镜下血尿的评估

肉眼不可见的血尿（non-visible haematuria, NVH）也称为镜下血尿，是指在清洁中段尿样中，每高倍视野下红细胞（red blood cell, RBC）≥3 个。[1]Barocas DA, Boorjian SA, Alvarez RD, et al. Microhematuria: AUA/SUFU Guideline. J Urol. 2020 Oct;204(4):778-86. https://www.auajournals.org/doi/10.1097/JU.0000000000001297 http://www.ncbi.nlm.nih.gov/pubmed/32698717?tool=bestpractice.com

尿试纸检测结果呈阳性（微量血或更多）并不能确定 NVH，而提示应该用显微镜进行进一步检查。[1]Barocas DA, Boorjian SA, Alvarez RD, et al. Microhematuria: AUA/SUFU Guideline. J Urol. 2020 Oct;204(4):778-86. https://www.auajournals.org/doi/10.1097/JU.0000000000001297 http://www.ncbi.nlm.nih.gov/pubmed/32698717?tool=bestpractice.com

1％-3％ 的 NVH 患者有尿道癌。[2]Tan WS, Feber A, Sarpong R, et al. Who should be investigated for haematuria? results of a contemporary prospective observational study of 3556 patients. Eur Urol. 2018 Jul;74(1):10-4. https://www.doi.org/10.1016/j.eururo.2018.03.008 http://www.ncbi.nlm.nih.gov/pubmed/29653885?tool=bestpractice.com [3]Samson P, Waingankar N, Shah P, et al. Predictors of genitourinary malignancy in patients with asymptomatic microscopic hematuria. Urol Oncol. 2018 Jan;36(1):10.e1-10.e6. https://www.doi.org/10.1016/j.urolonc.2017.09.011 http://www.ncbi.nlm.nih.gov/pubmed/28988782?tool=bestpractice.com

许多 NVH 病例为特发性；研究人群之间的差异可归因于年龄、性别、种族、职业和吸烟状况等因素。[4]Tomson C, Porter T. Asymptomatic microscopic or dipstick haematuria in adults: which investigations for which patients? A review of the evidence. BJU Int. 2002;90:185-198. http://www.ncbi.nlm.nih.gov/pubmed/12133052?tool=bestpractice.com [5]Wollin T, Laroche B, Psooy K. Canadian guidelines for the management of asymptomatic microscopic hematuria in adults. Can Urol Assoc J. 2009:3;77-80. http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2645872 http://www.ncbi.nlm.nih.gov/pubmed/19293985?tool=bestpractice.com [6]Hiatt RA, Ordonez JD. Dipstick urinalysis screening, asymptomatic microhematuria, and subsequent urological cancers in a population-based sample. Cancer Epidemiol Biomarkers Prev. 1994;3:439-443. [Published correction appears in Cancer Epidemiol Biomarkers Prev. 1994;3:523.] http://cebp.aacrjournals.org/cgi/reprint/3/5/439 http://www.ncbi.nlm.nih.gov/pubmed/7848421?tool=bestpractice.com [7]Edwards TJ, Dickinson AJ, Natale S, et al. A prospective analysis of the diagnostic yield resulting from 4020 patients at a protocol-driven haematuria clinic. BJU Int. 2006;97:301-305. http://www.ncbi.nlm.nih.gov/pubmed/16430634?tool=bestpractice.com [8]Cohen RA, Brown RS. Microscopic hematuria. N Engl J Med. 2003;348:2330-2338. http://www.ncbi.nlm.nih.gov/pubmed/12788998?tool=bestpractice.com [9]Chou R, Dana T. Screening adults for bladder cancer: a review of the evidence for the U.S. Preventive Services Task Force. Ann Intern Med. 2010;5:153:461-468. http://www.ncbi.nlm.nih.gov/pubmed/20921545?tool=bestpractice.com [10]Kang M, Lee S, Jeong SJ, et al. Characteristics and significant predictors of detecting underlying diseases in adults with asymptomatic microscopic hematuria: a large case series of a Korean population. Int J Urol. 2015 Apr;22(4):389-93. https://www.doi.org/10.1111/iju.12697 http://www.ncbi.nlm.nih.gov/pubmed/25581719?tool=bestpractice.com AUA: diagnosis, evaluation and follow-up of asymptomatic microhematuria (AMH) in adults Opens in new window

