Palliative Treatment of Head and Neck Cancer

  • Christian Seebauer
  • Hans-Robert Metelmann
  • Katherina Witzke
  • Jean-Michel Pouvesle
Chapter

Abstract

Cold atmospheric pressure plasma (CAP) is clinically known for inactivating microbial pathogens and stimulation of tissue regeneration in chronic wounds. Several authors have reported the effectiveness against cancer in different cell lines and animal models as well. There are first reports of patients with real clinical benefit following application of CAP, mostly in terms of palliation, but some of them with not only visible change of the tumor surface but lasting partial tumor remission.

These patients with locally advanced squamous cell carcinoma of the oropharynx suffering from open infected ulcerations had been treated with a jet plasma source (kINPen® MED, neoplas tools GmbH, Greifswald, Germany) to inactivate the microbial pathogens causing odor and pain. The palliative therapy program included repeated cycles of three single applications (1 min/cm2 from a distance of 8 mm) within 1 week, each followed by an intermittence of 1 week. CAP treatment resulted in most of the patients in a significant reduction of odor and of pain medication requirements, an improvement in social function and a positive emotional affect. In two patients further observance revealed partial tumor remission for at least 9 month beyond palliation. Incisional biopsies at remission demonstrate a moderate amount of apoptotic tumor cells and a desmoplastic reaction of the connective tissue.

Keywords

Oropharynx cancer Palliation Reduction of odor Pain relief Tumor shrinking Partial tumor remission Desmoplasia Apoptosis 

