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A Systematic Review on Prognostic DNA Methylation Markers for Renal Cell Carcinoma: Are We Moving Forward? 肾细胞癌预后 DNA 甲基化标记的系统性综述:我们在前进吗?
Pub Date : 2024-04-01 DOI: 10.1097/ju9.0000000000000133
S. Odeh, Beatrice Tavelli, S. Joosten, Maureen J. Aarts, Thomas Kerkhofs, Joep G. H. van Roermund, T. Marcelissen, Leo J. Schouten, Andres Matoso, M. van Engeland, I. Samarska, K. Smits
In this study, we update 2 previously published systematic reviews on prognostic DNA methylation markers for renal cell carcinoma and provide a comprehensive overview of the latest markers and methylation signatures that merit further validation. We performed a systematic literature search of PubMed, EMBASE, and Web of Science including all studies published after our previous systematic review (ie, between March 2017 and December 2021). Data extraction and evaluation using the Reporting Recommendations for Tumor Marker Prognostic Studies criteria and the level of evidence was performed for all 58 included studies. DNA methylation markers were considered promising when findings were validated in more than one study or within multiple cohorts. We identified 11 promising single DNA methylation markers (ie, RUNX3, EVI2A, HHLA2, TACSTD2, KEAP1, LAG3, NSD1, ZNF492, GPR149, LEP, and LEPR), three multimarker panels (ie, (1) RAC2, PLCB2, VAV1 and PARVG; (2) NCKAP1L, EVI2A, and BATF; and (3) GREM1, GATA5, LAD1, NEFH, and NEURL) and 5 DNA methylation signatures. Remarkably, since our previous systematic review, only part of the markers recommended for validation were evaluated in subsequent validation efforts, emphasizing the lack of validation in this field. Validation studies for prognostic DNA methylation markers have been scarce despite previously published recommendations. Nevertheless, since then, other novel DNA methylation markers or signatures have been proposed as promising biomarkers emphasizing the current focus on expanding evidence instead of further building the evidence on specific markers with the aim of clinical translation.
在本研究中,我们更新了之前发表的两篇关于肾细胞癌预后DNA甲基化标志物的系统综述,并全面概述了值得进一步验证的最新标志物和甲基化特征。 我们对PubMed、EMBASE和Web of Science进行了系统性文献检索,包括上一篇系统综述之后(即2017年3月至2021年12月之间)发表的所有研究。我们采用《肿瘤标志物预后研究报告建议》标准和证据级别对所有58项纳入研究进行了数据提取和评估。当研究结果在一项以上的研究或多个队列中得到验证时,DNA甲基化标记被认为是有前景的。 我们确定了 11 个有前景的单一 DNA 甲基化标记物(即 RUNX3、EVI2A、HHLA2、TACSTD2、KEAP1、LAG3、NSD1、ZNF492、GPR149、LEP 和 LEPR)、3 个多标记物面板(即 (1)RAC2、PLCB2、VAV1 和 PARVG;(2) NCKAP1L、EVI2A 和 BATF;以及 (3) GREM1、GATA5、LAD1、NEFH 和 NEURL)和 5 个 DNA 甲基化特征。值得注意的是,自我们之前的系统综述以来,只有部分推荐验证的标记物在随后的验证工作中进行了评估,这凸显了该领域缺乏验证。 尽管之前发表了一些建议,但针对预后DNA甲基化标记的验证研究一直很少。尽管如此,此后又有其他新型 DNA 甲基化标记或特征被提出作为有前景的生物标志物,这强调了目前的重点是扩大证据,而不是进一步建立特定标记的证据,以实现临床转化。
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引用次数: 0
From the Editor—April 2024: Elevating Scholarship for Patients with Rare Conditions 编辑的话-2024 年 4 月提高罕见病患者的奖学金水平
Pub Date : 2024-04-01 DOI: 10.1097/ju9.0000000000000156
Aditya Bagrodia, John W. Davis
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引用次数: 0
Expert Perspectives on Controversies in Castration-Sensitive Prostate Cancer Management: Narrative Review and Report of the First US Prostate Cancer Conference Part 1 阉割敏感性前列腺癌治疗争议的专家观点:第一届美国前列腺癌会议的叙述性回顾和报告(第一部分
Pub Date : 2024-04-01 DOI: 10.1097/ju9.0000000000000137
E. D. Crawford, Alan H. Bryce, Maha H. Hussain, Neeraj Agarwal, H. Beltran, M. Cooperberg, D. Petrylak, Neal Shore, Daniel E Spratt, S. Tagawa, Emmanuel S. Antonarakis, Ana M. Aparicio, Andrew J. Armstrong, Thomas P. Boike, J. Calais, Michael A. Carducci, B. Chapin, M. S. Cookson, John W Davis, Tanya B Dorff, S. Eggener, Felix Y. Feng, Martin Gleave, Celestia Higano, Andrei Iagaru, Alicia K Morgans, Michael Morris, Katie S. Murray, Wendy L. Poage, M. Rettig, Oliver Sartor, H. Scher, Paul Sieber, E. Small, Sandy Srinivas, Evan Y. Yu, Tian Zhang, Phillip J. Koo