NVH 在人群中的患病率为 2.4%-31.1% 不等，60 岁以上的男性以及吸烟或既往吸烟男性的患病率更高。[1]Barocas DA, Boorjian SA, Alvarez RD, et al. Microhematuria: AUA/SUFU Guideline. J Urol. 2020 Oct;204(4):778-86. https://www.auajournals.org/doi/10.1097/JU.0000000000001297 http://www.ncbi.nlm.nih.gov/pubmed/32698717?tool=bestpractice.com [10]Kang M, Lee S, Jeong SJ, et al. Characteristics and significant predictors of detecting underlying diseases in adults with asymptomatic microscopic hematuria: a large case series of a Korean population. Int J Urol. 2015 Apr;22(4):389-93. https://www.doi.org/10.1111/iju.12697 http://www.ncbi.nlm.nih.gov/pubmed/25581719?tool=bestpractice.com

最重要的一项初步诊断步骤是详细询问病史，旨在确定恶性肿瘤和肾内科疾病的危险因素。病史也可能提示不太严重的原因（例如，近期运动或性行为、泌尿道感染和月经）。

泌尿道恶性肿瘤风险随以下因素升高：年龄 >40 岁、性别为男性、血尿程度、血尿持续性、肉眼血尿史、吸烟、既往辐射暴露、尿路上皮癌（以前称为移行细胞癌）或 Lynch 综合征家族史、特定职业暴露（染料、苯系物、芳香胺类）、药物（例如非那西丁，仅在日本上市)、环磷酰胺或异环磷酰胺化疗，以及马兜铃酸（见于部分中草药成分的减重药）。[8]Cohen RA, Brown RS. Microscopic hematuria. N Engl J Med. 2003;348:2330-2338. http://www.ncbi.nlm.nih.gov/pubmed/12788998?tool=bestpractice.com 在男性中，无症状 NVH 更可能与泌尿道恶性肿瘤有关。[11]American College of Obstetricians and Gynecologists' Committee on Gynecologic Practice, American Urogynecologic Society. Committee opinion no. 703: asymptomatic microscopic hematuria in women. Jun 2017 [Internet publication]​​. https://www.acog.org/clinical/clinical-guidance/committee-opinion/articles/2017/06/asymptomatic-microscopic-hematuria-in-women ​​[3]Samson P, Waingankar N, Shah P, et al. Predictors of genitourinary malignancy in patients with asymptomatic microscopic hematuria. Urol Oncol. 2018 Jan;36(1):10.e1-10.e6. https://www.doi.org/10.1016/j.urolonc.2017.09.011 http://www.ncbi.nlm.nih.gov/pubmed/28988782?tool=bestpractice.com 肥胖和高血压是肾细胞癌的危险因素。[12]Escudier B, Porta C, Schmidinger M, et al. Renal cell carcinoma: ESMO clinical practice guidelines for diagnosis, treatment and follow-up. Ann Oncol. 2019 May 1;30(5):706-20. https://www.esmo.org/guidelines/genitourinary-cancers/renal-cell-carcinoma http://www.ncbi.nlm.nih.gov/pubmed/30788497?tool=bestpractice.com