References

  1. 1.
    Fridman G, Shereshevsky A, Jost MM, Brooks AD, Fridman A, Gutsol A, Vasilets V, Friedman G. Floating electrode dielectric barrier discharge plasma in air promoting apoptotic behavior in melanoma skin cancer cell lines. Plasma Chem Plasma Process. 2007;27(2):163–76.CrossRefGoogle Scholar
  2. 2.
    vonWoedtke T, Metelmann HR, Weltmann KD. Clinical plasma medicine: state and perspectives of in vivo application of cold atmospheric plasma. Contrib Plasma Phys. 2014;54(2):104–17.CrossRefGoogle Scholar
  3. 3.
    von Woedtke T, Reuter S, Masur K, Weltmanna KD. Plasmas for medicine. Phys Rep. 2013;530:291–320.CrossRefGoogle Scholar
  4. 4.
    Kim SJ, Chung TH. Cold atmospheric plasma jet-generated RONS and their selective effects on normal and carcinoma cells. Sci Rep. 2016;3(6):20332.CrossRefGoogle Scholar
  5. 5.
    Yan D, Sherman JH, Keidar M. Cold atmospheric plasma, a novel promising anti-cancer treatment modality. Oncotarget. 2017;8(9):15977–95.CrossRefGoogle Scholar
  6. 6.
    Gay-Mimbrera J, García MC, Isla-Tejera B, Rodero-Serrano A, García-Nieto AV, Ruano J. Clinical and biological principles of cold atmospheric plasma application in skin cancer. Adv Ther. 2016;33(6):894–909.CrossRefGoogle Scholar
  7. 7.
    Volotskova O, Hawley TS, Stepp MA, Keidar M. Targeting the cancer cell cycle by cold atmospheric plasma. Sci Rep. 2012;2:636.CrossRefGoogle Scholar
  8. 8.
    Keidar M, Walk R, Shashurin A, Srinivasan P, Sandler A, Dasgupta S, Ravi R, Guerrero-Preston R, Trink B. Cold plasma selectivity and the possibility of a paradigm shift in cancer therapy. Br J Cancer. 2011;105(9):1295–301.CrossRefGoogle Scholar
  9. 9.
    Hirst AM, Frame FM, Arya M, Maitland NJ, O’Connell D. Low temperature plasmas as emerging cancer therapeutics: the state of play and thoughts for the future. Tumour Biol. 2016;37(6):7021–31.CrossRefGoogle Scholar
  10. 10.
    Bauer G. The antitumor effect of singlet oxygen. Anitcancer Res. 2016;36:5649–64.CrossRefGoogle Scholar
  11. 11.
    Lee HJ, Shon CH, Kim YS, Kim S, Kim GC, Kong MG. Degradation of adhesion molecules of G361 melanoma cells by a non-thermal atmospheric pressure microplasma. New J Phys. 2009;11(11):115026.CrossRefGoogle Scholar
  12. 12.
    Kim GC, Kim GJ, Park SR, Jeon SM, Seo HJ, Iza F, Lee JK. Air plasma coupled with antibody-conjugated nanoparticles: a new weapon against cancer. J Phys D Appl Phys. 2009;42(3):032005.CrossRefGoogle Scholar
  13. 13.
    Daeschlein G, Scholz S, Lutze S, Arnold A, et al. Comparison between cold plasma, electro chemotherapy and combined therapy in a melanoma mouse model. Exp Dermatol. 2013;22:582–6.CrossRefGoogle Scholar
  14. 14.
    Yajima I, Iida M, Kumasaka MY, Omata Y, Ohgami N, Chang J, Ichihara S, Hori M, Kato M. Non-equilibrium atmospheric pressure plasmas modulate cell cycle-related gene expressions in melanocytic tumors of RET-transgenic mice. Exp Dermatol. 2014;23(6):424–5.CrossRefGoogle Scholar
  15. 15.
    Iida M, Yajima I, Ohgami N, Tamura H, Takeda K, Ichihara S, Hori M, Kato M. The effects of non-thermal atmospheric pressure plasma irradiation on expression levels of matrix metalloproteinases in benign melanocytic tumors in RETtransgenic mice. Eur J Dermatol. 2014;24(3):392–4.PubMedGoogle Scholar
  16. 16.
    Sensenig R, Kalghatgi S, Cerchar E, Fridman G, Shereshevsky A, Torabi B, et al. Non-thermal plasma induces apoptosis in melanoma cells via production of intracellular reactive oxygen species. Ann Biomed Eng. 2011;39(2):674–87.CrossRefGoogle Scholar
  17. 17.
    Zirnheld JL, Zucker SN, DiSanto TM, Berezney R, Etemadi K. Nonthermal plasma needle: development and targeting of melanoma cells. IEEE Trans Plasma Sci. 2010;38(4):948–52.CrossRefGoogle Scholar
  18. 18.
