Chronic Obstructive Pulmonary Disease Mortality in Bladder Cancer Patients: A SEER-Based Competing Risk Analysis.

PURPOSE: This study was designed to evaluate risk of mortality from chronic obstructive pulmonary disease (COPD) in patients with bladder cancer (BC). METHODS AND MATERIALS: Data on patients diagnosed with BC by pathology between 2000 and 2016 were collected from the Surveillance, Epidemiology, and End Results (SEER) database. Based on reference data from the general population, the standardized mortality rate (SMR) is calculated. Nelson-Aalen cumulative hazard curves were used for assessment of the risk of COPD mortality in BC patients. Multivariable competing risk models were conducted. The proportional hazards assumption was tested using Schoenfeld residuals, which were scaled and plotted over time for each risk factor. RESULTS: A total of 237,563 BC patients were identified for further analysis from the SEER database, 5,198 of these patients experienced COPD mortality; the overall SMR for COPD mortality in BC patients was 1.58 (95% CI: 1.54-1.63). Age, race, year of diagnosis, histologic type, summary stage, surgery, marital status, college education level, and median household income independently predicted COPD mortality in BC patients. CONCLUSIONS: In comparison to the general population, the risk of COPD mortality is significantly higher in patients with BC. Pre-identification of high-risk groups and respiratory care provisions are important measures to effectively improve survival in this group of patients.

Therapeutic responses to chemotherapy or immunotherapy by molecular subtype in bladder cancer patients: A meta-analysis and systematic review.

To systematically evaluate the differences in therapeutic response to chemotherapy or immunotherapy between different molecular subtypes of bladder cancer (BC). A comprehensive literature search was performed up to December 2021. Consensus clusters 1 (CC1), CC2 and CC3 molecular subtypes were used to perform meta-analysis. Pooled odds ratios (ORs) with 95% confidence intervals (CIs) were used to assess the therapeutic response by fix-effect modeling. Eight studies involving 1,463 patients were included. For immunotherapy, CC3 showed the highest response rate (CC1 vs. CC3: OR=0.52, 95% CI=0.34-0.78, p=0.002; CC2 vs. CC3: OR=0.42, 95% CI=0.28-0.62, p<0.001), which was mainly reflected in the highest response rate to atezolizumab (CC1 vs. CC3: OR=0.47, 95% CI=0.29-0.75, p=0.002; CC2 vs. CC3: OR=0.38, 95% CI=0.24-0.59, p<0.001). For chemotherapy, CC3 had the lowest response rate to the overall chemotherapy (CC1 vs. CC3: OR=2.05, 95% CI=1.23-3.41, p=0.006; CC2 vs. CC3: OR=2.48, 95% CI=1.50-4.10, p<0.001). Compared with CC2, CC3 responded poorly to both neo-adjuvant chemotherapy (NAC) (OR=1.93, 95% CI=1.09-3.41, p=0.020) and chemoradiation therapy (CRT) (OR=6.07, 95% CI=1.87-19.71, p<0.001). Compared with CC1, CC3 only showed a poorer response to CRT (OR=4.53, 95% CI=1.26-16.27, p=0.020), and no difference in NAC. Our study suggested that molecular classifications are important predictors of cancer treatment outcomes of BC patients and could identify subgroup patients who are most likely to benefit from specific cancer treatments.

High risk of non-cancer mortality in bladder cancer patients: evidence from SEER-Medicaid.

PURPOSE: The objective of this study was to investigate non-cancer causes of death and associated risk factors after bladder cancer (BC) diagnosis. METHODS: Eligible BC patients were obtained from the SEER database. SEER*Stat software 8.3.9.2 was used to calculate the standardized mortality ratios (SMRs). The proportions of different non-cancer cause of death were calculated and analyzed in different follow-up periods. Multivariate competing risk model was used to analyze the risk factors for death of BC and non-cancer diseases. RESULTS: In total, 240,954 BC patients were included and 106,092 patients experienced death, with 37,205 (35.07%), 13,208 (12.45%) and 55,679 (52.48%) patients experienced BC, other cancer and non-cancer disease-related deaths, respectively. Overall SMR for BC patients who died from non-cancer diseases was 2.42 (95% CI [2.40-2.44]). Cardiovascular diseases were the most common non-cancer cause of death, followed by respiratory diseases, diabetes mellitus, and infectious diseases. Multivariate competing risk analysis identified the following high-risk factors for non-cancer mortality: age > 60 years, male, whites, in situ stage, pathological type of transitional cell carcinoma, not receiving treatment (including surgery, chemotherapy, or radiation), and widowed. CONCLUSIONS: Cardiovascular diseases are the leading non-cancer cause of death in BC patients, followed by respiratory disease, diabetes mellitus and infectious diseases. Physicians should pay attention to the risk of death from these non-cancer diseases. Also, physicians should encourage patients to engage in more proactive self-surveillance and follow up.

