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Treatment



Several different treatments are used in the management of basal cell carcinoma. Each method may be more or less useful for specific clinical situations.

Surgery


Surgical excision is a highly effective treatment for BCC allowing for histological examination of the excised tissue.
Mohs' micrographic surgery, a method using microscopic control to evaluate the extent of tumor invasion, has the highest cure rate of all surgical treatments. Morpheiform basal cell carcinomas, recurrent tumors, basal cell carcinomas larger than 2 cm in size as well as tumors situated on the ears, lips, nose and nasolabial folds are indications for treatment.

Curettage and electrodessication


Basal cell carcinoma can be scraped away with a curette. Afterwards, electrosurgery may be used to stop bleeding or to apply more damage to the area involved. The adequacy of treatment cannot be assessed immediately since the surgeon cannot visually detect the depth of microscopic tumor invasion. This method should be used only for superficial basal cell carcinomas or small, well defined lesions in non-critical sites..

Cryosurgery


Liquid nitrogen is used to either chill a cryoprobe continuously or to spray on a surface. Individual techniques vary considerably, some clinicians applying up to three freeze/thaw cycles. This technique allows the local destruction of tissue to quite a considerable and calculable depth. It is simple, and complications are rare. However, the successful treatment of basal cell carcinomas requires adequate freezing of the tumor and the margin all round it, which is not always accomplished. Curettage of the tumor immediately prior to cryosurgery may help to increase the cure rate. This method should be used only for superficial basal cell carcinomas or small, well defined lesions in non-critical sites.

Radiotherapy


Radiotherapy includes a range of treatments using different types of equipment. It is best suited for patients of advanced age and poor general health. Radiation therapy can be used to treat many types of basal cell carcinoma, even those overlying bone and cartilage. Very large tumors are often resistant, though, and require radiation doses that closely approach tissue tolerance. Recurrent BCC after a previous radiation therapy prove to be difficult when treated with the same method again.


Topical 5-fluorouracil (5FU)


5-fluorouracil is a cytostatic agent which inhibits several enzymes in tumor cells, through interaction with RNA. It is applied locally in a thin layer and the lesion is subsequently covered with a plastic film. The treatment is repeated daily until the lesion erodes. This therapy may be useful in the management of multiple superficial basal cell carcinomas on the trunk and lower limbs. It cannot be expected to eradicate invasive BCC's.


The technique
PDT is based on the coaction of a photosensitizer, often a porphyrin-derivative, with visible light and oxygen. The photosensitizer specifically accumulates in rapid growing cells (e.g. tumor cells) and is activated by irradiation with visible light. The tumor destruction is caused by the formation of cytotoxic efficient reactive oxygen species, in particular singlet oxygen.

There are several photosenitizer presently in use (porphyrins, porphines, phthalocyanines, etc.) but most of them are not ideal for dermatological indications since they have to be administered systemically and cause general photosensitivity in patients. The most frequent used substance for PDT in dermatology is 5-ALA (d-aminolevulinic acid) and its derivatives. 5-Ala works as a prodrug that is metabolized intracellularly into protoporphyrin IX (PpIX) - the actual photosensitizer. PpIX will, when activated by light, generate singlet oxygen which will cause death of the tumor cells. Besides PDT the photosensitizer can also be activated by Wood light leading to fluorescence of the targeted lesion. In this way tumor lesions can be detected by photo diagnosis (PD).

The use
The standardized procedure for the treatment of AK involves the application of 20% ALA or its ester in a solution or cream. emulsion. 5-ALA then penetrates the skin and is metabolized into PpIX. ALA-uptake is higher by dysplastic cells and PpIX is synthesized more specifically in abnormal cells leading to a higher concentration of PpIX in abnormal than in healthy cells. After an application time of several hours the lesion will be exposed to light of a certain wavelength and intensity.

For irradiation of the lesion there are now several non-coherent light sources in use which differ mainly by their emission spectrum (red light, blue light, green light) and their radiation area.

PDT is not only used for the treatment of actinic keratosis but also seems to be very promising in the treatment of superficial basal cell carcinoma. To penetrate deeper into the skin a red light is used to induce the phototoxic reaction.

Interferon alpha


Treatment of BCC with intralesional Interferon alpha-2 is essentially investigational. The application of this substance intralesionally thrice weekly for a duration of three weeks during a pilot study led to histological evidence of tumor clearance. Studies reported a treatment failure between 20 and 45% 3 months following treatment and a 19% recurrence rate at 1 year. It is an expensive, time-consuming therapy, and long term cure rates are not yet available.


Imiquimod
Imiquimod is a new immune response modifier that induces cytokines including interferons. Applied to basal cell carcinoma topically as a 5% cream during clinical trials, it has proven effective. A treatment duration of several weeks (up to 18 weeks) was necessary, though. Local skin irritation was the predominant adverse effect.



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