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镜下血尿的评估

发布时间:2020-09-15   来源:白银市第一人民医院泌尿男科  

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镜下血尿的评估

镜下血尿(MH)可能是泌尿系统恶性肿瘤的初步表现,发现MH后,可能需要对患者进行一系列检查来评估是否存在泌尿系统恶性肿瘤。那么,应该怎么评估呢?来自梅奥诊所的Vignesh T. Packiam等人在《欧洲泌尿外科杂志》上发表了一篇评论,表示,目前,在标准化评估方面存在两个问题,第一,在标准化评估的制定方面,有的指南建议对所有出现MH的患者统一进行全面的检查,但这会导致过度评估;第二,在评估实践中,由于转诊等各种原因,对出现MH的患者进行恶性肿瘤评估时会出现评估不足。那么,针对这两个问题,应该怎么办呢?一起来看看。


The clinical significance and optimal evaluation of microscopic hematuria (MH) remain in debate. While MH may be the initial presentation for patients with a urologic malignancy, the overall incidence of cancer in the setting of MH is quite low. In this issue of European Urology, Jubber et al report results of a systematic review and meta-analysis evaluating the association between MH and diagnoses of bladder, upper tract urothelial, and kidney cancers. The authors used 78 manuscripts for systematic review and 40 studies with 19 193 patients for meta-analysis. Moderate heterogeneity was noted between the studies, with heterogeneity statistics (I2) of 90% for bladder, 39% for upper tract urothelial, and 62% for kidney cancer studies. The resultant findings—which identify low associated rates of each malignancy—add support to the importance of continued efforts to refine the evaluation of patients noted with MH.

目前,镜下血尿(MH)的临床意义和最佳评估方式仍存在争议。虽然MH可能是泌尿系统恶性肿瘤患者的最初表现,但出现MH的患者的癌症总体发病率很低。在《欧洲泌尿外科杂志》中,Jubber等人报告了一项系统性回顾和荟萃分析的结果,评估了MH与膀胱癌、上尿路尿路上皮癌和肾癌的诊断之间的关联。作者对78项研究进行了系统性回顾,对40项研究(共19 193例患者)进行了荟萃分析。研究之间的异质性为中等,对于膀胱癌研究,异质性分析中的统计量(I2)为90%,上尿路尿路上皮癌研究为39%,肾癌研究为62%。结果发现,在出现MH的患者中,恶性肿瘤发病率较低,这进一步支持,继续改善对MH患者的评估十分重要。


Two significant, and potentially linked, challenges currently face the development and implementation of a standardized MH evaluation. First, current guidelines recommend a relatively intense work-up when MH is detected, which, in the setting of the noted low prevalence of malignancy, results in overtesting for many patients. At the same time, practice-pattern studies have documented considerable underevaluation of hematuria in terms of both inadequate urologic referral and delays in evaluation, which in turn have been linked to downstream detrimental cancer outcomes, including survival. Thus, a paradox has emerged whereby guidelines suggest what would be a significant rate of negative testing, while in fact many clinicians are not practicing guideline-concordant care in evaluating MH.

目前,在标准化MH评估的制定和实施方面存在两个重大且潜在相关的挑战。第一,当前的指南建议在检测到MH时应进行大量的检查,那么,在目前出现MH的患者中恶性肿瘤发生率较低的背景下,这样的建议就会导致对许多患者过度检查。第二,分析实践的研究显示,由于泌尿科转诊不充分和评估延迟,目前血尿评估存在严重评估不足的现象,而这又与之后癌症患者结局(包括生存)较差有关。因此,出现了一个矛盾的现象,即指南提示阴性结果的发生率较高,但实际上许多临床医生在评估MH时并未使用指南推荐的方式。