NUF2 is correlated with a poor prognosis and immune infiltration in clear cell renal cell carcinoma.

BACKGROUND: Clear cell renal cell carcinoma (ccRCC) is one of the most common malignancies. Recently, immunotherapy has been considered a promising treatment for metastatic ccRCC. NUF2 is a crucial component of the Ndc80 complex. NUF2 can stabilize microtubule attachment and is closely related to cell apoptosis and proliferation. This research is dedicated to investigating the role of NUF2 in ccRCC and the possible mechanisms. METHODS: First, analysis of NUF2 mRNA expression levels in ccRCC and normal tissues by The Cancer Genome Atlas (TCGA) database and further verified by analysis of independent multiple microarray data sets in the Gene Expression Omnibus (GEO) database. Moreover, we evaluated and identified correlations between NUF2 expression, clinicopathologic variable, and overall survival (OS) in ccRCC by various methods. We investigated the relationship between NUF2 and tumor immune infiltration and the expression of corresponding immune cell markers via the Gene Expression Profiling Interactive Analysis (GEPIA) and Tumor Immune Estimation Resource (TIMER) databases. Then, we performed functional enrichment analysis of NUF2 co-expressed genes using R software and protein-protein interactions (PPIs) using the search tool used to retrieve interacting genes/proteins (STRING) databases. RESULTS: We discovered that NUF2 mRNA expression was upregulated in ccRCC tissues and was associated with sex, grade, pathological stage, lymph node metastasis, and worse prognosis. In addition, NUF2 was positively linked to tumor immune cells in ccRCC. Moreover, NUF2 was closely related to genetic markers of different immune cells. Finally, functional enrichment and protein-protein interaction (PPI) analysis suggested that NUF2 and its closely related genes may be involved in the regulation of the cell cycle and mitosis. Our results suggested that NUF2 is correlated with a poor prognosis and immune infiltration in ccRCC.

Incidence, Prognostic Factors, and Survival of Patients with Renal Cancer: A Population-Based Study.

BACKGROUND: The main objective of this article is to understand trends in the incidence of renal cancer and to construct a nomogram to predict the prognosis of patients with renal cancer by analyzing clinical parameters. METHODS: We extracted data from the Surveillance, Epidemiology and End Results (SEER) database for patients with renal cancer from 2010 to 2015. The incidence rate was calculated to understand the trend of renal cancer in recent years, and the Kaplan-Meier method was used to analyze the relationship between patients' clinical variables and overall survival. Nomogram and calibration curves were constructed based on factors predicted by multivariate Cox regression. RESULTS: Data from 68,496 eligible renal cancer patients were included in the study. The incidence of renal cancer was higher in men than women and tended to stabilize over time. We further found that age, gender, marital status, AJCC stage, histological type, metastatic disease, and surgery were independent parameters for prognosis in renal cancer patients. Finally, a nomogram was constructed based on the above parameters, and its validity was verified with the agreement index and calibration curve. CONCLUSION: Renal cancer incidence trend gradually stabilized. Seven independent parameters for renal cancer patients were obtained by analysis and utilized to construct a nomogram that could provide guidance for clinical practice.

Competing risk analysis of cardiovascular death in breast cancer: evidence from the SEER database.

Background: Cardiovascular disease (CVD) is the leading cause of death for all non-cancer deaths among breast cancer (BC) patients. The aim of this study was to investigate the risk of cardiovascular mortality (CVM) in patients with BC. Methods: Patients diagnosed with primary BC between 2010 and 2018 were identified through the Surveillance, Epidemiology and End Results (SEER) database. The standardized mortality ratio (SMR) for CVD was calculated to compare the CVM of BC patients with that of the general population. Multivariate competing risk models were performed to identify predictors of CVM in BC patients. Results: Overall, 399,014 BC patients were included from the SEER database, of whom 7,023 (1.8%) suffered death from CVD. The significantly higher overall SMR of CVM was observed in BC patients [SMR =4.84, 95% confidence interval (CI): 4.72-4.95]. Multivariate competing risk regression analysis revealed that age, race, American Joint Committee on Cancer (AJCC) stage, year of diagnosis, estrogen receptor (ER) status, progesterone receptor (PR) status, human epidermal growth factor receptor 2 (HER2) status, BC subtype, surgery, chemotherapy, radiation therapy, and median household income as independent predictors of CVM in BC patients. Conclusions: Compared to the general population, BC patients have a higher risk of experiencing CVM during the follow-up period after diagnosis. Early detection and intervention of cardiovascular risk factors would improve overall survival (OS) of BC patients.

