Reflectance confocal microscopy allows in vivo real‐time noninvasive assessment of the outcome of methyl aminolaevulinate photodynamic therapy of basal cell carcinoma

Background Photodynamic therapy (PDT) with methyl aminolaevulinate (MAL) is an approved noninvasive treatment option for basal cell carcinoma (BCC). In vivo reflectance confocal microscopy (RCM) is a noninvasive imaging technique that has proved useful for in vivo real‐time cytomorphological analysis of BCC cells infiltrating the epidermis. Objectives To investigate the use of in vivo RCM to assess the persistence of BCC cells surviving MAL‐PDT. Methods In vivo RCM images of 20 biopsy‐proven BCCs were taken before patients underwent a treatment cycle with MAL‐PDT. Follow‐up after 3 months was performed using clinical examination, RCM and conventional dermoscopy. Treated areas also underwent a targeted 3‐mm punch biopsy for standard haematoxylin and eosin histology stain to establish the clinical and instrumental correlation of the treatment outcome. Results Three months after PDT, clinical examination established that two out of 20 BCCs were persistent; dermoscopy found three out of 20 residual BCCs, but RCM showed that one of these lesions was a false positive, and showed persistent BCC foci in five out of 20 lesions. Histological analysis of targeted biopsies confirmed these results. Conclusions RCM provided noninvasive, early detection of incipient recurrences of BCC after MAL‐PDT. RCM findings steered targeted biopsies and surgical removal, or a new MAL‐PDT, of these subclinical recurrences with minimal invasiveness.     

Facial Basal cell carcinomas recurring after photodynamic therapy: a retrospective analysis of histological subtypes

Background: Photodynamic therapy (PDT) is an established treatment for basal cell carcinomas (BCCs). Although recurrences are sometime observed, their histological patterns have never been specifically studied or compared with the one of the initial tumor. Objective: To compare the histopathological aggressiveness of BCCs recurring after PDT with that of the primary tumors. Methods: The study population included 12 patients with 16 post PDT recurrent BCCs. Outcome measures were proportion of histologically aggressive subtypes in BCC recurrences vs. primary tumor. Results: 62.5% of recurrent BCCs displayed a transition from a non-aggressive to an aggressive subtype. Conclusions: Post PDT recurrences appear to display an increased histological aggressiveness, although the latter may reflect the natural course of tumor progression. Despite the presence of potential biases, our study raises the possibility that PDT favors the selection of more aggressive tumor cells. Better systematic large-scale follow-up studies are required to assess the exact frequency and histological types of BCC recurrences after PDT.     

Photodynamic therapy for basal cell carcinoma: clinical and pathological determinants of response

Background Photodynamic therapy (PDT) is increasingly used in the treatment of basal cell carcinoma (BCC). However, scant information is available about the impact of both patient‐ and lesion‐related characteristics on the effectiveness of therapy. Therefore, on the basis of the current data, it is difficult to draw clear‐cut indications to use PDT for treatment of BCC in clinical practice. Objective To investigate the clinical and pathological determinants of response of BCC to PDT with methylaminolevulinate (MAL) and red light. Methods The clinical and pathological characteristics of 194 BCCs in 135 patients, treated with MAL‐PDT, were evaluated. Lesions were treated with MAL‐PDT according to established methods and the response was assessed by clinical follow‐up of the patients. Results Complete response to PDT was 62%, with a better response for superficial BCC (95/116, 82%) than nodular BCC (26/78, 33%). When determinants of response were analysed, the nodular type and the location on the limbs emerged as significant clinical predictors of failure. Among the pathological characteristics, the nodular and infiltrative histotypes, as well as ulceration and tumour thickness were associated with a lower response to therapy. Patients’ age and gender, as well as the size of the lesions, were not found to be significant predictors. Conclusions Optimization of PDT procedure for BCC requires a careful selection of the lesions. In particular, superficial BCCs, preferentially located on the trunk, show the best therapeutic response.     