    Vandamme M, Robert E, Lerondel S, Sarron V, Ries D, Dozias S, Sobilo J, Gosset D, Kieda C, Legrain B, Pouvesle JM, Pape AL. ROS implication in a new antitumor strategy based on non-thermal plasma. Int J Cancer. 2012;130(9):2185–94.CrossRefGoogle Scholar
  19. 19.
    Tanaka H, Mizuno M, Ishikawa K, Nakamura K, Kajiyama H, Kano H, Kikkawa F, Hori M. Plasma-activated medium selectively kills glioblastoma brain tumor cells by down-regulating a survival signaling molecule, AKT kinase. Plasma Med. 2011;1(3–4).CrossRefGoogle Scholar
  20. 20.
    Kaushik NK, Attri P, Kaushik N, Choi EH. A preliminary study of the effect of DBD plasma and osmolytes on T98G brain cancer and HEK non-malignant cells. Molecules. 2013;18(5):4917–28.CrossRefGoogle Scholar
  21. 21.
    Tanaka H, Mizuno M, Ishikawa K, Nakamura K, Kajiyama H, Kano H, Kikkawa F, Hori M. Plasma-activated medium selectively kills Glioblastoma brain tumor cells by down-regulating a survival Signaling molecule, AKT kinase. Plasma Med. 2011;1(3–4):265–77.CrossRefGoogle Scholar
  22. 22.
    Tanaka H, Mizuno M, Ishikawa K, Nakamura K, Utsumi F, Kajiyama H, Kano H, Maruyama S, Kikkawa F, Hori M. Cell survival and proliferation signaling pathways are downregulated by plasma-activated medium in glioblastoma brain tumor cells. Plasma Med. 2012;2(4):207–20.CrossRefGoogle Scholar
  23. 23.
    Vandamme M, Robert E, Pesnel S, Barbosa E, Dozias S, Sobilo J, Lerondel S, Le Pape A, Pouvesle JM. Antitumor effect of plasma treatment on U87 glioma xenografts: preliminary results. Plasma Process Polym. 2010;7(3–4):264–73.CrossRefGoogle Scholar
  24. 24.
    Koritzer J, Boxhammer V, Schafer A, Shimizu T, Klampfl TG, Li YF, Welz C, Schwenk-Zieger S, Morfill GE, Zimmermann JL, Schlegel J. Restoration of sensitivity in chemo—resistant glioma cells by cold atmospheric plasma. PLoS One. 2013;8(5):e64498.  https://doi.org/10.1371/journal.pone.0064498.CrossRefPubMedPubMedCentralGoogle Scholar
  25. 25.
    Kaushik NK, Uhm H, Choi EH. Micronucleus formation induced by dielectric barrier discharge plasma exposure in brain cancer cells. Appl Phys Lett. 2012;100(8):084102.  https://doi.org/10.1063/1.3687172.CrossRefGoogle Scholar
  26. 26.
    Kaushik NK, Kim YH, Han YG, Choi EH. Effect of jet plasma on T98G human brain cancer cells (vol 13, pg 176, 2012). Curr Appl Phys. 2013;13(3):614–8.  https://doi.org/10.1016/j.cap.2012.10.009.CrossRefGoogle Scholar
  27. 27.
    Kim SJ, Chung TH, Bae SH, Leem SH. Induction of apoptosis in human breast cancer cells by a pulsed atmospheric pressure plasma jet. Appl Phys Lett. 2010;97(2):023702.CrossRefGoogle Scholar
  28. 28.
    Ninomiya K, Ishijima T, Imamura M, Yamahara T, Enomoto H, Takahashi K, Tanaka Y, Uesugi Y, Shimizu N. Evaluation of extra- and intracellular OH radical generation, cancer cell injury, and apoptosis induced by a non thermal atmospheric-pressure plasma jet. J Phys D Appl Phys. 2013;46(42):425401.CrossRefGoogle Scholar
  29. 29.
    Wang M, Holmes B, Cheng X, Zhu W, Keidar M, Zhang LG. Cold atmospheric plasma for selectively ablating metastatic breast cancer cells. PLoS One. 2013;8(9):e73741.CrossRefGoogle Scholar
  30. 30.
    Ahn HJ, Kim KI, Hoan NN, Kim CH, Moon E, Choi KS, Yang SS, Lee JS. Targeting cancer cells with reactive oxygen and nitrogen species generated by atmosphericpressure air plasma. PLoS One. 2014;9(1):e86173.CrossRefGoogle Scholar
  31. 31.
    Kim K, Jun Ahn H, Lee J-H, Kim J-H, Sik Yang S, Lee J-S. Cellular membrane collapse by atmospheric-pressure plasma jet. Appl Phys Lett. 2014;104(1):013701.CrossRefGoogle Scholar
  32. 32.
    Tan X, Zhao S, Lei Q, Lu X, He G, Ostrikov K. Single-cell-precision microplasma-induced cancer cell apoptosis. PLoS One. 2014;9(6):e101299.CrossRefGoogle Scholar
  33. 33.
