Effect of FGFR alteration on prognosis in 1963 urothelial carcinoma patients with immune checkpoint inhibitors: Implying combination of FGFR inhibitor and immunotherapy for FGFR-altered urothelial carcinoma.

Immune checkpoint inhibitors (ICIs) are essential for urothelial carcinoma (UC) treatment. Fibroblast growth factor receptor (FGFR) alterations, as common oncogenic drivers in UC, have been reported to drive T cell depletion of UC immune microenvironment via up-regulating FGFR signaling, which indicated FGFR alterations potentially result in reduced response to ICIs. In addition, the selective pan-FGFR inhibitor showed better clinical benefit in clinical trials, indicating FGFR has emerged as critical therapeutic target via inhibiting FGFR signaling. The present study aims to evaluate prognosis and response to ICIs between FGFR-altered UC patients and FGFR-wildtype UC patients via 1963 UC patients and offers new insights into personalized precision therapy and combination therapy for UC.

Expression and Clinical Significance of Non B Cell-Derived Immunoglobulins in the Urinary System and Male Reproductive System.

The urinary system comprises kidneys, ureters, bladder, and urethra with its primary function being excretion, referring to the physiological process of transporting substances that are harmful or surplus out of the body. The male reproductive system consists of gonads (testis), vas deferens, and accessory glands such as the prostate. According to classical immunology theory, the tissues and organs mentioned above are not thought to produce immunoglobulins (Igs), and any Ig present in the relevant tissues under physiological and pathological conditions is believed to be derived from B cells. For instance, most renal diseases are associated with uncontrolled inflammation caused by pathogenic Ig deposited in the kidney. Generally, these pathological Igs are presumed to be produced by B cells. Recent studies have demonstrated that renal parenchymal cells can produce and secrete Igs, including IgA and IgG. Glomerular mesangial cells can express and secrete IgA, which is associated with cell survival and adhesion. Likewise, human podocytes demonstrate the ability to produce and secrete IgG, which is related to cell survival and adhesion. Furthermore, renal tubular epithelial cells also express IgG, potentially involved in the epithelial-mesenchymal transition (EMT). More significantly, renal cell carcinoma, bladder cancer, and prostate cancer have been revealed to express high levels of IgG, which promotes tumour progression. Given the widespread Ig expression in the urinary and male reproductive systems, continued efforts to elucidate the roles of Igs in renal physiological and pathological processes are necessary.

Comparison of Eliminating Artificial Hydronephrosis and Creating Artificial Hydronephrosis in Percutaneous Nephrolithotomy in Oblique Supine Position.

INTRODUCTION: The safety and effectiveness of percutaneous nephroscopic surgery without artificial hydronephrosis remain controversial, and there are few relevant studies. This retrospective study aimed to compare the efficacy of two different methods of eliminating and creating artificial hydronephrosis in percutaneous nephrolithotomy (PCNL) in the oblique supine position. METHODS: This is a retrospective study. A total of 162 patients who underwent PCNL in an oblique supine position at our hospital were divided into two groups according to the surgical method: the free artificial hydronephrosis group (group A) and the artificial hydronephrosis group (group B). Group A was directly treated with PCNL under ultrasound guidance, and group B was treated with artificial hydronephrosis before PCNL. Several outcomes were measured, including procedure time, stone clearance rate, and incidence of complications. RESULTS: The procedure time in group A lower than that in group B, and the incidence of sepsis was significantly lower in group A than in group B (p < 0.05). There was no statistical difference in stone clearance rate, success rate of primary establishment of puncture channel, unilateral change in perioperative red blood cell count, change in perioperative renal function, and perioperative complications (except sepsis) between the two groups (p > 0.05). CONCLUSION: For experienced physicians, PCNL without artificial hydronephrosis in an oblique supine position can be attempted to reduce the number of surgical steps without affecting the stone clearance rate and increasing the occurrence of complications.

Effect of regional versus general anesthesia on recurrence of non-muscle invasive bladder cancer: a systematic review and meta-analysis of eight retrospective cohort studies.

