Matthew Nielsen, MD, MS; Amir Qaseem, MD, PhD; for the High Value Care Task Force of the American College of Physicians *
Disclaimer: The authors of this article are responsible for its contents, including any clinical or treatment recommendations.
Financial Support: Financial support for the development of this article comes exclusively from the American College of Physicians operating budget. Dr. Nielsen is supported by the American Cancer Society (grant MRSG-13-154-01-CPPB) and the Urology Care Foundation/Astellas (Rising Stars in Urology Research Award).
Disclosures: Dr. Nielsen reports personal fees from the American College of Physicians during the conduct of the study, other from Grand Rounds and Urology Care Foundation/Astellas outside the submitted work, and grants from the American Cancer Society and National Institutes of Health outside the submitted work. Authors not named here have disclosed no conflicts of interest. Forms can also be viewed at www.acponline.org/authors/icjme/ConflictOfInterestForms.do?msNum=M15-1496. Authors followed the policy regarding conflicts of interest described at www.annals.org/article.aspx?articleid=745942. A record of disclosures of interest is kept for each High Value Care Task Force meeting and conference call and can be viewed at http://hvc.acponline.org/clinrec.html.
Editors' Disclosures: Christine Laine, MD, MPH, Editor in Chief, reports that she has no financial relationships or interests to disclose. Darren B. Taichman, MD, PhD, Executive Deputy Editor, reports that he has no financial relationships or interests to disclose. Cynthia D. Mulrow, MD, MSc, Senior Deputy Editor, reports that she has no relationships or interests to disclose. Deborah Cotton, MD, MPH, Deputy Editor, reports that she has no financial relationships or interest to disclose. Jaya K. Rao, MD, MHS, Deputy Editor, reports that she has stock holdings/options in Eli Lilly and Pfizer. Sankey V. Williams, MD, Deputy Editor, reports that he has no financial relationships or interests to disclose. Catharine B. Stack, PhD, MS, Deputy Editor for Statistics, reports that she has stock holdings in Pfizer.
Requests for Single Reprints: Amir Qaseem, MD, PhD, MHA, American College of Physicians, 190 N. Independence Mall West, Philadelphia, PA 19106; e-mail, firstname.lastname@example.org.
Current Author Addresses: Dr. Nielsen: University of North Carolina Lineberger Comprehensive Cancer Center, 2107 Physicians Office Building, Campus Box 7235, Chapel Hill, NC 27599.
Dr. Qaseem: American College of Physicians, 190 N. Independence Mall West, Philadelphia, PA 19106.
Author Contributions: Conception and design: M. Nielsen, A. Qaseem.
Analysis and interpretation of the data: M. Nielsen, A. Qaseem.
Drafting of the article: M. Nielsen, A. Qaseem.
Critical revision of the article for important intellectual content: M. Nielsen, A. Qaseem.
Final approval of the article: M. Nielsen, A. Qaseem.
Statistical expertise: A. Qaseem.
Obtaining of funding: A. Qaseem.
Administrative, technical, or logistic support: A. Qaseem.
Collection and assembly of data: M. Nielsen.
The presence of blood in the urine, or hematuria, is a common finding in clinical practice and can sometimes be a sign of occult cancer. This article describes the clinical epidemiology of hematuria and the current state of practice and science in this context and provides suggestions for clinicians evaluating patients with hematuria.
A narrative review of available clinical guidelines and other relevant studies on the evaluation of hematuria was conducted, with particular emphasis on considerations for urologic referral.
Clinicians should include gross hematuria in their routine review of systems and specifically ask all patients with microscopic hematuria about any history of gross hematuria.
Clinicians should not use screening urinalysis for cancer detection in asymptomatic adults.
Clinicians should confirm heme-positive results of dipstick testing with microscopic urinalysis that demonstrates 3 or more erythrocytes per high-powered field before initiating further evaluation in all asymptomatic adults.
Clinicians should refer for further urologic evaluation in all adults with gross hematuria, even if self-limited.
Clinicians should consider urology referral for cystoscopy and imaging in adults with microscopically confirmed hematuria in the absence of some demonstrable benign cause.
Clinicians should pursue evaluation of hematuria even if the patient is receiving antiplatelet or anticoagulant therapy.
Clinicians should not obtain urinary cytology or other urine-based molecular markers for bladder cancer detection in the initial evaluation of hematuria.
Table 1. Organizational Recommendations for the Initial Evaluation of Average-Risk Patients With Asymptomatic Microscopic Hematuria
Table 2. Common Risk Factors for Urinary Tract Cancer in Patients With Microhematuria*
Table 3. Costs of Tests Included in Hematuria Evaluation
Summary of recommendations for the evaluation of patients with hematuria.
AMH = asymptomatic microscopic hematuria; CT = computed tomography; HPF = high-powered field; UA = urinalysis.
* See Table 1 for more details.
Summary of the American College of Physicians advice for high-value care on the evaluation of hematuria as a marker of occult urinary tract tumors.
HPF = high-powered field.
