Low Expression of GRIM-19 Correlates with Poor Prognosis in Patients with Upper Urinary Tract Urothelial Carcinoma.

PURPOSE: This study aimed to clarify the expression of a gene associated with Retinoid- Interferon-Induced Mortality-19 (GRIM-19) in Upper Urinary Tract Urothelial Carcinoma (UUTUC) and its prognostic significance for UUTUC patients. MATERIALS AND METHODS: Immunohistochemical (IHC) staining was used to determine the GRIM-19 expression in 70 paired samples. Progression-Free Survival (PFS) and Cancer-Specific Survival (CSS) were assessed using the Kaplan-Meier method. The independent prognostic factors for PFS and CSS were analyzed by multivariable Cox regression models. RESULTS: IHC staining showed that GRIM-19 expression was significantly decreased in UUTUC, and its cellular location changed from being both cytoplasmic and nuclear to only cytoplasmic. Kaplan- Meier analysis revealed that the patients with tumors expressing low GRIM-19 had a significantly higher risk for tumor progression (P = 0.002) and cancer-specific mortality (P < 0.001) compared to those with high GRIM-19 levels. The Cox regression showed that both GRIM-19 expression (P = 0.025) and lymph node metastasis (LN) (P = 0.007) were independent predictors of progression in the muscle-invasive (MIC) subgroup. GRIM-19 expressions (entire cohort: P = 0.011; MIC subgroup: P = 0.025), LN (entire cohort: P = 0.019; MIC subgroup: P = 0.007), and progression (entire cohort: P < 0.001; MIC subgroup: P < 0.001) were independent predictors of cancer-specific survival. CONCLUSION: Low expression of GRIM-19 in patients with UUTUC had significantly shorter PFS or CSS compared to those with high GRIM-19-expressing tumors. High GRIM-19 expression was also strongly associated with longer PFS in MIC patients. It indicates that GRIM-19 might serve as a promising prognostic biomarker for UUTUC patients.

[Analysis of minimally invasive treatment in the management of prostatic abscess].

OBJECTIVE: To analyze the proper time and method for treatment of prostatic abscess (PA). METHODS: This is a retrospective study that included 18 patients diagnosed with and treated for prostatic abscess between February 2017 and July 2022. After obtaining data from the patients' medical records, we analyzed their clinical features as well as the therapeutic methods opted for and their effectiveness. Results： Of the 18 patients included, one achieved a full recovery after a spontaneous rupture of the abscess. Transrectal ultrasound (TRUS)-guided aspiration was performed in the remaining 17 patients, of whom 14 had a complete resolution after this procedure whereas 3 experienced recurrence. The recurrent cases were successfully managed with transurethral (TU) de-roofing. CONCLUSION: TRUS-guided aspiration is a treatment modality with a marked curative effect for simple PAs. For refractory abscesses (recurrent, multifocal, incomplete or unsuccessful drainage) or PA located near the urethra, TU de-roofing can be considered as a first choice to shorten the course of the disease and alleviate the medical treatment expenses due to recurrence.

Preoperative Predictors of Biochemical Recurrence-Free Survival in High-Risk Prostate Cancer Following Radical Prostatectomy.

Background: D'Amico high-risk prostate cancer (Pca) patients experience poor and heterogeneous oncological outcomes. This heterogeneity highlights a need to extensively explore factors associated with poor outcomes to guide decision-making. Objective: To assess predictors of biochemical recurrence (BCR)-free survival in high-risk patients following radical prostatectomy (RP), and subsequently establish a model predicting outcomes. Methods: We retrospectively identified D'Amico high-risk non-metastatic Pca patients who underwent RP between 2013 and 2019 in our hospital. We collected data including PSA level, clinical stage, biopsy Gleason score (GS), number of D'Amico high-risk factors (RF), the inflammatory status (Neutrophil-to-lymphocyte ratio [NLR], derived NLR [dNLR], platelet-to-lymphocyte ratio [PLR] and LDH). Kaplan-Meier methods were used to analyze BCR-free survival. Univariate and multivariate analyses were performed using Cox proportional hazards model to evaluate the association between clinicopathological parameters and BCR-free survival. Results: The median follow-up time for the 101 patients' cohort was 26 months (range: 3-81 months). The number of RF (1RF vs. ≥2RF), biopsy GS (<8 vs. ≥8), clinical stage (≤cT2c vs. >cT2c), pathological stage, and the presence of adverse pathological features were significant predictors of BCR (P < 0.05). Other parameters including inflammatory status (dNLR, NLR, PLR, and LDH) were not of predictive value. On multivariable analysis, biopsy GS (<8 vs. ≥8; HR 2.439) and clinical stage (≤cT2c vs. >cT2c; HR 3.271) were the independent predictors of BCR. Based on these two independent predictors, patients were stratified into three risk subgroups: favorable (0 risk factor; 47% of patients), intermediate (1 risk factor; 42 %), unfavorable (2 risk factors; 11%). The intermediate and unfavorable subgroups have a significantly shorter median BCR-free survival compared to the favorable subgroup (P < 0.001). Conclusion: Several factors are associated with BCR. Clinical stage (≤cT2c vs. >cT2c) and biopsy GS (<8 vs. ≥8) are the independent predictors of BCR. The stratification of high-risk patients into risk subgroups based on these two predictors shows that the intermediate and unfavorable subgroups have a significantly shorter median BCR-free survival compared to the favorable subgroup. The preoperative stratification model may help urologists and patients during decision-making. In non-metastatic high-risk patients, preoperative inflammatory markers (NLR, dNLR, PLR, and LDH) are not of prognostic value.