Topical photodynamic therapy significantly reduces epidermal Langerhans cells during clinical treatment of basal cell carcinoma

Background Topical photodynamic therapy (PDT) is a widely applied treatment for basal cell carcinoma (BCC). PDT‐induced immunosuppression leading to reduced antitumour immune responses may be a factor in treatment failure. Objectives To examine the impact of topical PDT on leucocyte trafficking following clinical treatment of BCC. Methods Superficial BCCs in eight white caucasian patients were treated with methyl aminolaevulinate (MAL)‐PDT. Biopsies for immunohistochemical assessment were taken from BCCs pre‐PDT, 1 h and 24 h post‐PDT and from untreated healthy skin. Results Treatment of BCC with MAL‐PDT produced a rapid neutrophil infiltration, commencing by 1 h and significantly increased at 24 h post‐PDT (P < 0·05 compared with baseline). An associated increase in the number of blood vessels expressing E‐selectin was observed at 1 h and 24 h post‐PDT (both P < 0·05 compared with baseline). In contrast, the number of epidermal Langerhans cells fell sharply by 1 h post‐PDT, and remained significantly reduced at 24 h post‐PDT (both P < 0·05 compared with baseline). Conclusions Reduction of Langerhans cells during clinical treatment of BCC might potentially impact negatively on antitumour responses through reduced activation of tumour‐specific effector cells. Investigation of modified PDT protocols with the aim to minimize immunosuppressive effects while maintaining antitumour efficacy is warranted.     

Pulsed ultrasound measurements of depth and regression of basal cell carcinomas after photodynamic therapy: relationship to probability of 1-year local control

BACKGROUND: The regression of clinical basal cell carcinoma (BCC) after photodynamic therapy (PDT) is poorly understood, but is potentially important when, as is increasingly the case, a second treatment is contemplated. High-frequency pulsed ultrasound provides noninvasive information on skin and lesion thickness. OBJECTIVES: To relate pulsed ultrasound measurements before and after PDT to the probability of local control of BCC by PDT. METHODS: Skin thickness and lesion thickness were measured by 20-MHz pulsed ultrasound in 181 patients diagnosed as having BCC. Maximal lesion thickness was determined by repeatedly sampling the BCCs. Measurements were made immediately prior to PDT with aminolaevulinic acid plus 630 nm visible light, and then at 1, 6 and 12 months. RESULTS: Skin thickness in individual patients did not vary with time in this study (mean +/- SD 2.3 +/- 0.6 mm; P = 0.8). In contrast, BCC mean +/- SD maximal thickness 4-6 weeks after PDT was significantly smaller than pretreatment (0.6 +/- 0.8 mm vs. 1.3 +/- 0.8 mm; P < 0.001). The overall probability of 1-year local control fell from 85% when only BCCs 相似文献   

Non‐invasive management of non‐melanoma skin cancer in patients with cancer predisposition genodermatosis: a role for confocal microscopy and photodynamic therapy

Background Patients with genodermatosis such as Gorlin syndrome (GS) and Xeroderma pigmentosum (XP) require a close follow‐up for early diagnosis and treatment of skin cancer. We aimed to evaluate the efficacy of methyl‐aminolevulinate (MAL) photodynamic therapy (PDT) in basal cell carcinomas (BCCs) from patients with GS and XP, and to determine the utility of reflectance confocal microscopy (RCM) in the diagnosis and the evaluation of therapeutic response. Patients and methods We included four patients with GS and two siblings with XP. Single or multiple lesions in localized areas were treated with 1–3 cycles of MAL PDT. RCM was performed before and 3 months after the treatment in target lesions in all the patients. Patients were followed up for 3 years. Results In XP patients, we treated 13 pigmented BCCs on the face. All the lesions responded to the treatment and six lesions showed a complete clinical clearing. In GS patients, facial or trunk areas with multiple BCCs were treated (up to 200). Complete clinical remission was obtained in 25–67% of the lesions. Some nodular and pigmented lesions failed to achieve a complete remission. RCM could identify already described confocal features for BCC. Tumour remissions could be assessed by this technique. Conclusions Methyl‐aminolevulinate PDT may be useful for the treatment of superficial BCC in GS and XP. In some nodular lesions, PDT may complement surgery reducing tumour size. RCM may be regarded in the future as a complementary technique in BCC for the diagnosis and post‐treatment assessment to non‐invasive therapeutic modalities.     