Robert S Brown
Beth Israel Deaconess Medical Center, Boston, MA
April 6, 2016
What is high-value care for hematuria that is only microscopic?
While I applaud Nielsen, Qaseem and the High Value Care Task Force of theAmerican College of Physicians in promoting guidelines for care in the management of patients with hematuria (1), I take issue with advice that needs to be more nuanced for those with microscopic, rather than gross, hematuria. First, while occult cancer may be the most serious concern in those with gross hematuria, glomerular disease with its attendant risks of chronic kidney disease and premature death is another serious condition in those with microscopic hematuria, particularly in the office practice of patients not referred to specialty clinics. A careful urinary sediment examination looking for red blood cell casts or >5% acanthocytes which have almost 100% specificity for glomerular disease (2–4) is a noninvasive way to spare patients from unnecessary imaging or cystoscopy. So rather than a mere peripheral mention on Figure 1, examination of red blood cell morphology should be added to their “High-Value Care Advice 3: Clinicians should confirm heme positive results of dipstick testing with microscopic urinalysis that demonstrates 3 or more erythrocytes per high-powered field before initiating further evaluation in all asymptomatic adults”. Second, “High-Value Care Advice 5: Clinicians should consider urology referral for cystoscopy and imaging in adults with microscopically confirmed hematuria in the absence of some demonstrable benign cause” is unbalanced. It suggests that urologic referral is needed for cystoscopy and imaging. I would argue that many physicians feel competent to consider whether ultrasound, CT scanning or magnetic resonance imaging is appropriate, and almost always such imaging should precede cystoscopy. Moreover, since there is little evidence to support cystoscopy in patients under 40 years of age that have only microscopic hematuria without risk factors for bladder cancer (5), urologic referral of such young patients is usually unnecessary. 1. 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 Apr 5;164(7):488-97. doi:10.7326/M15-1496.2. Köhler H, Wandel E, Brunck B. Acanthocyturia--a characteristic marker for glomerular bleeding. Kidney Int. 1991 Jul;40(1):115–20. 3. Kitamoto Y, Tomita M, Akamine M, Inoue T, Itoh J, Takamori H, et al. Differentiation of hematuria using a uniquely shaped red cell. Nephron. 1993 Jan;64(1):32–6. 4. Nagahama D, Yoshiko K, Watanabe M, Morita Y, Iwatani Y, Matsuo S. A useful new classification of dysmorphic urinary erythrocytes. Clin Exp Nephrol. 2005 Dec;9(4):304–9. 5. Niemi MA, Cohen RA. Evaluation of microscopic hematuria: a critical review and proposed algorithm. Adv Chronic Kidney Dis. 2015 Jul;22(4):289–96.
Matthew Nielsen, MD, Amir Qaseem, MD, PhD
American College of Physicians
June 20, 2016
We appreciate Dr. Brown’s thoughtful feedback on our paper. His first point, addressing cases where glomerular sources are suggested by the clinical presentation, is well taken. As discussed in our paper, current guidelines differ in recommendations for evaluation of patients with hematuria who have findings suggestive of potential nephrologic disorders, such as hypertension, renal insufficiency, cellular casts, proteinuria or dysmorphic erythrocytes. The American Urological Association and British Association of Urologic Surgeons recommend concurrent urologic evaluation in this context, whereas the Canadian and Dutch Guidelines suggest referral to a nephrologist as an alternative starting point in such cases (outlined in the second paragraph on page 490; references 29-32 in the paper). We also note (in the paragraph beginning on the bottom of page 492, continued on page 493) in the section “Limitations of Evidence,” that such presentations logically suggest nephrology consultation as the appropriate first and potentially only consult, but that a detailed examination of practice in that context was beyond the scope of our article. We appreciate his provision of excellent references to support the suggested approach.With regard to his second point, regarding the High Value Care Advice Statement 5, “Clinicians should consider urology referral for cystoscopy and imaging in adults with microscopically confirmed hematuria in the absence of some demonstrable benign cause,” urologic referral is, in our experience, needed for cystoscopy. The recommendation for cystoscopy in the evaluation of hematuria as a marker of occult urinary tract malignancy was consistent across the guidelines we reviewed (Table 1 in the paper), consistent with the fact that bladder cancer is the most common malignancy found in the evaluation of patients with hematuria. We did not find any evidence to support noninvasive imaging alone as an adequate diagnostic evaluation to exclude the presence of bladder cancer. Nevertheless, we share Dr. Brown’s concern that limited evidence supports the recommendation for cystoscopy in patients with microhematuria under 40 years of age without risk factors for bladder cancer. Uncertainty around criteria for referral, as well as uncertainty regarding which, if any, modality of upper urinary tract imaging is indicated for a given patient, represent unmet needs frustrating the goal of high value care for this common clinical presentation.Matthew E. Nielsen, MDAmir Qaseem, MD, PhD
Nielsen M, Qaseem A, for the 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. [Epub ahead of print 26 January 2016]. doi: https://doi.org/10.7326/M15-1496
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Published: Ann Intern Med. 2016;164(7):488-497.
Published at www.annals.org on 26 January 2016
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