Abstract: Background. Early detection of oral cancer improves the results of treatment. Fluorescence diagnostics (FD) helps to identify the real margins of malignant tumour. However, in some cases the artefactual fluorescence of healthy mucous appears. The aim of this study was to investigate the possibilities of fluorescence diagnostics of oral cancer as a more sensitive, effective and more specific method of FD. Materials and methods. A total of 84 patients with morphologically verified malignant tumours underwent fluorescence diganostics. They were grouped into three groups. The first group consisted of 20 patients with malignant recurrent oral cancer, who underwent systemic (intravenous) photosensitizer administration (2.5 mg/kg). After 24–48 h, visual fluorescence diagnostics and spectroscopic measurements were performed. The second group consisted of 60 patients with different malignant tumours except oral cancer. They also underwent systemic (intravenous) photosensitizer administration (2.5 mg/kg). After 24–48 h, visual fluorescence diagnostics and spectroscopic measurements were performed. The third group consisted of 7 patients with malignant recurrent morphologically verified oral cancer; they underwent I/a FD. A catheter was inserted selectively into the feeding artery of the tumour via the superficial temporal artery. Photofrin (10 mg) was injected via the catheter directly into the tumour. Immediately after injection, 1 h and 4 h after injection, the visualization of mucosal tissues of the hypopharyngeal and oropharyngeal regions was performed under illumination of λ = 405 ± 5 nm light. Spectroscopic investigations of malignant and healthy tissues were also performed. Besides, there was the fourth group which consisted of 30 healthy volunteers. They were provided no treatment. The visual fluorescence diagnostics and spectroscopic measurements of healthy mucosa were performed for these volunteers. Results. A specific pink fluorescence of malignant tissue was noted while illuminating a tumour with violet light. The margins of fluorescence usually coincided with those of a malignant tumour. In doubtful cases, biopsy and morphological examination of the tissue were performed. All malignant tumours, except melanoma, showed a specific pink fluorescence when illuminated with violet light, and no fluorescence was noted in normal mucosa. However, in some cases glow artefacts were observed. We identified these “glow artefacts” – a nonspecific lilac fluorescence – in the healthy mucosa of 20 patients (in 6 patients from the first group and in 14 from the second group). Usually, artefactual fluorescence was noted in the gums (in 18 patients from 20) and at the basis of the tongue (in 11 patients from 20). There was no artefactual fluorescence in 7 patients who underwent I/a FD. Conclusions. Fluorescence diagnostics is useful for early detection of primary and recurrent malignant oral tumours, except melanoma. However, an artefactual fluorescence in the gums or in the basis of the tongue can appear. I/a FD allows avoiding this artefactual fluorescence. Keywords: fluorescence diagnostics, oral cancer, intra-arterial

Abstract: Laima Bloznelytė-Plėšnienė1, 2, Daiva sendiulienė1, Jurgita Liutkevičiūtė-Navickienė1, Laimutė Rutkovskienė1, Valerijus Ostapenko1, Narimantas Evaldas Samalavičius1 1 Vilniaus universiteto Onkologijos institutas, Santariškių g. 1, LT-08406 Vilnius2 Klaipėdos universitetas, Herkaus Manto g. 84, LT-92294, KlaipėdaEl. paštas: pdt@mail.lt TikslasNustatyti sensibilizuotų navikų terapijos galimybes gydant išplitusį krūties vėžį. Ligoniai ir metodaiNuo 2001 m. 54 ligonėms išplitusiam krūties vėžiui gydyti taikyta sensibilizuotų navikų terapija (SNT). 