Survival benefit of radical prostatectomy in patients with advanced TURP-diagnosed prostate cancer: a population-based real-world study.

OBJECTIVES: A considerable number of patients are diagnosed with prostate cancer (PCa) by transurethral resection of the prostate (TURP). We aimed to evaluate whether radical prostatectomy (RP) brings survival benefits for these patients, especially in the elderly with advanced PCa. PATIENTS AND METHODS: We used the Surveillance, Epidemiology, and End Results (SEER) database to obtain PCa cases diagnosed with TURP. After the propensity matching score (PSM) for case matching, univariate, multivariate, and subgroup analyses were performed to investigate whether RP impacts the survival benefit. RESULTS: 4,677 cases diagnosed with PCa by TURP from 2010 to 2019 were obtained, including 1,313 RP patients and 3,364 patients with no RP (nRP). 9.6% of RP patients had advanced PCa. With or without PSM, cancer-specific mortality (CSM) and overall mortality (OM) were significantly reduced in the RP patients compared to the nRP patients, even for older (> 75 ys.) patients with advanced stages (all p < 0.05). Except for RP, younger age (≤ 75 ys.), being married, and earlier stage (localized) contributed to a significant reduction of CSM risk (all p < 0.05). These survival benefits had no significant differences among patients of different ages, married or single, and at different stages (all p for interaction > 0.05). CONCLUSIONS: Based on this retrospective population-matched study, we first found that in patients diagnosed with PCa by TURP, RP treatment may lead to a survival benefit, especially a reduction in CSM, even in old aged patients (> 75 ys.) with advanced PCa.

Case report: Systemic presentation of ALK-positive Histiocytosis.

ALK-positive Histiocytosis (ALK-HSs) is a recently identified rare clinical entity characterized by tissue histiocytic alterations associated with ALK gene rearrangement. Clinical presentations can be solitary, multifocal, or systemic (involving multiple sites and organs). Due to limited reported cases, there is inadequate understanding of this disease. This report presents a case of ALK-HSs in a 71-year-old male patient who presented with hematuria for one week. Imaging studies conducted at an external hospital showed multiple lesions in the penis, bilateral testes, back skin, and the third lumbar vertebra. Histopathological findings included spindle and histiocytic cell proliferation with mild or indistinct cellular atypia, interstitial infiltration of lymphocytes, plasma cells, foamy histiocytes, and fibrous tissue proliferation. Immunohistochemistry of the lesion cells revealed positivity for CD68, CD163, ALK1, ALK (D5F3), and Vimentin. FISH testing indicated ALK gene separation in the lesion cells. NGS testing identified the fusion genes KIF5B(NM_004521) and ALK(NM_004304) in the lesion cells. We combined the characteristics of this case with a review of the literature to enhance our understanding of this rare clinical entity.

BHLHE41 inhibits bladder cancer progression via regulation of PYCR1 stability and thus inactivating PI3K/AKT signaling pathway.

BACKGROUND: The basic helix-loop-helix family member e41 (BHLHE41) is frequently dysregulated in tumors and plays a crucial role in malignant progression of various cancers. Nevertheless, its specific function and underlying mechanism in bladder cancer (BCa) remain largely unexplored. METHODS: The expression levels of BHLHE41 in BCa tissues and cells were examined by qRT-PCR and western blot assays. BCa cells stably knocking down or overexpressing BHLHE41 were constructed through lentivirus infection. The changes of cell proliferation, cell cycle distribution, migration, and invasion were detected by CCK-8, flow cytometry, wound healing, transwell invasion assays, respectively. The expression levels of related proteins were detected by western blot assay. The interaction between BHLHE41 and PYCR1 was explored by co-immunoprecipitation analysis. RESULTS: In this study, we found that BHLHE41 was lowly expressed in bladder cancer tissues and cell lines, and lower expression of BHLHE41 was associated with poor overall survival in bladder cancer patients. Functionally, by manipulating the expression of BHLHE41, we demonstrated that overexpression of BHLHE41 significantly retarded cell proliferation, migration, invasion, and induced cell cycle arrest in bladder cancer through various in vitro and in vivo experiments, while silence of BHLHE41 caused the opposite effect. Mechanistically, we showed that BHLHE41 directly interacted with PYCR1, decreased its stability and resulted in the ubiquitination and degradation of PYCR1, thus inactivating PI3K/AKT signaling pathway. Rescue experiments showed that the effects induced by BHLHE41 overexpression could be attenuated by further upregulating PYCR1. CONCLUSION: BHLHE41 might be a useful prognostic biomarker and a tumor suppressor in bladder cancer. The BHLHE41/PYCR1/PI3K/AKT axis might be a potential therapeutic target for bladder cancer intervention.

A population-based propensity score matching analysis of risk factors and the impact on survival associated with refusal of cancer-directed surgery in patients with prostate cancer.

Cancer-directed surgeries (CDS) play a crucial role in prostate cancer (PCa) management along with possible survival and therapeutic benefits. However, barriers such as socioeconomic factors may affect patients' decision of refusing recommended CDS. This study aimed to uncover risk factors and the impact on survival associated with CDS refusal. We retrospectively reviewed the Surveillance, Epidemiology, and End Results database for patients diagnosed with PCa between 2000 and 2019. Multiple sociodemographic and clinical characteristics were extracted to assess predictors for physicians' surgical recommendations and patients' surgical refusal, respectively. Propensity score matching was performed to balance the covariates. The impact of surgical refusal on mortality risk was also investigated. A total of 185,540 patients were included. The physician's recommendation of CDS was significantly influenced by the patient's age, race, income, home location, diagnosis year, Gleason score, prostate-specific antigen (PSA), and TNM stage. About 5.6% PCa patients refused CDS, most of whom were older, non-White race, lack of partners, living outside of metropolitan areas, with higher PSA or lower clinical TNM stage. Patients who refused CDS had an increased risk of cancer-specific mortality and overall mortality than those who performed CDS. Physicians may weigh a host of sociodemographic and clinical factors prior to making a CDS recommendation. Patients' refusal of recommended CDS affected survival and was potentially modifiable by certain sociodemographic factors. Physicians should fully consider the hindrances behind patients' CDS refusal to improve patient-doctor shared decision-making, guide patients toward the best alternative and achieve better outcomes.

