common skin tumors like basal- and squamous - cell carcinoma present a serious problem in modern medicine .
it is confirmed that a variety of biological consequences such as increases in skin cancer or cataract may result from the increased uv exposure due to ozone depletion and atmospheric ozone hole .
uv radiation may also be produced by artificial sources , for example by quartz lamps frequently used in tanning parlors .
carcinogenesis of skin tumors is very often associated with chronic exposure to uv radiation , and frequent sunburns in childhood may lead to skin cancer in later age .
uv - a and uv - b radiation are responsible for photoaging , an accelerated aging of skin .
photoaging is characterized by loss of skin elasticity , roughness , deep wrinkles and pigmentations .
one of the most common malignant skin tumors is basal cell carcinoma ( bcc ) .
bcc most commonly occurs in middle - aged and elderly persons ( 5070 years old ) , mainly in caucasians who were exposed to sunlight radiation .
one of the most important biological features is low degree of malignancy and low rate of local growth ; however , over time it may contribute to local destruction of surrounding tissues , resulting in deep ulcerations .
bcc is mainly located on the skin exposed to uv light , especially on the head , neck and limbs .
these lesions more often recur after incomplete surgical treatment , but generally bcc has a good prognosis .
surgery , cryosurgery , electrodissection and co2 laser therapy are typical treatment methods [ 48 ] .
photodynamic therapy ( pdt ) comprises 2 main agents : light and a specific chemical compound called a photosensitizer .
photosensitizers have a high affinity to malignant cells and after absorption of energy from light they shift into an excited state .
a photosensitizer in the excited state causes photochemical reactions that lead to necrosis and apoptosis in pathological tissues . for many years pdt
was used to detect and to treat different lesions located in the skin and mucosa [ 913 ] .
photosensitizers show a high affinity to rapidly proliferating cells such as atypical and cancer cells . in the present study we used levulan as a natural precursor of porphyrins , which is metabolized in vivo into protoporphyrin ix ( pp ix ) .
since 1990 , aminolevulinic acid ( ala ) as a precursor of protoporphyrin ix was frequently used in local pdt . at present ,
ala is successfully applied in treatment of basal cell carcinoma , squamous cell carcinoma ( scc ) , solar keratosis , and urothelial cancer of the urinary bladder [ 1416 ] .
tau - like receptors of dendritic cells and macrophages under the influence of imiquimod respond with secretion of cytokines and chemokines such as interferon ( inf- , inf- ) , tnf- , and interleukins ( il-1 , il6 , and il-8 ) .
moreover , imiquimod stimulates langerhans cells to present antigens of transformed cells to lymphocytes t in regional lymph nodes . using natural mechanisms of the immune system
, aldara is approved for treating condyloma of the genital organs , solar keratosis and superficial form of basal cell carcinoma ( bcc ) .
uniquely , imiquimod abolishes immunosuppressive phenomena generated by exogenous factors that allow precancerous and cancerous lesions to propagate .
since the uses of imiquimod and pdt separately are well documented , we decided to combine both methods .
the aim of our study was to evaluate the effectiveness of local photodynamic therapy supplemented with topical application of aldara in treatment of basal cell carcinoma .
thirty - four patients ages 50 to 68 years were enrolled into the trial and underwent pdt treatment .
all these cases were previously treated using routine methods ( cryosurgery , laser therapy or surgical excision ) without satisfactory results .
lesions were located on the skin of the face ( nose , nasolabial sulcus , cheek , suborbital region ) with common bcc features : small , pearl - like nodules , with medium diameter of 0.5 cm , sometimes with erosions on the surface , with bleeding upon rubbing .
some lesions were located in the scar left after previous surgical treatment . a double - blind , placebo - controlled group was used .
patients were divided into 2 random groups : 10 patients were subjected to local pdt and placebo ( eucerin as vehicle cream ) , and 24 patients were subjected to pdt and imiquimod .
lesions after levulan application were protected from direct light exposure using an occlusion dressing which was removed before irradiation .
total time of irradiation was 30 minutes ( 215 minutes ) , wavelength was 63520 nm and total energy dose was 100 j / cm .
imiquimod ( aldara ) was topically applied in 24 patients 72 hours after irradiation and then applied again twice a week before sleep for 5 weeks .
ten patients received placebo ( vehicle only ) , which was applied in the same manner as imiquimod .
photodynamic diagnosis ( pdd ) was used to detect and visualize suspicious sites ( including cancer lesions ) that were not seen during the routine examination using white light .
it comprised local application of precursor , which , after an uptake by cancer cells and irradiation at 405 nm wavelength , emitted red fluorescence .
lesions after application of precursor were covered using occlusion dressing and after 2 hours irradiated for 34 minutes .
, cancer sites emitted red fluorescence and the tumor borders were found to spread beyond the area seen in the white light .
the size of lesions was estimated during routine examination in white light and during the pdd session .
the result of white light examination is shown in figure 1 , and the effect of the pdd session is shown in figure 2 . the size of lesion during the pdd session was found to be larger and more irregular than during the white light examination .
most patients during and after pdt complained of erythema and edema that persisted for several days .
patients complained of increasing symptoms such as burning sensation , itching , painful and large edema , and strong irritation of skin , with erosions , after each application of imiquimod .
our study reveals that combination of pdt and aldara may increase adverse effects of pdt , such as burning and edema .
due to previously mentioned reasons , 4 patients had to apply imiquimod only once a week .
these adverse effects disappeared after completion of therapy with imiquimod , and treated sites scabbed .
local adverse effects typical for imiquimod in the group of patients treated with pdt and placebo were not observed .
