNETs, VATS treatment was used in 39 (30.9%). Advanced age and Masaoka-Koga staging were found to be independent prognostic factors for both TCs and TNETs, through a multifactorial Cox regression analysis. There was no significant difference in survival between the VATS and open groups before and after PSM; however, the VATS group had better perioperative-related indicators. There were no significant differences between the groups in terms of mortality at 30 days, mortality at 90 days, R0 resection rate, and 5-year survival rate (67.5% vs. 58.5% [P = 0.260] in the VATS group compared to the open group, in a PSM analysis of the 27 VATS and 27 open groups). Compared to the open group, the VATS group had a shorter length of hospital stay (13 days vs. 16 days, P = 0.015), a shorter level I care (0 days vs. 1 day, P = 0.016), and less intraoperative bleeding (50 mL vs. 300 mL, P < 0.001). CONCLUSIONS: In this single-center retrospective study of TCs and TNETs, survival rates were comparable between the VATS group and the open group, and the VATS group showed improved perioperative-related parameters.

Epidemiology of and factors associated with overall survival for patients with head and neck adenoid cystic carcinoma.

BACKGROUND: Updated epidemiologic and survival data of head and neck adenoid cystic carcinoma (HNACC) are lacking. This retrospective study aimed to clarify the incidence, prevalence, and overall survival (OS) of patients with HNACC and establish relevant nomogram. METHODS: Trends in incidence, limited-duration prevalence, and relative survival (RS) rates were evaluated using data from the Surveillance, Epidemiology, and End Results (SEER) database, and annual percent change (APC) in rates was calculated using joinpoint regression. Data on age, sex, site, stage, and surgery were used in construction and validation of the nomogram. RESULTS: The study included 6474 patients; 57.7% were female and 78.6% were white. The age-adjusted incidence rates of HNACC decreased significantly from 0.41 to 0.25 per 100,000 [1975-2018; average annual percent change (AAPC): - 1.37, P < 0.001], which was dominated by the localized stage. The 20-year limited duration prevalence increased from 0.00028% to 0.00262%. The 5- and 10-year RS rates of all HNACC patients were 80.0% and 65.5%, respectively. RS rates in HNACC showed a slight increase over time, with APC values of 0.03 for 5-year (P < 0.05) and 0.13 for 10-year (P < 0.05) RS. A prognostic model was constructed. The C-indices for the training and testing sets were both 0.734. The nomogram's discrimination efficiency was evaluated using the receiver operating characteristic curve and had moderate predictive power. CONCLUSIONS: Over the past 40 years, the incidence of HNACC decreased accompanied by slightly improved survival rates. Nomogram was capable of predicting the 5- and 10-year OS rates with moderate accuracy.

Hyperoside exerts protective effects against anticardiolipin antibody-induced recurrent pregnancy loss in vivo and in vitro.

BACKGROUND: Women with antiphospholipid syndrome (APS) or antiphospholipid antibodies (aPLs) are at high risk for obstetric complications, including recurrent pregnancy loss (RPL). However, effective treatments for RPL are lacking. OBJECTIVE: This study aimed to reveal the function and underlying mechanism of hyperoside (Hyp) in RPL associated with antiphospholipid antibodies (aCLs). METHODS: The pregnant rats (N = 24) were divided randomly into four groups: normal human-IgG (NH-IgG); aCL-pregnancy loss (aCL-PL); aCL-PL + Hyp (40 mg/kg/day); aCL-PL + low molecular weight heparin (LMWH, 525 µg/kg/day). HTR-8 cells were treated with 80 µg/mL aCL to establish the cell models of miscarriage. RESULTS: In pregnant rats, aCL-IgG injection raised the abortion rate of embryos, while Hyp treatment inhibited the effects. Additionally, Hyp inhibited the platelet activation and uteroplacental insufficiency caused by aCL. In vivo and in vitro experiments further suggested that Hyp suppressed aCL-induced inflammation and apoptosis by downregulating NOD-like receptor family pyrin domain-containing 3 (NLRP3) inflammasome-related factors and decreasing apoptotic rates. After aCL administration, Hyp therapy downregulated the expression of purinergic ligand-gated ion channel 7 (P2X7), which is reported to induce cytokine release and apoptosis. Furthermore, we found that the treatment of 3'-O-(4-Benzoyl) benzoyl-ATP (BzATP, an agonist of the P2X7 receptor) reversed the inhibitory effects of Hyp on cell function. CONCLUSIONS: Hyp exerts protective effects on aCL-induced pregnancy loss by preventing platelet activation-mediated P2X7/NLRP3 pathway. Therefore, Hyp may provide a feasible pharmaceutical strategy for the treatment of RPL.

