Background: The significance of circular RNA in tumour biology is increasingly recognized. This study aims to explore the value of circFAM64A(3) in the proliferation and immune evasion of bladder cancer. Methods: Bioinformatics were used to identify the differentially expressed circular RNAs in bladder cancer. Proliferation assay, co-culture assay and flow cytometry assay confirmed the oncogenic and immune-evading characteristics of circFAM64A(3) in bladder cancer in vitro and in vivo. Further, mRNA sequencing, RNA pulldown, and RNA immunoprecipitation were used to confirm the downstream targets and pathways regulated by circFAM64A(3). CUT&TAG assay confirmed HIF-1 alpha promoted the expression of circFAM64A(3) under hypoxic. Results: CircFAM64A(3) was significantly high expression in bladder cancer tissues and related with poor prognosis of bladder cancer patients. CircFAM64A(3) promoted bladder cancer cells proliferation and immune evasion in vitro and in vivo. Mechanistically, circFAM64A(3) acted as a sponge to miR-149-5p and reduced the binding of miR-149-5p to IL-6 3 '-UTR. Then, IL-6 activated the JAK/STAT pathway and caused an increase of PDL1. Under hypoxic environment, HIF-1 alpha bound to the promoter of FAM64A and promoted circFAM64A(3) transcription. Conclusion: HIF-1 alpha/circFAM64A(3)/miR-149-5p/IL-6 axis was an important regulatory pathway in bladder cancer proliferation and immune evasion. CircFAM64A(3) may serve as a novel and potentially valuable biological target.

N6-methyladenosine (m6A) is important in the physiological processes of many species.Methyltransferase-like 16 (METTL16) is a novel discovered m6A methylase, regulating various tumors in an m6A-dependent manner.However, its function in bladder cancer (BLCA) remains largely unclear.In the present study, we found that low expression of METTL16 predicted poor survival in BLCA patients.METTL16 inhibited the proliferation and cisplatin-resistance function of bladder cancer cells in vitro and in vivo.In addition, METTL16 reduced the mRNA stability of prostate transmembrane protein androgen induced-1 (PMEPA1) via binding to its m6A site in the 3'-UTR, thereby inhibited the proliferation of bladder cancer cells and increased the sensitivity of cisplatin through PMEPA1-mediated autophagy pathway.Finally, we found that hypoxia-inducible factor 2α (HIF-2α) exerted its tumor-promoting effect by binding the METTL16 promoter region to repress its transcription.Taken together, High expression of METTL16 predicted better survival in BLCA.METTL16 significantly inhibited bladder cancer cell proliferation and sensitized bladder cancer cells to cisplatin via HIF-2α-METTL16-PMEPA1-autophagy axis in a m6A manner.These findings might provide fresh insights into BLCA therapy.

You have accessJournal of UrologyBladder Cancer: Non-invasive II (PD30)1 May 2024PD30-04 UNVEILING THE NECESSITY: SHOULD (VERY) HIGH-RISK NMIBC PATIENTS UNDERGOING RC OPT FOR PELVIC LYMPH NODE DISSECTION?—A PROSPECTIVE COHORT STUDY Qiang Lyu, Xiao Yang, Qiang Cao, and Juntao Zhuang Qiang LyuQiang Lyu , Xiao YangXiao Yang , Qiang CaoQiang Cao , and Juntao ZhuangJuntao Zhuang View All Author Informationhttps://doi.org/10.1097/01.JU.0001008848.77629.6f.04AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookLinked InTwitterEmail Abstract INTRODUCTION AND OBJECTIVE: While Radical Cystectomy (RC) accompanied by Pelvic Lymph Node Dissection (PLND) stands as the cornerstone treatment for Muscle-Invasive Bladder Cancer (MIBC), its necessity remains a subject of contemplation for (very) high-risk Non-Muscle Invasive Bladder Cancer (NMIBC) due to the possible operative complications. This study was aimed to elucidate the necessity of PLND during RC for patients within the (very) high-risk NMIBC. METHODS: From January 2021, patients diagnosed with (very) high-risk NMIBC, displaying no signs of swollen lymph nodes (or lymph nodes ≤8mm) as per MRI/CT scans, were prospectively enrolled. The patients were then randomized to undergo either RC with PLND or RC only (NCT: 05123625). Comprehensive perioperative clinical data, 90-day postoperative complications, and related medical expenses were documented. The endpoint was progression-free survival (PFS) and overall survival (OS). RESULTS: From September 20, 2023, 101 patients were prospectivelly enrolled, though 6 cases were subsequently excluded due to muscle invasiveness. The cohort consisted of 81 males and 41 females. Within the RC+PLND group (40 cases), the median age was 66.5 years (IQR: 57-73), encompassing 17 high-risk and 23 very high-risk cases. The pathological evaluations revealed 37 high-grade and 3 low-grade cases, with stage distribution being Ta/Tis in 6 cases and T1 in 34 cases. An average of 14 lymph nodes were dissected, yet none tested positive. In the RC only group (55 cases), the median age was 66 years (IQR: 59-73), dividing into 36 high-risk and 19 very-high risk cases. Pathologically, there were 51 high-grade and 4 low-grade cases, with Ta/Tis in 9 cases and T1 in 46 cases. Operation time (253±65 min vs. 297±81 min, p=0.004) and intraoperative blood loss (244±165 ml vs. 303±220 ml, p=0.142) were significantly lower in the RC group compared to the RC+PLND group. Additionally, the postoperative hospital stay was shorter (7.7±2.5 days vs. 10.2±5.7 days, p=0.016), and the incidence of Clavien-Dindo grade III complications was lower (6.7% vs. 41.7%, p=0.06) in the RC group. Besides, at a median follow-up of 13.5 months (IQR: 4.4-20.4), no significant difference was observed in PFS and OS between the two groups. CONCLUSIONS: For (very) high-risk NMIBC patients, combined PLND has no survival benefit but increases the incidence of complications. Source of Funding: This study has received funding by the National Natural Science Foundation of China. (No: 82072832, 82273152) © 2024 by American Urological Association Education and Research, Inc.FiguresReferencesRelatedDetails Volume 211Issue 5SMay 2024Page: e625 Advertisement Copyright & Permissions© 2024 by American Urological Association Education and Research, Inc.Metrics Author Information Qiang Lyu More articles by this author Xiao Yang More articles by this author Qiang Cao More articles by this author Juntao Zhuang More articles by this author Expand All Advertisement PDF downloadLoading ...