Castration-sensitive prostate cancer (CSPC) is a complex and heterogeneous condition encompassing a range of clinical presentations. As new approaches have expanded management options, clinicians are left with myriad questions and controversies regarding the optimal individualized management of CSPC. The US Prostate Cancer Conference (USPCC) multidisciplinary panel was assembled to address the challenges of prostate cancer management. The first annual USPCC meeting included experts in urology, medical oncology, radiation oncology, and nuclear medicine. USPCC co-chairs and session moderators identified key areas of controversy and uncertainty in prostate cancer management and organized the sessions with multidisciplinary presentations and discussion. Throughout the meeting, experts responded to questions prepared by chairs and moderators to identify areas of agreement and controversy. The USPCC panel discussion and question responses for CSPC-related topics are presented. Key advances in CSPC management endorsed by USPCC experts included the development and clinical utilization of gene expression classifiers and artificial intelligence (AI) models for risk stratification and treatment selection in specific patient populations, the use of advanced imaging modalities in patients with clinically localized unfavorable intermediate or high-risk disease and those with biochemical recurrence, recommendations of doublet or triplet therapy for metastatic CSPC (mCSPC), and consideration of prostate and/or metastasis-directed radiation therapy in select patients with mCSPC. CSPC is a diverse disease with many therapeutic options and the potential for adverse outcomes associated with either undertreatment or overtreatment. Future studies are needed to validate and clinically integrate novel technologies, including genomics, AI, and advanced imaging, to optimize outcomes among patients with CSPC.
阉割敏感性前列腺癌(CSPC)是一种复杂的异质性疾病,临床表现多种多样。随着新方法扩大了治疗选择范围,临床医生在如何对 CSPC 进行最佳个体化治疗方面仍存在无数问题和争议。 美国前列腺癌会议(USPCC)多学科小组的成立就是为了应对前列腺癌治疗方面的挑战。第一届 USPCC 年会的与会者包括泌尿外科、肿瘤内科、肿瘤放射科和核医学专家。USPCC 联合主席和会议主持人确定了前列腺癌管理中存在争议和不确定性的关键领域,并组织了多学科发言和讨论。在整个会议期间,专家们回答了主席和主持人准备的问题,以确定意见一致和存在争议的领域。 本文介绍了 USPCC 小组讨论和 CSPC 相关主题的问题回答。USPCC 专家认可的 CSPC 管理方面的主要进展包括:开发基因表达分类器和人工智能 (AI) 模型并将其用于临床,以对特定患者群体进行风险分层和治疗选择;在临床定位不利的中危或高危疾病患者和生化复发患者中使用先进的成像模式;建议对转移性 CSPC (mCSPC) 采用双联或三联疗法;考虑对选定的 mCSPC 患者进行前列腺和/或转移灶定向放射治疗。 CSPC 是一种多样化的疾病,有许多治疗方案,但也有可能因治疗不足或治疗过度而导致不良后果。未来的研究需要对基因组学、人工智能和先进成像等新技术进行验证和临床整合,以优化 CSPC 患者的治疗效果。
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引用次数: 1
Physician Perspectives on the Nonclinical Factors That Contribute to Decision-Making for Advanced Prostate Cancer Care: A Qualitative Study. 医生对有助于晚期前列腺癌治疗决策的非临床因素的看法:定性研究。
Pub Date : 2024-03-01 Epub Date: 2024-02-29 DOI: 10.1097/ju9.0000000000000118
Deborah R Kaye, Karissa Tu, J Kelly Davis, Ada Campagna, Sharron L Docherty, Jeremy Kurnot, Tian Zhang, Daniel J George, Peter A Ubel

Introduction: Promising new treatments exist for advanced prostate cancer. Decision-making is complicated: there is minimal comparative effectiveness data; differing routes of administration, drug mechanisms-of-action and side effects; and significant price differences. These challenges contribute to variations in care and quality, treatment disparities, and lack of concordance with patient values. The aim of this study was to examine physician perspectives of factors influencing decision-making for first-line advanced prostate cancer treatments.