Association between radiotherapy for surgically treated oral cavity cancer and secondary lung cancer.

Background: There is limited research on the incidence of secondary lung cancer (SLC) after radiotherapy (RT) for oral cavity cancer (OCC). Therefore, we investigated the association between RT for OCC and the risk of SLC and the overall survival of these patients. Methods: Patients diagnosed with OCC between 1975 and 2015 were selected from the Surveillance, Epidemiology, and End Results database. The cumulative incidence of SLC, relative risk (RR) of RT vs. no RT (NRT), standardized incidence ratios (SIR), and survival outcomes were assessed. Results: A total of 10,936 patients with OCC were included. Of these, 429 (3.92%) patients developed SLC, where 136 (5.02%) received RT and 293 (3.56%) did not. The cumulative incidence of SLC during follow-up was 6.89% and 4.84% in the RT and NRT patients, respectively. RT was associated with a higher risk of SLC. In the subset analysis, the results showed that a higher risk of developing SLC among patients with index OCC in most subgroups. Dynamic RR and SIR revealed a decreased risk of SLC with increasing latency time. No difference was observed in the 10-year survival rates for patients with SLC who received RT or not or compared with primary lung cancer. Conclusion: RT was associated with a higher risk of SLC, and patients diagnosed with OCC could be followed for 5-10 years after diagnosis.

Association between a prior cancer history and prognosis in adult patients with high­grade glioma.

Patients with a prior cancer history are often excluded from clinical trials. This study aimed to investigate the prognostic impact of prior cancer history on patients with high-grade glioma. Data of patients with high-grade glioma as the first or second primary malignancy were obtained from the Surveillance, Epidemiology, and End Results database. Propensity score matching (PSM) was performed to balance the heterogeneity baseline characteristics. The survivals of patients with or without prior cancers were analyzed. A total of 46,200 patients were included in this study, 2471 (5.3 %) of whom carried a prior cancer history. Prostate (37.7 %), breast (12.2 %), colon and rectal (7.9 %), and skin (6.9 %) cancers were the most common types of prior cancers. Overall survival rates were similar between patients with and without a prior cancer history (hazard ratio [HR], 1.02; 95 % confidence interval [CI], 0.96-1.08; P = 0.525). However, a prior cancer history served as a protective factor against glioma-specific mortality (sub-distribution HR = 0.90; 95 % CI, 0.84-0.96; P = 0.001) in comparison with having no prior cancer history. The subgroup stratified by time intervals and types of prior cancer history showed that a prior cancer history was not a significant prognostic factor for survival in patients, except for breast cancers within 5 years and prostate cancers over 5 years. Our study shows that except for patients with high-grade gliomas with a history of stable tumors, the inclusion of patients with a prior history of tumors in clinical trials requires careful consideration.

The role of postoperative radiation therapy in stage I-III male breast cancer: A population-based study from the surveillance, epidemiology, and End Results database.

BACKGROUND: This study aimed to investigate the role of postoperative radiation therapy in a large population-based cohort of patients with stage I-III male breast cancer (MaBC). METHODS: Patients with stage I-III breast cancer treated with surgery were selected from the Surveillance, Epidemiology, and End Results cancer database from 2010 to 2015. Multivariate logistic regression identified the predictors of radiation therapy administration. Multivariate Cox regression model was used to evaluate the predictors of survival. RESULTS: We identified 1321 patients. Age, stage, positive regional nodes, surgical procedure, and HER2 status were strong predictors of radiation therapy administration. There was no difference between patients who received radiation therapy and those who did not (P = 0.46); however, after propensity score matching, it was associated with improved OS (P = 0.04). In the multivariate analysis of the unmatched cohort, the factors associated with better OS were administration of radiation therapy and chemotherapy. In the subset analysis of the unmatched cohort, postoperative radiation therapy was associated with improved OS in men undergoing breast-conserving surgery (BCS), with four or more node-positive or larger primary tumours (T3/T4). Furthermore, we found no benefit of radiation therapy, regardless of the type of axillary surgery in mastectomy (MS). In older MaBC patients with T1-2N1 who underwent MS, radiation therapy showed no significant effects, regardless of chemotherapy. CONCLUSION: Postoperative radiation therapy could improve the survival of MaBC patients undergoing BCS, with four or more node-positive or larger primary tumours. Moreover, it should be carefully considered in patients undergoing MS and older T1-2N1 patients.