    Leduc M, Guay D, Leask RL, Coulombe S. Cell permeabilization using a non-thermal plasma. New J Phys. 2009;11:115021.  https://doi.org/10.1088/1367-2630/11/11/115021.CrossRefGoogle Scholar
  34. 34.
    Ahn HJ, Kim KI, Kim G, Moon E, Yang SS, Lee JS. Atmospheric-pressure plasma jet induces apoptosis involving mitochondria via generation of free radicals. PLoS One. 2011;6(11):e28154.  https://doi.org/10.1371/journal.pone.0028154.CrossRefPubMedPubMedCentralGoogle Scholar
  35. 35.
    Sato T, Yokoyama M, Johkura K. A key inactivation factor of HeLa cell viability by a plasma flow. J Phys D Appl Phys. 2011;44(37):372001.  https://doi.org/10.1088/0022-3727/44/37/372001.CrossRefGoogle Scholar
  36. 36.
    Huang J, Chen W, Li H, Wang PY, Yang SZ. Inactivation of He la cancer cells by an atmospheric pressure cold plasma jet. Acta Phys Sin-Ch Ed. 2013;62(6):065201.  https://doi.org/10.7498/Aps.62.065201.CrossRefGoogle Scholar
  37. 37.
    Ja Kim S, Min Joh H, Chung TH. Production of intracellular reactive oxygen species and change of cellviability induced by atmospheric pressure plasma in normal and cancer cells. Appl Phys Lett. 2013;103(15):153705.CrossRefGoogle Scholar
  38. 38.
    Kim JY, Ballato J, Foy P, Hawkins T, Wei Y, Li J, Kim SO. Apoptosis of lung carcinoma cells induced by a flexible optical fiber-based cold microplasma. Biosens Bioelectron. 2011;28(1):333–8.CrossRefGoogle Scholar
  39. 39.
    Huang J, Chen W, Li H, Wang XQ, Lv GH, Khosa ML, Guo M, Feng KC, Wang PY, Yang SZ. Deactivation of A549 cancer cells in vitro by a dielectric barrier discharge plasma needle. J Appl Phys. 2011;109(5):053305.  https://doi.org/10.1063/1.3553873.CrossRefGoogle Scholar
  40. 40.
    Kim K, Choi JD, Hong YC, Kim G, Noh EJ, Lee JS, Yang SS. Atmospheric-pressure plasma-jet from micronozzle array and its biological effects on living cells for cancer therapy. Appl Phys Lett. 2011;98(7):073701.  https://doi.org/10.1063/1.3555434.CrossRefGoogle Scholar
  41. 41.
    Adachi T, Tanaka H, Nonomura S, Hara H, Kondo SI, Hori M. Plasma-activated medium induces A549 cell injury via a spiral apoptotic cascade involving the mitochondrial- nuclear network. Free Radic Biol Med. 2014;79C:28–44.  https://doi.org/10.1016/j.freeradbiomed.2014.11.014.CrossRefGoogle Scholar
  42. 42.
    Panngom K, Baik KY, Nam MK, Han JH, Rhim H, Choi EH. Preferential killing of human lung cancer cell lines with mitochondrial dysfunction by nonthermal dielectric barrier discharge plasma. Cell Death Dis. 2013;4:e642.  https://doi.org/10.1038/cddis.2013.168.CrossRefPubMedPubMedCentralGoogle Scholar
  43. 43.
    Torii K, Yamada S, Nakamura K, Tanaka H, Kajiyama H, Tanahashi K, Iwata N, Kanda M, Kobayashi D, Tanaka C, Fujii T, Nakayama G, Koike M, Sugimoto H, Nomoto S, Natsume A, Fujiwara M, Mizuno M, Hori M, Saya H, Kodera Y. Effectiveness of plasma treatment on gastric cancer cells. Gastric Cancer. 2014;18(3):635–43.  https://doi.org/10.1007/s10120-014-0395-6.CrossRefPubMedPubMedCentralGoogle Scholar
  44. 44.
    Brullé L, Vandamme M, Ries D, Martel E, Robert E, Lerondel S, Trichet V, Richard S, Pouvesle JM, Le Pape A. Effects of a non thermal plasma treatment alone or in combination with gemcitabine in a MIA PaCa2-luc orthotopic pancreatic carcinoma model. PLoS One. 2012;7(12):e52653.  https://doi.org/10.1371/journal.pone.0052653.CrossRefPubMedPubMedCentralGoogle Scholar
  45. 45.
    Partecke LI, Evert K, Haugk J, Doering F, Normann L, Diedrich S, Weiss FU, Evert M, Huebner NO, Guenther C, Heidecke CD, Kramer A, Bussiahn R, Weltmann KD, Pati O, Bender C, von Bernstorff W. Tissue tolerable plasma (TTP) induces apoptosis in pancreatic cancer cells in vitro and in vivo. BMC Cancer. 2012;12:473.  https://doi.org/10.1186/1471-2407-12-473.CrossRefPubMedPubMedCentralGoogle Scholar
  46. 46.