GRIM-19 deficiency promotes clear cell renal cell carcinoma progression and is associated with high TNM stage and Fuhrman grade.

Clear cell renal cell carcinoma (ccRCC) exhibits the highest mortality among all urological malignancies. The investigation of the potential disease progression markers can improve ccRCC diagnosis and treatment. Gene associated with retinoid-interferon-induced mortality-19 (GRIM-19) is involved in carcinogenesis and cancer progression in a variety of cancer types including RCC. While, its role in ccRCC remains unclear, this cancer type is considered the most aggressive RCC subtype. In the present study, RT-qPCR, western blotting and immunohistochemical (IHC) assays demonstrated that GRIM-19 protein and mRNA levels were downregulated in ccRCC tumor tissues compared with the corresponding levels noted in paracancerous non-tumor tissues. The deficiency of this protein contributed in relaxed and/or collapsed structures of the kidney tubules and collecting duct noted in tumor tissues. Moreover, the reduction in GRIM-19 expression was associated with high tumor, lymph nodes and metastasis (TNM) stage and Fuhrman grade of ccRCC tumors. The data suggested that GRIM-19 acted as a tumor suppressor and that its deficiency promoted ccRCC development and progression. GRIM-19 can be considered a potential tumor marker for ccRCC.

miR-429-CRKL axis regulates clear cell renal cell carcinoma malignant progression through SOS1/MEK/ERK/MMP2/MMP9 pathway.

The pathogenesis and tumorigenesis of clear cell renal cell carcinoma (ccRCC) remain unclear. The deregulations of miR-429, a member of miR-200 family, and v-crk sarcoma virus CT10 oncogene homologue (avian)-like (CRKL), an adaptor protein of CRK family, are involved in the development, metastasis and prognosis of various cancers. Current study aimed to demonstrate the differential expressions of miR-429 and CRKL with their correlationship and molecular regulation mechanism in ccRCC malignancy. miR-429 and CRKL separately showed suppressing and promoting effects in ccRCC. Lower miR-429 expression and higher CRKL expression were negatively correlated in surgical cancerous tissues by promoting the advance of ccRCC. By binding to the 3'-UTR of CRKL, miR-429 reversely regulated CRKL for its functionalities in ccRCC cells. CRKL knockdown and overexpression separately decreased and increased the in vitro migration and invasion of 786-O cells, which were consistent with the influences of miR-429 overexpression and knockdown on 786-O through respectively downregulating and upregulating CRKL via SOS1/MEK/ERK/MMP2/MMP9 pathway. The enhancements of CRKL expression, migration and invasion abilities and SOS1/MEK/ ERK/MMP2/MMP9 activation induced by TGF-ß stimulation in 786-O cells could be antagonized by miR-429 overexpression. Exogenous re-expression of CRKL abrogated miR-429 suppression on the migration and invasion of 786-O cells. Collectively, miR-429 deficiency negatively correlated with CRKL overexpression promoted the aggressiveness of cancer cells and advanced the clinical progression of ccRCC patients. miR-429-CRKL axial regulation provides new clues to the fundamental research, diagnosis and treatment of ccRCC.

Renal Cell Carcinoma Metastasizing to Left Atrium With Coronary Sinus Invasion: A Rare Site of Metastasis Mimicking Myxoma.

Renal cell carcinoma (RCC) metastasizing to the heart with inferior vena cava (IVC) involvement is well-documented. However, its metastasis to the right heart without venous involvement is very rare. To the left atrium, metastasis is even rarer with only a few cases reported in medical literature. Herein, we report a case of a 56-year-old man who presented to our department for the treatment of a right renal mass and a right adrenal mass discovered on a follow-up plain computed tomography (CT) 13 years after left laparoscopic radical nephrectomy. During the workup, a transthoracic echocardiography (TTE) revealed a left atrial mass with a suspicion of a myxoma. This finding prompted a cardiac surgery consult which proposed a surgical removal of the mass. Intraoperatively, the tumor was found to invade the coronary sinus as well. The entire tumor was successfully removed and surgical repair of the unroofed coronary sinus was performed. Pathological examination of the tumor along with immunohistochemistry-showing positivity for CAIX, CD10, Vimentin, and PAX-8-pointed to a diagnosis of metastatic clear cell RCC. Eight months postoperatively, he was free of any symptom. In conclusion, RCC metastasizing to the left atrium is extremely rare. A comprehensive search revealed only nine reports in the literature. We report, to our knowledge, the first case of RCC metastasizing to the left atrium with concomitant invasion of coronary sinus. Surgical resection combined with unroofed coronary sinus repair allowed a complete removal of the tumor. In patients with a history of RCC, a metastasis should be thought of when a left atrial mass is present.

