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Persistent Asymptomatic Isolated Microscopic Hematuria in Adolescents is not Associated With an Increased Risk for Early Onset Urinary Tract Cancer

  • Author Footnotes
    # Both authors contributed equally.
    Adi Leiba
    Footnotes
    # Both authors contributed equally.
    Affiliations
    Israeli Defense Forces, Medical Corps, Tel Hashomer, Ramat Gan, Israel

    Division of Nephrology and Hypertension, Assuta Ashdod Hospital, Ashdod, Israel

    Faculty of Health Sciences, Ben Gurion University of the Negev, Beersheba, Israel

    Harvard Medical School, Cambridge, MA
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  • Author Footnotes
    # Both authors contributed equally.
    Sivan Zino
    Footnotes
    # Both authors contributed equally.
    Affiliations
    Faculty of Health Sciences, Ben Gurion University of the Negev, Beersheba, Israel
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  • Avital Angel Korman
    Affiliations
    Division of Nephrology and Hypertension, Assuta Ashdod Hospital, Ashdod, Israel

    Faculty of Health Sciences, Ben Gurion University of the Negev, Beersheba, Israel
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  • Vladimir Rappaport
    Affiliations
    Division of Nephrology and Hypertension, Assuta Ashdod Hospital, Ashdod, Israel

    Faculty of Health Sciences, Ben Gurion University of the Negev, Beersheba, Israel
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  • Asaf Vivante
    Affiliations
    Sackler School of Medicine, Tel Aviv University, Tel Aviv, Israel

    Pediatric Department B and Pediatric Nephrology Unit, Edmond and Lily Safra Children's Hospital, Sheba Medical Center, Tel Hashomer, Ramat Gan, Israel
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  • Tamar Fishman
    Affiliations
    Pharmacy Services, Sheba Medical Center, Tel Hashomer, Ramat Gan, Israel
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  • Gadi Shlomai
    Affiliations
    Sackler School of Medicine, Tel Aviv University, Tel Aviv, Israel

    Internal Medicine D Department, Sheba Medical Center, Tel Hashomer, Ramat Gan, Israel

    Institute of Endocrinology, Diabetes and Metabolism, Sheba Medical Center, Tel Hashomer, Ramat Gan, Israel
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  • Tsahi T. Lerman
    Affiliations
    Sackler School of Medicine, Tel Aviv University, Tel Aviv, Israel

    Department of Internal Medicine F-Recanati, Rabin Medical Center, Beilinson Hospital, Petah Tikva, Israel
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  • Estela Derazne
    Affiliations
    Sackler School of Medicine, Tel Aviv University, Tel Aviv, Israel
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  • Arnon Afek
    Affiliations
    Sackler School of Medicine, Tel Aviv University, Tel Aviv, Israel

    Central Management, Sheba Medical Center, Tel Hashomer, Ramat Gan, Israel
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  • Boris Fishman
    Correspondence
    Address correspondence to: Boris Fishman, M.D., M.P.H., Sheba Medical Center, Tel Hashomer, 2 Derech Sheba, Migdal Ishpuz, 3rd floor, Ramat Gan 5265601, Israel.
    Affiliations
    Israeli Defense Forces, Medical Corps, Tel Hashomer, Ramat Gan, Israel

    Sackler School of Medicine, Tel Aviv University, Tel Aviv, Israel

    Leviev Heart Center, Sheba Medical Center, Tel Hashomer, Ramat Gan, Israel
    Search for articles by this author
  • Author Footnotes
    # Both authors contributed equally.

      Abstract

      Objective

      To elucidate the association between adolescent microscopic hematuria and early onset urothelial carcinoma and renal cell carcinoma.

      Methods

      Nationwide, population-based, retrospective cohort study using medical data of 970,366 adolescents aged 16 through 19 years (58.6% male) examined for fitness for military service between 1980 and 1997. Diagnoses of persistent isolated microscopic hematuria were given after thorough work up process excluding any other renal abnormalities. Incident cases of urothelial carcinoma and renal cell carcinoma diagnosed during the years of 1982-2012 were retrieved from the Israeli National Cancer Registry. Cox proportional hazards models were used to estimate the hazard ratio (HR) separately for urothelial carcinoma and renal cell carcinoma.