results of treatment are shown in table 1 . in the group of patients who were treated using pdt and placebo , 6 patients ( 60% )
bcc located on the nose increased after 6 months in 2 patients and recurrent tumor in the scar left after previous surgical excision was observed in 1 patient ( table 1 ) . in the group of patients
treated with pdt and imiquimod , 18 lesions ( 75% ) totally disappeared , and 6 lesions significantly diminished . in 1 patient small foci of previously excised bcc developed again in the scar after 10 months from the first control examination .
there is ample evidence supporting the dangers of uv radiation , especially within the context of skin cancer . the popularity of sunbathing and tanning parlors , and chronic sun exposure associated with professional activity results in an increase in a high morbidity rate of skin cancer in middle - aged people .
localization of lesions in the exposed parts of the body , especially on the face , is an important esthetic problem .
patients who are still professionally active expect to receive dermatology treatment that gives the best cosmetic effects .
the main method of skin cancer therapy for decades was surgical excision , very often associated with skin graft transplantation .
c02 laser and cryosurgery were added to the arsenal of methods used against skin cancer in recent years , but each of these methods leaves scarring .
unfortunately , skin cancers are very often irregular in shape and invade beyond the tumor borders that are clearly visible in routine examination .
this irregular shape and difficulties in complete removal of a lesion using standard methods may result in frequent recurrences .
surgical excision usually requires a margin 3 to 10 mm wide , but using dermoscopy - guided surgery this may be reduced to 2 mm .
. moreover , bccs located on the nose and around the orbit are usually more aggressive than tumors located in other sites .
therefore , it is very important to find an effective therapy that also yields good cosmetic effects .
pdt , as a local treatment method , was used for many years with success in cases of skin precancerous lesions and skin cancers .
levulan - based pdt ( levulan - pdt ) enables destruction of pathological lesions which are too small to be visible on routine examination .
pdt is also responsible for destruction of vessels and induction of immunological response against cancer cells .
one of many advantages of pdt is the lack of significant adverse effects ( besides burning and edema during pdt and within the next 24 hours ) .
other advantages are the possibility of repeating and healing without scarring and ease of use . a clear disadvantage of levulan - pdt is weak penetration of levulan into skin .
the other indication for application of levulan - pdt is a superficial lesion on the skin , such as solar keratosis .
our study showed that pdd enables estimation of the true shape of a lesion and allows the microfoci of the tumor to be found .
aldara is often used in dermatological lesions , such as warts , condyloma of reproductive organs and the superficial form of bcc or scc [ 2124 ] .
due to its effects on immunological memory , imiquimod may protect patients against recurrences of lesions , and it is used as an additional agent in cases of incomplete surgical excision .
other studies indicated that pdt in treatment of superficial bcc is effective in 7697% of cases [ 2830 ] .
pdt is generally more effective in treating superficial bcc than nodular bcc . in cases of the nodular form of bcc ,
co2 laser surgery and pdt appear to play a synergistic role in the treatment of that lesion . in this study
the bcc in that localization shows more aggressive growth with recurrences , therefore our previous efforts in bcc eradication resulted in only 60% complete responses .
this combined therapy enables induction of local natural immunological mechanisms . the 75% success rate obtained in the group treated with pdt and
moreover , the synergistic effect of aldara on immunological response cells seems to decrease the number of bcc recurrences ( 1 recurrence after 10 months and 1 after 15 months ; see table 1 ) .
the combination of local pdt and imiquimod results in higher efficiency of bcc treatment in cases of previous unsuccessful treatment such as surgery , cryosurgery and laser therapy .
there is one more important benefit from combined therapy  the high level of acceptance by treated patients .
lack of adverse effects after pdt and very good cosmetic outcomes positively influence the psychological condition of a patient .
patients confirmed their readiness to undergo repeated therapy in case of any recurrence , but they refused other treatment methods , such as routine surgical excision . at present , dermatological patients are younger than in the past and physical appearance is very important for such young people . in our opinion
the combination of pdt with local immunomodulator seems to be an effective method of treatment in such group of patients .
although this is a preliminary report , the presented modification of pdt seems to be reasonable and promising in treating basal - cell carcinoma .
 summarybackgroundcommon skin tumors like basal- and squamous - cell carcinoma present a serious problem in modern medicine . 
 exposure to ultraviolet solar radiation is the main cause of these lesions . since application of aldara and pdt 
 separately is well documented , we decided to use both methods together.the aim of our study was to evaluate the effectiveness of local photodynamic therapy supplemented with topical application of aldara in basal - cell carcinoma.material/methodsthirty-four patients ages 50 to 68 years were enrolled to the trial and underwent pdt treatment . 
 each case of bcc was histopathologically confirmed . 
 ten patients were subjected to local levulan-pdt and placebo ( eucerin as vehicle cream ) , and 24 patients were subjected to levulan-pdt and imiquimod . 
 photodynamic diagnosis ( pdd ) was used to detect and visualize suspicious foci ( including cancer lesions).resultsin the group of patients who were treated using levulan-pdt and placebo , 6 patients ( 60% ) were totally cured and 4 lesions ( 40% ) significantly decreased in size . in the group of patients treated with levulan-pdt and imiquimod , 
 18 lesions totally disappeared ( 75% ) , 6 lesions significantly diminished , and in 1 patient small foci of previously excised bcc developed again in scar tissue 10 month after the first control examination.conclusionscure was achieved without any scarring and with very good cosmetic effects . 
 although this is the preliminary report , the presented modification of pdt seems to be reasonable and promising in treating basal - cell carcinoma . 
Background
Material and Methods
Results
Discussion
Conclusions