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Photodynamic therapy in the head and neck
Örebro University, School of Health and Medical Sciences, Örebro University, Sweden.
2014 (English)Doctoral thesis, comprehensive summary (Other academic)Alternative title
Fotokemisk behandling av tumörer inom huvud- och halsområdet (Swedish)
Abstract [en]

Photodynamic therapy, PDT, is a method to diagnose and treat cancer. In PDT a sensitizer is administered to the patient and this sensitizer is accumulated in tumors. If the sensitizer-containing tumor is subjected to a laser of a specific wavelength the tumor is fluorescing allowing diagnostics. If other wavelengths are used a process involving reactive oxygen species and singlet oxygen is started and the tumor cells are killed. This process thus requires oxygen as well.

This thesis investigates how UV-induced damage of the skin and different physiological factors of the skin influences the uptake of 5- aminolevulinic acid, ALA, and its conversion to the active sensitizer protoporphyrin IX, PpIX. It shows that UV-induced damage affects both the uptake and production of PpIX. UV-induced damage lowers the PpIX produced after ALA application both if the damage is acute and in chronically UV-affected skin.

The PpIX production differs inter and intra individually. When looking how different physiological factors affect the PpIX production after topically applied ALA the thesis shows that an increase of temperature increases the production. No correlation between the formation of PpIX and the density of hair follicles was found and a weak correlation was seen comparing the epidermal and total dermal thickness and PpIX production

The thesis also shows how PDT is used in treating laryngeal malignancies. It shows that it is possible to cure laryngeal tumors (both squamous cell carcinomas and sarcomas) using PDT primarily, and that the cure rate as well as outcome of voice and patient safety is comparable to the conventional treatment modalities.

PDT can also be used as a function and organ sparing treatment for recurring laryngeal cancers, both squamous cell carcinomas and sarcomas.

Place, publisher, year, edition, pages
Örebro: Örebro university , 2014. , p. 74
Series
Örebro Studies in Medicine, ISSN 1652-4063 ; 110
Keywords [en]
Photo Dynamic Therapy, Cancer, Skin, Larynx, 5-ALA, UVradiation, sarcoma, squamous cell carcinoma, porfimer sodium, temoporfin, voice
National Category
Surgery
Research subject
Surgery
Identifiers
URN: urn:nbn:se:oru:diva-35953ISBN: 978-91-7529-039-3 (print)OAI: oai:DiVA.org:oru-35953DiVA, id: diva2:737767
Public defence
2014-09-19, Universitetssjukhuset, B-hus aulan, Södra Grev Rosengatan, Örebro, 09:00 (Swedish)
Opponent
Supervisors
Available from: 2014-08-14 Created: 2014-08-14 Last updated: 2017-10-17Bibliographically approved
List of papers
1. The influence of UV exposure on 5-aminolevulinic acid-induced protoporphyrin IX production in skin
Open this publication in new window or tab >>The influence of UV exposure on 5-aminolevulinic acid-induced protoporphyrin IX production in skin
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2001 (English)In: Photochemistry and Photobiology, ISSN 0031-8655, E-ISSN 1751-1097, Vol. 74, no 6, p. 825-828Article in journal (Refereed) Published
Abstract [en]

The skin of nude mice was exposed to erythemogenic doses of UV radiation, which resulted in erythema with edema. An ointment containing 5-aminolevulinic acid (ALA) was topically applied on mouse and human skin. Differences in the kinetics of protoporphyrin accumulation were investigated in normal and UV-exposed skin. At 24 and 48 h after UV exposure, skin produced significantly less protoporphyrin IX (PpIX) than skin unexposed to UV. Human skin on body sites frequently exposed to solar radiation (the lower arm) also produced less PpIX than skin exposed more rarely to the sun (the upper arm). It is concluded that UV radiation introduces persisting changes in the skin, relevant to its capability of producing PpIX from ALA. The observed differences in ALA-induced PpIX fluorescence may be the result of altered penetration of ALA through the stratum corneum or altered metabolizing ability of normal and UV-exposed skin (or both).

National Category
Medical Biotechnology (with a focus on Cell Biology (including Stem Cell Biology), Molecular Biology, Microbiology, Biochemistry or Biopharmacy)
Research subject
Molecular Cellbiology; Microbiology
Identifiers
urn:nbn:se:oru:diva-38179 (URN)10.1562/0031-8655(2001)0740825TIOUEO2.0.CO2 (DOI)000172863800012 ()11783939 (PubMedID)2-s2.0-0035790603 (Scopus ID)
Note

The present work was supported by the Research Foundation of the Norwegian Radium Hospital and by the Örebro Medical Center Hospital. The authors are thankful to Even Angell-Petersen and Saulius Bagdonas for their help during the experiment.