Incidence, prognostic factors and survival in bladder cancer patients: a population-based study.

Background: The aim of this study was to investigate the incidence, epidemiologic characteristics, prognostic factors and survival of patients with bladder cancer. Methods: Bladder cancer patients diagnosed between 2010 and 2015 were identified from the Surveillance, Epidemiology, and End Results (SEER) database. Univariate and multivariate Cox proportional hazards regression analyses were used to identify the independent prognostic factors for overall survival. Kaplan-Meier survival analysis and nomogram analysis were constructed based on the identified independent prognostic factors. Results: A total of 95,329 eligible bladder cancer patients were included in this study. Eight independent risk factors, including age, histologic type, race, tumor, node and metastasis (TNM) stage, American Joint Committee on Cancer (AJCC) stage, surgery, tumor metastasis and summary stage, were recognized by using multivariate logistic regression models. By comprising these factors, a predictive nomogram was constructed to predict the 1-, 3-, and 5-year overall survival possibilities. The concordance index and calibration curve showed that the nomogram had robust and accurate performance. Conclusions: Bladder cancer is the most common cancer of the urinary system, but the overall incidence has been decreasing yearly since 1992. Our results demonstrate eight factors significantly associated with overall survival in bladder cancer patients. Based on these factors, we established and validated a nomogram, which has the potential to provide an individualized prediction of overall survival in patients with bladder cancer.

Cardiovascular Mortality Risk in Patients with Bladder Cancer: A Population-Based Study.

BACKGROUND: The purpose of this study was to evaluate the risk of cardiovascular mortality (CVM) among patients with bladder cancer (BC). METHODS AND MATERIALS: Data were collected from the Surveillance, Epidemiology, and End Results (SEER) database for patients who were diagnosed with BC by pathology between 2000 and 2016. The standardized mortality rate (SMR) was calculated based on reference data from the general population. Nelson-Aalen cumulative hazard curves were used to assess the risk of experiencing CVM in BC patients. Multivariate competing risk models were performed. RESULTS: In total, data from 237,563 BC patients were obtained from the SEER database for further analysis, of which 21,822 patients experienced CVM; the overall SMR for CVM in BC patients was 1.16 (95% CI: 1.14-1.17). Age, race, sex, year of diagnosis, histologic type, summary stage, surgery, marital status, and college education level were independent predictors of CVM in patients with BC. CONCLUSIONS: Patients with BC have a significantly increased risk of experiencing CVM compared to the general population. Pre-identification of high-risk groups and cardiovascular protection interventions are important measures to effectively improve survival in this group of patients.

Efficacy and safety of raltitrexed-based transcatheter arterial chemoembolization for intermediate and advanced hepatocellular carcinoma: A multicenter real-world study.

AIM: This study aimed to evaluate efficacy and safety of raltitrexed-based transcatheter arterial chemoembolization (TACE) for intermediate and advanced hepatocellular carcinoma (HCC) using real-world evidence. METHODS: All eligible HCC cases were collected from multiple centers in Chongqing, China, from January 2013 to December 2018 and divided into the raltitrexed group (raltitrexed + lobaplatin + pirarubicin) and control group (lobaplatin + pirarubicin). Propensity score matching (PSM) with a 1:1 ratio was used to eliminate the imbalance of potential confounding factors between groups. The primary end-point was overall survival (OS) and the secondary end-points were progression-free survival (PFS) and disease control rate. RESULTS: The median follow-up period for patients in the raltitrexed and control groups was 8.7 and 5.9 months, respectively. After PSM, median OS was 10.0 months in the raltitrexed group and 7.0 months in the control group (p = 0.002). The 6-month, 1-year, and 2-year OS rates of the raltitrexed group were significantly higher than those of the control group (78.2% vs. 60.9%, p = 0.010; 43.5% vs. 22.8%, p = 0.030; and 17.4% vs. 2.2% p = 0.001, respectively). Multivariate analysis of these propensity score-matched HCC patients revealed treatment, age, tumor size, lipiodol accumulation, and the number of TACE cycles as independent predictors of OS (all p < 0.05). The disease control rate of the raltitrexed and control groups was 87.4% and 65.8%, respectively (p < 0.001). CONCLUSIONS: Raltitrexed-based TACE can prolong the OS of patients with intermediate and advanced HCC in a real-world clinical setting, and is safe and tolerable.

