Skip to main content

Advertisement

SpringerLink
Log in

Systemic inflammatory changes and their clinical implications following thoracic cancer surgery

  • Review Article
  • Published:
Indian Journal of Thoracic and Cardiovascular Surgery Aims and scope Submit manuscript

Abstract

Trauma that follows every surgical procedure triggers an inflammatory response, which in the majority of the cases reflects the associated tissue damage. Tissue regeneration, postoperative outcomes, and systemic antibacterial activity are highly dependent on the initial inflammatory response elicited by surgical trauma. More specifically, in thoracic surgery, systemic cytokine and cellular changes have an impact on several measured postoperative outcomes. Lastly, the introduction of video-assisted and robotic-assisted thoracic surgery has been shown to provide improved postoperative outcomes with altered systemic inflammatory response, when compared to open thoracic surgery. This review outlines the major systemic inflammatory changes observed in thoracic cancer surgery as well as its clinical significance.

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

Similar content being viewed by others

References

  1. Mcbride WT, Mcbride ER. Oxford textbook of cardiothoracic anaesthesia. In: The inflammatory response to cardiothoracic surgery. 1st ed. Oxford: Oxford University Press; 2015.

    Google Scholar 

  2. Antoniak S. The coagulation system in host defense. Res Pract Thromb Haemost. 2018;2:549–57. https://doi.org/10.1002/rth2.12109.

    Article  PubMed  PubMed Central  Google Scholar 

  3. Lord JM, Midwinter MJ, Chen Y-F, et al. The systemic immune response to trauma: an overview of pathophysiology and treatment. Lancet. 2014;384:1455–65. https://doi.org/10.1016/S0140-6736(14)60687-5.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  4. Jacobi CA, Wenger F, Opitz I, Muller JM. Immunologic changes during minimally invasive surgery. Dig Surg. 2002;19:459–63. https://doi.org/10.1159/000067597.

    Article  CAS  PubMed  Google Scholar 

  5. Doll R, Kinlen L. Immunosurveillance and cancer: epidemiological evidence. Br Med J. 1970;4:420–2. https://doi.org/10.1136/bmj.4.5732.420.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  6. Domagala-Kulawik J. The role of the immune system in non-small cell lung carcinoma and potential for therapeutic intervention. Transl Lung Cancer Res. 2015;4:177–90. https://doi.org/10.3978/j.issn.2218-6751.2015.01.11.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  7. Rhodin KE, Rucker AJ, Ready NE, D’Amico TA, Antonia SJ. The immunotherapeutic landscape in non-small cell lung cancer and its surgical horizons. J Thorac Cardiovasc Surg. 2020;159:1616–23. https://doi.org/10.1016/j.jtcvs.2019.08.138.

    Article  CAS  PubMed  Google Scholar 

  8. Mok TSK, Wu Y-L, Kudaba I, et al. Pembrolizumab versus chemotherapy for previously untreated, PD-L1-expressing, locally advanced or metastatic non-small-cell lung cancer (KEYNOTE-042): a randomised, open-label, controlled, phase 3 trial. Lancet. 2019;393:1819–30. https://doi.org/10.1016/S0140-6736(18)32409-7.

    Article  CAS  PubMed  Google Scholar 

  9. Hellmann MD, Ciuleanu T-E, Pluzanski A, et al. Nivolumab plus ipilimumab in lung cancer with a high tumor mutational burden. N Engl J Med. 2018;378:2093–104. https://doi.org/10.1056/NEJMoa1801946.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  10. Antonia SJ, Villegas A, Daneil D, et al. Durvalumab after chemoradiotherapy in stage III non-small-cell lung cancer. N Engl J Med. 2017;377:1919–29. https://doi.org/10.1056/NEJMoa1709937.

  11. Chen Z, Zhang P, Xu Y, et al. Surgical stress and cancer progression: the twisted tango. Mol Cancer. 2019;18:132. https://doi.org/10.1186/s12943-019-1058-3.