    Georgescu N, Lupu AR. Tumoral and normal cells treatment with high-voltage pulsed cold atmospheric plasma jets. IEEE T Plasma Sci. 2010;38(8):1949–55.CrossRefGoogle Scholar
  47. 47.
    Ishaq M, Evans MDM, Ostrikov K. Atmospheric pressure gas plasma-induced colorectal cancer cell death is mediated by Nox2–ASK1 apoptosis pathways and oxidative stress is mitigated by Srx–Nrf2 anti-oxidant system. Biochim Biophys Acta. 2014;1843(12):2827–37.CrossRefGoogle Scholar
  48. 48.
    Plewa J-M, Yousfi M, Frongia C, Eichwald O, Ducommun B, Merbahi N, Lobjois V. Low-temperature plasmainduced antiproliferative effects on multi-cellular tumor spheroids. New J Phys. 2014;16(4):043027.CrossRefGoogle Scholar
  49. 49.
    Lupu AR, Georgescu N, Calugaru A, Cremer L, Szegli G, Kerek F. The effects of cold atmospheric plasma jets on B16 and COLO320 tumoral cells. Roum Arch Microbiol Immunol. 2009;68(3):136–44.PubMedGoogle Scholar
  50. 50.
    Kim CH, Kwon S, Bahn JH, Lee K, Jun SI, Rack PD, Baek SJ. Effects of atmospheric nonthermal plasma on invasion of colorectal cancer cells. Appl Phys Lett. 2010;96(24):243701.  https://doi.org/10.1063/1.3449575.CrossRefPubMedPubMedCentralGoogle Scholar
  51. 51.
    Hirst AM, Frame FM, Maitland NJ, O'Connell D. Low temperature plasma: a novel focal therapy for localized prostate cancer? Biomed Res Int. 2014;2014:878319.  https://doi.org/10.1155/2014/878319.CrossRefPubMedPubMedCentralGoogle Scholar
  52. 52.
    Barekzi N, Laroussi M. Dose-dependent killing of leukemia cells by low-temperature plasma. J Phys D Appl Phys. 2012;45(42):422002.CrossRefGoogle Scholar
  53. 53.
    Thiyagarajan M, Waldbeser L, Whitmill A. THP-1 leukemia cancer treatment using a portable plasma device. Stud Health Technol Inform. 2011;173:515–7.Google Scholar
  54. 54.
    Thiyagarajan M, Anderson H, Gonzales XF. Induction of apoptosis in human myeloid leukemia cells by remote exposure of resistive barrier cold plasma. Biotechnol Bioeng. 2014;111(3):565–74.CrossRefGoogle Scholar
  55. 55.
    Thiyagarajan M, Sarani A, Gonzales X. Characterization of portable resistive barrier plasma jet and its direct and indirect treatment for antibiotic resistant bacteria and THP-1 leukemia cancer cells. IEEE T Plasma Sci. 2012;40(12):3533–45.CrossRefGoogle Scholar
  56. 56.
    Zhang X, Li M, Zhou R, Feng K, Yang S. Ablation of liver cancer cells in vitro by a plasma needle. Appl Phys Lett. 2008;93(2):021502.CrossRefGoogle Scholar
  57. 57.
    Zhao S, Xiong Z, Mao X, Meng D, Lei Q, Li Y, Deng P, Chen M, Tu M, Lu X, Yang G, He G. Atmospheric pressure room temperature plasma jets facilitate oxidative and nitrative stress and lead to endoplasmic reticulum stress dependent apoptosis in HepG2 cells. PLoS One. 2013;8(8):e73665.CrossRefGoogle Scholar
  58. 58.
    Gweon B, Kim M, Kim DB, Kim D, Kim H, Jung H, Shin JH, Choe W. Differential responses of human liver cancer and normal cells to atmospheric pressure plasma. Appl Phys Lett. 2011;99(6):063701.  https://doi.org/10.1063/1.3622631.CrossRefGoogle Scholar
  59. 59.
    Kaushik NK, Kaushik N, Park D, Choi EH. Altered antioxidant system stimulates dielectric barrier discharge plasma- induced cell death for solid tumor cell treatment. PLoS One. 2014;9(7):e103349.  https://doi.org/10.1371/journal.pone.0103349.CrossRefPubMedPubMedCentralGoogle Scholar
  60. 60.
    Chang JW, Kang SU, Shin YS, Kim KI, Seo SJ, Yang SS, Lee JS, Moon E, Lee K, Kim CH. Non-thermal atmospheric pressure plasma inhibits thyroid papillary cancer cell invasion via cytoskeletal modulation, altered MMP-2/-9/ uPA activity. PLoS One. 2014;9(3):e92198.  https://doi.org/10.1371/journal.pone.0092198.CrossRefPubMedPubMedCentralGoogle Scholar
  61. 61.