      Results

      During a cumulative follow-up of 22,115,629 person-years (median follow-up, 22.8), persistent isolated microscopic hematuria was diagnosed among 5509 (0.6%) adolescents. Urothelial carcinoma and renal cell carcinoma developed in 332 (3 among those with persistent isolated microscopic hematuria) and 292 (2) individuals, respectively. The adjusted HR for incident urothelial carcinoma among adolescents with isolated microscopic hematuria was 1.17 (95% CI, 0.38-3.66) and the adjusted HR for renal cell carcinoma was 1.02 (95% CI, 0.25-4.12).

      Conclusion

      Persistent asymptomatic isolated microscopic hematuria at adolescence was not associated with increased risk for urothelial carcinoma nor renal cell carcinoma.

      Abbreviations:

      ESRD (end stage renal disease), RCC (renal cell carcinoma), IDF (Israeli defense forces), INCR (Israeli National Cancer Registry), BMI (body mass index), CT (computed tomography)
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      References

        • Cohen RA
        • Brown RS.
        Microscopic Hematuria.
        N Engl J Med. 2003; 348: 2330-2338https://doi.org/10.1056/NEJMcp012694
        • Moreno JA
        • Sevillano Á
        • Gutiérrez E
        • et al.
        Glomerular hematuria: cause or consequence of renal inflammation?.
        Int J Mol Sci. 2019; 20https://doi.org/10.3390/ijms20092205
        • Vivante A.
        Persistent asymptomatic isolated microscopic hematuria in Israeli adolescents and young adults and risk for end-stage renal disease.
        JAMA. 2011; 306: 729https://doi.org/10.1001/jama.2011.1141
        • Siegel RL
        • Miller KD
        • Jemal A.
        Cancer statistics, 2020.
        CA Cancer J Clin. 2020; 70: 7-30https://doi.org/10.3322/caac.215901
        • Barocas DA
        • Boorjian SA
        • Alvarez RD
        • et al.
        Microhematuria: AUA/SUFU guideline.
        J Urol. 2020; 204: 778-786https://doi.org/10.1097/JU.0000000000001297
        • Fishman B
        • Zloof Y
        • Orr O
        • et al.
        The opposing trends of body mass index and blood pressure during 1977–2020; nationwide registry of 2.8 million male and female adolescents.
        Cardiovasc Diabetol. 2021; 20: 1-10https://doi.org/10.1186/s12933-021-01433-0
        • Fishman B
        • Leiba A
        • Twig G
        • et al.
        Ethnic variability among jews is associated with hypertension: results of a nationwide study of 1.44 million adolescents.
        Am J Hypertens. 2020; 33: 175-181https://doi.org/10.1093/ajh/hpz167
        • Zohar L
        • Rottenberg Y
        • Twig G
        • et al.
        Adolescent overweight and obesity and the risk for pancreatic cancer among men and women: a nationwide study of 1.79 million Israeli adolescents.
        Cancer. 2019; 125: 118-126https://doi.org/10.1002/cncr.31764
        • Furer A
        • Afek A
        • Sommer A
        • et al.
        Adolescent obesity and midlife cancer risk: a population-based cohort study of 2·3 million adolescents in Israel.
        Lancet Diabetes Endocrinol. 2020; 8: 216-225https://doi.org/10.1016/S2213-8587(20)30019-X
        • Fishman B
        • Grossman E
        • Zucker I
        • et al.
        Adolescent hypertension and risk for early-onset type 2 diabetes: a nationwide study of 1.9 million Israeli adolescents.
        Diabetes Care. 2020; dc201752https://doi.org/10.2337/dc20-1752
        • Fishman B
        • Shlomai G
        • Twig G
        • et al.
        Renal glucosuria is associated with lower body weight and lower rates of elevated systolic blood pressure: results of a nationwide cross-sectional study of 2.5 million adolescents.
        Cardiovasc Diabetol. 2019; 18: 124https://doi.org/10.1186/s12933-019-0929-7
        • Robinson E
        • Silverman BG
        • Keinan-Boker L.
        Using Israel's national cancer registry database to track progress in the war against cancer: a challenge for health services.
        Isr Med Assoc J. 2017; 19: 221-224
        • Pak JS
        • Wang EY
        • Lee K
        • Pina LA
        • McKiernan JM
        • Anderson CB.
        Diagnostic yield of repeat evaluation for asymptomatic microscopic hematuria after negative initial workup.
        Urol Oncol Semin Orig Investig. 2020; (Published online)https://doi.org/10.1016/j.urolonc.2020.11.032
        • Saxon GM
        • Patil D
        • Hammett J.
        Microhematuria in women: prevalence of malignancy and risk score evaluation.
        Urology. 2022; 160: 34-39https://doi.org/10.1016/j.urology.2021.11.003
        • Ghandour R
        • Freifeld Y
        • Singla N
        • Lotan Y.
        Evaluation of hematuria in a large public health care system.
        Bl Cancer. 2019; 5: 119-129https://doi.org/10.3233/BLC-190221
        • Matulewicz RS
        • Rademaker A
        • Meeks JJ.
        A simplified nomogram to assess risk of bladder cancer in patients with a new diagnosis of microscopic hematuria.
        Urol Oncol Semin Orig Investig. 2020; 38: 240-246https://doi.org/10.1016/j.urolonc.2019.12.010
      1. Barocas DA, Boorjian SA, Alvarez RD, et al. Trauma /reconstruction / diversion microhematuria : AUA / SUFU Guideline. Published online 2020:778-786.

