The Effects of Preoperative Oral Carbohydrate on Frequency of T and NK Cells in Patients with Cervical Cancer Treated Using Neoadjuvant Chemotherapy and Surgery: A Prospective Cohort Study

Fuqing Zhang, Mengxia Yao, Zhiping Lin, Yili Chen, Hui Jiang, Meina Zeng, Wenhua Chen, Fuqing Zhang, Mengxia Yao, Zhiping Lin, Yili Chen, Hui Jiang, Meina Zeng, Wenhua Chen

Abstract

Background: Immune dysfunction can occur after neoadjuvant chemotherapy (NAC) and surgery for cancer. We investigated whether preoperative oral carbohydrate affected the postoperative percentages of T cells (CD4+ and CD8+) and natural killer (NK) cells in patients with cervical cancer treated with NAC and surgery.

Methods: This prospective cohort study enrolled consecutive patients with cervical cancer treated by radical hysterectomy with PLND at the Gynecologic Oncology Department of Fujian Provincial Cancer Hospital (China) between January 2018 and December 2018. Patients were divided into three groups according to the treatment method: NAC (two cycles, surgery 1 month later), NAC+CHO (chemotherapy and surgical methods same as with the NAC group but with 300 mL of oral carbohydrate administered 2 h before surgery), and non-NAC (surgery alone). Percentages of NK, CD3+, CD4+, and CD8+ cells were evaluated by flow cytometry the day after the first admission, just before surgery, immediately after tracheal tube removal, and the day after surgery. This trial is registered with NCT03872635 at clinicaltrials.com.

Results: The final analysis included 77 patients (non-NAC group, n = 26; NAC group, n = 25; and NAC-CHO group, n = 26). Baseline characteristics and preoperative NK, CD3+, CD4+, and CD8+ cell percentages were similar between groups. Postoperatively, all groups exhibited reductions in NK, CD3+, and CD4+ cell percentages and increases in CD8+ cell percentages (all P < 0.05). The changes in NK, CD3+, CD4+, and CD8+ cell percentages were attenuated in the NAC-CHO group (P < 0.05 vs. both other groups).

Conclusion: Preoperative oral carbohydrate can improve the postoperative populations of NK and T cells after the treatment of cervical cancer by NAC and surgery.

Conflict of interest statement

The authors declare that they have no competing interests.

Copyright © 2020 Fuqing Zhang et al.

Figures

Figure 1
Figure 1
Flow chart showing patient enrollment in the study. CHO: carbohydrate; NAC: neoadjuvant chemotherapy.