  12. Chaft JE, Hellmann MD, Velez MJ, Travis WD, Rusch VW. Initial experience with lung cancer resection after treatment with T-cell checkpoint inhibitors. Ann Thorac Surg. 2017;104:e217–18. https://doi.org/10.1016/j.athoracsur.2017.03.038.

  13. Provencio-Pulla M, Nadal-Alforja E, Cobo M, et al. Neoadjuvant chemo/immunotherapy for the treatment of stages IIIA resectable non-small cell lung cancer (NSCLC): a phase II multicenter exploratory study—NADIM study-SLCG. J Clin Oncol. 2018. https://doi.org/10.1200/JCO.2018.36.15_suppl.8521.

    Article  Google Scholar 

  14. Rusch VW, Chaft JE, Johnson B, et al. Neoadjuvant atezolizumab in resectable non-small cell lung cancer (NSCLC): initial results from a multicenter study (LCMC3). J Clin Oncol. 2018. https://doi.org/10.1200/JCO.2018.36.15_suppl.8541.

    Article  PubMed  PubMed Central  Google Scholar 

  15. Cascone T, William WN, Weissferdt A, et al. Neoadjuvant nivolumab (N) or nivolumab plus ipilimumab (NI) for resectable non-small cell lung cancer (NSCLC): clinical and correlative results from the NEOSTAR study. J Clin Oncol. 2019. https://doi.org/10.1200/JCO.2019.37.15_suppl.8504.

    Article  Google Scholar 

  16. Chiou VL, Burotto M. Pseudoprogression and immune-related response in solid tumors. J Clin Oncol. 2015;33:3541–3. https://doi.org/10.1200/JCO.2015.61.6870.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  17. Novak-Jankovic V, Markovic-Bozic J. Regional anaesthesia in thoracic and abdominal surgery. Acta Clin Croat. 2019;58:96–100. https://doi.org/10.20471/acc.2019.58.s1.14.

    Article  PubMed  PubMed Central  Google Scholar 

  18. Endo H, Inoue M. Dormancy in cancer. Cancer Sci. 2019;110:474–80. https://doi.org/10.1111/cas.13917.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  19. Atwell DM, Grichnik KP, Newman MF, Reves JG, McBride WT. Balance of proinflammatory and antiinflammatory cytokines at thoracic cancer operation. Ann Thorac Surg. 1998;66:1145–50. https://doi.org/10.1016/s0003-4975(98)00592-x.

    Article  CAS  PubMed  Google Scholar 

  20. Shimura T, Hagihara M, Takebe K, et al. The study of tumor necrosis factor beta gene polymorphism in lung cancer patients. Cancer. 1994. https://doi.org/10.1002/1097-0142(19940215)73:4<1184::aid-cncr2820730410>3.0.co;2-y.

  21. Shakhar G, Ben-Eliyahu S. Potential prophylactic measures against postoperative immunosuppression: could they reduce recurrence rates in oncological patients? Ann Surg Oncol. 2003;10:972–92. https://doi.org/10.1245/aso.2003.02.007.

    Article  PubMed  Google Scholar 

  22. Waller DA, Keavey P, Woodfine L, Dark JH. Pulmonary endothelial permeability changes after major lung resection. Ann Thorac Surg. 1996;61:1435–40. https://doi.org/10.1016/0003-4975(96)00103-8.

    Article  CAS  PubMed  Google Scholar 

  23. Okawa K, Onda M, Miyashita M, Sasajima K. Systemic and pulmonary responses of inflammatory cytokines following esophagectomy. Nihon Ika Daigaku Zasshi. 1998. https://doi.org/10.1272/jnms1923.65.42.

    Article  PubMed  Google Scholar 

  24. Ng CSH, Wan S, Hui CWC, et al. Video-assisted thoracic surgery lobectomy for lung cancer is associated with less immunochemokine disturbances than thoracotomy. Eur J Cardiothorac Surg. 2007;31:83–7. https://doi.org/10.1016/j.ejcts.2006.10.019.