Available from: 2014-10-27 Created: 2014-10-27 Last updated: 2017-12-05Bibliographically approved
2. Influence of physiological parameters on the production of protoporphyrin IX in human skin by topical application of 5-aminolevulinic acid and its hexylester
Open this publication in new window or tab >>Influence of physiological parameters on the production of protoporphyrin IX in human skin by topical application of 5-aminolevulinic acid and its hexylester
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2006 (English)In: Journal of Medical Sciences, ISSN 1682-4474, E-ISSN 1812-5727, Vol. 6, no 4, p. 546-553Article in journal (Refereed) Published
Abstract [en]

Formation of protoporphyrin IX (PpIX) after topical application of 5-aminolevulinic acid (ALA) and its hexylester derivative (ALA-Hex) was studied on healthy human skin. Temperature, density of hair follicles, epidermal and skin thickness were measured on the application sites. The skin temperature was found to be the strongest determinant for PpIX formation. The PpIX fluorescence increase was about 25% per degree Celsius. Formation of PpIX was found to be independent of the density of hair follicles. A weak correlation was found between the PpIX fluorescence and the thickness of epidermis and skin. Sun exposure seems to reduce the production of PpIX slightly.

Place, publisher, year, edition, pages
A N S I Network, 2006
Keywords
5-aminolevulinic acid esters, Epidermal thickness, Fluorescence, Hair follicles, Skin physiology, Skin thickness, Spectroscopy, Temperature, aminolevulinic acid, aminolevulinic acid hexyl ester, protoporphyrin, adult, article, controlled study, correlation analysis, density, epidermis, fluorescence analysis, hair follicle, human, human experiment, male, normal human, ointment, protein synthesis, skin temperature, skinfold thickness, sun exposure, volunteer
National Category
Medical Biotechnology (with a focus on Cell Biology (including Stem Cell Biology), Molecular Biology, Microbiology, Biochemistry or Biopharmacy)
Research subject
Microbiology; Molecular Cellbiology
Identifiers
urn:nbn:se:oru:diva-38183 (URN)10.3923/jms.2006.546.553 (DOI)- ()- (PubMedID)2-s2.0-33750387149 (Scopus ID)
Available from: 2014-10-27 Created: 2014-10-27 Last updated: 2018-02-20Bibliographically approved
3. Outcome of primary treatment of early laryngeal malignancies using photodynamic therapy
Open this publication in new window or tab >>Outcome of primary treatment of early laryngeal malignancies using photodynamic therapy
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2014 (English)In: Acta Oto-Laryngologica, ISSN 0001-6489, E-ISSN 1651-2251, Vol. 134, no 8, p. 852-858Article in journal (Refereed) Published
Abstract [en]

Conclusion: Photodynamic therapy (PDT) is a viable and safe option for early laryngeal cancer that would be less suitably treated with radiation or trans-oral laser surgery (TLS). The cure rates with PDT appear to be comparable to those of conventional therapy, and the voice outcomes are also comparable. In the case of many sarcomas, PDT appears to be an organ- and function-sparing therapy, although it is more costly than other treatments.

Objectives: The aim of this study was to show the results of PDT when it is used as a primary treatment of early laryngeal cancer. Methods: We studied the results of PDT when used as a primary treatment. We looked at survival, effect on tumor, side effects, voice, and costs.

Results: The follow-up period was a median of 59 months. Nine of 10 patients were cured of their laryngeal cancer. PDT alone cured seven patients. All four of the sarcomas were cured using temoporfin. Two of three tumors that involved the anterior commissure were cured using only interstitial illumination with PDT. No serious side effects were noted. The patient's voices were improved after treatment in 5 of 10 cases, and none had a worsened voice.

Keywords
Cancer, larynx, PDT, sarcoma, squamous cell carcinoma, porfimer sodium, temoporfin, voice
National Category
Otorhinolaryngology
Research subject
Oto-Rhino-Laryngology
Identifiers
urn:nbn:se:oru:diva-36374 (URN)10.3109/00016489.2014.906748 (DOI)000340137200013 ()24856450 (PubMedID)2-s2.0-84904327200 (Scopus ID)
Available from: 2014-09-03 Created: 2014-09-03 Last updated: 2018-06-09Bibliographically approved
4. Outcome of treatment of recurring laryngeal malignancies using photodynamic therapy
Open this publication in new window or tab >>Outcome of treatment of recurring laryngeal malignancies using photodynamic therapy
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(English)Manuscript (preprint) (Other academic)
National Category
Cancer and Oncology
Research subject
Oncology
Identifiers
urn:nbn:se:oru:diva-38185 (URN)
Available from: 2014-10-27 Created: 2014-10-27 Last updated: 2017-10-17Bibliographically approved

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