Basal cell carcinoma in a series of renal transplant recipients: epidemiology and clinicopathologic features

Background Basal cell carcinoma (BCC) is the most common malignancy among Caucasians worldwide. The risk of BCC is 10–16 times higher among immunosuppressed transplant recipients compared with the general population. Objective To analyze the incidence, clinical presentation, histologic features, treatment and recurrence rate of BCC in a cohort of 69 renal transplant recipients (RTRs; 53 male). Methods Retrospective population‐based cohort study of immunosuppressed RTRs. Results Ten of 69 patients (14.5%, five male) developed a total of 17 BCCs, mostly on the head. Mean age at first diagnosis of BCC was 65.5 ± 8.5 years, and latency between kidney transplantation and diagnosis of the first BCC was 11.1 ± 6.3 years (mean ± SD). The risk of female RTRs to develop BCCs appeared to be three times higher than the risk of male RTRs, and female RTRs developed BCCs earlier after transplantation. Nodular BCC was the most common histologic subtype. Most BCCs in these RTRs were treated by complete surgical excision. Recurrence after surgical excision was observed in one of the 10 patients (10%). Conclusion Our results suggest female RTRs to be at higher risk to develop cutaneous BCCs than male RTRs. There are no differences in localization and clinicopathologic presentation of BCCs developing in RTRs compared with immunocompetent patients. Therefore, BCCs in RTRs do not require different treatment than in other patient groups. As patients tend to develop a second BCC, close follow‐up is mandatory.     

Photodynamic therapy with topical methyl aminolaevulinate for 'difficult-to-treat' basal cell carcinoma

BACKGROUND: Basal cell carcinoma (BCC) may be difficult to treat by conventional means, particularly if the lesions are large or located in the mid-face (H-zone). Photodynamic therapy (PDT) using topical methyl aminolaevulinate (MAL) may be a good noninvasive option for these patients. OBJECTIVES: To investigate the efficacy and safety of PDT using MAL for BCCs defined as 'difficult to treat', i.e. large lesions, in the H-zone, or in patients at high risk of surgical complications. METHODS: This was a prospective, multicentre, noncomparative study. Patients were assessed 3, 12 and 24 months after the last PDT treatment. One hundred and two patients with 'difficult-to-treat' BCC were treated with MAL PDT, using 160 mg g(-1) cream and 75 J cm(-2) red light (570-670 nm), after lesion preparation and 3 h of cream exposure. Results Ninety-five patients with 148 lesions were included in the per protocol analysis. The histologically confirmed lesion complete response rate at 3 months was 89% (131 of 148). At 12 months, 10 lesions had reappeared, and therefore the cumulative treatment failure rate was 18% (27 of 148). At 24 months, an additional nine lesions had reappeared, resulting in a cumulative treatment failure rate of 24% (36 of 148). The estimated sustained lesion complete response rate (assessed using a time-to-event approach) was 90% at 3 months, 84% at 12 months and 78% at 24 months. Overall cosmetic outcome was judged as excellent or good in 79% and 84% of the patients at 12 and 24 months, respectively. Follow-up is continuing for up to 5 years. CONCLUSIONS: MAL PDT is an attractive option for 'difficult-to-treat' BCC. Because of the excellent cosmetic results, the treatment is particularly well suited for lesions that would otherwise require extensive surgical procedures.     

Bowen's disease, solar keratoses and superficial basal cell carcinomas treated by photodynamic therapy using a large-field incoherent light source

BACKGROUND: Photodynamic therapy (PDT) has not yet been demonstrated to be superior to conventional treatment in the treatment of superficial skin cancers and premalignant skin conditions. A limitation for PDT is the absence to date of a light source suitable for the treatment of larger lesions or 'field changes' where several lesions are present on one anatomical site. OBJECTIVES: To investigate the safety and efficacy of a large field light source, the Waldmann PDT 1200, in the treatment of Bowen's disease (BD), superficial basal cell carcinomas (BCCs) and solar keratoses (SKs). METHODS: After application of 5-aminolaevulinic acid for 4-6 h, each lesion was irradiated with 105 J cm-2 of incoherent red light centred on 640 nm. Eighty-eight patients with 239 lesions were recruited. RESULTS: Within two treatments, 88% of BD lesions, 95% of BCCs and 99% of SKs showed complete clinical clearance. At 12 months the complete response rates were 69% for BD, 82% for BCC and 72% for SK. CONCLUSIONS: This study confirms that PDT is a useful treatment and that selected superficial BCCs and SKs respond well to PDT. The PDT 1200 light source proved capable of treating multiple lesions amounting to a 'field change' and also lesions up to 10 cm in diameter within an acceptable treatment time. Thus far, PDT has failed to become established as a routine treatment for small premalignant and malignant skin lesions as it has not proved superior to simple cheaper conventional therapies such as cryotherapy, curettage and cautery, topical chemotherapy with 5-fluorouracil, or surgery. However, PDT has become established as a treatment for selected cases in some centres. This study suggests a role for PDT in the treatment of large premalignancies, superficial BCCs and field change where existing treatments may be problematic.     