    Article  PubMed  Google Scholar 

  25. Liotta LA, Tryggvason K, Garbisa S, Hart I, Foltz CM, Shafie S. Metastatic potential correlates with enzymatic degradation of basement membrane collagen. Nature. 1980;284:67–8. https://doi.org/10.1038/284067a0.

    Article  CAS  PubMed  Google Scholar 

  26. Kodate M, Kasai T, Hashimoto H, Yasumoto K, Iwata Y, Manabe H. Expression of matrix metalloproteinase (gelatinase) in T1 adenocarcinoma of the lung. Pathol Int. 1997;47:461–9. https://doi.org/10.1111/j.1440-1827.1997.tb04525.x.

  27. Zucker S, Lysik RM, Malik M, Bauer BA, Caamano J, Klein-Szanto AJ. Secretion of gelatinases and tissue inhibitors of metalloproteinases by human lung cancer cell lines and revertant cell lines: not an invariant correlation with metastasis. Int J Cancer. 1992;52:366–71. https://doi.org/10.1002/ijc.2910520307.

    Article  CAS  PubMed  Google Scholar 

  28. Frick VO, Justinger C, Rubie C, Graeber S, Schilling MK, Lindemann W. Thoracotomy procedures effect cytokine levels after thoracoabdominal esophagectomy. Oncol Rep. 2011;27:258–64. https://doi.org/10.3892/or.2011.1493.

    Article  CAS  PubMed  Google Scholar 

  29. Bhatia M, Moochhala S. Role of inflammatory mediators in the pathophysiology of acute respiratory distress syndrome. J Pathol. 2004;202:145–56. https://doi.org/10.1002/path.1491.

    Article  CAS  PubMed  Google Scholar 

  30. Kutlu CA, Williams EA, Evans TW, Pastorino U, Goldstraw P. Acute lung injury and acute respiratory distress syndrome after pulmonary resection. Ann Thorac Surg. 2000;69:376–80. https://doi.org/10.1016/s0003-4975(99)01090-5.

    Article  CAS  PubMed  Google Scholar 

  31. Gothard J. Lung injury after thoracic surgery and one-lung ventilation. Curr Opin Anaesthesiol. 2006;19:5–10. https://doi.org/10.1097/01.aco.0000192783.40021.c1.

    Article  PubMed  Google Scholar 

  32. Baudouin SV. Lung injury after thoracotomy. Br J Anaesth. 2003;91:131–42. https://doi.org/10.1093/bja/aeg083.

    Article  Google Scholar 

  33. Yim AP, Wan S, Lee TW, Arifi AA. VATS lobectomy reduces cytokine responses compared with conventional surgery. Ann Thorac Surg. 2000;70:243–7. https://doi.org/10.1016/s0003-4975(00)01258-3.

    Article  CAS  PubMed  Google Scholar 

  34. Jones RO, Anderson NH, Murchison JT, et al. Innate immune responses after resection for lung cancer via video-assisted thoracoscopic surgery and thoracotomy. Innovations (Phila). 2014;9:93–103. https://doi.org/10.1097/IMI.0000000000000061.

    Article  PubMed  Google Scholar 

  35. Han L, Cheng H, Liu J, et al. Effect of video-assisted thoracoscopic surgery on immune function and trauma in patients with non-small cell lung cancer. Int J Clin Exp Med. 2018;11:12437–44.

  36. Yamada T, Hisanaga M, Nakajima Y, et al. Serum interleukin-6, interleukin-8, hepatocyte growth factor, and nitric oxide changes during thoracic surgery. World J Surg. 1998;22:783–90. https://doi.org/10.1007/s002689900470.

    Article  CAS  PubMed  Google Scholar 

  37. Nagahiro I, Andou A, Aoe M, Sano Y, Date H, Shimizu N. Pulmonary function, postoperative pain, and serum cytokine level after lobectomy: a comparison of VATS and conventional procedure. Ann Thorac Surg. 2001;72:362–5. https://doi.org/10.1016/s0003-4975(01)02804-1.

  38. Watkins LR, Maier SF, Goehler LE. Immune activation: the role of pro-inflammatory cytokines in inflammation, illness responses and pathological pain states. Pain. 1995;63:289–302. https://doi.org/10.1016/0304-3959(95)00186-7.