e16599 Background: Although multiple single-arm clinical trials have shown promising pathologic complete response (pCR) rates with neoadjuvant ICIs combined with gemcitabine plus cisplatin in MIBC, lymph node‐positive bladder cancer is generally excluded. Our specific aim was to compare the efficacy and prognosis of neoadjuvant tislelizumab combined with gemcitabine plus cisplatin in patients with lymph node‐positive bladder cancer. Methods: In this single arm phase II study, eligible patients had cT2-T4a N+ M0 MIBC, cisplatin-eligible, and to be planned radical cystectomy (RC). Patients received tislelizumab 200 mg in day D8, cisplatin 70 mg/m2 D2, and gemcitabine 1000 mg/m2 D1 and D8 every 21 days for 3 or 4 cycles. RC was performed within 6 weeks after last dose treatment. The primary endpoint was pathologic complete response (pCR, ypT0). Secondary endpoints included pathologic downstaging ( < ypT2), EFS, OS and safety. Results: By Jan 2023, 17 eligible pts (2cT2, 10 cT3, 5 cT4) were enrolled. 14 pts have completed neoadjuvant therapy, with median age of 67 (60-81) years, among whom 10 pts underwent RC and two declined RC. According to RECIST 1.1, 6 pts achieved a clinical complete response (cCR)(6/14,42.8%). Pathological results revealed 5 pCR (ypT0N0, 50%), 3 ypT1N0, and 2 ypT2/T3N0. A complete nodal response (pN0) occurred in 10 (100%) pts post- tislelizumab +chemotherapy and 8 ( < ypT2N0,80%) pts achieved pathologic downstaging. Most common neoadjuvant therapy related AEs of any grade were hematologic toxicities (11/14,78.5%), nausea (9/14,64.2%), vomiting (8/14,57.1%), decreased appetite (6/14,42.8%), fatigue (4/14,28.5%), pruritus (3/14,21.4%) and ALT/AST increased (4/14,28.5%). Grade ≥3 neoadjuvant therapy related AEs were neutropenia (n = 3), thrombocytopenia (n = 2), anemia (n = 2). One patient discontinued GC plus tislelizumab due to AEs. Conclusions: Patients with clinically lymph node‐positive bladder cancer have significant pN0 after neoadjuvant therapy. Neoadjuvant tislelizumab plus gemcitabine/cisplatin was feasible and provided meaningful pathologic responses in lymph node‐positive bladder cancer. Clinical trial information: NCT04570410 .

