Christian Seebauer

Triterpenes for Well-Balanced Scar Formation in Superficial Wounds

Triterpenes are demonstrably effective for accelerating re-epithelialisation of wounds and known to improve scar formation for superficial lesions. Among the variety of triterpenes, betuline is of particular medical interest. Topical betuline gel (TBG) received drug approval in 2016 from the European Commission as the first topical therapeutic agent with the proven clinical benefit of accelerating wound healing. Two self-conducted randomized intra-individual comparison clinical studies with a total of 220 patients involved in TBG treatment of skin graft surgical wounds have been screened for data concerning the aesthetic aspect of wound healing. Three months after surgery wound treatment with TBG resulted in about 30% of cases with more discreet scars, and standard of care in about 10%. Patients themselves appreciate the results of TBG after 3 months even more (about 50%) compared to standard of care (about 10%). One year after surgery, the superiority of TBG counts for about 25% in comparison with about 10%, and from the patients’ point of view, for 25% compared to 4% under standard of care. In the majority of wound treatment cases, there is no difference visible between TBG treatment and standard of care after 1 year of scar formation. However, in comparison, TBG still offers a better chance for discreet scars and therefore happens to be superior in good care of wounds.

Clinical Studies Applying Physical Plasma in Head and Neck Cancer - Key Points and Study Design

Cold atmospheric pressure plasma (CAP) is known to very effectively inactivate multi-resistant strains of microorganisms. Whether or not application of CAP also inactivates cancer cells is a matter of intense clinical interest. There is a need for prospective, randomized, blindly evaluated clinical trials. This paper outlines the key points of such a study program.

Palliative Treatment of Head and Neck Cancer

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.

Physical plasma and leukocytes – immune or reactive?

Abstract Leukocytes are professionals in recognizing and removing pathogenic or unwanted material. They are present in virtually all tissues, and highly motile to enter or leave specific sites throughout the body. Less than a decade ago, physical plasmas entered the field of medicine to deliver their delicate mix of reactive species and other physical agents for mainly dermatological or oncological therapy. Plasma treatment thus affects leukocytes via direct or indirect means: immune cells are either present in tissues during treatment, or infiltrate or exfiltrate plasma-treated areas. The immune system is crucial for human health and resolution of many types of diseases. It is therefore vital to study the response of leukocytes after plasma treatment in vitro and in vivo. This review gathers together the major themes in the plasma treatment of innate and adaptive immune cells, and puts these into the context of wound healing and oncology, the two major topics in plasma medicine.

Abstract 18: Therapeutic potential of cold physical plasma in palliative cancer care: Introduction and perspectives

Background: Patients suffering from advanced head and neck tumors frequently suffer from superinfected chronic wounds caused by necrotic tissue due to progressive tumor growth, weak systemic and local immunologic response and various accompanying illnesses. Because of wound vulnerability, local antiseptic wound care of microbial-contaminated tumor areas is frequently complicated by bleeding, pain and patient dissatisfaction. Plasma medicine in cancer is of palliative benefit in these cases and among the fastest growing of the current applications of cold atmospheric pressure physical plasma (CAP). Since several plasma medical devices have received approval for treatment of infected skin and ulcerations by the relevant agencies, limited clinical tests have begun on humans and palliative treatment of cancer patients with contaminated ulcers. This report as part of a large-scale study program illustrates one recent impressive application of CAP to a patient suffering from advanced head and neck cancer. Materials and Methods: After curably intended surgical cancer treatment of a well-differentiated squamous cell carcinoma of the left cheek January 2015, the 51-year-old patient noticed a rapidly progressive swelling on the left neck in June. CT scan indicated a large contrast enhancing mass, which was suspected to be tumor recurrence. Operative findings revealed inoperability due to infiltrating the vascular wall of the external carotid. After a palliative intended combined radio-chemotherapy, the tumor was characterized by progressive growth with exulceration. Due to the vulnerability of the extended bacterially contaminated wound and the underlying carotid artery, wound care was difficult. Since October 2015, a supportive palliative cancer treatment using CAP has been started with the patient9s written consent. The exulcerative tumor growth region received treatment with the kINPenMED (Neoplas GmbH, Greifswald, Germany) by scanning the surface for 5 minutes in a meandering manner. Plasma treatment continued to be performed every 3 days. Wound care was implemented in conjunction with an antiseptic wound dressing. Results: The superinfected necrotic tumor areas appeared to be clean of cell detritus and bacteria. Microbiological examination revealed a reduction of bacterial colonization which led to decrease of wound odor, too. Due to the decrease of inflammation, vulnerability and pain have been reduced significantly. Upon CAP therapy a partial tumor response with tumor mass reduction was observed. The ulcerated tumor area has been reduced to one-quarter of its original size. The underlying carotid artery is still intact and ultrasound investigation revealed a regular blood flow. Histologic examinations revealed an increased amount of apoptic tumor cells and a local increase of immune defense. Furthermore, a desmoplastic reaction of the conjunctive tissue represented by a higher proliferation rate of fibroblasts could be depicted. No plasma-relevant systemic side effects have occurred. Conclusion: By sufficient reduction of bacterial colonization, decrease of inflammation, wound vulnerability and pain, CAP constitutes an innovative and valuable treatment option in palliative cancer care. Local tumor mass reduction is an unexpected and promising response during CAP treatment and has to be further examined. Plasma-unique synergies between reactive species, charges and electric fields must be more fully explored and understood. The impressive demonstration of medical efficacy of CAP in cancer ulcerations supports optimism for trials of plasma medical devices with the intention of an adaptive cancer treatment protocol. Citation Format: Christian Seebauer, Thomas von Woedtke, Klaus-Dieter Weltmann, Vandana Miller, Masaru Hori, Hans-Robert Metelmann. Therapeutic potential of cold physical plasma in palliative cancer care: Introduction and perspectives [abstract]. In: Proceedings of the AACR-AHNS Head and Neck Cancer Conference: Optimizing Survival and Quality of Life through Basic, Clinical, and Translational Research; April 23-25, 2017; San Diego, CA. Philadelphia (PA): AACR; Clin Cancer Res 2017;23(23_Suppl):Abstract nr 18.

Palliative Plasmabehandlung von Kopf-Hals-Tumoren und kurative Konzepte

Die Behandlung von Tumoren im Kopf-Hals-Bereich mit CAP („cold atmospheric pressure plasma“) hat fur die Patienten einen palliativen Nutzen, wenn im fortgeschrittenen Krankheitsstadium eine Dekontamination der infizierten Tumorgeschwure gelingt, verbunden mit Schmerzlinderung, Verminderung der Sepsisgefahr und Beseitigung des typischen ublen Geruchs von vereiterten Tumoren. Die Kopf-Hals-Karzinome eignen sich auch als Modelltumor zur Entwicklung von kurativen Konzepten der Plasmatumortherapie. Als Nebeneffekt der Dekontamination ist regelmasig eine klinisch erkennbare, morphologische Veranderung der CAP-behandelten Tumoroberflache zu beobachten, auf der es zur Tumorschrumpfung kommt, zum Stopp des Wachstums, zur verstarkten Durchblutung oder zum Biofilmverlust. Eine Klassifikation der morphologischen Tumorveranderungen unter Einwirkung von CAP unterstutzt die strukturierte weitere Forschung auf dem Weg zu einer kurativen Plasmatumortherapie.