With regard to the issue of overtesting, Jubber et al observed low prevalence of malignancy among MH patients, with pooled detection rates of bladder, upper tract urothelial, and kidney cancers of 3.2%, 0.042%, and 0.28%, respectively. Existing guidelines generally recommend fairly intensive work-up for MH that entails cystoscopic evaluation of the bladder and urethra, imaging of the upper urinary tract, and selective use of urine cytology. For example, the American Urological Association (AUA) recommends cystoscopy and a multiphase computed tomography (CT) urogram for all patients aged ≥35 yr with asymptomatic MH (≥3 red blood cells per high- power field on one sample) in whom benign causes are ruled out. Such non-risk-adapted strategies result in unnecessary testing in the majority of cases, posing societal burdens of cost and resource utilization. In addition, patients may experience anxiety and discomfort from cystoscopy as well as toxicity from exposure to contrast medium and ionizing radiation. Interestingly, a recent modeling analysis determined that per 10 000 patients evaluated for asymptomatic MH, replacing CT urography with ultrasound would detect one less cancer and would result in cost savings of more than $6 million. Similarly, a simulation study by Georgieva et al compared detection rates, secondary malignancies, and costs between the AUA and less intense guidelines for both gross and microscopic hematuria. These investigators projected that per 100 000 patients with hematuria, the existing AUA protocol of non-risk-adapted cystoscopy and CT urography could result in up to 82 fewer missed cases of malignancy versus other guidelines at the expense of up to 467 radiation-induced secondary cancers and approximately double the monetary cost.

关于过度检测的问题,Jubber等人观察到,MH患者的恶性肿瘤患病率较低,膀胱癌、上尿路尿路上皮癌和肾癌的合并检出率分别为3.2%、0.042%和0.28%。现有指南通常建议对MH患者统一进行全面检查,包括针对膀胱和尿道的膀胱镜检查、上尿路影像学检查以及选择性使用尿液细胞学检查。例如,美国泌尿外科学会(AUA)建议,应对所有年龄≥35岁且排除了良性病因的无症状MH(一个样本的每个高倍镜视野中红细胞≥3个)患者进行膀胱镜检查和多相计算机断层扫描(CT)尿路造影。这种不根据风险进行分层的检查策略在大多数情况下会导致不必要的检查,从而带来成本和资源利用等社会负担。而且,患者可能会对膀胱镜检查感到焦虑和不适,并且因暴露于造影剂和电离辐射而出现毒性反应。有趣的是,最近的一项建模分析显示,在每一万例因无症状MH而接受评估的患者中,用超声替代CT尿路造影会降低癌症检测率,也会使成本减少600多万美元。AUA指南推荐的是不根据风险进行分层的检查策略,而有些指南是根据肉眼血尿和镜下血尿的不同风险给出不同的建议,所以Georgieva等人进行了一项模拟研究,比较了AUA与这些指南之间的检出率、继发性恶性肿瘤发生率和成本。研究发现,与其他指南相比,如果根据目前的AUA指南,进行无风险分层的膀胱镜和CT尿路造影检查,那么每10万血尿患者中,恶性肿瘤患者漏诊数量会减少82例,但是有467例患者会出现辐射诱发的继发性癌症,成本也会翻一倍。


In parallel with the issue of guideline-recommended overtesting is the concern of practice underevaluation of patients with MH. For example, an institutional study by Elias et al found that only 12.8% of MH patients who would be classified as high risk for malignancy according to age >50 yr, smoking history of ≥ 10 yr, and/or environmental exposure of ≥ 15 yr were referred for urologic evaluation. Furthermore, several studies have shown that women with hematuria undergo less imaging and have a significant delay in bladder cancer diagnosis. Delays in diagnosis can in turn result in inferior survival, as Hollenbeck at al demonstrated for bladder cancer. While the reasons for underevaluation of patients with MH are probably multifactorial, lack of knowledge on the part of primary providers regarding referral indications as well as a perceived suboptimal risk-benefit ratio of current guidelines may be underlying contributing etiologies.