53 ligonėms rastos dauginės metastazės. Metastazės smegenyse diagnozuotos 19 ligonių, kauluose – 29, kepenyse – 15, plaučiuose – 12, limfmazgiuose – 16, minkštuosiuose audiniuose – 13 ir odoje – 15 ligonių. Taikydami SNT į veną suleisdavome 2,5 mg/kg hematoporfirino darinio (HpD) ir jis po 24 val. selektyviai susikaupdavo navikiniame audinyje. Praėjus 24 val. po HpD suleidimo jam aktyvinti navikus apšviesdavome raudona 635 nm šviesa – tai vadinamoji fotosensibilizuotų navikų terapija (FDT), ir (arba) taikydavome radiosensibilizuotų navikų terapiją (RST) – praėjus 24, 48 bei 72 val. po HpD suleidimo naviką apšvitindavome 60Co skleidžiamais gama spinduliais 2 Gy doze. Suminė dozė – 6 Gy. RST taikėme visoms 54 ligonėms.FDT taikėme: 16 ligonių vietiškai krūtinės odoje ir poodyje išplitusiam vėžiui gydyti bei 1 ligonei metastazei akies tinklainėje gydyti. Visų odos ir poodžio navikų riboms patikslinti taikėme ir fotodinaminę diagnostiką. Praėjus 24–78 val. po HpD suleidimo, įtartinus odos plotus apšviesdavome violetine 405 nm šviesa. Navikinis audinys švytėdavo avietine spalva. RezultataiPritaikius SNT 54 ligonėms išplitusiam krūties vėžiui gydyti, 33 pacientėms per 7–10 dienų po RST labai pakilo Karnovskio indeksas, šešioms pacientėms visi navikai visiškai regresavo, 14 moterų visi gydyti navikai regresavo daugiau nei 50 %, ligos remisija truko ilgiau nei 6 mėn. Šešiolika ligonių navikų regresija buvo dalinė, 18 ligonių gydymas buvo neveiksmingas. SNT buvo ypač efektyvi krūties vėžio metastazėms smegenyse ir kauluose gydyti. Vienai ligonei po dviejų RST kursų visiškai išnyko visos trys metastazės galvos smegenyse. Šešioms ligonėms visos metastazės smegenyse regresavo daugiau nei 50 %, ligos remisija truko daugiau nei 6 mėnesius. Dauginių krūties vėžio metastazių smegenyse turinčių 19 ligonių vidutinis išgyvenamumas nuo metastazių smegenyse diagnozavimo buvo 12 mėnesių. Pritaikius RST 29 ligonėms dauginėms krūties vėžio metastazėms kauluose gydyti, 7 ligonėms gauta visiška visų dauginių kaulinių metastazių regresija. Ligos remisija (moterys buvo kliniškai sveikos) truko 95; 48; 21; 19; 12; 11 ir 4 mėn. nuo RST. IšvadosSensibilizuotų navikų terapija yra perspektyvus išplitusio krūties vėžio gydymo metodas. Šis metodas ypač veiksmingas gydant krūties vėžio metastazes galvos smegenyse ir kauluose. Tikslinga toliau tyrinėti šį gydymo metodą, siekiant jį modifikuoti pagal ligos išplitimą ir metastazių lokalizaciją. Reikšminiai žodžiai: išplitęs krūties vėžys, sensibilizuotų navikų terapija, hematoporfirino darinys. Sensitized treatment and diagnostics of advanced breast cancer Laima Bloznelytė-Plėšnienė1, 2, Daiva sendiulienė1, Jurgita Liutkevičiūtė-Navickienė1, Laimutė Rutkovskienė1, Valerijus Ostapenko1, Narimantas Evaldas Samalavičius1 1 Vilnius University, Institute of Oncology, Santariškių Str. 1, LT-08406 Vilnius, Lithuania2 Klaipėda University, Herkaus Manto Str. 84, LT-92294, Klaipėda, LithuaniaE-mail: pdt@mail.lt Background / objectiveThe current methodologies used in oncology are of quite limited possibilities. Therefore, there is a constant search for the new perspective treatment methods that could prolong the life of cancer patients and improve its qualitaty. One of such methods is sensitized tumour therapy based on quite selective porphyrin accumulation in tumours. This study presents our primary results in radiosensitized advanced breast cancer therapy using hematoporphyrin derivatives as photo-and radiosensitizers. Patients and methodsIn 2001–2010, a total of 54 female patients with advanced breast cancer underwent radiosensitized treatment (RST). All patients had undergone chemotherapy and / or radiotherapy and surgical treatment before RST. In all cases, any radical method of treatment was impossible. Multiplex metastatic lesions were established in 