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Perioperative Detection of Circulating Tumor Cells in Radical or Partial Nephrectomy for Renal Cell Carcinoma

Annals of Surgical Oncology volume 27, pages 1272–1281 (2020)Cite this article

Abstract

Background

The current study was conducted to clarify the frequency of systemic circulating tumor cells (CTCs) appearing after surgery for renal cell carcinoma and to evaluate the differences in postoperative CTCs between different surgical procedures.

Methods

This prospective, cohort study included 60 consecutive patients who underwent laparoscopic radical nephrectomy (RN) (n = 22), laparoscopic partial nephrectomy (PN) (n = 19), open RN (n = 8), or open PN (n = 11). In this study CTCs were measured by the FISHMAN-R system, and CTCs drawn from a peripheral artery were collected just before and immediately after surgery. The number of pre- and postoperative CTCs and the perioperative changes in CTCs were measured for each surgical method.

Results

Six patients were excluded from the current analyses. Preoperative CTCs did not differ significantly by surgical approach (laparoscopic RN: 3.4 ± 4.2; laparoscopic PN: 3.4 ± 4.1; open RN: 7.7 ± 6.8; open PN: 6.0 ± 7.6; P = 0.19). Open RN resulted in a significantly greater number of postoperative CTCs (laparoscopic RN: 4.8 ± 3.7; laparoscopic PN: 7.9 ± 9.1; open RN: 22.5 ± 26.3; open PN: 6.4 ± 6.3; P < 0.001) and perioperative changes in CTCs (laparoscopic RN: 1.3 ± 5.3; laparoscopic PN: 4.5 ± 9.6; open RN: 14.7 ± 25.0; open PN: 0.4 ± 6.3; P < 0.001). No significant differences in these were observed among the three groups except in the open RN group. In the multivariate analysis, the surgical approach was significantly correlated with the number of postoperative CTCs (P = 0.016) and the perioperative change in CTCs (P = 0.01).

Conclusions

This proof-of-concept study indicated that after surgery, more cancer cells can be expelled into the bloodstream, especially after open RN. Sufficient and careful follow-up assessment for the emergence of distant metastases is needed for patients undergoing open RN.

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References

  1. Campbell SC, Novick AC, Belldegrun A, et al. Guideline for management of the clinical T1 renal mass. J Urol. 2009;182:1271.

    Article  PubMed  Google Scholar 

  2. Calaway AC, Monn MF, Bahler CD, et al. A novel preoperative model to predict 90-day surgical mortality in patients considered for renal cell carcinoma surgery. Urol Oncol. 2018;36:470.e11.

    Google Scholar 

  3. Pierorazio PM, Johnson MH, Patel HD, et al. Management of renal masses and localized renal cancer: systematic review and meta-analysis. J Urol. 2016;196:989.

    Article  PubMed  PubMed Central  Google Scholar 

  4. Wang ZL, Zhang P, Li HC, et al. Dynamic changes of different phenotypic and genetic circulating tumor cells as a biomarker for evaluating the prognosis of RCC. Cancer Biol Ther. 2019;20:505–12.

    Article  CAS  PubMed  Google Scholar 

  5. Cohen SJ, Punt CJ, Iannotti N, et al. Relationship of circulating tumor cells to tumor response, progression-free survival, and overall survival in patients with metastatic colorectal cancer. J Clin Oncol. 2008;26:3213.

    Article  PubMed  Google Scholar 

  6. Bidard FC, Mathiot C, Delaloge S, et al. Single circulating tumor cell detection and overall survival in nonmetastatic breast cancer. Ann Oncol. 2010;21:729.

    Article  PubMed  Google Scholar 

  7. Harouaka R, Kang Z, Zheng SY, et al. Circulating tumor cells: advances in isolation and analysis, and challenges for clinical applications. Pharmacol Ther. 2014;141:209.

    Article  CAS  PubMed  Google Scholar 

  8. de Bono JS, Scher HI, Montgomery RB, et al. Circulating tumor cells predict survival benefit from treatment in metastatic castration-resistant prostate cancer. Clin Cancer Res. 2008;14:6302.

    Article  PubMed  Google Scholar 

  9. Amin MB, Greene FL, Edge SB, et al. The eighth-edition AJCC cancer staging manual: continuing to build a bridge from a population-based to a more “personalized” approach to cancer staging. CA Cancer J Clin. 2017;67:93.

    Article  PubMed  Google Scholar 

  10. Kutikov A, Uzzo RG. The R.E.N.A.L. nephrometry score: a comprehensive standardized system for quantitating renal tumor size, location, and depth. J Urol. 2009;182:844.

    Article  Google Scholar 

  11. Watanabe M, Serizawa M, Sawada T, et al. A novel flow cytometry-based cell capture platform for the detection, capture, and molecular characterization of rare tumor cells in blood. J Transl Med. 2014;12:143.

    Article  PubMed  PubMed Central  Google Scholar 

  12. Takao M, Takeda K. Enumeration, characterization, and collection of intact circulating tumor cells by cross-contamination-free flow cytometry. Cytometry A 2011;79:107.

    Article  PubMed  Google Scholar 

  13. Sawada T, Watanabe M, Fujimura Y, et al. Sensitive cytometry-based system for enumeration, capture, and analysis of gene mutations of circulating tumor cells. Cancer Sci. 2016;107:307.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  14. Okegawa T, Ninomiya N, Masuda K, et al. AR-V7 in circulating tumor cells cluster as a predictive biomarker of abiraterone acetate and enzalutamide treatment in castration-resistant prostate cancer patients. Prostate 2018;78:576.

    Article  CAS  PubMed  Google Scholar 

  15. Watanabe M, Uehara Y, Yamashita N, et al. Multicolor detection of rare tumor cells in blood using a novel flow cytometry-based system. Cytometry A 2014;85:206.