References

    1. Torre L. A., Bray F., Siegel R. L., Ferlay J., Lortet-Tieulent J., Jemal A. Global cancer statistics, 2012. CA: A Cancer Journal for Clinicians. 2015;65(2):87–108. doi: 10.3322/caac.21262.
    1. Chen W., Zheng R., Baade P. D., et al. Cancer statistics in China, 2015. CA: A Cancer Journal for Clinicians. 2016;66(2):115–132. doi: 10.3322/caac.21338.
    1. Somashekhar S. P., Ashwin K. R. Management of early stage cervical cancer. Reviews on Recent Clinical Trials. 2015;10(4):302–308. doi: 10.2174/1574887110666150923113629.
    1. Carneiro S. R., Fagundes M. A., do Rosário P. J. O., Neves L. M. T., Souza G. S., Pinheiro M. C. N. Five-year survival and associated factors in women treated for cervical cancer at a reference hospital in the Brazilian Amazon. PloS One. 2017;12(11, article e0187579) doi: 10.1371/journal.pone.0187579.
    1. Koh W. J., Abu-Rustum N. R., Bean S., et al. Cervical cancer, version 3.2019, NCCN clinical practice guidelines in oncology. Journal of the National Comprehensive Cancer Network: JNCCN. 2019;17(1):64–84. doi: 10.6004/jnccn.2019.0001.
    1. Kumar L., Pramanik R., Kumar S., Bhatla N., Malik S. Neoadjuvant chemotherapy in gynaecological cancers - implications for staging. Best Practice & Research Clinical Obstetrics & Gynaecology. 2015;29(6):790–801. doi: 10.1016/j.bpobgyn.2015.02.008.
    1. Benedetti Panici P., Palaia I., Marchetti C., et al. Dose-dense neoadjuvant chemotherapy plus radical surgery in locally advanced cervical cancer: a phase II study. Oncology. 2015;89(2):103–110. doi: 10.1159/000381461.
    1. Mousavia A. S., Vahidi S., Karimi-Zarchi M., Modarress-Gilania M., Ghaemmaghamia F. Response to neoadjuvant chemotherapy with paclitaxel and cisplatin in locally advanced cervical cancer. European Journal of Gynaecological Oncology. 2013;34(6):527–531.
    1. Zhang R., Li B., Bai P., et al. Neoadjuvant chemotherapy with paclitaxel and cisplantin or carboplatin for patients with locally advanced uterine cervical cancer. Zhonghua zhong liu za zhi [Chinese Journal of Oncology] 2011;33(8):616–620.
    1. Prueksaritanond N., Chaisarn P., Yanaranop M. The efficacy of neoadjuvant paclitaxel-carboplatin chemotherapy followed by radical hysterectomy compared to radical hysterectomy alone in bulky stage IB2-IIA cervical cancer. Journal of the Medical Association of Thailand. 2012;95(Suppl 3):S55–S61.
    1. Rydzewska L., Tierney J., Vale C. L., Symonds P. R. Neoadjuvant chemotherapy plus surgery versus surgery for cervical cancer. The Cochrane Database of Systematic Reviews. 2008;(1, article CD007406)
    1. Rutkowski M. R., Svoronos N., Perales-Puchalt A., Conejo-Garcia J. R. The tumor macroenvironment: cancer-promoting networks beyond tumor beds. Advances in Cancer Research. 2015;128:235–262. doi: 10.1016/bs.acr.2015.04.011.
    1. Kurmyshkina O. V., Kovchur P. I., Schegoleva L. V., Volkova T. O. T- and NK-cell populations with regulatory phenotype and markers of apoptosis in circulating lymphocytes of patients with CIN3 or microcarcinoma of the cervix: evidence for potential mechanisms of immune suppression. Infectious Agents and Cancer. 2017;12(1) doi: 10.1186/s13027-017-0166-1.
    1. Chang W. C., Li C. H., Chu L. H., Huang P. S., Sheu B. C., Huang S. C. Regulatory T cells suppress natural killer cell immunity in patients with human cervical carcinoma. International Journal of Gynecological Cancer: Official Journal of the International Gynecological Cancer Society. 2016;26(1):156–162.
    1. Bell M. C., Edwards R. P., Partridge E. E., et al. CD8+ T lymphocytes are recruited to neoplastic cervix. Journal of Clinical Immunology. 1995;15(3):130–136. doi: 10.1007/bf01543104.
    1. Liu S., Gu X., Zhu L., et al. Effects of propofol and sevoflurane on perioperative immune response in patients undergoing laparoscopic radical hysterectomy for cervical cancer. Medicine. 2016;95(49, article e5479) doi: 10.1097/MD.0000000000005479.
    1. Marana H. R., Andrade J. M., Silva J. S. Natural killer cells and interleukin-12 in patients with advanced cervical cancer under neoadjuvant chemotherapy. Brazilian Journal of Medical and Biological Research = Revista brasileira de pesquisas medicas e biologicas. 1996;29(4):473–477.
    1. Cosiski Marana H. R., Santana da Silva J., Moreira de Andrade J. NK cell activity in the presence of IL-12 is a prognostic assay to neoadjuvant chemotherapy in cervical cancer. Gynecologic Oncology. 2000;78(3):318–323. doi: 10.1006/gyno.2000.5878.
    1. Garzetti G. G., Ciavattini A., Provinciali M., Valensise H., Romanini C., Fabris N. Influence of neoadjuvant polychemotherapy on natural killer cell activity in patients with locally advanced cervical squamous carcinoma. Gynecologic Oncology. 1994;52(1):39–43. doi: 10.1006/gyno.1994.1008.
    1. Fraser D. A., Thoen J., Reseland J. E., Forre O., Kjeldsen-Kragh J. Decreased CD4+ lymphocyte activation and increased interleukin-4 production in peripheral blood of rheumatoid arthritis patients after acute starvation. Clinical Rheumatology. 1999;18(5):394–401. doi: 10.1007/s100670050125.
    1. Nygren J., Thorell A., Jacobsson H., et al. Preoperative gastric emptying. Effects of anxiety and oral carbohydrate administration. Annals of Surgery. 1995;222(6):728–734. doi: 10.1097/00000658-199512000-00006.