53 patients. Brain multiplex metastases were diagnosed in 19 patients and multiplex bone metastases in 29 patients. Lung metastatic lesions were found in 12 patients, liver in 15 patients, lymph node metastases in 16 patients. The hematoporphyrin derivative was injected intravenously; 24, 48 and 72 hours after injection of the sensitizer, the tumorus were irradiated with gamma rays from radioactive 60Co, 2 Gy at a time (6 Gy per course). In all cases when it was possible, patients undervent also photodynamic therapy. Tumours were irradiated with red 630 nm laser light. ResultsAs a result of RST, complete regression of all treated tumours was observed in 6 patients after two or more RST courses. A significant response – regression of more than 50% of all brain metastases and remission of the disease for over 6 months – was established in 14 patients. Partial response was observed in 16 patients with malignant brain tumours. For the rest of 18 patients the treatment was ineffective. The Karnofsky performance scale index increased immediately in 33 patients following RST treatment. RST was especially effective in the treatment of brain and bone metastatic lesions. As regards brain metastazes, in one patient all three brain metastatic lesions completely disappeared and there were no evidence of any recurrence in brain for 8 months. In 6 patients, regression of more than 50% of all brain metastases and remission of the disease for over 6 months was established. The median survival of 19 patients with multiplex brain metastases was 12 months from the moment of brain metastases detection. As regards bone metastazes, as a result of RST, all metastatic bone lesions completely disappeared in 7 patients. ConclusionRadiosensitized advanced metastatic breast cancer treatment is a hopeful method, especially when lesi ons involve the brain and bones. Keywords: advanced breast cancer, radiosensitized treatment, hematoporphyrin derivative.

Abstract: Background. Radiosensitizers are used in order to increase the efficacy of radiotherapy. Most of the presently known radiosensitizing agents have a poor selectivity and are not tumour-specific. Porphyrins have a selective uptake in tumour relative to the surrounding normal tissue. The aim of the present work was to test the capability of two photosensitizers – hematoporphyrin derivative (HpD) or temoporfin (mTHPC) – and gamma rays to produce some kind of selective inhibition of tumour cell proliferation. Materials and methods. Dark toxicity experiments were carried out using a sensitizer concentration range 0–50 μg/ml for HpD, or 0–5 μg/ml for mTHPC. For the radiosensitized treatment of rat C6 glioma cells, HpD was added at a final concentration of 1 μg/ml and mTHPC at a final concentration of 0.1 μg/ml. The irradiation with gamma rays was performed using doses ranging from 0 to 8 Gy. Cell survival was determined using the colony forming assay. Results. HpD (1 μg/ml) and mTHPC (0.1 μg/ml) were found to have no toxic effects on C6 glioma cells. A cytotoxic dose without drugs, inducing a reduction in colony survival by 20%, was achieved at 2 Gy and by 50% at 4 Gy. The radiosensitized treatment of cells with HpD resulted in a significant (p ≤ 0.05) decline in cell survival as compared with irradiation alone. For C6 treated with mTHPC, the results did not differ between the two groups (with and without the drug). Conclusions. The results of this study have shown that mTHPC (0.1 μg/ml) does not act as a radiosensitizer, whereas HpD can act, under certain conditions, as a tumour radiosensitizer. These findings suggest that HpD is a potential agent in combination with radiation therapy of malignant gliomas. Keywords: rat C6 glioma cells, radiosensitization, porphyrins, colony forming assay