BACKGROUND: Regional anesthesia appears to reduce cancer recurrence, but the optimal anesthesia modality for non-muscle invasive bladder cancer (NMIBC) were still under debate. Therefore, we sought to assess the effect of regional and GA only upon the recurrence and long-term prognosis of NMIBC through this meta-analysis. METHODS: We performed an extensive literature search of PubMed, Embase, Web of Science, the Cochrane Library and China National Knowledge Infrastructure (up to October 30, 2022) to identify eligible articles on the possible impact of different anesthetic modalities for the recurrence rate of NMIBC. RESULTS: Eight studies comprising 3764 participants, including 2117 subjects with RA and 1647 with GA, were finally enrolled. Cancer recurrence rate was significantly lower in subjects with RA than those with GA (RR 0.84, 95%CI 0.72-0.98, P = 0.03). We didn't detect the differences between GA and RA in the time of recurrence (SMD 2.07, 95% CI -0.49-4.63, P = 0.11) and cancer progression (RR 1.14, 95%CI 0.71-1.84, P = 0.59). Results from subgroup analysis demonstrated that spinal anesthesia could significantly decrease the incidence of cancer recurrence in comparison with general anesthesia (RR 0.80, 95%CI 0.72-0.88, P < 0.001) and high-risk NMIBC patients who received RA tended to have less recurrence (HR 0.55, 95%CI 0.39-0.79, P = 0.001) than those receiving GA. CONCLUSIONS: RA, especially spinal anesthesia, may be effective in reducing the recurrence rate after transurethral resection of NMIBC. More prospective experimental and clinical studies are needed to validate our findings. TRIAL REGISTRATION: INPLASY registration INPLASY2022110097.

Intratumoral fibrosis and patterns of immune infiltration in clear cell renal cell carcinoma.

BACKGROUND: Intratumoral fibrosis was positively correlated with histological grade of renal clear cell carcinoma (ccRCC) and intratumoral inflammation. However, the association of intratumoral fibrosis with the immune infiltration of ccRCC was few evaluated. METHODS: We used the second harmonic generation (SHG)-based imaging technology and evaluated the intratumoral fibrosis in ccRCC, and then divided the patients into the high fibrosis group (HF) and the low fibrosis group (LF). Meanwhile, the Kaplan-Meier survival curve analysis was performed to analyze the relationship between intratumoral fibrosis and the disease-free survival rate. Antibody arrays were used for seeking difference in cytokines and immune infiltration between the HF group (N = 11) and LF group (N = 11). The selected immune infiltration marker was then verified by immunohistochemistry (IHC) staining in 45 ccRCC samples. RESULTS: Out of 640 cytokines and immune infiltration markers, we identified 115 proteins that were significantly different in quantity between ccRCC and adjacent normal tissues. In addition, the Venn diagram indicated that six proteins, including Cytotoxic T-Lymphocyte Associated Protein 4 (CTLA4), were significantly associated with intratumoral fibrosis (p < 0.05). The GO/KEGG enrichment analysis indicated that the proteins associated with intratumoral fibrosis were involved in the immunity and tumor-infiltrating lymphocytes. The expression of the CTLA4 was negatively correlated with collagen level, confirmed by IHC staining of CTLA4 (p < 0.05). CONCLUSIONS: The study indicated that the intratumoral fibrosis level was negatively correlated with the expression of CTLA4 in the tumor immune microenvironment of the ccRCC, which posed the potential value of targeting the stroma of the tumor, a supplement to immunotherapy. However, the specific mechanism of this association is still unclear and needs further investigation.

Predicting ureteral status below the ureteral calculi in patients undergoing ureteroscopic lithotomy.

BACKGROUND: During ureteroscopy, severe ureter straightness or contortion may occur before the stone is passed. PURPOSE: To identify clinical factors associated with distal ureteral status below the ureteral calculi in patients before surgery. MATERIAL AND METHODS: From October 2016 to March 2017, 101 patients with ureteral calculi who underwent ureteroscopic lithotripsy were reviewed. Patients who lacked clinical data and underwent preoperative indwelling ureteral stent placement were excluded. Univariate and multivariate analyses were performed to determine the clinical factors associated with intraoperative findings. RESULTS: A total of 101 patients were enrolled in the study (mean age = 54 years; mean stone size = 7.9 ± 4.5 mm). Overall, 25 of the 101 patients (24.7%) were diagnosed with poor distal ureteral status defined as intraoperative ureterostenosis or contortion resulting in a ureteroscope being unable to pass during the initial attempt. Univariate analysis showed significant differences in renal parenchyma thickness, ureteral wall thickening on imaging, and stone location (all, P < 0.05) with and without poor distal ureteral status. On multivariable analysis, renal parenchyma thickness (adjusted odds ratio [aOR] 0.288; 95% confidence interval [CI] 0.099-0.838; P = 0.022) and ureteral wall thickening on imaging (aOR 6.114; 95% CI 2.015-18.548; P = 0.001) independently predicted poor distal ureteral status. However, only renal parenchyma thickness was associated with severe ureter straightness or tortuosity that resulted in conversion. CONCLUSION: In conclusion, renal parenchyma thickness and ureteral wall thickening on imaging were associated with poor distal ureteral status. Therefore, patients with these predictive factors should undergo more intensive preparation before surgery.

Cancer-driven IgG promotes the development of prostate cancer though the SOX2-CIgG pathway.