  39. Yang C, Chang H, Zhang T, Liang C, Li E. Pre-emptive epidural analgesia improves post-operative pain and immune function in patients undergoing thoracotomy. ANZ J Surg. 2015;85:472–7. https://doi.org/10.1111/ans.12746.

  40. Yamashiro S, Arakaki R, Kise Y, Kuniyoshi Y. Prevention of pulmonary edema after minimally invasive cardiac surgery with mini-thoracotomy using neutrophil elastase inhibitor. Ann Thorac Cardiovasc Surg. 2018;24:32–9. https://doi.org/10.5761/atcs.oa.17-00102.

    Article  PubMed  Google Scholar 

  41. Johnson JL, Moore EE, Tamura DY, Zallen G, Biffl WL, Silliman CC. Interleukin-6 augments neutrophil cytotoxic potential via selective enhancement of elastase release. J Surg Res. 1998;76:91–4. https://doi.org/10.1006/jsre.1998.5295.

  42. Wu C-Y, Lu Y-F, Wang M-L, et al. Effects of dexmedetomidine infusion on inflammatory responses and injury of lung tidal volume changes during one-lung ventilation in thoracoscopic surgery: a randomized controlled trial. Mediators Inflamm. 2018. https://doi.org/10.1155/2018/2575910.

  43. Ito N, Suzuki Y, Taniguchi Y, Ishiguro K, Nakamura H, Ohgi S. Prognostic significance of T helper 1 and 2 and T cytotoxic 1 and 2 cells in patients with non-small cell lung cancer. Anticancer Res. 2005;25:2027–31.

  44. Gu C-Y, Zhang J, Qian Y-N, Tang Q-F. Effects of epidural anesthesia and postoperative epidural analgesia on immune function in esophageal carcinoma patients undergoing thoracic surgery. Mol Clin Oncol. 2015;3:190–6. https://doi.org/10.3892/mco.2014.405.

  45. Ng CSH, Lee TW, Wan S, et al. Thoracotomy is associated with significantly more profound suppression in lymphocytes and natural killer cells than video-assisted thoracic surgery following major lung resections for cancer. J Invest Surg. 2005;18:81–8. https://doi.org/10.1080/08941930590926320.

    Article  PubMed  Google Scholar 

  46. Leaver HA, Craig SR, Yap PL, Walker WS. Lymphocyte responses following open and minimally invasive thoracic surgery. Eur J Clin Invest. 2000;30:230–8. https://doi.org/10.1046/j.1365-2362.2000.00622.x.

    Article  CAS  PubMed  Google Scholar 

  47. Mineo T, Ambrogi V. Immune effects after uniportal nonintubated video-thoracoscopic operations. Video-assist Thorac Surg. 2018;3:4. https://doi.org/10.21037/vats.2018.01.02.

    Article  Google Scholar 

  48. Craig SR, Leaver HA, Yap PL, Pugh GC, Walker WS. Acute phase responses following minimal access and conventional thoracic surgery. Eur J Cardiothorac Surg. 2001;20:455–63. https://doi.org/10.1016/s1010-7940(01)00841-7.

    Article  CAS  PubMed  Google Scholar 

  49. Lei P, Wang J, Gao S, et al. Impact of post-thoracotomy analgesia with dexmedetomidine and morphine on immunocytes: a randomized clinical trial. Braz J Anesthesiol. 2020;70:153–8. https://doi.org/10.1016/j.bjane.2020.04.017.

  50. Zhu R, Xiang J, Tan M. Effects of different anesthesia and analgesia on cellular immunity and cognitive function of patients after surgery for esophageal cancer. Minerva Chir. 2020;75:449–56. https://doi.org/10.23736/S0026-4733.20.08283-8.

  51. Park S-K, Hong S, Eum S-Y, et al. Changes in cell-mediated immune response after lung resection surgery for MDR-TB patients. Tuberculosis (Edinb). 2011;91:300–7. https://doi.org/10.1016/j.tube.2011.02.003.