miR-4521-FAM129A axial regulation on ccRCC progression through TIMP-1/MMP2/MMP9 and MDM2/p53/Bcl2/Bax pathways.

Clear cell renal cell carcinoma (ccRCC) is the most aggressive RCC subtype with high metastasis, chemotherapy and radiotherapy resistance, and poor prognosis. This study attempted to establish the deregulations of miR-4521 and FAM129A together with their correlation to and mechanism of regulation of ccRCC development and progression. FAM129A acted as tumor promotor and miR-4521 acted as a suppressor in ccRCC. As measured in surgical tumorous tissues from ccRCC patients, FAM129A overexpression and miR-4521 deficiency together contributed to ccRCC progression by promoting advances in patients' TNM stage and Fuhrman grade. Both the FAM129A knockdown and miR-4521 overexpression could reduce the in vitro migration and invasion abilities of renal cancer cells 786-O and ACHN, through the TIMP-1/MMP2/MMP9 pathway and could decrease their proliferation by promoting their apoptosis through the MDM2/p53/Bcl2/Bax pathway. By directly targeting the 3'-UTR domain of FAM129A, miR-4521 was negatively correlated with FAM129A/FAM129A levels in ccRCC progression and renal cancer cell malignancies. This work establishes the miR-4521-FAM129A axial regulation mechanism in ccRCC. Micro-4521 deficiency leads to FAM129A/FAM129A upregulation, which synergistically enhances the migration and invasion of renal cancer cells due to the induced decrease of TIMP-1 and increases of MMP2 and MMP9, and increases their growth through escaping apoptosis by suppressing p53 by way of upregulation of induced MDM2. The current work provides new clues to assist fundamental research into the diagnosis and treatment of ccRCC.

High expression of spindle and kinetochore- associated protein 1 predicts early recurrence and progression of non-muscle invasive bladder cancer.

BACKGROUND: Spindle and kinetochore-associated protein 1 (SKA1) is a component of SKA, which is essential for proper chromosome segregation. Recently, SKA1 was found to be over-expressed in several types of human cancers. However, reports on the relationship between SKA1 expression and the prognosis of bladder cancer, in particular, are lacking. OBJECTIVES: To clarify the clinical significance of SKA1 as a prognostic biomarker for early recurrence and progression of patients with non-muscle invasive bladder cancer (NMIBC). METHODS: The differential expression levels of SKA1 of 148 NMIBC tissues were determined by immunohistochemical staining. Quantitative real-time PCR and western blot analysis were further performed to confirm the immunohistochemistry results. Recurrence and progression free interval were assessed by Kaplan-Meier method and differences between groups calculated by log-rank statistics. The prognostic value of SKA1 for early recurrence and progression was analyzed by multivariate Cox proportional hazard regression models. RESULTS: SKA1 expression was significantly different in various NMIBC tissues. Kaplan-Meier analysis revealed that patients with high SKA1 expression showed high early recurrence (p< 0.001) and progression (p< 0.05) rates. Although univariate Cox regression analysis revealed that several other factors had an impact on recurrence and progression, upon multivariate analysis, high SKA1expression was the only independent predictor for early recurrence (hazards ratio [HR], 0.246; 95% confidence interval [CI], 0.131-0.461; p= 0.000) and progression (HR, 0.194; 95% CI, 0.052-0.715; p= 0.014). CONCLUSIONS: High SKA1 expression is associated with early recurrence and progression in patients with NMIBC, indicating SKA1 may serve as a promising prognostic biomarker for this disease.

[Pneumoscrotum induced by spontaneous colon perforation: a case report and review of the literature].

One case of pneumoscrotum associated with spontaneous colon perforation was reported. The patient was a 66-year-old man, presented with high temperature, mild abdominal pain and an enlarged scrotum. Physical examination revealed scrotal swelling, abdominal tenderness Case Report and muscular defense. Computed tomography (CT) of the abdomen showed swelling and pneumatosis of the left major psoas and iliopsoas muscles, and ultrasound found subcutaneous emphysema of the scrotum. Surgical investigation discovered a retroperitoneal perforation in the descending colon connected with a huge retroperitoneal vomica and scrotal sac. Spontaneous colon perforation induced pneumoscrotum is rare clinically. It may present as colon perforation, which calls for special attention.