BACKGROUND: Although androgen deprivation therapy (ADT) is the initial treatment strategy for prostate cancer (PCa), recurrent castration-resistant prostate cancer (CRPC) eventually ensues. In this study, cancer-derived immunoglobulin G (CIgG) is found to be induced after ADT, identifying CIgG as a potential CRPC driver gene. METHODS: The expression of CIgG and its clinical significance in PCa tissue was analyzed by The Cancer Genome Atlas database and immunohistochemistry. Subsequently, the sequence features of prostate cell line VHDJH rearrangements were analyzed. We also assessed the effect of CIgG on the migratory, invasive and proliferative abilities of PCa cells in vitro and vivo. Suspended microsphere, colony formation and drug-resistant assays were performed using PC3 cells with high CIgG expression (CIgGhigh ) and low CIgG expression (CIgG-/low ), and A nonobese diabetic/severe combined immunodeficiency mouse tumor xenograft model was developed for the study of the tumorigenic effects of the different cell populations. The SOX2-CIgG signaling pathway was validated by immunohistochemistry, immunofluorescence, quantitative reverse transcription-polymerase chain reaction, Western blot, luciferase, and chromatin immunoprecipitation assays and bioinformatics analyses. Finally, we investigated the effect of RP215 inhibition on the progression of PCa in vivo using a Babl/c nude mouse xenograft model. RESULTS: CIgG is frequently expressed in PCa and associated with clinicopathological characteristics, moreover, CIgG transcripts with unique patterns of VHDJH rearrangements are found in PCa cells. Functional analyses identified that CIgG was induced by ADT and upregulated by SOX2 (SRY (sex determining region Y)-box 2) in PCa, promoting the development of PCa. In addition, our findings underscore a novel role of CIgG signaling in the maintenance of stemness and the progression of cancer through mitogen activated protein kinase/extracellular-signal-regulated kinase and AKT in PCa. In vivo experiments further demonstrated that depleting CIgG significantly suppressed the growth of PCa cell xenografts. Furthermore, a CIgG monoclonal antibody named RP215 exhibits tumor inhibitory effect as well. CONCLUSION: Our data suggests that CIgG could be a driver of PCa development, and that targeting the SOX2-CIgG axis may therefore inhibit PCa development after ADT.

[Advances in Pelvic Lymph Node Dissection for Bladder Cancer].

Bladder cancer has high morbidity and mortality rates worldwide. Its incidence is high in western countries and has shown an increasing trend in China. While radical cystectomy combined with pelvic lymph node dissection (PLND) is the standard treatment for bladder cancer,the optimal range of PLND remains controversial. In addition,the prognostic value of lymph node factors is also unclear. This article reviews research advances in PLND.

Knocking down glycoprotein nonmetastatic melanoma protein B suppresses the proliferation, migration, and invasion in bladder cancer cells.

Glycoprotein nonmetastatic melanoma protein B is a type 1 transmembrane protein that has been recently found to play a role in cancer cell proliferation, angiogenesis, and invasion. Due to its potential responsibility in cancer aggressiveness, the main objective of this work was to investigate its expression in bladder cancer and the biological functions in bladder cancer cells. Using immunohistochemistry, western blot, and reverse transcription polymerase chain reaction, we analyzed the expression of glycoprotein nonmetastatic melanoma protein B in bladder cancer tissues and bladder cancer cell lines. The effects of glycoprotein nonmetastatic melanoma protein B on proliferation, migration, and invasion were tested after knocking down the glycoprotein nonmetastatic melanoma protein B in bladder cancer cells with small interfering RNAs by CCK-8, Transwell, and Matrigel assays. Our results showed that glycoprotein nonmetastatic melanoma protein B protein was highly expressed in the bladder cancer tissues and cell lines. Downregulating glycoprotein nonmetastatic melanoma protein B could suppress the proliferation, migration, and invasion in bladder cancer cells. Glycoprotein nonmetastatic melanoma protein B expression was related to the poor differentiation and recurrence by immunohistochemistry analysis. The survival analysis also showed that glycoprotein nonmetastatic melanoma protein B was related to the patient prognosis. In conclusion, Glycoprotein nonmetastatic melanoma protein B protein was highly expressed in the bladder cancer, which was related to the poor prognosis in bladder cancer patients. Glycoprotein nonmetastatic melanoma protein B promoted the proliferation, migration, and invasion in bladder cancer cells.

Establishment and Evaluation of Patient-Specific Virtual Ureteroscopy in Assisting Flexible Ureteroscopy for Urolithiasis.