Photodynamic therapy for actinic keratosis in organ transplant patients

Background The incidence of actinic keratoses (AK) and non‐melanoma skin cancer (NMSC) in organ transplant recipients (OTRs) is significantly higher than in immunocompetent patients. Rates of progression and recurrence following treatment are higher too, in part due to the effects of the immunosuppressant drugs. Conventional therapies for AK, using curettage, cryotherapy, surgical excision, topical therapies and photodynamic therapy (PDT), are often less effective, and may be inappropriate, for treating the greater numbers and extent of lesions in OTRs. Moreover, there are no specific protocols for treating this patient population that take into account the need for more frequent treatment and the increased pain associated with treating larger areas. Objectives Recently, a pan‐European group of dermatologists with expertise in this area met to share current best practice in PDT for the treatment of AK in OTRs. Methods The group identified areas where PDT currently is not meeting the needs of these patients and discussed how these gaps might be addressed. Results/Conclusions This position article summarizes those discussions and makes recommendations concerning a standardized protocol for treating OTRs, for a large randomized controlled trial to provide robust data on safety, efficacy and optimal pain control, and to provide pharmaco‐economics data that can be used to support extended reimbursement in this patient group. The authors also recommend a second clinical trial to further investigate induced immunosuppression with PDT in healthy volunteers.     

Multiple large surface photodynamic therapy sessions with topical methylaminolaevulinate in PTCH heterozygous mice

BACKGROUND: Photodynamic therapy (PDT) combines the administration of a photosensitizer with its subsequent activation by light of the appropriate wavelength. Methylaminolaevulinate (MAL) is a photosensitizer precursor, transformed by cells into protoporphyrin IX. The PTCH gene plays a central role in the genesis of basal cell carcinoma (BCC). The PTCH transgenic mouse develops microscopic BCCs when chronically exposed to ultraviolet (UV) or ionizing radiation. OBJECTIVES: The aim of this study was to explore the ability of multiple large surface MAL-PDT to prevent BCC, using the PTCH heterozygous mouse as a model. METHODS: Thirty-five mice were exposed to UV radiation for a total of 20 weeks. Group 1 (20 mice) was exposed only to UV whereas group 2 (15 mice) was exposed to UV and weekly to MAL-PDT. At 28 weeks the mice were killed and the skin of the back processed for standard histopathology. Assessment was blind and any slide showing the presence of BCC was counted as a single BCC. The number of mice in groups 1 and 2 showing BCC were compared using Fisher's exact test. RESULTS: Nineteen BCCs in nine mice from group 1 were found, but no BCCs in mice from group 2. The difference was statistically significant (P = 0.001). CONCLUSIONS: Weekly suberythematous PDT sessions with topical MAL were able to delay the development of microscopic BCCs in PTCH mice chronically exposed to UV radiation.     

Photodynamic therapy for large or multiple patches of Bowen disease and basal cell carcinoma

BACKGROUND: Photodynamic therapy (PDT) using topical delta-aminolevulinic acid (delta-ALA) is an effective treatment for Bowen disease and certain basal cell carcinomas (BCCs), but its place in clinical practice remains to be established. Patients with large and/or multiple lesions of Bowen disease or BCC can represent a considerable therapeutic challenge. We suggest that delta-ALA PDT may be of particular benefit in such patients. OBSERVATION: In an open study, 35 (88%) of 40 large patches of Bowen disease, all with a maximum diameter greater than 20 mm, cleared following 1 to 3 treatments of delta-ALA PDT, although 4 patches recurred within 12 months. delta-Aminolevulinic acid PDT was also used to treat 40 large BCCs, with an identical 88% initial clearance (after 1-3 treatments), with 4 recurrences within 34 months (range, 12-60 months). In 10 further patients with multiple (> or =3) patches of Bowen disease, 44 (98%) of 45 patches cleared following delta-ALA PDT, although 4 lesions recurred over 12 months. In 3 patients with multiple BCCs, PDT cleared 52 (90%) of 58 lesions, with 2 recurrences during 41 months (range, 12-52 months). Treatments were well tolerated, with only 5 patients with solitary large lesions requiring local anesthesia. CONCLUSIONS: delta-Aminolevulinic acid PDT is an effective tissue-sparing modality achieving good cosmesis. We propose that delta-ALA PDT be considered as a first-line therapy for large and/or multiple areas of Bowen disease and superficial BCCs.     