Stereotactic Biopsy for Brainstem Lesions: A Meta-analysis with Noncomparative Binary Data.

OBJECTIVES: To evaluate the diagnostic yield and safety of brainstem stereotactic biopsy for brainstem lesions. METHODS: We performed a meta-analysis of English articles retrieved from the PubMed, Web of Science, Cochrane Library, and APA psycInfo databases up to May 12, 2021. A binary fixed-effect model, the inverse variance method, or a binary random-effect model, the Dersimonian Laird method, were utilized for pooling the data. This meta-analysis was registered with INPLASY, INPLASY202190034. FINDINGS: A total of 41 eligible studies with 2792 participants were included. The weighted average diagnostic yield was 97.0% (95% confidential interval [CI], 96.0-97.9%). The weighted average proportions of temporary complications, permanent deficits, and deaths were 6.2% (95% CI, 4.5-7.9%), .5% (95% CI, .2-.8%), and .3% (95% CI, .1-.5%), respectively. The subgroup analysis indicated a nearly identical weighted average diagnostic yield between MRI-guided stereotactic biopsy and CT-guided stereotactic biopsy (95.9% vs 95.8%) but slightly increased proportions of temporary complications (7.9% vs 6.0%), permanent deficits (1.9% vs .2%), and deaths (1.1% vs .4%) in the former compared to the latter. Moreover, a greater weighted average diagnostic yield (99.2% vs 97.6%) and lower proportions of temporary complications (5.1% vs 6.8%) and deaths (.7% vs 1.5%) were shown in the pediatric patient population than in the adult patient population. CONCLUSIONS: Brainstem stereotactic biopsy demonstrates striking accuracy plus satisfying safety in the diagnosis of brainstem lesions. The diagnostic yield, morbidity, and mortality mildly vary based on the diversity of assistant techniques and subject populations.

Breast Cancer Subtypes and Mortality of Breast Cancer Patients With Brain Metastasis at Diagnosis: A Population-Based Study.

BACKGROUND: Brain metastasis is an important cause of breast cancer-related death. AIM: We evaluated the relationships between breast cancer subtype and prognosis among patients with brain metastasis at the initial diagnosis. METHODS: The Surveillance, Epidemiology, and End Results database was searched to identify patients with brain metastasis from breast cancer between 2010 and 2015. Multivariable Cox proportional hazard models were used to identify factors that were associated with survival among patients with initial brain metastases. The Kaplan-Meier method was used to compare survival outcomes according to breast cancer subtype. RESULTS: Among 752 breast cancer patients with brain metastasis at diagnosis, 140 patients (18.6%) underwent primary surgery and 612 patients (81.4%) did not undergo surgery, while 460 patients (61.2%) received chemotherapy and 292 patients (38.8%) did not receive chemotherapy. Multivariable analysis revealed that, relative to HR+/HER2- breast cancer, HR-/HER2- breast cancer was associated with significantly poorer overall survival (hazard ratio: 2.52, 95% confidence interval: 1.99-3.21), independent of age, sex, race, marital status, insurance status, grade, liver involvement, lung involvement, primary surgery, radiotherapy, and chemotherapy. The median overall survival intervals were 12 months for HR+/HER2-, 19 months for HR+/HER2+, 11 months for HR-/HER2+, and 6 months for HR-/HER2- (P < .0001). Relative to HR+/HER2- breast cancer, HR-/HER2- breast cancer was associated with a significantly higher risk of mortality among patients, and the association was stronger among patients who received chemotherapy (p for interaction = .005). CONCLUSIONS: Breast cancer subtype significantly predicted overall survival among patients with brain metastasis at diagnosis.