Objective:To compare the prognosis and complications of muscle-invasive bladder cancer (MIBC) and non-muscle-invasive bladder cancer (NMIBC) patients undergoing radical cystectomy (RC) followed by ileal neobladder.Methods:The clinical data of 103 patients who underwent orthotopic ileal neobladder in Jiangsu Province Hospital from April 2010 to October 2021 were retrospectively analyzed. There were 51 MIBC patients and 52 NMIBC patients. In the MIBC group, there were 49 males and 2 females, aged (58.1 ± 8.9) years, with American Society of Anesthesiologists (ASA) score of 1-2 in 48 cases and 3 in 3 cases. Open radical cystectomy (ORC) was performed in 2 cases, laparoscopic (LRC) in 34 cases and robot-assisted radical cystectomy (RARC) in 15 cases. In the NMIBC group, there were 49 males and 3 females, aged (55.7 ± 9.9) years, ASA score of 1-2 in 51 cases and ASA score of 3 in 1 case. LRC was performed in 41 cases, and RARC in 11 cases. There were no statistically differences between the two groups in above indicators ( P>0.05). The Clavien-Dindo grading system (CCS) was used to assess the complications, defining CCS Ⅰ-Ⅱ as mild complications and CCS Ⅲ-Ⅴ as severe complications. According to their relationship to the neobladder, complications were be classified as neobladder-related and non-neobladder-related complications. The occurrence of complications and the prognosis of neobladder between MIBC and NMIBC were compared. Results:The average operation time of the MIBC group and NMIBC group were (421.2 ± 119.7) min vs. (439.8 ± 106.2) min. The blood loss were 400 (300, 700) ml vs. 400 (300, 625) ml. The frequency of lymph nodes removed were (14.9 ± 8.3) vs. (14.8 ± 8.5). The postoperative defecation time were 5 (4, 6) d vs. 5 (3, 6) d. And the postoperative hospital stay were 20 (15, 28) d vs. 22 (19, 28) d. There were no statistically differences between the two groups in above indicators ( P>0.05). The MIBC group had a significantly lower rate of pelvic lymph node metastasis [17.6% (9/51) vs. 0(0/52), P=0.001] and tumor thrombosis [23.5% (12/51) vs. 5.8% (3/51), P=0.011] than the MIBC group. Moreover, the NMIBC group had a considerably superior 5-year overall survival (OS) (97.6% vs. 70.2%, P=0.035). The proportion of pads needed in the daytime of the MIBC group and NMIBC group were 14.6% (7/46) vs. 6.7% (3/45). The frequency of urination were (2.0 ± 0.7) h vs. (2.4 ± 0.7) h. Furthermore, The proportion of pads needed at night were 47.9% (23/48) vs. 53.3% (24/45). The frequency of nocturnal urination were 3.1±1.5 vs. 2.3 ± 1.7. And the number of pads needed at night were all 1 (0, 1) pad. The daytime and nighttime incontinence rate were 25.0% (12/48) and 62.5% (30/48) respectively in MIBC, compared to 11.1% (5/45) and 62.2% (28/45) respectively in NMIBC. And the proportion of erectile function retention were 15.8% (6/38) vs. 25.0% (10/40). There were no statistically significant differences in the prognosis of neobladder function between the two groups ( P>0.05). Furthermore, the proportions of mild complications in the MIBC group and NMIBC group were [41.2% (21/51) vs. 51.9 (27/52)]. The proportions of severe complications were [21.6% (11/51) vs. 19.2% (27/52)]. The proportions of neobladder-related complications were [27.5% (14/51) vs. 25.0% (13/52)]. And the proportions of non-neobladder-related complications were [39.2% (20/51) vs. 25.0% (13/52)]. There were no statistically significant differences in the complications between the two groups ( P>0.05). Conclusions:There was no statistically significant difference in functional prognosis and complications of neobladder between MIBC group and NMIBC group, and NMIBC had a better oncologic prognosis.

You have accessJournal of UrologyCME1 Apr 2023PD36-03 VESICAL IMAGING REPORTING AND DATA SYSTEM (VI-RADS) COULD PREDICT THE PROGNOSIS OF BLADDER CANCER PATIENTS RECEIVED RADICAL CYSTECTOMY Qiang Lv, Xiao Yang, Qiang Cao, and Juntao Zhuang Qiang LvQiang Lv More articles by this author , Xiao YangXiao Yang More articles by this author , Qiang CaoQiang Cao More articles by this author , and Juntao ZhuangJuntao Zhuang More articles by this author View All Author Informationhttps://doi.org/10.1097/JU.0000000000003334.03AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookLinked InTwitterEmail Abstract INTRODUCTION AND OBJECTIVE: Vesical Imaging Reporting and Data System (VI-RADS) has shown a good potential in determining muscle-invasive bladder cancer (MIBC) patients. However, whether the VI-RADS could predict the prognosis of radical cystectomy (RC) patients has not been reported. METHODS: We retrospectively analyzed the information of bladder cancer patients admitted to our center from June 2012 to June 2022. All patients who underwent multiparametric magnetic resonance imaging (mpMRI) and underwent RC were included. The exclusion criteria were: 1) Pathology was not urothelial carcinoma. 2) Receive neoadjuvant chemotherapy. 3) VI-RADS could not be evaluated. 4) The follow-up data was incomplete. VI-RADS were scored by two radiologists, blinded to clinical data. Patients’ clinical features, pathology data and imaging information were recorded. All statistical analyses were performed in SPSS26.0 and R software. RESULTS: Overall, 219 patients were finally included in the study. There were 188 males and 31 females with a median age of 66 (IQR: 61-74) years. Pathology showed 23 patients of low grade and 196 cases of high grade. Among them, 126 patients were MIBC. Patients with VI-RADS≥3 had worse progression-free survival (PFS) and overall survival (OS) than those with VI-RADS <3. In addition, we divided into two groups with a cut-off of VI-RADS 4, and found the same trends. The AUC of VI-RADS predicting 3-year PFS was 0.822 (sensitivity=0.832 and negative predictive value=0.923). Multivariate COX regression analysis showed that VI-RADS≥3 and lymph node metastasis were independent risk factors for PFS (HR=2.871, p=0.029 and HR=3.886, p<0.001, respectively). The results of COX regression are shown in Table 1. In the MIBC subgroup, patients with VI-RADS≥4 had worse PFS and OS. In the NMIBC subgroup, the prognosis of patients with VI-RADS≥3 is still worse. VI-RADS was no significance to distinguish the prognosis if patients had multi-walled. CONCLUSIONS: The prognosis of RC patients with VI-RADS≥3 is worse than those with VI-RADS <3. Even if the pathology is NMIBC, the prognosis of them is still worse. In patients with multi-walled tumors, VI-RADS was less valuable in predicting prognosis. Source of Funding: None © 2023 by American Urological Association Education and Research, Inc.FiguresReferencesRelatedDetails Volume 209Issue Supplement 4April 2023Page: e980 Advertisement Copyright & Permissions© 2023 by American Urological Association Education and Research, Inc.MetricsAuthor Information Qiang Lv More articles by this author Xiao Yang More articles by this author Qiang Cao More articles by this author Juntao Zhuang More articles by this author Expand All Advertisement PDF downloadLoading ...