[Huanshao Capsules for oligoasthenospermia: A multicentered clinical trial].

Objective: To investigate the clinical efficacy and safety of Huanshao Capsules (HSC) in the treatment of oligoasthenospermia with spleen and kidney asthenia. METHODS: This randomized, open, multicentered, positive drug controlled clinical trial included 200 cases of oligoasthenospermia with spleen and kidney asthenia, which were assigned to a trial and a control group of equal number to be treated with HSC at the dose of 3 capsules tid and Wuziyanzong Pills at 6 g bid, respectively, both for 12 weeks. We compared the semen volume, sperm concentration, sperm count, sperm motility and percentage of progressively motile sperm (PMS) as the main therapeutic indicators as well as the pregnancy rate as the secondary therapeutic indicator between the two groups of patients before and at 4, 8 and 12 weeks after medication. RESULTS: Totally, 190 of the patients completed the clinical observation, 96 in the trial and 94 in the control group. Compared with the baseline, the patients of the trial group showed significant time-dependent increases at 4, 8 and 12 weeks after medication in the mean sperm concentration (14.78 vs 15.33, 20.98 and 28.78 ×106/ml, P < 0.05), percentage of grade a sperm (12.17% vs 15.05%, 21.17% and 26.97%, P < 0.05), PMS (24.78% vs 28.97%, 37.23% and 47.67%, P < 0.05), and sperm viability (38.64% vs 44.18%, 51.67% and 60.45%, P < 0.05). The pregnancy rate was significantly higher in the trial than in the control group 29.17% vs 18.09%, P < 0.05). CONCLUSIONS: Huanshao Capsules can improve the semen quality and pregnancy rate in the treatment of oligoasthenospermia patients with spleen and kidney asthenia, and therefore deserves a wide clinical application.

Effect of aromatase inhibitor letrozole on the proliferation of spermatogonia by regulating the MAPK pathway.

The molecular mechanism of the aromatase inhibitor letrozole was investigated. It promotes the proliferation of spermatogonia by regulating the mitogen-activated protein kinase (MAPK) pathway. Six different concentrations were selected for letrozole in order to incubate mouse spermatogonia [GC-1 spermatogonia (spg)] for 24, 48 and 72 h, respectively. Cell Counting Kit-8 (CCK-8) was used to observe the effect of letrozole on the proliferation of GC-1 spg cells, and the effect was further verified by cell plate clone formation assay. Reverse transcription-polymerase chain reaction (RT-PCR) and western blot analysis were used to detect the effects of letrozole on MAPK signaling pathways [Ras/extracellular signal-regulated kinase 1 (ERK1)/c-Myc], proliferation indexes [Ki-67 and proliferating cell nuclear antigen (PCNA)]. Bromodeoxyuridine (BrdU) staining was used to study the effects of letrozole and MAPK signaling pathways on cell proliferation. The results of CCK-8 showed that the proliferation rate of GC-1 spg cells was improved. Study results also revealed a significant increase in letrozole concentration along with the time of action. The results of plate clone formation assay further indicated that letrozole could significantly promote the proliferation capacity of GC-1 spg cells (p<0.05). The results of RT-PCR and western blot analysis confirmed letrozole significantly activated the expression of Ras/ERK1/c-Myc in the classical MAPK pathway. A significant increase was noted in the protein levels of Ki-67 and PCNA (p<0.05). By contrast, inhibition of the MAPK pathway resulted in a significant decrease in the levels of the above indexes (p<0.05). The number of BrdU cells in the letrozole group was also higher than that of the control group, while the number of BrdU-stained cells in the letrozole + MAPK inhibition group showed a significant decrease in comparison to the letrozole group. In conclusion, letrozole activated the MAPK signaling pathway and promoted the proliferation of mouse spermatogonia GC-1 spg cells. The present study provides a theoretical basis for the clinical application of letrozole.