Methods: We conducted a qualitative descriptive study of physicians who treat patients with advanced prostate cancer from 09/2021-06/2022. Participants were purposively sampled from across the United States.

Results: Twenty-seven physicians participated. We identified seventeen domains and three overarching themes affecting physician decision-making for advanced prostate cancer care. The themes were: 1) physician and practice factors impact prescribing decisions, 2) health practice resource availability affects the likelihood patients will receive the recommended treatment, and that the treatment will be in-line with patients' values and 3) patient non-clinical factors influence physician decision-making, but patient values could be better incorporated into prescribing decisions. Based upon the analyses, we constructed a preliminary framework of clinician decision-making for advanced prostate cancer.

Conclusions: Physicians perceive non-clinical patient, physician, and practice factors impact decision-making. These factors, therefore, must be considered when implementing programs to optimize a physician's ability to provide quality cancer care, reduce health care disparities and patient financial burden and provide patient goal-concordant care. The preliminary theoretical model of clinician decision-making for advanced prostate cancer care may also be used to inform these efforts.

前言晚期前列腺癌的新疗法前景广阔。决策过程十分复杂:比较疗效数据极少;给药途径、药物作用机制和副作用各不相同;价格差异巨大。这些挑战导致了护理和质量的差异、治疗差异以及与患者价值观的不一致。本研究旨在考察医生对影响一线晚期前列腺癌治疗决策的因素的看法:我们在 2021 年 9 月至 2022 年 6 月期间对治疗晚期前列腺癌患者的医生进行了一项定性描述性研究。结果:27 名医生参与了研究:结果:27 名医生参与了研究。我们确定了影响医生晚期前列腺癌治疗决策的十七个领域和三个总体主题。这些主题是1)医生和实践因素影响处方决策;2)医疗实践资源的可用性影响患者接受推荐治疗的可能性,以及治疗是否符合患者的价值观;3)患者的非临床因素影响医生的决策,但患者的价值观可以更好地融入处方决策中。根据分析结果,我们构建了晚期前列腺癌临床医生决策的初步框架:结论:医生认为患者、医生和临床实践等非临床因素会影响决策。因此,在实施计划以优化医生提供优质癌症治疗、减少医疗差距和患者经济负担以及提供与患者目标一致的治疗时,必须考虑这些因素。临床医生晚期前列腺癌治疗决策的初步理论模型也可为这些工作提供参考。
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引用次数: 0
Office-Based Transperineal Laser Ablation for Benign Prostatic Hyperplasia Under Local Anesthesia: 2-Year Results from a Dose Range Confirmatory Trial 局部麻醉下办公室经会阴激光消融治疗良性前列腺增生:剂量范围确认试验的两年结果
Pub Date : 2024-02-01 DOI: 10.1097/ju9.0000000000000105
Fernando J. Bianco, E. Luna, A. Lopez-Prieto, Pedro González, E. Gheiler, Ariel M. Kaufman, L. Avila, Giuseppe Maiolino
To evaluate the safety and tolerability profile of transperineal laser ablation (TPLA) for patients with benign prostatic hyperplasia in an office setting under sedative-free anesthesia, including the functional outcome results at 24 months. This is a prospective, single-center, dose range confirmatory trial involving 20 male patients. TPLA was performed by urologists in an office setting, using nonsedative local anesthesia. Self-administered nitrous oxide/oxygen dissociating gas was optional. Tolerability was assessed using a visual analog scale. Safety was evaluated by recording Grade 3 or worse adverse events within 30 days after the procedure. International Prostate Symptom Score, Sexual Health Inventory for Men, ejaculation function, and uroflowmetry parameters were assessed at 6, 12, and 24 months. All 20 procedures were performed as intended without request of cessation from any patient, who tolerated them very well, recording a median pain score of 2 (range 1-4). It is important to note that there was a rapid escalation of dose, and the last 18 consecutive patients were initiated at the maximal energy dose of 7 watts. No hospital transfers were recorded, and no urgent hospital admissions within 30 days post-procedure occurred. There was 1 Grade 3 complication registered during the 24-month study interval. We observed a statistically significant and sustained reduction in the median International Prostate Symptom Score at 6 months (6, 3-8), 12 months (3, 5-2), and 24 months (3, 2-4) when compared with baseline values (14, 12-17). Uroflowmetry parameters showed a similar trend. The median Sexual Health Inventory for Men values did not change significantly, and only approximately 10% of patients reported absence of anterograde ejaculation at 12 and 24 months. TPLA for benign prostatic hyperplasia is a safe and well-tolerated office-based procedure, with durable benefits on functional outcomes over 2 years of follow-up. Further studies are required to confirm these results. NCT04760483.