    Article  PubMed  Google Scholar 

  16. Liu F, Wang S, Lu Z, et al. A simple pyramid-shaped microchamber towards highly efficient isolation of circulating tumor cells from breast cancer patients. Biomed Microdev. 2018;20:83.

    Article  Google Scholar 

  17. Zhao XH, Wang ZR, Chen CL, et al. Molecular detection of epithelial-mesenchymal transition markers in circulating tumor cells from pancreatic cancer patients: potential role in clinical practice. World J Gastroenterol. 2019;25:138.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  18. Wang L, Zhou S, Zhang W, et al. Circulating tumor cells as an independent prognostic factor in advanced colorectal cancer: a retrospective study in 121 patients. Int J Colorectal Dis. 2019;34:589–97.

    Article  PubMed  Google Scholar 

  19. Pinzani P, Scatena C, Salvianti F, et al. Detection of circulating tumor cells in patients with adrenocortical carcinoma: a monocentric preliminary study. J Clin Endocrinol Metab. 2013;98:3731.

    Article  CAS  PubMed  Google Scholar 

  20. Gradilone A, Iacovelli R, Cortesi E, et al. Circulating tumor cells and “suspicious objects” evaluated through CellSearch(R) in metastatic renal cell carcinoma. Anticancer Res. 2011;31:4219.

    CAS  PubMed  Google Scholar 

  21. Engilbertsson H, Aaltonen KE, Bjornsson S, et al. Transurethral bladder tumor resection can cause seeding of cancer cells into the bloodstream. J Urol. 2015;193:53.

    Article  PubMed  Google Scholar 

  22. Tsumura H, Satoh T, Ishiyama H, et al. Perioperative search for circulating tumor cells in patients undergoing prostate brachytherapy for clinically nonmetastatic prostate cancer. Int J Mol Sci. 2017;18:128.

    Article  PubMed Central  Google Scholar 

  23. Hopkins MP, Dulai RM, Occhino A, et al. The effects of carbon dioxide pneumoperitoneum on seeding of tumor in port sites in a rat model. Am J Obstet Gynecol. 1999;181:1329.

    Article  CAS  PubMed  Google Scholar 

  24. Mathew G, Watson DI, Ellis TS, et al. The role of peritoneal immunity and the tumour-bearing state on the development of wound and peritoneal metastases after laparoscopy. Aust N Z J Surg. 1999;69:14.

    Article  CAS  PubMed  Google Scholar 

  25. Gitzelmann CA, Mendoza-Sagaon M, Talamini MA, et al. Cell-mediated immune response is better preserved by laparoscopy than laparotomy. Surgery 2000;127:65.

    Article  CAS  PubMed  Google Scholar 

  26. Asthana R, Oblak ML. In vitro evaluation of a simulated pneumoperitoneum environment using carbon dioxide on canine transitional cell carcinoma. Vet Surg. 2018;47:412–20.

    Article  PubMed  Google Scholar 

  27. Mo X, Yang Y, Lai H, et al. Does carbon dioxide pneumoperitoneum enhance wound metastases following laparoscopic abdominal tumor surgery? A meta-analysis of 20 randomized control studies. Tumour Biol. 2014;35:7351.

    Article  PubMed  Google Scholar 

  28. Mocellin S, Keilholz U, Rossi CR, et al. Circulating tumor cells: the “leukemic phase” of solid cancers. Trends Mol Med. 2006;12:130.

    Article  CAS  PubMed  Google Scholar 

  29. Santoni M, Cimadamore A, Cheng L, et al. Circulating tumor cells in renal cell carcinoma: recent findings and future challenges. Front Oncol. 2019;9:228.

    Article  PubMed  PubMed Central  Google Scholar 

  30. 30. Cimadamore A, Gasparrini S, Massari F, et al. Emerging molecular technologies in renal cell carcinoma: liquid biopsy. Cancers 2019;11:196.

    Article  CAS  PubMed Central  Google Scholar 

  31. Trzpis M, McLaughlin PM, de Leij LM, et al. Epithelial cell adhesion molecule: more than a carcinoma marker and adhesion molecule. Am J Pathol. 2007;171:386.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  32. Liu S, Tian Z, Zhang L, et al. Combined cell surface carbonic anhydrase 9 and CD147 antigens enable high-efficiency capture of circulating tumor cells in clear cell renal cell carcinoma patients. Oncotarget. 2016;7:59877.

    PubMed  PubMed Central  Google Scholar 

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Acknowledgment

The authors thank Professor Okada, whose statistical support and insightful comments were invaluable during the course of their study.

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Authors and Affiliations

  1. Department of Urology, Fukushima Medical University School of Medicine, Fukushima, Japan

    Nobuhiro Haga MD, Akifumi Onagi MD, Tomoyuki Koguchi MD, Seiji Hoshi MD, Soichiro Ogawa MD, Hidenori Akaihata MD, Junya Hata MD, Hiroyuki Hiraki, Ruriko Honda MD, Ryo Tanji MD, Kanako Matsuoka MD, Masao Kataoka MD, Yuichi Sato MD, Kei Ishibashi MD & Yoshiyuki Kojima MD

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  1. Nobuhiro Haga MD
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Correspondence to Nobuhiro Haga MD.

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Haga, N., Onagi, A., Koguchi, T. et al. Perioperative Detection of Circulating Tumor Cells in Radical or Partial Nephrectomy for Renal Cell Carcinoma. Ann Surg Oncol 27, 1272–1281 (2020). https://doi.org/10.1245/s10434-019-08127-8

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  • DOI: https://doi.org/10.1245/s10434-019-08127-8

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