Abstract Background The response rate to immunotherapy in patients with bladder cancer (BCa) remains relatively low. Considering the stable existence and important functions in tumour metabolism, the role of circRNAs in regulating immune escape and immunotherapy sensitivity is receiving increasing attention. Methods Circular RNA (circRNA) sequencing was performed on five pairs of BCa samples, and circFAM13B (hsa_circ_0001535) was screened out because of its remarkably low expression in BCa. Further mRNA sequencing was conducted, and the association of circFAM13B with glycolysis process and CD8+ T cell activation was confirmed. The functions of circFAM13B were verified by proliferation assays, glycolysis assays, BCa cells-CD8+ T cell co-culture assays and tumorigenesis experiment among human immune reconstitution NOG mice. Bioinformatic analysis, RNA–protein pull down, mass spectrometry, RNA immunoprecipitation, luciferase reporter assay and fluorescence in situ hybridization were performed to validate the HNRNPL/circFAM13B/IGF2BP1/PKM2 cascade. Results Low expression of circFAM13B was observed in BCa, and it was positively associated with lower tumour stage and better prognosis among patients with BCa. The function of CD8+ T cells was promoted by circFAM13B, and it could attenuate the glycolysis of BCa cells and reverse the acidic tumour microenvironment (TME). The production of granzyme B and IFN-γ was improved, and the immunotherapy (PD-1 antibodies) sensitivity was facilitated by the inhibition of acidic TME. Mechanistically, circFAM13B was competitively bound to the KH3-4 domains of IGF2BP1 and subsequently reduced the binding of IGF2BP1 and PKM2 3’UTR. Thus, the stability of the PKM2 mRNA decreased, and glycolysis-induced acidic TME was inhibited. The generation of circFAM13B was explored by confirming whether heterogeneous nuclear ribonucleoprotein L (HNRNPL) could promote circFAM13B formation via pre-mRNA back-splicing. Conclusions HNRNPL-induced circFAM13B could repress immune evasion and enhance immunotherapy sensitivity by inhibiting glycolysis and acidic TME in BCa through the novel circFAM13B/IGF2BP1/PKM2 cascade. Therefore, circFAM13B can be used as a biomarker for guiding the immunotherapy among patients with BCa.

目的 探讨影像报告与数据系统(VI-RADS)评分在膀胱癌患者术后预后评估中的应用价值.方法 回顾性分析南京医科大学第一附属医院2012年2月年至2019年9月收治的294例病理诊断为膀胱尿路上皮癌患者的病例资料.根据手术方式将患者分为2组.经尿道膀胱肿瘤切除术(TURBT)组121例,男102例,女19例;年龄(66.7±12.3)岁,＜65岁52例,≥65岁69例;Ⅵ-RADS评分＜3分84例,≥3分37例.根治性膀胱切除术(RC)组173例,男 154例,女19例;年龄(65.7±10.8)岁,＜65岁77例,≥65岁96例;Ⅵ-RADS评分＜3分51例,≥3分122例.分析TURBT组和RC组预后的影响因素,分析Ⅵ-RADS评分对膀胱癌患者术后总生存期(OS)和无进展生存期(PFS)的预测价值.结果 本研究294例,术后病理诊断均为尿路上皮癌,病理分期:Ta期104例(35.4％),T1 期 82 例(27.9％),T2 期 58 例(19.7％),T3 期 34 例(11.6％),T4 期 16 例(5.4％).病理分级:低度恶性潜能乳头状尿路上皮肿瘤11例(3.7％),低级别77例(26.2％),高级别206例(70.1％).非肌层浸润性膀胱癌(NMIBC)组186例(63.3％),肌层浸润性膀胱癌(MIBC)组108例(36.7％).TURBT组中,NMIBC 组 114 例(94.2％),MIBC 组7 例(5.8％);RC 组中,NMIBC 组 72 例(41.6％),MIBC组101例(58.4％).NMIBC组中,Ⅵ-RADS评分＜3分和≥3分分别为128例(68.8％)和58 例(31.2％)(P＜0.01);MIBC 组中,Ⅵ-RADS 评分＜3 分和≥3分分别为 101 例(93.5％)和7例(6.5％)(P＜0.01).病理高级别组中,Ⅵ-RADS评分＜3分和≥3分分别为62例(30.1％)和144例(69.9％)(P＜0.01);非高级别组中,Ⅵ-RADS评分＜3分和≥3分分别为73例(83.0％)和 15 例(17.0％)(P＜0.01).本研究 294 例的中位 OS 为 27.4(16.6,38.1)个月,中位 PFS为24.7(14.0,36.8)个月.单因素分析结果显示,年龄≥65岁(OS:HR=6.09,P=0.01;PFS:HR=1.71,P=0.035)、肿瘤肌层浸润(OS:HR=4.66,P＜0.01;PFS:HR=2.24,P=0.001)、肿瘤高级别(OS:HR=4.26,P=0.008;PFS:HR=1.92,P=0.023)、Ⅵ-RADS 评分≥3 分(OS:HR=4.24,P=0.001;PFS:HR=2.21,P=0.002)与患者较差的OS和PFS相关.多因素分析结果显示,Ⅵ-RADS评分≥3分是患者OS(HR=3.41,P=0.012)和PFS(HR=2.23,P=0.016)的独立危险因素.TURBT组的单因素分析结果显示,Ⅵ-RADS评分≥3分(HR=2.05,P=0.053)和病理高级别(HR=2.77,P=0.005)与患者较差的PFS相关;多因素分析结果显示,仅病理高级别(HR=2.54,P=0.013)是患者PFS的独立危险因素.Ⅵ-RADS评分≥3分(HR=3.29,P=0.032)和年龄≥65岁(HR=5.37,P=0.001)是RC组OS的独立危险因素.生存曲线显示,Ⅵ-RADS评分≥3分组和＜3分组5年总生存率分别为93.9％和73.1％(P＜0.01),5年无进展生存率分别为76.5％和53.0％(P＜0.01),差异均有统计学意义.结论 Ⅵ-RADS评分≥3分是膀胱癌患者RC术后预后的独立危险因素,对接受TURBT的患者预后无明显预测作用.