目的:评估经会阴激光消融术(TPLA)在无镇静剂麻醉的诊室环境下治疗良性前列腺增生症患者的安全性和耐受性,包括24个月时的功能结果。 这是一项前瞻性、单中心、剂量范围确认试验,共有 20 名男性患者参与。TPLA由泌尿科医生在诊室环境下进行,采用无镇静剂局部麻醉。可选择自行使用一氧化二氮/氧气解离气体。耐受性采用视觉模拟量表进行评估。安全性通过记录术后 30 天内 3 级或更严重的不良事件进行评估。在 6 个月、12 个月和 24 个月时对国际前列腺症状评分、男性性健康量表、射精功能和尿流参数进行评估。 所有 20 项手术均按计划进行,没有任何患者要求停止手术,患者的耐受性非常好,疼痛评分中位数为 2(范围 1-4)。值得注意的是,手术剂量迅速增加,最后连续 18 名患者都是在 7 瓦的最大能量剂量下开始手术的。没有转院记录,术后 30 天内也没有发生紧急入院情况。在为期 24 个月的研究期间,共发生了 1 起三级并发症。我们观察到,与基线值(14,12-17)相比,6 个月(6,3-8)、12 个月(3,5-2)和 24 个月(3,2-4)的国际前列腺症状评分中位数均有统计学意义的持续下降。尿流率参数也显示出类似的趋势。男性性健康量表的中位值没有明显变化,只有约 10% 的患者报告在 12 个月和 24 个月时没有前向射精。 TPLA治疗良性前列腺增生症是一种安全、耐受性良好的诊室手术,在2年的随访中对功能结果有持久的益处。要证实这些结果,还需要进一步的研究。 NCT04760483。
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引用次数: 1
Editorial Comment: Office-Based Transperineal Laser Ablation for Benign Prostatic Hyperplasia Under Local Anaesthesia: 2-Year Results from a Dose Range Confirmatory Trial 编辑评论:局部麻醉下办公室经会阴激光消融治疗良性前列腺增生:剂量范围确认试验的两年结果
Pub Date : 2024-02-01 DOI: 10.1097/ju9.0000000000000115
Mario I. Fernández, Alberto Bustamante
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引用次数: 0
Editorial Comment: Case Report: Sacral Neuromodulation with Suspected Neuromuscular Blockade Secondary to a Butyrylcholinesterase (BCHE) Variant 编辑评论病例报告:丁酰胆碱酯酶(BCHE)变异引起的骶神经调节与疑似神经肌肉阻滞
Pub Date : 2023-12-01 DOI: 10.1097/ju9.0000000000000085
J. Kikuchi
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引用次数: 0
Case Report: Sacral Neuromodulation with Suspected Neuromuscular Blockade Secondary to Butyrylcholinesterase Variant 病例报告:疑因丁酰胆碱酯酶变异而导致神经肌肉阻滞的骶神经调节术
Pub Date : 2023-12-01 DOI: 10.1097/ju9.0000000000000083
Nadia Megahed, Prapti Singh, Yaseen Maleki, Rachel A. High, Julie Stewart
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引用次数: 1
Editorial Comment: Postoperative Oral Care Pathways Are Not Required at the Time of Buccal Mucosa Harvest 编辑评论:颊黏膜采集时不需要术后口腔护理路径
Pub Date : 2023-12-01 DOI: 10.1097/ju9.0000000000000086
Ryan Terlecki, Ethan Matz, Connor Policastro
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引用次数: 0
Reply to Editorial Comment: Pelvic Floor Dysfunction: A Common Cause of Chronic Orchialgia 回复编辑评论:盆底功能障碍:慢性睾丸炎的常见病因
Pub Date : 2023-12-01 DOI: 10.1097/ju9.0000000000000091
Amy Zheng, Susan M. MacDonald
{"title":"Reply to Editorial Comment: Pelvic Floor Dysfunction: A Common Cause of Chronic Orchialgia","authors":"Amy Zheng, Susan M. MacDonald","doi":"10.1097/ju9.0000000000000091","DOIUrl":"https://doi.org/10.1097/ju9.0000000000000091","url":null,"abstract":"","PeriodicalId":74033,"journal":{"name":"JU open plus","volume":"770 ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2023-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139018704","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
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