        • Bryan RT
        • Kockelbergh RC.
        Asymptomatic microscopic haematuria and significant urinary tract disease.
        Bl Cancer. 2019; 5: 115-117https://doi.org/10.3233/BLC-199006
        • Mishriki SF
        • Nabi G
        • Cohen NP.
        Diagnosis of urologic malignancies in patients with asymptomatic dipstick hematuria: prospective study with 13 years’ follow-up.
        Urology. 2008; 71: 13-16https://doi.org/10.1016/j.urology.2007.08.031
        • Matulewicz RS
        • DeLancey JO
        • Pavey E
        • Schaeffer EM
        • Popescu O
        • Meeks JJ.
        Dipstick urinalysis as a test for microhematuria and occult bladder cancer.
        Bl Cancer. 2017; 3: 45-49https://doi.org/10.3233/BLC-160068
        • Madeb R
        • Golijanin D
        • Knopf J
        • et al.
        Long-term outcome of patients with a negative work-up for asymptomatic microhematuria.
        Urology. 2010; 75: 20-25https://doi.org/10.1016/j.urology.2009.06.107
        • Georgieva MV
        • Wheeler SB
        • Erim D
        • et al.
        Comparison of the harms, advantages, and costs associated with alternative guidelines for the evaluation of hematuria.
        JAMA Intern Med. 2019; 179: 1352-1362https://doi.org/10.1001/jamainternmed.2019.2280
        • Yecies T
        • Bandari J
        • Fam M
        • Macleod L
        • Jacobs B
        • Davies B.
        Risk of radiation from computerized tomography urography in the evaluation of asymptomatic microscopic hematuria.
        J Urol. 2018; 200: 967-972https://doi.org/10.1016/j.juro.2018.05.118
        • Skaggs AW
        • Loehfelm TW
        • Fananapazir G
        • Dall'Era M
        • Corwin MT
        Utilization and yield of CT urography: are the american urological association guidelines for imaging of patients with asymptomatic microscopic hematuria being followed?.
        Am J Roentgenol. 2021; 216: 106-110https://doi.org/10.2214/AJR.20.22998
        • Clark M
        • Aronoff S
        • Del Vecchio M.
        Etiologies of asymptomatic microscopic hematuria in children – systematic review of 1092 subjects.
        Diagnosis. 2015; 2: 211-216https://doi.org/10.1515/dx-2015-0020
        • Lee HM
        • Hyun JI
        • Min J-W
        • et al.
        31.6.909 •.
        J Korean Med Sci. 2016; 31 (http://dx.doi.org/10.3346/jkms.2016.31.6.909): 909-914
        • Pani A
        • Porta C
        • Cosmai L
        • et al.
        Glomerular diseases and cancer: evaluation of underlying malignancy.
        J Nephrol. 2016; 29: 143-152https://doi.org/10.1007/s40620-015-0234-9
        • Leiba A
        • Kark JD
        • Afek A
        • et al.
        Adolescent obesity and paternal country of origin predict renal cell carcinoma: a cohort study of 1.1 million 16 to 19-year-old males.
        J Urol. 2013; 189: 25-29https://doi.org/10.1016/j.juro.2012.08.184
        • Rasmussen M
        • Madsen MG
        • Therkildsen C.
        Immunohistochemical screening of upper tract urothelial carcinomas for lynch syndrome diagnostics: a systematic review.
        Urology. 2022; (Published online)https://doi.org/10.1016/j.urology.2022.02.006