目的 探讨膀胱癌根治性膀胱切除术(RC)联合原位新膀胱患者的术后并发症及其影响因素、处理措施及转归,并对不同亚组间并发症情况进行比较.方法 回顾性分析2010年4月至2021年10月行RC+原位回肠新膀胱术的103例患者的临床资料,以及术后并发症发生情况、处理措施及转归,并对机器人辅助根治性膀胱切除术(RARC)与腹腔镜根治性膀胱切除术(LRC)、U型膀胱与W型膀胱、肌层浸润性膀胱癌(MIBC)与非肌层浸润性膀胱癌(NMIBC)组间的并发症情况进行比较.结果 103例患者中,男98例,女5例;平均年龄(56.9±9.4)岁,中位随访时间为46(5～137)个月,总体并发症发生率为56.3％.Logistic回归分析显示,RARC为新膀胱术后并发症发生的保护性因素(OR=0.182,95％CI=0.044～0.755,P=0.019).此外,卡方检验显示,RARC组的总体并发症(23.1％vs 66.7％)、早期并发症(11.5％vs 52.0％)和CCSⅠ～Ⅱ(23.1％vs 54.7％)、CCSⅢ～Ⅴ(3.8％vs 25.3％)、新膀胱相关(3.8％vs 34.7％)、非新膀胱相关(19.2％vs 49.3％)并发症发生率均显著低于LRC组(P<0.05).对于不同新膀胱类型的患者,U型膀胱的总体并发症(61.9％v s 31.6％)和新膀胱相关并发症(31.0％v s 5.3％)发生率显著高于W型膀胱,其在CCSⅠ～Ⅱ(51.2％vs 26.3％)中亦有显现(P<0.05).MIBC与NMIBC患者的并发症发生率差异无统计学意义.结论 RC联合原位新膀胱术后并发症大多可以得到较好的处理和转归.RARC相较于LRC能够显著降低并发症发生率,膀胱癌分期并不会影响术后并发症的发生.

You have accessJournal of UrologyCME1 Apr 2023MP08-07 IS PELVIC LYMPH NODE DISSECTION NECESSARY IN NMIBC PATIENTS UNDERGOING RC? Qiang Lv, Xiao Yang, Qiang Cao, and Juntao Zhuang Qiang LvQiang Lv More articles by this author , Xiao YangXiao Yang More articles by this author , Qiang CaoQiang Cao More articles by this author , and Juntao ZhuangJuntao Zhuang More articles by this author View All Author Informationhttps://doi.org/10.1097/JU.0000000000003223.07AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookLinked InTwitterEmail Abstract INTRODUCTION AND OBJECTIVE: Radical cystectomy (RC) combined with pelvic lymph node dissection (PLND) is the principle for muscle invasive bladder cancer (MIBC), but it is unclear whether PLND is necessary for high-risk non-muscle invasive bladder cancer (NMIBC). METHODS: From January 2021, patients diagnosed as high-risk NMIBC without swollen lymph nodes (or lymph nodes ≤8mm) on MRI/CT were prospectively enrolled, and randomly received RC+PLND or RC alone (NCT: 05123625). Perioperative clinical data, 90-day complications, and medical expenses, et al were recorded. The endpoint was progression-free survival (PFS) and overall survival (OS). All statistical analyses were performed in SPSS26.0 and R software (version 3.6.3). RESULTS: As of September 19, 2022, a total of 63 patients were enrolled, with 40 patients received ileal conduit, 5 patients received orthotopic neobladder, and 18 received ureteral cutaneous diversion. Among all patients, 26 cases were in RC+PLND group, with the age of 65.5 (IQR: 57.25-72.75) years. Laparoscopic surgery was performed in 15 cases, robotic-assisted in 10 cases, and open surgery in 1 case due to excessive bleeding. Pathological stage was Ta/ Tis: 6 cases and T1: 20 cases. None positive lymph node was found. There were 37 cases in RC only group, with the age of 66 (IQR: 59-73) years. Laparoscopic surgery was performed in 7 cases, and robotic-assisted in 30 cases. Pathological stage was Ta/Tis: 6 cases and T1: 31 cases. The operation time of RC group was significantly shorter than that of RC+PLND group (241±63 min vs. 335±83 min, p < 0.001), and the intraoperative blood loss was significantly lower than that of RC+PLND group (p=0.026). The average daily postoperative drainage volume of patients in RC group was significantly less than that in RC+PLND group (p=0.002), and the time from postoperative to discharge was shorter (8.0±2.4 vs. 11.2±6.3 days, p=0.019). Within 90 days after operation, the incidence of Clavien-Dindo grade II-III complications in RC group were lower than that in RC+PLND group (2.7% vs 19.2%, p=0.073). At the median follow-up of 9.5 (IQR: 6.9-12.8) months, there was no significant difference in PFS and OS between the two groups (Figure 1). CONCLUSIONS: For high-risk NMIBC patients, combined PLND has no survival benefit but increases the incidence of complications. Source of Funding: None © 2023 by American Urological Association Education and Research, Inc.FiguresReferencesRelatedDetails Volume 209Issue Supplement 4April 2023Page: e95 Advertisement Copyright & Permissions© 2023 by American Urological Association Education and Research, Inc.MetricsAuthor Information Qiang Lv More articles by this author Xiao Yang More articles by this author Qiang Cao More articles by this author Juntao Zhuang More articles by this author Expand All Advertisement PDF downloadLoading ...