Comparison of the Oncological Efficacy Between Intraoperative Radiotherapy With Whole-Breast Irradiation for Early Breast Cancer: A Meta-Analysis.

BACKGROUND: Intraoperative radiotherapy (IORT) and whole-breast irradiation (WBI) are both effective radiotherapeutic interventions for early breast cancer patients undergoing breast-conserving surgery; however, an issue on whether which one can entail the better prognosis is still controversial. Our study aimed to investigate the 5-year oncological efficacy of the IORT cohort and the WBI cohort, respectively, and compare the oncological efficacy between the cohorts. MATERIALS AND METHODS: We conducted a computerized retrieval to identify English published articles between 2000 and 2021 in the PubMed, the Web of Science, the Cochrane Library, and APA PsycInfo databases. Screening, data extraction, and quality assessment were performed in duplicate. RESULTS: A total of 38 studies were eligible, with 30,225 analyzed participants. A non-comparative binary meta-analysis was performed to calculate the weighted average 5-year local recurrence-free survival (LRFS), distant metastasis-free survival (DMFS), and overall survival (OS) in the two cohorts, respectively. The LRFS, DMFS, and OS (without restriction on the 5-year outcomes) between the two cohorts were further investigated by a comparative binary meta-analysis. The weighted average 5-year LRFS, DMFS, and OS in the IORT cohort were 96.3, 96.6, and 94.1%, respectively, and in the WBI cohort were 98.0, 94.9, and 94.9%, respectively. Our pooled results indicated that the LRFS in the IORT cohort was significantly lower than that in the WBI cohort (pooled odds ratio [OR] = 2.36; 95% confidential interval [CI], 1.66-3.36). Nevertheless, the comparisons of DMFS (pooled OR = 1.00; 95% CI, 0.76-1.31), and OS (pooled OR = 0.95; 95% CI, 0.79-1.14) between the IORT cohort with the WBI cohort were both not statistically significant. CONCLUSIONS: Despite the drastically high 5-year oncological efficacy in both cohorts, the LRFS in the IORT cohort is significantly poorer than that in the WBI cohort, and DMFS and OS do not differ between cohorts.

Increased CDKL3 expression predicts poor prognosis and enhances malignant phenotypes in esophageal squamous cell carcinoma.

BACKGROUND: Cyclin-dependent kinase-like 3 (CDKL3) is a putative protein serine kinase and plays an important role in the regulation of cell growth and/or differentiation. However, studies on the function of CDKL3 in esophageal squamous cell carcinoma (ESCC) is limited. In our study, we explored the role and prognosis of CDKL3 in ESCC and underlying mechanism. MATERIALS AND METHODS: The expression of CDKL3 was investigated by quantitative reverse transcription polymerase chain reaction and immunohistochemical staining. CDKL3 expression was downregulated by the RNAi-mediated knockdown. The functions of CDKL3 on cell growth were assessed by Celigo image cytometry, MTT assay, cell-cycle analysis, Annexin V assay, and caspase-3/7 activity analysis. The effect of CDKL3 on cellular invasive was investigated by the Transwell assay. Pathscan Stress Signaling Antibody Array was used to study the underlying mechanism. Additionally, the association between the survival and CDKL3 expression in ESCC were evaluated based on the TCGA data. RESULTS: CDKL3 was highly expressed in ESCC tissues and cell lines. TE-1 cells transfected with CDKL3-shRNA-lentivirus significantly decreased CDKL3 expression and resulted in inhibiting cell proliferation, inducing the S-phase cell-cycle arrest, attenuating cellular invasive and increasing cell apoptosis. The expression of pERK1/2, p-Akt, p-Smad2, p-p38 mitogen-activated protein kinase, cleaved caspase-7, and phospho-Chk1 were significantly decreased by CDKL3 knockdown. In addition, high expression of CDKL3 was associated with shorter overall survival. CONCLUSION: Our findings suggest that higher expression of CDKL3 is correlated with poor prognosis in patients with ESCC and play a vital role in the malignant phenotype of ESCC cell lines, which indicating that CDKL3 may be as a new therapeutic target in ESCC.