    1. Smith M. D., McCall J., Plank L., et al. Preoperative carbohydrate treatment for enhancing recovery after elective surgery. The Cochrane Database of Systematic Reviews. 2014;(8, article CD009161) doi: 10.1002/14651858.cd009161.pub2.
    1. Nygren J., Thorell A., Ljungqvist O. Preoperative oral carbohydrate therapy. Current Opinion in Anaesthesiology. 2015;28(3):364–369. doi: 10.1097/ACO.0000000000000192.
    1. Oyama Y., Iwasaka H., Shiihara K., et al. Effects of preoperative oral carbohydrates and trace elements on perioperative nutritional status in elective surgery patients. Middle East Journal of Anaesthesiology. 2011;21(3):375–383.
    1. Kaška M., Grosmanová T.'., Havel E., et al. The impact and safety of preoperative oral or intravenous carbohydrate administration versus fasting in colorectal surgery--a randomized controlled trial. Wiener Klinische Wochenschrift. 2010;122(1-2):23–30. doi: 10.1007/s00508-009-1291-7.
    1. Cakar E., Yilmaz E., Cakar E., Baydur H. The effect of preoperative oral carbohydrate solution intake on patient comfort: a randomized controlled study. Journal of Perianesthesia Nursing: Official Journal of the American Society of Peri Anesthesia Nurses. 2017;32(6):589–599. doi: 10.1016/j.jopan.2016.03.008.
    1. Gianotti L., Biffi R., Sandini M., et al. Preoperative oral carbohydrate load versus placebo in major elective abdominal surgery (PROCY): a randomized, placebo-controlled, Multicenter, Phase III Trial. Annals of Surgery. 2018;267(4):623–630. doi: 10.1097/SLA.0000000000002325.
    1. Bilku D. K., Dennison A. R., Hall T. C., Metcalfe M. S., Garcea G. Role of preoperative carbohydrate loading: a systematic review. Annals of the Royal College of Surgeons of England. 2014;96(1):15–22. doi: 10.1308/003588414X13824511650614.
    1. Kim H. J., Cantor H. CD4 T-cell subsets and tumor immunity: the helpful and the not-so-helpful. Cancer Immunology Research. 2014;2(2):91–98. doi: 10.1158/2326-6066.CIR-13-0216.
    1. Pace M., Williams J., Kurioka A., et al. Histone deacetylase inhibitors enhance CD4 T cell susceptibility to NK cell killing but reduce NK cell function. PLoS Pathogens. 2016;12(8, article e1005782) doi: 10.1371/journal.ppat.1005782.
    1. Maneo A., Chiari S., Bonazzi C., Mangioni C. Neoadjuvant chemotherapy and conservative surgery for stage IB1 cervical cancer. Gynecologic Oncology. 2008;111(3):438–443. doi: 10.1016/j.ygyno.2008.08.023.
    1. Liu R., Zhang J., He C., Jiang Q., Liu J., Fan R. Impact of the radiotherapy combined with cisplatin plus paclitaxel chemotherapy on the immunologic functions in the patients with esophageal cancer. Pakistan Journal of Pharmaceutical Sciences. 2016;29(4 Suppl):1387–1390.
    1. Krantz D., Hartana C. A., Winerdal M. E., et al. Neoadjuvant Chemotherapy Reinforces Antitumour T cell Response in Urothelial Urinary Bladder Cancer. European Urology. 2018;74(6):688–692. doi: 10.1016/j.eururo.2018.06.048.
    1. Chu Y., Wang L. X., Yang G., et al. Efficacy of GM-CSF-producing tumor vaccine after docetaxel chemotherapy in mice bearing established Lewis lung carcinoma. Journal of Immunotherapy. 2006;29(4):367–380. doi: 10.1097/.
    1. Chen Y., Liang M., Zhu Y., Zhou D. The effect of propofol and sevoflurane on the perioperative immunity in patients under laparoscopic radical resection of colorectal cancer. Zhonghua Yi Xue Za Zhi. 2015;95(42):3440–3444.
    1. Torrance H. D. T., Longbottom E. R., Vivian M. E., et al. Post-operative immune suppression is mediated via reversible, interleukin-10 dependent pathways in circulating monocytes following major abdominal surgery. PloS One. 2018;13(9, article e0203795) doi: 10.1371/journal.pone.0203795.
    1. Hildebrand F., van Griensven M., Giannoudis P., et al. Impact of hypothermia on the immunologic response after trauma and elective surgery. Surgical Technology International. 2005;14:41–50.
    1. Amodeo G., Bugada D., Franchi S., et al. Immune function after major surgical interventions: the effect of postoperative pain treatment. Journal of Pain Research. 2018;Volume 11:1297–1305. doi: 10.2147/JPR.S158230.
    1. von Kanel R., Mills P. J., Dimsdale J. E. Short-term hyperglycemia induces lymphopenia and lymphocyte subset redistribution. Life Sciences. 2001;69(3):255–262. doi: 10.1016/S0024-3205(01)01127-4.
    1. Lachmann G., von Haefen C., Wollersheim T., Spies C. Severe perioperative hyperglycemia attenuates postoperative monocytic function, basophil count and T cell activation. Minerva Anestesiologica. 2017;83(9):921–929. doi: 10.23736/S0375-9393.17.11638-X.
    1. Steiner J., Bernstein H. G., Schiltz K., et al. Immune system and glucose metabolism interaction in schizophrenia: A chicken- egg dilemma. Progress in Neuro-Psychopharmacology & Biological Psychiatry. 2014;48:287–294. doi: 10.1016/j.pnpbp.2012.09.016.
    1. Madani M., Alizadeh K., Ghazaee S. P., et al. Elective percutaneous coronary intervention: the relationship between preprocedural blood glucose levels and periprocedural myocardial injury. Texas Heart Institute Journal. 2013;40(4):410–417.

Source: PubMed

3
Abonnere