Angiomyolipoma (AML) complicated with tumour thrombus extending to the confluence of inferior vena cava (IVC) with right atrium is rarely observed. We report a female AML patient admitted to our centre on January 21, 2020, with complication of tumour thrombus extending to the confluence of IVC with right atrium and had no sign of difficult breathing. She underwent whole-abdominal enhanced CT for abdominal pain and was diagnosed with a possible renal AML with tumour thrombus. Open radical nephrectomy and thrombectomy of vena cava were performed. Intraoperative transoesophageal echocardiography indicated that the tumour thrombus has reached the confluence of IVC with right atrium. The operation took 255 min with an intraoperative haemorrhage of 800mL. The patient was discharged 7 days after surgery. Pathology revealed lipoma-like AML. Immunohistochemistry showed vimentin (+), EMA (-), HMB45 (+), S-100 (-), SMA (+), TFE-3 (-), melan A (+). After 2 years of follow-up, we found that the patient showed full recovery and had no recurrence. Therefore, lipoma-like AML should also be followed closely for recurrence and metastasis. When AML involves IVC tumour thrombus, open thrombectomy and radical nephrectomy are safe and effective methods.

目的 基于标化表观扩散系数(ADC)值预测膀胱癌患者人表皮生长因子受体2(HER2)的表达状态.方法 回顾性研究127例膀胱尿路上皮癌患者的术前盆腔3.0T核磁共振(MRI)扫描图像,计算标化ADC值.采用免疫组织化学法(IHC)检测术后组织标本中的 HER2表达状态.在 HER2各表达水平间、不同表达状态划分间比较标化 ADC 值的差异.标化 ADC 值与HER2表达状态行相关性分析.受试者工作曲线(ROC)分析用于确定标化 ADC值区分不同表达状态的最佳诊断阈值.结果 标化 ADC值与 HER2表达水平呈负相关(tau-b=-0.180,P=0.008).标化ADC值比较中,HER2过表达(IHC2+、3+)低于HER2阴性(IHC0、1+)(P=0.081),HER2表达(IHC1+、2+、3+)显著低于 HER2零表达(IHC0)(P=0.020),HER2强阳性(IHC3+)显著低于 HER2非强阳性(IHC0、1+、2+)(P=0.024).标化 ADC值区分 HER2强阳性和非强阳性的最佳诊断阈值为0.849,敏感度0.621,特异度0.909,准确度0.765;区分 HER2过表达和 HER2阴性的最佳诊断阈值为0.909,敏感度0.547,特异度0.667,准确度0.607.结论 病灶的标化 ADC值与 HER2表达水平呈负相关.标化 ADC 值是预测 HER2表达水平的潜在工具.

Accumulating evidence has proven that circRNAs play vital roles in tumor progression. Nevertheless, the mechanisms underlying circRNAs in bladder cancer (BCa) remain largely unknown. The purpose of this study was to identify the role and investigate the potential molecular mechanisms of hsa_circ_0003098 in BCa. We confirmed that hsa_circ_0003098 expression was significantly upregulated in BCa tissues, of which expression was remarkably associated with poor prognosis. Functionally, overexpression of hsa_circ_0003098 promoted BCa cell proliferation, migration, and invasion in vitro as well as tumor growth in vivo. Mechanistically, hsa_circ_0003098 promoted upregulation of ACAT2 expression and induced cholesteryl ester accumulation via acting as a sponge for miR-377-5p. Thus, hsa_circ_0003098 plays an oncogenic role in BCa and may serve as a potential biomarker and therapeutic target for BCa.

