Skip to main content

Advertisement

SpringerLink
Log in

Laparoscopic surgery minimizes the release of circulating tumor cells compared to open surgery for hepatocellular carcinoma

  • Published:
Surgical Endoscopy Aims and scope Submit manuscript

Abstract

Background

The aim of this study was to determine whether tumor manipulation enhances cancer cell release from the primary tumor in HCC patients and which surgical approach, open surgery or laparoscopic resection, is superior with respect to preventing tumor cells from scattering in the blood.

Methods

A total of 26 HCC patients were prospectively randomized to receive either open surgery (n = 14) or laparoscopic surgery (n = 12). Blood samples were obtained at three time points: preoperative, postoperative, and 24 h after surgery. The CD45−/CD44+/CD90+ cells were obtained and counted using quantitative flow cytometry. The serum levels of interleukin-6 (IL-6), interleukin-8 (IL-8), and tumor necrosis factor (TNF-α) were also compared between the two groups.

Results

There was no significant difference between the laparoscopic and open groups in terms of patient characteristics. The levels of CCSCs increased immediately after surgical manipulation, and the laparoscopy group released fewer tumor cells into the blood stream. The amount of CCSCs in both groups decreased to reach a similar level 24 h after surgery. Both IL-6 and IL-8 increased after surgery, and the mean postoperative increases in IL-6 and IL-8 serum levels were significantly less in the laparoscopic group than in the open group. The TNF-α levels showed no differences at any time point.

Conclusions

Our results showed that patients with laparoscopic surgery have lower IL-6, IL-8 secretion and less CTCs, which may suggest an advantage by restricting CTCs release and a preserved immune response. Further studies are needed to investigate the relationship between the number of CCSCs after surgery and long-term survival rates.

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.

Fig. 1
Fig. 2
Fig. 3

Similar content being viewed by others

References

  1. Llovet JM, Burroughs A, Bruix J (2003) Hepatocellular carcinoma. Lancet 362:1907–1917

    Article  PubMed  Google Scholar 

  2. Fan ST, Mau Lo C, Poon RT, Yeung C, Leung Liu C, Yuen WK, Ming Lam C, Ng KK, Ching Chan S (2011) Continuous improvement of survival outcomes of resection of hepatocellular carcinoma: a 20-year experience. Ann Surg 253:745–758

    Article  PubMed  Google Scholar 

  3. Fan ST, Yang ZF, Ho DW, Ng MN, Yu WC, Wong J (2011) Prediction of posthepatectomy recurrence of hepatocellular carcinoma by circulating cancer stem cells: a prospective study. Ann Surg 254:569–576

    Article  PubMed  Google Scholar 

  4. Allard WJ, Matera J, Miller MC, Repollet M, Connelly MC, Rao C, Tibbe AG, Uhr JW, Terstappen LW (2004) Tumor cells circulate in the peripheral blood of all major carcinomas but not in healthy subjects or patients with nonmalignant diseases. Clin Cancer Res 10:6897–6904

    Article  PubMed  Google Scholar 

  5. Chaffer CL, Weinberg RA (2011) A perspective on cancer cell metastasis. Science 331:1559–1564

    Article  CAS  PubMed  Google Scholar 

  6. Reya T, Morrison SJ, Clarke MF, Weissman IL (2001) Stem cells, cancer, and cancer stem cells. Nature 414:105–111

    Article  CAS  PubMed  Google Scholar 

  7. Yang ZF, Ho DW, Ng MN, Lau CK, Yu WC, Ngai P, Chu PW, Lam CT, Poon RT, Fan ST (2008) Significance of CD90+ cancer stem cells in human liver cancer. Cancer Cell 13:153–166

    Article  CAS  PubMed  Google Scholar 

  8. Yang ZF, Ngai P, Ho DW, Yu WC, Ng MN, Lau CK, Li ML, Tam KH, Lam CT, Poon RT, Fan ST (2008) Identification of local and circulating cancer stem cells in human liver cancer. Hepatology 47:919–928

    Article  CAS  PubMed  Google Scholar 

  9. Romsdahl MM, McGrath RG, Hoppe E, McGrew EA (1965) Experimental model for the study of tumor cells in the blood. Acta Cytol 9:141–145