与指南建议的过度检测同时出现的问题是,在实践中MH患者的评估不足。例如,Elias等人的一项研究发现,在根据年龄>50岁、吸烟史≥10年和/或环境暴露≥15年评估恶性肿瘤风险为高风险的MH患者中,只有12.5%的患者会被转诊进行泌尿学评估。此外,多项研究发现,出现血尿的女性患者更少接受影像学检查,并且膀胱癌的诊断显著延迟。Hollenbeck等人的研究表明,膀胱癌诊断延迟可能导致生存率下降。MH患者评估不足的原因可能有很多,其中初级医疗人员对转诊适应症认识不足以及当前指南认为风险获益比欠佳可能是主要原因。


How can the seemingly competing issues of guideline-recommended overtesting and in-practice underevaluation be resolved? One opportunity lies in the development of risk-stratified approaches to MH evaluation. Such a strategy could effectively both decrease overtesting and correct underevaluation at large. Jubber et al emphasized that age, male gender, and smoking history have been significantly associated with a higher likelihood of urologic malignancy, highlighting the potential to utilize identified risk factors to guide evaluation. Indeed, the DETECT-1 investigators recently developed and validated a risk-stratified approach using age, gross versus microscopic hematuria, gender, and smoking history. While the effort is a commendable step in the right direction, the resulting algorithm is relatively complex, which may limit its generalized adoption, so there remains a need for a simplified, user-friendly risk strategy that would increase practical utility. Moreover, as inadequate urologic referral from primary physicians once MH is detected, long waiting times to be seen by a urologist on referral, and delay in efficient work-up after referral may also contribute to the underevaluation of MH, telemedicine may represent an opportunity to expedite the process. Safir et al showed that this approach improved satisfaction among patients. In addition, hematuria clinic models driven by a "one-stop” protocol have been explored as a means to efficiently evaluate patients after referral, entailing clinic evaluation, cystoscopy, and imaging in a single day, with expedited definitive management of malignancy.

如何解决指南推荐导致的过度检测和实践中评估不足这些问题?一种方法是开发出基于风险分层的MH评估方法。这样的策略可以有效地减少过度检测并从整体上改变评估不足。Jubber等人强调,年龄、男性和吸烟史与泌尿系统恶性肿瘤患病风险显著相关,这强调了可以利用已识别的风险因素指导评估。实际上,DETECT-1研究人员最近开发并验证了一种基于风险分层的评估方法,其中使用的风险因素包括年龄、肉眼血尿vs镜下血尿、性别和吸烟史。这是研究人员们朝着正确方向迈出的值得称赞的一步,但是,他们最终的算法相对复杂,可能会限制其普遍应用性,因此目前仍然需要开发根据风险进行评估的简化且易于使用的方法,以提高实用性。此外,初级医疗人员发现MH后没有进行足够的泌尿科转诊,转诊单位的泌尿科医师的等待时间较长,以及转诊后有效检查的延迟也可能导致MH的评估不足,因此远程医疗可能会有所帮助。Safir等人表明,远程医疗可以提高患者的满意度。此外,有研究受到“一站式”方案的启发,探索了血尿诊所模型,该模型在同一天对患者进行诊所评估、膀胱镜检查和影像学检查,有助于对患者进行转诊后的有效评估,尽快对恶性肿瘤进行明确管理。


Overall, the study here adds important data to the highly relevant issue of MH. Moving forward, simplified risk-stratified models to guide evaluation may both limit resource expenditure at a population level and enhance appropriate evaluation at an individual patient level. Finally, we must also improve our efforts at education and information dissemination to avoid underevaluation and delayed diagnoses.

总体而言,本研究为与MH高度相关的问题提供了重要数据。未来,根据风险分层来评估MH患者的简化方法既可以降低整个患者人群的资源使用,又可以针对每个患者进行更好的个性化适当评估。最后,还必须提升教育和信息传播水平,以避免评估不足和诊断延迟。


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