BACKGROUND:Vesical Imaging-Reporting and Data System (VI-RADS) has been developed for assessing bladder cancer from multiparametric (mp) MRI but its performance in diagnosing muscle-invasive bladder cancer (MIBC) is suboptimal. PURPOSE:To investigate associations between normalized apparent diffusion coefficient (NADC) and clinicopathological characteristics and to determine whether the inclusion of NADC can improve the performance of VI-RADS in diagnosing MIBC. STUDY TYPE:Retrospective. POPULATION:Two hundred seventy-five patients with pathologically confirmed bladder cancer (101 MIBC and 174 non-MIBC [NMIBC]) underwent preoperative mpMRI (233 male, 42 female). FIELD STRENGTH/SEQUENCE:3-T, T2-weighted imaging (turbo spin-echo), diffusion-weighted imaging (free-breathing spin-echo), and dynamic contrast-enhanced imaging (gradient-echo). ASSESSMENT:NADC was the mean ADC of tumor divided by that of the iliopsoas muscles in trans caput femoris plane. Associations between NADC and clinicopathological characteristics were evaluated. Models were established for differentiating MIBC and NMIBC: VI-RADS model; VN model (VI-RADS and NADC), Images model (significant variables from imaging associated with MIBC), LN model (Images model without NADC), and Full model (all significant variables associated with MIBC). STATISTICAL TESTS:Variables for model development were based on logistic regression. Models were evaluated by receiver operating characteristic (ROC) curve. Comparison of the area under the curves (AUCs) for the models used DeLong's test. A P value <0.05 was considered statistically significant. RESULTS:NADC was significantly lower in lesions with diameter ≥ 3 cm, MIBC, histological high grade, lymph node metastasis, and lymphovascular invasion. Compared with VI-RADS model, the AUCs for VN model (VI-RADS score and NADC), Images model (VI-RADS score, NADC and tumor size) and Full model (VI-RADS score, NADC, tumor size and histological grade) were significantly higher. No significant differences were observed between the AUCs for VN model and Images model (P = 0.051). DATA CONCLUSION:NADC reflects information about the aggressiveness of bladder cancer. Combining VI-RADS with NADC can improve performance in diagnosing MIBC. EVIDENCE LEVEL:4 TECHNICAL EFFICACY: Stage 2.

OBJECTIVE:Hospital management and medical treatment changed during the coronavirus disease 2019 (COVID-19) pandemic. This study investigated the impact of the COVID-19 pandemic on patients with bladder cancer.METHODS:In this multicenter retrospective study, we collected information from the electronic medical records of outpatients who underwent cystoscopy and inpatients with confirmed bladder cancer in three hospitals in Nanjing (two province-level and one county-level hospitals) in 2019 and 2020. Patients' home addresses, treatment methods, length of stay, and pathology were compared between the periods.RESULTS:In total, 4048 outpatients and 1242 inpatients were included. The average number of cystoscopies decreased significantly during the lockdown. In province-level hospitals, the number of cystoscopies increased gradually as the pandemic was brought under control but remained lower than that in 2019, whereas the number grew in 2020 in county-level hospitals. The rates of recurrence and radical cystectomy were higher in 2020 than in 2019. No significant difference in the pathological grade was observed. More patients who underwent radical cystectomy were diagnosed with muscle-invasive bladder cancer during the 2020 lockdown.CONCLUSION:The pandemic severely affected patients with bladder cancer, mainly in their choice of institution and treatment.

Purpose The aim of this study was to compare surgical treatment outcomes of pediatric medial epicondyle fractures with and without elbow dislocation.Methods A total of 139 patients (75 boys and 64 girls; mean & PLUSMN; SD age, 9.6 & PLUSMN; 3.3 years) who received surgical treatment for medial epicondyle fractures at the Children's Hospital of Nanjing Medical University from January 2012 to December 2018 were included in our study. There were 99 cases that had a medial epicondyle fracture alone (group A) and 40 cases had a concomitant elbow dislocation (group B). Pain, ulnar nerve palsy, and stability of the elbow joint were recorded. Robert's criteria was used to assess elbow function.Results The prevalence of ulnar nerve palsy was lower in group A compared to group B, both before and after surgery. More patients underwent ulnar nerve transposition in group B than in group A. The incidence of elbow valgus instability was higher in group B than in group A. At the final follow-up, all patients had achieved good radiographic restoration of the elbow joint. Clinical outcomes in group A, according to Robert's criteria, were better than those in group B.Conclusions Elbow dislocation was associated with poorer functional outcomes following surgical treatment of medial epicondyle fractures in children. (J Hand Surg Am. 2023;48(9):949.e1-e6. Copyright & COPY; 2023 by the American Society for Surgery of the Hand. All rights reserved.) Type of study/level of evidence Therapeutic IV.

Vesical Imaging Reporting and Data System (VI-RADS) shows good potential in determining muscle-invasive bladder cancer (MIBC) patients. However, whether VI-RADS could predict the prognosis of radical cystectomy (RC) patients has not been reported. Our purpose is to determine whether VI-RADS contributed to predict oncologic outcomes. In this retrospective study, we analysed the information of bladder cancer patients who admitted to our centre from June 2012 to June 2022. All patients who underwent multiparametric magnetic resonance imaging (mpMRI) and underwent RC were included. VI-RADS scoring was performed by two radiologists blinded to the clinical data. Patients’ clinical features, pathology data, and imaging information were recorded. Kaplan–Meier method was used to estimate patients' overall survival (OS) and progression-free survival (PFS). Log-rank test was used to assess statistical differences. COX regression analysis was used to estimate risk factors. Ultimately, we included 219 patients, with 188 males and 31 females. The median age was 66 (IQR = 61–74.5) years. The VI-RADS scores were as follows: VI-RADS 1, 4 (1.8%); VI-RADS 2, 68 (31.1%); VI-RADS 3, 40 (18.3%); VI-RADS 4, 69 (31.5%); and VI-RADS 5, 38 (17.4%). Patients with VI-RADS ≥ 3 had poorer OS and PFS than those with VI-RADS < 3. The AUC of VI-RADS predicting 3-year OS was 0.804, with sensitivity of 0.824 and negative predictive value of 0.942. Multivariate COX analysis showed that VI-RADS ≥ 3 was risk factors for OS (HR = 3.517, P = 0.003) and PFS (HR = 4.175, P < 0.001). In the MIBC subgroup, patients with VI-RADS ≥ 4 had poorer OS and PFS. In the non-muscle invasive bladder cancer (NMIBC) subgroup, the prognosis of patients with VI-RADS ≥ 3 remained poorer. VI-RADS scores could effectively predict the survival of patients after RC.