    Guerrero-Preston R, Ogawa T, Uemura M, Shumulinsky G, Valle BL, Pirini F, Ravi R, Sidransky D, Keidar M, Trink B. Cold atmospheric plasma treatment selectively targets head and neck squamous cell carcinoma cells. Int J Mol Med. 2014;34(4):941–6.CrossRefGoogle Scholar
  62. 62.
    Kang SU, Cho JH, Chang JW, Shin YS, Kim KI, Park JK, Yang SS, Lee JS, Moon E, Lee K, Kim CH. Nonthermal plasma induces head and neck cancer cell death: the potential involvement of mitogen-activated protein kinasedependent mitochondrial reactive oxygen species. Cell Death Dis. 2014;5:e1056.CrossRefGoogle Scholar
  63. 63.
    Hasse S, Tran TD, Hahn O, Weltmann KD, Metelmann HR, Masur K. Plasma application in human skin—molecular analyses in situ. Exp Dermatol. 2014;23:e51.Google Scholar
  64. 64.
    Han X, Klas M, Liu YY, Stack MS, Ptasinska S. DNA damage in oral cancer cells induced by nitrogen atmospheric pressure plasma jets. Appl Phys Lett. 2013;102(23):233703.  https://doi.org/10.1063/1.4809830.CrossRefGoogle Scholar
  65. 65.
    Chang JW, Kang SU, Shin YS, Kim KI, Seo SJ, Yang SS, Lee JS, Moon E, Baek SJ, Lee K, Kim CH. Non-thermal atmospheric pressure plasma induces apoptosis in oral cavity squamous cell carcinoma: Involvement of DNA-damage- triggering sub-G(1) arrest via the ATM/p53 pathway. Arch Biochem Biophys. 2014a;545:133–40.CrossRefGoogle Scholar
  66. 66.
    Metelmann H-R, Nedrelow DS, Seebauer C, Schuster M, von Woedtke T, Weltmann K-D, Kindler S, Metelmann PH, Finkelstein SE, Von Hoff DD, Podmelle F. Head and neck cancer treatment and physical plasma. Clin Plasma Med. 2015;3(1):17–23.CrossRefGoogle Scholar
  67. 67.
    Schuster M, Seebauer C, Rutkowski R, Hauschild A, Podmelle F, Metelmann C, Metelmann B, von Woedtke T, Hasse S, Weltmann KD, Metelmann HR. Visible tumor surface response to physical plasma and apoptotic cell kill in head and neck cancer. J Craniomaxillofac Surg. 2016;44(9):1445–52.CrossRefGoogle Scholar
  68. 68.
    Metelmann HR, Seebauer C, Miller V, Friedman A, Bauer G, Graves DB, Pouvesle JM, Rutkowski R, Schuster M, Bekeschus S, Wende K, Masur K, Hasse S, Gerling T, Hori M, Tanaka H, Choi EH, Weltmann KD, Metelmann PH, Von Hoff DD, von Woedtke T. Clinical experience with cold plasma in the treatment of locally advanced head and neck cancer. Clin Plasma Med. 2017.  https://doi.org/10.1016/j.cpme.2017.09.001.
  69. 69.
    Isbary G, Morfill G, Schmidt HU, Georgi M, Ramrath K, Heinlin J, et al. A first prospective randomized controlled trial to decrease bacterial load using cold atmospheric argon plasma on chronic wounds in patients. Br J Dermatol. 2010;163:78–82.PubMedPubMedCentralGoogle Scholar
  70. 70.
    Isbary G, Zimmermann JL, Shimizu T, Li YF, Morfill GE, Thomas HM, et al. Non-thermal plasma – more than five years of clinical experience. J Clin Plasma Med. 2013;1:19–23.CrossRefGoogle Scholar
  71. 71.
    Miller V, Lin A, Fridman A. Why target immune cells for plasma treatment of cancer. Plasma Chem Plasma Process. 2016;36(1):259–68.CrossRefGoogle Scholar
  72. 72.
    Ishaq M, Han ZJ, Kumar S, Evans MD, Ostrikov KK. Atmospheric-pressure plasma-and TRAIL-induced apoptosis in TRAIL-resistant colorectal cancer cells. Plasma Process Polym. 2015;12(6):574–82.CrossRefGoogle Scholar

Copyright information

© Springer International Publishing AG, part of Springer Nature 2018

Authors and Affiliations

  • Christian Seebauer
    • 1
    • 2
    • 3
  • Hans-Robert Metelmann
    • 1
    • 3
  • Katherina Witzke
    • 1
    • 3
  • Jean-Michel Pouvesle
    • 4
  1. 1.Department of Oral and Maxillofacial Surgery/Plastic SurgeryUniversity Medicine GreifswaldGreifswaldGermany
  2. 2.Leibniz Institute for Plasma Science and TechnologyGreifswaldGermany
  3. 3.National Center of Plasma MedicineBerlinGermany
  4. 4.GREMIOrleansFrance

Personalised recommendations