    CAS  PubMed  Google Scholar 

  10. Atkin G, Chopada A, Mitchell I (2005) Colorectal cancer metastasis: in the surgeon’s hands? Int Semin Surg Oncol 2:5

    Article  PubMed Central  PubMed  Google Scholar 

  11. Fan ZC, Yan J, Liu GD, Tan XY, Weng XF, Wu WZ, Zhou J, Wei XB (2012) Real-time monitoring of rare circulating hepatocellular carcinoma cells in an orthotopic model by in vivo flow cytometry assesses resection on metastasis. Cancer Res 72:2683–2691

    Article  CAS  PubMed  Google Scholar 

  12. Park SY, Choi GS, Park JS, Kim HJ, Ryuk JP, Choi WH (2012) Influence of surgical manipulation and surgical modality on the molecular detection of circulating tumor cells from colorectal cancer. J Korean Surg Soc 82:356–364

    Article  PubMed Central  PubMed  Google Scholar 

  13. Nguyen KT, Gamblin TC, Geller DA (2009) World review of laparoscopic liver resection-2,804 patients. Ann Surg 250:831–841

    Article  PubMed  Google Scholar 

  14. Rao A, Rao G, Ahmed I (2011) Laparoscopic left lateral liver resection should be a standard operation. Surg Endosc 25:1603–1610

    Article  PubMed  Google Scholar 

  15. Ahn KS, Han HS, Yoon YS, Cho JY (2011) Laparoscopic anatomic S4 segmentectomy for hepatocellular carcinoma. Surg Laparosc Endosc Percutan Tech 21:e183–e186

    Article  PubMed  Google Scholar 

  16. Abu Hilal M, Pearce NW (2008) Laparoscopic left lateral liver sectionectomy: a safe, efficient, reproducible technique. Dig Surg 25:305–308

    Article  CAS  PubMed  Google Scholar 

  17. Chan AC, Poon RT, Cheung TT, Chok KS, Chiu DW, Chan SC, Lo CM (2014) Laparoscopic versus open liver resection for elderly patients with malignant liver tumors: a single center experience. J Gastroenterol Hepatol 29:1279–1283

    Article  PubMed  Google Scholar 

  18. Fallahzadeh MK, Zibari GB, Hamidian Jahromi A, Chu Q, Shi R, Shokouh-Amiri H (2013) Laparoscopic versus open liver resection for benign and malignant solid liver tumors: a case-matched study. J Laparoendosc Adv Surg Tech A 23:908–911

    Article  PubMed  Google Scholar 

  19. Fancellu A, Rosman AS, Sanna V, Nigri GR, Zorcolo L, Pisano M, Melis M (2011) Meta-analysis of trials comparing minimally-invasive and open liver resections for hepatocellular carcinoma. J Surg Res 171:e33–e45

    Article  PubMed  Google Scholar 

  20. Kim H, Suh KS, Lee KW, Yi NJ, Hong G, Suh SW, Yoo T, Park MS, Choi Y, Lee HW (2013) Long-term outcome of laparoscopic versus open liver resection for hepatocellular carcinoma: a case-controlled study with propensity score matching. Surg Endosc 28:950–960

    Article  PubMed  Google Scholar 

  21. Li N, Wu YR, Wu B, Lu MQ (2012) Surgical and oncologic outcomes following laparoscopic versus open liver resection for hepatocellular carcinoma: a meta-analysis. Hepatol Res 42:51–59

    Article  PubMed  Google Scholar 

  22. Parks KR, Kuo YH, Davis JM, O’ Brien B, Hagopian EJ (2014) Laparoscopic versus open liver resection: a meta-analysis of long-term outcome. HPB (Oxford) 16:109–118

    Article  Google Scholar 

  23. Rao AM, Ahmed I (2013) Laparoscopic versus open liver resection for benign and malignant hepatic lesions in adults. Cochrane Database Syst Rev 5:CD010162

    PubMed  Google Scholar 

  24. Simillis C, Constantinides VA, Tekkis PP, Darzi A, Lovegrove R, Jiao L, Antoniou A (2007) Laparoscopic versus open hepatic resections for benign and malignant neoplasms—a meta-analysis. Surgery 141:203–211