Background:The immunotherapy sensitivity of patients with bladder cancer (BCa) remains low.As the role of protein methylation in tumorigenesis and development becomes clearer, the role of lysine N-methyltransferase SET domain containing 7 (SETD7) in the progression and immune escape of BCa is worth studying.Methods: The correlation between lysine methyltransferase family and prognosis or immunotheray sensitivity of BCa patients were analyzed, and SETD7 was screened out because of the significant correlation between its expression and survival data or immunotherapy sensitivity.The expression of SETD7 in BCa tissues and cell lines were explored.The functions of SETD7 were investigated by proliferation and migration assays.The role of SETD7 in BCa immune escape was validated by analyzing the correlation between SETD7 expression and tumor microenvironment (TME)-related indicators.The results were further confirmed by conducting BCa cell-CD8 + T cell co-culture assays and tumorigenesis experiment in human immune reconstitution NOG mice (HuNOG mice).Bioinformatic prediction, CO-IP, qRT-PCR, and western blot were used to validate the SETD7/STAT3/PD-L1 cascade.Results: SETD7 was highly expressed in BCa, and it was positively associated with high histological grade and worse prognosis.SETD7 promoted the proliferation and migration of BCa cells.The results of bioinformatics, in vitro co-culture, and in vivo tumorigenesis assays showed that SETD7 could inhibit the chemotoxis and cytotoxicity of CD8 + T cells in BCa TME.Mechanistically, bioinformatics analysis, CO-IP assay, qRT-PCR, and western blot results indicated that SETD7 could increase the expression of PD-L1 via binding and promoting STAT3.Conclusions: Taken together, SETD7 indicated poor prognosis and promoted the progression and immune escape of BCa cells.It has great potential to act as a new indicator for BCa diagnosis and treatment, especially immunotherapy.

目的 探讨盆腔淋巴结清扫(PLND)对根治性膀胱切除术(RC)患者预后的影响.方法 回顾性分析2013年11月至2019年12月南京医科大学第一附属医院接受RC且未接受新辅助化疗的339例膀胱癌患者的临床资料.男284例,女55例.年龄(67.4±10.9)岁.术后病理诊断为MIBC 171 例,NMIBC 168 例.MIBC 组中 124 例(72.5％)接受 PLND,NMIBC 组中 118 例(70.2％)接受PLND,差异无统计学意义(P=0.643).PLND的淋巴结清扫数量为(13.7±7.1)枚.分析MIBC组和NMIBC组的预后影响因素,以及PLND对预后的影响.结果 MIBC组中26例淋巴结阳性,98例淋巴结阴性;144例为高级别尿路上皮癌;47例接受辅助治疗.NMIBC组中4例淋巴结阳性,114例淋巴结阴性;99例为高级别尿路上皮癌;15例接受辅助治疗.术后中位随访24(13,43)个月,5年总生存率(OS)为63.6％,NMIBC组为79.1％,MIBC组为47.5％.单因素分析结果显示,年龄≥65岁(HR=2.07,95％CI 1.21～3.54,P=0.009)、肿瘤高级别(HR=9.76,95％CI 2.39～39.90,P＜0.01)、淋巴结阳性(HR=2.47,95％CI 1.27～4.78,P=0.008)是 MIBC 预后的危险因素,PLND(HR=0.37,95％CI 0.23～0.60,P＜0.01)、辅助治疗(HR=0.21,95％CI0.10～0.46,P＜0.01)是 MIBC 预后的保护性因素;肿瘤高级别(HR=6.66,95％CI 1.51～29.50,P=0.012)是NMIBC预后的危险因素,PLND(HR=1.32,95％CI0.37～4.75,P=0.667)不是预后的影响因素.多因素分析结果显示,肿瘤高级别(HR=6.38,95％CI 1.54～26.50,P=0.011)是 MIBC 预后的独立危险因素,PLND(HR=0.59,95％CI 0.35～0.99,P=0.047)和辅助治疗(HR=0.30,95％CI0.13～0.68,P=0.004)是MIBC预后的独立保护因素.生存曲线分析结果显示,MIBC组中,淋巴结阴性组的5年OS(62.4％)优于未清扫组(16.1％)(P＜0.01)和淋巴结阳性组(32.3％)(P=0.005),未清扫组与淋巴结阳性组的5年OS差异无统计学意义(P=0.438).NMIBC组中,淋巴结阴性组和未清扫组的5年OS分别81.3％和66.6％,差异无统计学意义(P=0.764).结论 PLND是MIBC患者RC术后预后的独立保护因素,但对NMIBC患者预后无显著影响.

Additional file 5: Table S5. Mean expression level of KRT6B.