  52. Abebe F, Bjune G. The protective role of antibody responses during Mycobacterium tuberculosis infection. Clin Exp Immunol. 2009;157:235–43. https://doi.org/10.1111/j.1365-2249.2009.03967.x.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  53. Erb KJ, Kirman J, Delahunt B, Chen W, Le Gros G. IL-4, IL-5 and IL-10 are not required for the control of M. bovis-BCG infection in mice. Immunol Cell Biol. 1998;1:41–6.

  54. Hirsch CS, Toossi Z, Othieno C, et al. Depressed T-cell interferon-gamma responses in pulmonary tuberculosis: analysis of underlying mechanisms and modulation with therapy. J Infect Dis. 1999;180:2069–73. https://doi.org/10.1086/315114.

    Article  CAS  PubMed  Google Scholar 

  55. Seah GT, Scott GM, Rook GA. Type 2 cytokine gene activation and its relationship to extent of disease in patients with tuberculosis. J Infect Dis. 2000;181:385–9. https://doi.org/10.1086/315200.

    Article  CAS  PubMed  Google Scholar 

  56. Kaplan G, Post FA, Moreira AL, et al. Mycobacterium tuberculosis growth at the cavity surface: a microenvironment with failed immunity. Infect Immun. 2003;71:7099–108. https://doi.org/10.1128/IAI.71.12.7099-7108.2003.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  57. Tiberi S, Torrico MM, Rahman A, et al. Managing severe tuberculosis and its sequelae: from intensive care to surgery and rehabilitation. J Bras Pneumol. 2019;45:e20180324. https://doi.org/10.1590/1806-3713/e20180324.

  58. Matteelli A, Centis R, D’Ambrosio L, et al. WHO strategies for the programmatic management of drug-resistant tuberculosis. Expert Rev Respir Med. 2016;10:991–1002. https://doi.org/10.1080/17476348.2016.1199278.

    Article  CAS  PubMed  Google Scholar 

  59. Wu YE, Peng WG, Cai YM, et al. Decrease in CD4+CD25+FoxP3+ Treg cells after pulmonary resection in the treatment of cavity multidrug-resistant tuberculosis. Int J Infect Dis. 2010;14:e815-22. https://doi.org/10.1016/j.ijid.2010.04.005.

    Article  CAS  PubMed  Google Scholar 

  60. Mahmoud K, Ammar A. Immunomodulatory effects of anesthetics during thoracic surgery. Anesthesiol Res Pract. 2011. https://doi.org/10.1155/2011/317410.

Download references

Funding

None.

Author information

Authors and Affiliations

  1. Department of Thoracic Surgery, University College London Hospitals, NHS Foundation Trust, London, UK

    Massimiliano Fornasiero, Georgios Geropoulos, Julian Aquilina, Niraj Kumar, Kunal Bhakhri & Nikolaos Panagiotopoulos

  2. Institute of Health System Science, Feinstein Institute for Medical Research, Manhasset, NY, USA

    Dimitrios Giannis

  3. Royal Hampshire Country Hospital, NHS Foundation Trust, Winchester, UK

    Joshua Enson

Authors
  1. Massimiliano Fornasiero
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Georgios Geropoulos
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Dimitrios Giannis
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Joshua Enson
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Julian Aquilina
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Niraj Kumar
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. Kunal Bhakhri
    View author publications

    You can also search for this author in PubMed Google Scholar

  8. Nikolaos Panagiotopoulos
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Georgios Geropoulos.

Ethics declarations

Conflict of interest

The authors declare no competing interests.

Ethics approval, Human and animal rights statement, informed consent

Not required for this review article.

Additional information

Publisher’s note

Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Fornasiero, M., Geropoulos, G., Giannis, D. et al. Systemic inflammatory changes and their clinical implications following thoracic cancer surgery. Indian J Thorac Cardiovasc Surg 38, 487–496 (2022). https://doi.org/10.1007/s12055-021-01301-2

Download citation

  • Received:

  • Revised:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s12055-021-01301-2

Keywords

Search

Navigation