    Article  PubMed  Google Scholar 

  25. Lin S, Hoffmann K, Schemmer P (2012) Treatment of hepatocellular carcinoma: a systematic review. Liver Cancer 1:144–158

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  26. Huang MT, Wei PL, Wang W, Li CJ, Lee YC, Wu CH (2009) A series of laparoscopic liver resections with or without HALS in patients with hepatic tumors. J Gastrointest Surg 13:896–906

    Article  PubMed  Google Scholar 

  27. Chen XP, Zhao H, Zhao XP (2002) Alternation of AFP-mRNA level detected in blood circulation during liver resection for HCC and its significance. World J Gastroenterol 8:818–821

    CAS  PubMed  Google Scholar 

  28. Taketa K (1990) Alpha-fetoprotein: reevaluation in hepatology. Hepatology 12:1420–1432

    Article  CAS  PubMed  Google Scholar 

  29. Aselmann H, Wolfes H, Rohde F, Frerker M, Deiwick A, Jager MD, Klempnauer J, Schlitt HJ (2001) Quantification of alpha 1-fetoprotein mRNA in peripheral blood and bone marrow: a tool for perioperative evaluation of patients with hepatocellular carcinoma. Langenbecks Arch Surg 386:118–123

    Article  CAS  PubMed  Google Scholar 

  30. Xu W, Cao L, Chen L, Li J, Zhang XF, Qian HH, Kang XY, Zhang Y, Liao J, Shi LH, Yang YF, Wu MC, Yin ZF (2011) Isolation of circulating tumor cells in patients with hepatocellular carcinoma using a novel cell separation strategy. Clin Cancer Res 17:3783–3793

    Article  PubMed  Google Scholar 

  31. Wu LJ, Pan YD, Pei XY, Chen H, Nguyen S, Kashyap A, Liu J, Wu J (2012) Capturing circulating tumor cells of hepatocellular carcinoma. Cancer Lett 326:17–22

    Article  CAS  PubMed  Google Scholar 

  32. Yamashita T, Forgues M, Wang W, Kim JW, Ye Q, Jia H, Budhu A, Zanetti KA, Chen Y, Qin LX, Tang ZY, Wang XW (2008) EpCAM and alpha-fetoprotein expression defines novel prognostic subtypes of hepatocellular carcinoma. Cancer Res 68:1451–1461

    Article  CAS  PubMed  Google Scholar 

  33. de Boer CJ, van Krieken JH, Janssen-van Rhijn CM, Litvinov SV (1999) Expression of Ep-CAM in normal, regenerating, metaplastic, and neoplastic liver. J Pathol 188:201–206

    Article  PubMed  Google Scholar 

  34. Juratli MA, Sarimollaoglu M, Siegel ER, Nedosekin DA, Galanzha EI, Suen JY, Zharov VP (2013) Real-time monitoring of circulating tumor cell release during tumor manipulation using in vivo photoacoustic and fluorescent flow cytometry. Head Neck

  35. Wind J, Tuynman JB, Tibbe AG, Swennenhuis JF, Richel DJ, van Berge Henegouwen MI, Bemelman WA (2009) Circulating tumour cells during laparoscopic and open surgery for primary colonic cancer in portal and peripheral blood. Eur J Surg Oncol 35:942–950

    Article  CAS  PubMed  Google Scholar 

  36. Akiyoshi S, Mimori K, Sudo T, Tanaka F, Shibata K, Mori M (2013) Laparoscopic surgery minimizes the surgical manipulation of isolated tumor cells leading to decreased metastasis compared to open surgery for colorectal cancer. Surg Today 43:20–25

    Article  PubMed  Google Scholar 

  37. Wang SW, Sun YM (2014) The IL-6/JAK/STAT3 pathway: potential therapeutic strategies in treating colorectal cancer (review). Int J Oncol 44:1032–1040

    CAS  PubMed  Google Scholar 

  38. Taniguchi K, Karin M (2014) IL-6 and related cytokines as the critical lynchpins between inflammation and cancer. Semin Immunol 26:54–74

