Skip to main content

Advertisement

SpringerLink
Log in

Urinary pH Levels are Strongly Associated with Bladder Recurrence After Nephroureterectomy in Upper Tract Urothelial Carcinoma Patients with a Smoking History

  • Urologic Oncology
  • Published:
Annals of Surgical Oncology Aims and scope Submit manuscript

Abstract

Purpose

Aromatic amines, well-known bladder carcinogens, derived from cigarette smoke are activated by acidic urine. We herein determined whether urinary pH levels are associated with bladder recurrence in upper tract urothelial carcinoma patients with a positive smoking history.

Methods

A total of 256 upper tract urothelial carcinoma patients who were surgically treated at our institution between 1990 and 2013 were included. Urinary pH levels were defined as the median of at least two consecutive measurements within 1 month of surgery.

Results

Ninety-six patients (37.5 %) had pH <5.5 and 160 (62.5 %) had pH ≥5.5, and urinary pH levels were identified as one of the significant predictors for bladder recurrence in univariate but not multivariate Cox regression analysis in overall. In patients with a positive smoking history among those without a history of bladder tumor (N = 110), the 5-year bladder recurrence-free survival rate was 52.5 % in patients with pH ≥5.5, which was significantly higher than that in those with pH <5.5 (25.9 %, p = 0.032). In the multivariate analysis, urinary pH <5.5 (p = 0.022, HR; 1.86) was independently associated with bladder recurrence. No significant difference for bladder recurrence was observed between these two groups in patients with no smoking history among them.

Conclusions

Urinary pH <5.5 is associated with an increased risk of bladder recurrence in upper tract urothelial carcinoma patients with a positive smoking history among those without a history of bladder tumor. Modifications to pH for urine alkalization may prevent bladder recurrence.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1
Fig. 2
Fig. 3

Similar content being viewed by others

References

  1. Oosterlinck W. Ureteral tumour: a specific upper urinary tract transitional cell carcinoma. Eur Urol. 2007;51(5):1164–5.

    Article  PubMed  Google Scholar 

  2. Margulis V, Shariat SF, Matin SF, et al. Outcomes of radical nephroureterectomy: a series from the upper tract urothelial carcinoma collaboration. Cancer. 2009;115(6):1224–33.

    Article  PubMed  Google Scholar 

  3. Cha EK, Shariat SF, Kormaksson M, et al. Predicting clinical outcomes after radical nephroureterectomy for upper tract urothelial carcinoma. Eur Urol. 2012;61(4):818–25.

    Article  PubMed  Google Scholar 

  4. Zhang Z, Fang D, Chen X, et al. Predictive role of preoperative hydronephrosis on poor pathological outcomes and prognosis in upper tract urothelial carcinoma patients: experience from a nationwide high-volume center in China. Oncol Lett. 2015;10(5):3113–22.

    PubMed  PubMed Central  Google Scholar 

  5. Favaretto RL, Shariat SF, Chade DC, et al. Comparison between laparoscopic and open radical nephroureterectomy in a contemporary group of patients: are recurrence and disease-specific survival associated with surgical technique? Eur Urol. 2010;58(5):645–51.

    Article  PubMed  PubMed Central  Google Scholar 

  6. Fradet V, Mauermann J, Kassouf W, et al. Risk factors for bladder cancer recurrence after nephroureterectomy for upper tract urothelial tumors: results from the Canadian upper tract collaboration. Urol Oncol. 2014;32(6):839–45.

    Article  PubMed  Google Scholar 

  7. Ishioka J, Saito K, Kijima T, et al. Risk stratification for bladder recurrence of upper urinary tract urothelial carcinoma after radical nephroureterectomy. BJU Int. 2015;115(5):705–12.

    Article  PubMed  Google Scholar 

  8. Zigeuner RE, Hutterer G, Chromecki T, Rehak P, Langner C. Bladder tumour development after urothelial carcinoma of the upper urinary tract is related to primary tumour location. BJU Int. 2006;98(6):1181–6.