如果基于高风险或中等风险特征怀疑是恶性肿瘤，则需要对整个尿道进行评估，包括上泌尿道影像学检查和下泌尿道的膀胱镜检查。[1]Barocas DA, Boorjian SA, Alvarez RD, et al. Microhematuria: AUA/SUFU Guideline. J Urol. 2020 Oct;204(4):778-86. https://www.auajournals.org/doi/10.1097/JU.0000000000001297 http://www.ncbi.nlm.nih.gov/pubmed/32698717?tool=bestpractice.com 相比之下，低风险患者的检查可以更专注于可能的病因，而不必对整个尿路进行调查。英国国家卫生与临床优化研究所推荐，若年龄≥60 岁的患者有原因不明的 NVH 以及尿痛或血检显示白细胞计数升高，则应在 2 周内按照疑似膀胱癌的转诊方式进行预约转诊。[13]National Institute for Health and Care Excellence. Suspected cancer: recognition and referral. Dec 2021 [internet publication]. https://www.nice.org.uk/guidance/ng12

考虑出血的解剖部位来源，能够提供一种系统化的分类方案。上尿路包括肾脏（肾小球或非肾小球性）和输尿管，剩余的部分为下尿路。这些分类标准在病史询问和体格检查时有很大价值，同时，这也可体现在安排诊断性检查时，因为没有单项诊断性检查能全面评估整个尿路。

诊断性检查必须首先确认存在 NVH。此后，检查可能鉴别上泌尿道肾小球源性血尿与其他原因引起的血尿，从而完成更精确的诊断检查。但是，对于具有泌尿道恶性肿瘤危险因素的所有患者，仍然有必要进行上泌尿道和下泌尿道的诊断性检查（影像学检查和膀胱镜检查）。

在 NVH 患者中最常发现的癌症是尿路上皮癌。[7]Edwards TJ, Dickinson AJ, Natale S, et al. A prospective analysis of the diagnostic yield resulting from 4020 patients at a protocol-driven haematuria clinic. BJU Int. 2006;97:301-305. http://www.ncbi.nlm.nih.gov/pubmed/16430634?tool=bestpractice.com [14]Messing EM, Madeb R, Young T, et al. Long-term outcome of hematuria home screening for bladder cancer in men. Cancer. 2006;107:2173-2179. http://onlinelibrary.wiley.com/doi/10.1002/cncr.22224/full http://www.ncbi.nlm.nih.gov/pubmed/17029275?tool=bestpractice.com [15]Friedman GD, Carroll PR, Cattolica EV, et al. Can hematuria be a predictor as well as a symptom or sign of bladder cancer? Cancer Epidemiol Biomarkers Prev. 1996;5:993-996. http://cebp.aacrjournals.org/cgi/reprint/5/12/993 http://www.ncbi.nlm.nih.gov/pubmed/8959322?tool=bestpractice.com [16]Sugimura K, Ikemoto S, Kawashima H, et al. Microscopic hematuria as a screening marker for urinary tract malignancies. Int J Urol. 2001;8:1-5. http://www.ncbi.nlm.nih.gov/pubmed/11168689?tool=bestpractice.com [17]Jones R, Latinovic R, Charlton J, et al. Alarm symptoms in early diagnosis of cancer in primary care: cohort study using general practice research database. BMJ. 2007;334:1040. http://www.bmj.com/cgi/content/full/334/7602/1040 http://www.ncbi.nlm.nih.gov/pubmed/17493982?tool=bestpractice.com

美国预防服务工作组（US Preventive Services Task Force）建议不要进行常规筛查，估计提示膀胱癌的 NVH 阳性预测值为 5％-8％。[9]Chou R, Dana T. Screening adults for bladder cancer: a review of the evidence for the U.S. Preventive Services Task Force. Ann Intern Med. 2010;5:153:461-468. http://www.ncbi.nlm.nih.gov/pubmed/20921545?tool=bestpractice.com [18]Nielsen M, Qaseem A; High Value Care Task Force of the American College of Physicians. Hematuria as a marker of occult urinary tract cancer: advice for high-value care from the American College of Physicians. Ann Intern Med. 2016;164:488-497. http://annals.org/article.aspx?articleid=2484287 http://www.ncbi.nlm.nih.gov/pubmed/26810935?tool=bestpractice.com