    Article  CAS  PubMed  Google Scholar 

  39. Benoy IH, Salgado R, Van Dam P, Geboers K, Van Marck E, Scharpe S, Vermeulen PB, Dirix LY (2004) Increased serum interleukin-8 in patients with early and metastatic breast cancer correlates with early dissemination and survival. Clin Cancer Res 10:7157–7162

    Article  CAS  PubMed  Google Scholar 

  40. Bachelot T, Ray-Coquard I, Menetrier-Caux C, Rastkha M, Duc A, Blay JY (2003) Prognostic value of serum levels of interleukin 6 and of serum and plasma levels of vascular endothelial growth factor in hormone-refractory metastatic breast cancer patients. Br J Cancer 88:1721–1726

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  41. Fisher DT, Appenheimer MM, Evans SS (2014) The two faces of IL-6 in the tumor microenvironment. Semin Immunol 26:38–47

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  42. Leibovich-Rivkin T, Liubomirski Y, Bernstein B, Meshel T, Ben-Baruch A (2013) Inflammatory factors of the tumor microenvironment induce plasticity in nontransformed breast epithelial cells: EMT, invasion, and collapse of normally organized breast textures. Neoplasia 15:1330–1346

    Article  PubMed Central  PubMed  Google Scholar 

  43. Lacy AM, Delgado S, Castells A, Prins HA, Arroyo V, Ibarzabal A, Pique JM (2008) The long-term results of a randomized clinical trial of laparoscopy-assisted versus open surgery for colon cancer. Ann Surg 248:1–7

    Article  PubMed  Google Scholar 

  44. Aminsharifi A, Salehipoor M, Arasteh H (2012) Systemic immunologic and inflammatory response after laparoscopic versus open nephrectomy: a prospective cohort trial. J Endourol 26:1231–1236

    Article  PubMed  Google Scholar 

  45. Tai LH, de Souza CT, Belanger S, Ly L, Alkayyal AA, Zhang J, Rintoul JL, Ananth AA, Lam T, Breitbach CJ, Falls TJ, Kirn DH, Bell JC, Makrigiannis AP, Auer RA (2013) Preventing postoperative metastatic disease by inhibiting surgery-induced dysfunction in natural killer cells. Cancer Res 73:97–107

    Article  CAS  PubMed  Google Scholar 

  46. Smerage JB, Budd GT, Doyle GV, Brown M, Paoletti C, Muniz M, Miller MC, Repollet MI, Chianese DA, Connelly MC, Terstappen LW, Hayes DF (2013) Monitoring apoptosis and Bcl-2 on circulating tumor cells in patients with metastatic breast cancer. Mol Oncol 7:680–692

    Article  CAS  PubMed  Google Scholar 

Download references

Acknowledgments

This work was supported by research grants obtained from the National Science Foundation Council of China (81372562).

Disclosures

Drs Wenda Li, Xue Zhou, ZeJian Huang, Hongwei Zhang, Lei Zhang, Changzhen Shang, Yajin Chen have no conflicts of interest or financial ties to disclose.

Author information

Authors and Affiliations

  1. Department of Hepatobiliary Surgery, The Sun Yat-sen Memorial Hospital of Sun Yat-sen University, No. 107 Yanjiang West Road, Guangzhou, 510120, Guangdong, People’s Republic of China

    Wenda Li, ZeJian Huang, Hongwei Zhang, Lei Zhang, Changzhen Shang & Yajin Chen

  2. Department of Anesthesiology, The First Affiliated Hospital of Sun Yat-sen University, Guangzhou, 510120, Guangdong, People’s Republic of China

    Xue Zhou

Authors
  1. Wenda Li
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Xue Zhou
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. ZeJian Huang
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Hongwei Zhang
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Lei Zhang
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Changzhen Shang
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. Yajin Chen
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Yajin Chen.

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Li, W., Zhou, X., Huang, Z. et al. Laparoscopic surgery minimizes the release of circulating tumor cells compared to open surgery for hepatocellular carcinoma. Surg Endosc 29, 3146–3153 (2015). https://doi.org/10.1007/s00464-014-4041-5

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s00464-014-4041-5

Keywords

Search

Navigation