    Article  PubMed  Google Scholar 

  9. Li CC, Chang TH, Wu WJ, et al. Significant predictive factors for prognosis of primary upper urinary tract cancer after radical nephroureterectomy in Taiwanese patients. Eur Urol. 2008;54(5):1127–34.

    Article  PubMed  Google Scholar 

  10. Soga N, Arima K, Sugimura Y. Adjuvant methotrexate, vinblastine, adriamycin, and cisplatin chemotherapy has potential to prevent recurrence of bladder tumors after surgical removal of upper urinary tract transitional cell carcinoma. Int J Urol. 2008;15(9):800–3.

    Article  CAS  PubMed  Google Scholar 

  11. Kusuda Y, Miyake H, Terakawa T, Kondo Y, Miura T, Fujisawa M. Gender as a significant predictor of intravesical recurrence in patients with urothelial carcinoma of the upper urinary tract following nephroureterectomy. Urol Oncol. 2013;31(6):899–903.

    Article  PubMed  Google Scholar 

  12. Seisen T, Granger B, Colin P, et al. A Systematic review and meta-analysis of clinicopathologic factors linked to intravesical recurrence after radical nephroureterectomy to treat upper tract urothelial carcinoma. Eur Urol. 2015;67(6):1122–33.

    Article  PubMed  Google Scholar 

  13. Sankin A, Tin AL, Mano R, et al. Impact of ureteroscopy before nephroureterectomy for upper tract urothelial carcinoma on oncologic outcomes. Urology. 2016;94:148–53.

    Article  PubMed  Google Scholar 

  14. Hagiwara M, Kikuchi E, Tanaka N, et al. Impact of smoking status on bladder tumor recurrence after radical nephroureterectomy for upper tract urothelial carcinoma. J Urol. 2013;189(6):2062–8.

    Article  PubMed  Google Scholar 

  15. O’Brien T, Ray E, Singh R, Coker B, Beard R, British Association of Urological Surgeons Section of O. Prevention of bladder tumours after nephroureterectomy for primary upper urinary tract urothelial carcinoma: a prospective, multicentre, randomised clinical trial of a single postoperative intravesical dose of mitomycin C (the ODMIT-C trial). Eur Urol. 2011;60(4):703–10.

    Article  PubMed  Google Scholar 

  16. Ito A, Shintaku I, Satoh M, et al. Prospective randomized phase II trial of a single early intravesical instillation of pirarubicin (THP) in the prevention of bladder recurrence after nephroureterectomy for upper urinary tract urothelial carcinoma: the THP Monotherapy Study Group Trial. J Clin Oncol. 2013;31(11):1422–7.

    Article  CAS  PubMed  Google Scholar 

  17. Dalton JT, Wientjes MG, Badalament RA, Drago JR, Au JL. Pharmacokinetics of intravesical mitomycin C in superficial bladder cancer patients. Cancer Res. 1991;51(19):5144–52.

    CAS  PubMed  Google Scholar 

  18. Maeda T, Kikuchi E, Matsumoto K, Miyajima A, Oya M. Urinary pH is highly associated with tumor recurrence during intravesical mitomycin C therapy for nonmuscle invasive bladder tumor. J Urol. 2011;185(3):802–6.

    Article  CAS  PubMed  Google Scholar 

  19. Kadlubar FF, Miller JA, Miller EC. Hepatic microsomal N-glucuronidation and nucleic acid binding of N-hydroxy arylamines in relation to urinary bladder carcinogenesis. Cancer Res. 1977;37(3):805–14.

    CAS  PubMed  Google Scholar 

  20. Babu SR, Lakshmi VM, Huang GP, Zenser TV, Davis BB. Glucuronide conjugates of 4-aminobiphenyl and its N-hydroxy metabolites. pH stability and synthesis by human and dog liver. Biochem Pharmacol. 1996;51(12):1679–85.