Investigating the association between inflammation mediated by mushroom consumption and mild cognitive impairment in Chinese older adults.

Background: Chronic inflammatory stimulation is a major risk factor for mild cognitive impairment. Mushroom consumption and inflammatory factors may play an important role in the pathogenesis of mild cognitive impairment. Additionally, consuming mushrooms can reduce the levels of inflammatory cytokines and preserve cognitive function. Therefore, this study aimed to investigate the relationship between mushroom consumption and serum inflammatory cytokines and mild cognitive impairment (MCI). Methods: Binary logistic regression was used to determine the relationship between mushroom consumption and MCI in 550 participants. Subsequently, mediation analysis was used to analyze the relationship between mushroom consumption, inflammatory factors, and the Montreal Cognitive assessment (MoCA) score in 248 participants. Results: Mushroom consumption was associated with MCI (odds ratio = 0.623, 95% confidence interval = 0.542-0.715, P < 0.001). The association between mushroom intake and MCI was mediated by interleukin-6 (IL-6) and hypersensitive C-reactive protein (hs-CRP), and the MoCA score was 12.76% and 47.59%, respectively. Conclusion: A high intake of mushrooms was associated with a low risk of MCI. Serum inflammatory factors including IL-6 and hs-CRP play a partial mediating role between mushroom intake and the MoCA score, and the underlying mechanism needs to be further explored.

Diagnosis and management of urinary bladder paragangliomas: A Sino-American-European retrospective observational study.

OBJECTIVE: Paragangliomas of the urinary bladder (UBPGLs) are rare neuroendocrine tumours and pose a diagnostic and surgical challenge. It remains unclear what factors contribute to a timely presurgical diagnosis. The purpose of this study is to identify factors contributing to missing the diagnosis of UBPGLs before surgery. DESIGN, PATIENTS AND MEASUREMENTS: A total of 73 patients from 11 centres in China, and 51 patients from 6 centres in Europe and 1 center in the United States were included. Clinical, surgical and genetic data were collected and compared in patients diagnosed before versus after surgery. Logistic regression analysis was used to identify clinical factors associated with initiation of presurgical biochemical testing. RESULTS: Among all patients, only 47.6% were diagnosed before surgery. These patients were younger (34.0 vs. 54.0 years, p < .001), had larger tumours (2.9 vs. 1.8 cm, p < .001), and more had a SDHB pathogenic variant (54.7% vs. 11.9%, p < .001) than those diagnosed after surgery. Patients with presurgical diagnosis presented with more micturition spells (39.7% vs. 15.9%, p = .003), hypertension (50.0% vs. 31.7%, p = .041) and catecholamine-related symptoms (37.9% vs. 17.5%, p = .012). Multivariable logistic analysis revealed that presence of younger age (<35 years, odds ratio [OR] = 6.47, p = .013), micturition spells (OR = 6.79, p = .007), hypertension (OR = 3.98, p = .011), and sweating (OR = 41.72, p = .013) increased the probability of initiating presurgical biochemical testing. CONCLUSIONS: Most patients with UBPGL are diagnosed after surgery. Young age, hypertension, micturition spells and sweating are clues in assisting to initiate early biochemical testing and thus may establish a timely presurgical diagnosis.

LINC00887 regulates malignant progression and T-cell chemotaxis in clear cell renal cell carcinoma by activating CD70 via recruitment of SPI1.

BACKGROUND: LINC00887 has been mentioned in several articles regarding its involvement in various cancers like nasopharyngeal carcinoma, lung cancer and glioma. However, the mechanism of LINC00887 in the malignant progression of clear cell renal cell carcinoma (ccRCC) is still unclear. The topic of our study is mainly centered on exploring how LINC00887 exactly affects ccRCC malignant progression. METHODS: The bioinformatics method predicted the downstream TF and target genes of LINC00887 by the "LncRNA-transcription factor (TF)-Gene" triplet model. RNA immunoprecipitation, chromatin immunoprecipitation analysis, and Dual-luciferase reporter assay determined the regulatory relationship between LINC00887 and its downstream genes. The LINC00887 expression and its downstream gene expression in ccRCC cells were examined by qRT-PCR and Western blot. The effect of LINC00887-SPI1-CD70 modulation axis on proliferative transfer, cell stemness and T cell chemotaxis of ccRCC cells was examined in cellular and animal experiments. RESULTS: Our research demonstrated an upregulation of LINC00887 in ccRCC, which facilitated tumor growth and stemness in vivo. In addition, LINC00887 could upregulate the CD70 expression by recruiting transcriptional factor SPI1. The results of in vitro experiments illustrated that the LINC00887-SPI1-CD70 regulatory axis facilitated ccRCC malignant progression by promoting cell stemness and hindering T-cell chemotaxis. CONCLUSION: LINC00887, by recruiting SPI1, activated CD70 transcription, thereby propelling malignant progression and cell stemness and suppressing T cell chemotaxis in ccRCC. Based on our findings, we believed that the LINC00887-SPI1-CD70 regulatory axis had the potential to be a critical breakthrough for treating ccRCC.