OBJECTIVES: To establish virtual ureteroscopy (VU) through computed tomography urography (CTU) data from patients with upper urinary tract (UUT) stones indicated for flexible ureteroscopy (fURS) and to validate its effectiveness. METHODS: Patient-specific VU generation was accomplished through incorporating CTU data into specialized software (Crusher) developed on the open access Visualization Tools Kit (VTK). These were then presented to fURS experts and novice urologists for evaluation and comparison using modified Likert-type questionnaire of 10-point rating scales (1 = not at all useful/not at all realistic/poor, 10 = very useful/very realistic/ excellent). RESULTS: Face and content validation of VU from 5 fURS experts in 3 different centers: overall usefulness 7.4 ± 0.5, graphics 7.4 ± 0.5, intrarenal anatomy 8.4 ± 0.5, stone details 7.8 ± 0.4, usefulness in surgical planning and training 7.6 ± 0.9. Significant increase of detection in the number of calyces and stones was found from using CTU only to CTU-VU combined in the novice group ( P = .000). Before VU observation, novices found much fewer calyces and stones than experts ( P = .004 and .000, respectively). However, this gap disappeared after VU observation ( P = .327 and .292, respectively). VU feedback from the novices was superb. CONCLUSIONS: Establishing patient-specific VU through CTU data from renal stone patients is feasible. The present VU can significantly improve novice urologists' comprehension of intrarenal anatomy and stone information before fURS procedures. Face and content validity is also proved. This novel modality may serve as an important tool for fURS surgical planning, navigation, and training.

Research Advances in CKLFSF-like MARVEL Transmembrane Domain Containing Member 3.

CKLF-like MARVEL transmembrane domain containing member/chemokine-like factor super family member (CKLFSF/CMTM) is a novel tumor suppressor gene. CMTM3 is broadly expressed in normal human tissues and evolutionary conserved,especially in testis,spleen,and some cells of peripheral blood mononuclear cells. However,its expression is undetectable or down-regulated in most carcinoma cell lines and tissues. Restoration of CMTM3 may inhibit the proliferation,migration,and invasion of carcinoma cells. Although the exact mechanism of its anti-tumor activity remains unclear,CKLFSF3/CMTM3 is closely connected with immune system and associated with sex during tumorigenesis. The study advances of CKLFSF3/CMTM3 are elaborated in this review as CMTM3 may be a new target in the gene therapies for tumors,especially genitourinary tumors,while further studies on CMTM3 and its anti-tumor mechanisms are warranted.

[Expression and significance of CMTM5 and epidermal growth factor receptor in prostate cancer].

OBJECTIVE: To investigate the expression patterns of CKLF-like MARVEL transmembrane domain containing 5 (CMTM5), a novel tumor suppressor, and epidermal growth factor receptor (EGFR) in prostate cancer (PCa) tissues and cells and to analyze the relationship between CMTM5 and EGFR in PCa. METHODS: The expression patterns of CMTM5 and EGFR in PCa tissues and cells were detected by immunohistochemistry and Western blot, respectively. RESULTS: CMTM5 was highly expressed in 75% (27/36) of benigh prostatic hyperplasia (BPH) tissues but 35.9% (23/64) of PCa tissues (P<0.001). There was a significant difference of CMTM5 expression between the two groups of PCa tissues with different Gleason scores (P=0.003), though its expression was not related to the age, clinical stage, and metastatic situation (P>0.05). EGFR was highly expressed in 57.8% (37/64) of PCa tissues, it had statistical significance between EGFR and CMTM5 expressions in PCa tissues. Furthermore, 23 cases (35.9%) had low CMTM5 expression and high EGFR expression. Western blot showed that CMTM5 was undetectable in PCa cells, in which the EGFR expression was upregulated. CONCLUSION: The loss of CMTM5 may participate in the progression of PCa resulting from deregulated EGFR.

[Expression of glycoprotein non-metastatic melanoma protein B in clear-cell renal cell carcinoma and clinical implication thereof].

OBJECTIVE: To elucidate the glycoprotein non-metastatic melanoma protein B(Gpnmb) expression in clear-cell renal cell carcinoma (ccRCC) and to determine its potential prognostic relevance. METHODS: A total of 12 pairs of ccRCC tissue specimens were collected from patients undergoing surgery in our hospital from March 2009 to March 2012. Gpnmb expression were determined by immunohistochemistry and correlated with clinical variables. Survival analysis was carried out for another 43 evaluable patients. RESULTS: The expression level of Gpnmb was significantly higher in metastatic ccRCCs than that in matched primary samples ((6.36±4.01) vs (3.14±2.38) scores, P=0.036). The high expression of Gpnmb was not affected by age, gender, clinical stage and pathological grade (all P>0.05). Kaplan-Meier analysis disclosed significant differences in overall survival for patients with higher and lower average Gpnmb expression levels (P=0.020). Cox regression analysis revealed that a high Gpnmb protein expression level in the tumor cell could be identified as an independent poor prognostic marker of overall survival in ccRCC patients (P=0.049). CONCLUSION: Over expression of Gpnmb in tumour cell predicts a poor prognosis of patients with ccRCC.