    Article  CAS  PubMed  Google Scholar 

  21. Alguacil J, Kogevinas M, Silverman DT, et al. Urinary pH, cigarette smoking and bladder cancer risk. Carcinogenesis. 2011;32(6):843–7.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  22. Zenser TV, Lakshmi VM, Hsu FF, Davis BB. Metabolism of N-acetylbenzidine and initiation of bladder cancer. Mutat Res. 2002;506–507:29–40.

    Article  PubMed  Google Scholar 

  23. Pichler M, Hutterer GC, Stoeckigt C, et al. Validation of the pre-treatment neutrophil-lymphocyte ratio as a prognostic factor in a large European cohort of renal cell carcinoma patients. Br J Cancer. 2013;108(4):901–7.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  24. Babu SR, Lakshmi VM, Hsu FF, Kane RE, Zenser TV, Davis BB. N-acetylbenzidine-N’-glucuronidation by human, dog and rat liver. Carcinogenesis. 1993;14(12):2605–11.

    Article  CAS  PubMed  Google Scholar 

  25. Lakshmi VM, Hsu FF, Zenser TV. Transformation and activation of benzidine by oxidants of the inflammatory response. Chem Res Toxicol. 2003;16(3):367–74.

    Article  CAS  PubMed  Google Scholar 

  26. Bois FY, Krowech G, Zeise L. Modeling human interindividual variability in metabolism and risk: the example of 4-aminobiphenyl. Risk Anal. 1995;15(2):205–13.

    Article  CAS  PubMed  Google Scholar 

  27. Fang D, Li XS, Xiong GY, Yao L, He ZS, Zhou LQ. Prophylactic intravesical chemotherapy to prevent bladder tumors after nephroureterectomy for primary upper urinary tract urothelial carcinomas: a systematic review and meta-analysis. Urol Int. 2013;91(3):291–6.

    Article  CAS  PubMed  Google Scholar 

  28. Au JL, Badalament RA, Wientjes MG, et al. Methods to improve efficacy of intravesical mitomycin C: results of a randomized phase III trial. J Natl Cancer Inst. 2001;93(8):597–604.

    Article  CAS  PubMed  Google Scholar 

  29. Miyamoto H, Yang Z, Chen YT, et al. Promotion of bladder cancer development and progression by androgen receptor signals. J Natl Cancer Inst. 2007;99(7):558–68.

    Article  CAS  PubMed  Google Scholar 

Download references

Acknowledgment

The authors thank Nobuyuki Tanaka, M.D., for data collection.

Author information

Authors and Affiliations

  1. Department of Urology, Keio University School of Medicine, Shinjuku-ku, Tokyo, Japan

    Hiroki Ide MD, Eiji Kikuchi MD, PhD, Masayuki Hagiwara MD, Nozomi Hayakawa MD, Hiroshi Hongo MD, Akira Miyajima MD, PhD & Mototsugu Oya MD, PhD

Authors
  1. Hiroki Ide MD
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Eiji Kikuchi MD, PhD
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Masayuki Hagiwara MD
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Nozomi Hayakawa MD
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Hiroshi Hongo MD
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Akira Miyajima MD, PhD
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. Mototsugu Oya MD, PhD
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Eiji Kikuchi MD, PhD.

Ethics declarations

Disclosure

No conflicts of interest were disclosed.

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Ide, H., Kikuchi, E., Hagiwara, M. et al. Urinary pH Levels are Strongly Associated with Bladder Recurrence After Nephroureterectomy in Upper Tract Urothelial Carcinoma Patients with a Smoking History. Ann Surg Oncol 23 (Suppl 5), 1029–1038 (2016). https://doi.org/10.1245/s10434-016-5555-y

Download citation

  • Received:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1245/s10434-016-5555-y

Keywords

Search

Navigation