Methyl aminolevulinate-photodynamic therapy for basal cell carcinoma

Basal cell carcinomas (BCCs) are the most common malignant tumors of the skin. Treatment of BCCs should be chosen according to clinical type, tumor size, and location. Methyl aminolevulinate (MAL) photodynamic therapy (PDT) has the potential to become a therapy with equal effectiveness to classical therapeutic modalities with an excellent cosmesis, but without complications like scar formation, requirement for grafts, need of repetitive treatments over longer time periods, or pigmentary changes. MAL is licensed in Europe, Australia, New Zealand, and Brazil for the treatment of actinic keratoses, Bowen's disease, and nodular and superficial BCC. Conclusions are drawn from extensive studies in past years using MAL-PDT for both nodular and superficial BCCs.     

A follow-up study of recurrence and cosmesis in completely responding superficial and nodular basal cell carcinomas treated with methyl 5-aminolaevulinate-based photodynamic therapy alone and with prior curettage

BACKGROUND: Methyl 5-aminolaevulinate (mALA) is an ester derivative of 5-aminolaevulinic acid (ALA) with increased lipophilicity compared with ALA. OBJECTIVES: To assess long-term cure rate, cosmesis, recurrence rate and extent of fibrosis after mALA-based photodynamic therapy (PDT) of superficial and nodular basal cell carcinomas (BCCs) showing early complete response to treatment. METHODS: Of 350 BCCs treated, 310 responded completely. These were in 59 patients who were followed for 2-4 years (mean 35 months) after mALA-PDT. Nodular tumours were curetted before PDT, and mALA 160 mg g(-1) was applied to all tumours for 24 h or 3 h before illumination from a broad-band halogen light source with light doses from 50 to 200 J cm(-2). Fibrosis was assessed histologically in 23 biopsies. RESULTS: The overall cure rate for 350 BCCs, including non-responders and recurrences was 79%. Of 310 lesions, 277 (89%) remained in complete response, and the cosmetic outcome was excellent or good in 272 of the completely responding lesions (98%). Histological examination showed dermal fibrosis in one of 23 biopsies. CONCLUSIONS: We conclude that mALA-based PDT with prior curettage of nodular lesions is a promising new method for the treatment of BCC.     

Photodynamic therapy with delta-aminolaevulinic acid for nodular basal cell carcinomas using a prior debulking technique

The incidence of basal cell carcinomas (BCCs) is still increasing, and there is a demand for an easy, effective and selective non-invasive treatment such as topical photodynamic therapy (PDT). Twenty-three patients with 24 nodular BCCs were treated once with delta-aminolaevulinic acid (delta-ALA) PDT (100 mW cm(-2), 120 J/cm2) 3 weeks after prior debulking of the BCCs. Three months after PDT, all lesions were surgically excised and histopathologically evaluated for residual tumour. Twenty-two (92%) of the 24 nodular BCCs showed a complete response on clinical and histopathological examination. PDT for superficially abraded nodular BCCs with topically applied delta-ALA and the VersaLight as light source is an easy, effective and safe therapy, with excellent cosmetic results and no serious side-effects, in cases where non-surgical treatment of BCCs is indicated.     

Mohs' micrographic surgery for treatment of basal cell carcinoma of the face--results of a retrospective study and review of the literature

BACKGROUND: The incidence of skin cancer and especially basal cell carcinoma (BCC) has increased in the last decade and is still increasing. Many treatment modalities can be used to treat BCC; surgical excision is the most frequently used. Mohs' micrographic surgery (MMS) is an advanced excision technique which is often used to treat BCC in the U.S.A. In Europe it is practised less frequently. OBJECTIVE: The aim of this article was to evaluate the efficiency of MMS for the treatment of facial BCC. METHODS: In a retrospective study recurrence rates after the treatment of facial BCC by MMS were estimated by reviewing the records of all patients with BCCs (620 patients with 720 BCCs) treated by MMS in our department from April 1992 until December 1999. RESULTS: The 5-year recurrence rates estimated from this study were 3.2% for primary BCC and 6.7% for recurrent BCC. Prognostic factors for recurrence are: an aggressive histopathological subtype, more than four Mohs' stages, a large defect size and a recurrent BCC. CONCLUSION: Based on the fact that MMS provides the lowest recurrence rates, it is the treatment of first choice for primary facial BCCs with an aggressive histopathological subtype and for recurrent BCCs in the face.     

Treatment of Gorlin syndrome (nevoid basal cell carcinoma syndrome) with methylaminolevulinate photodynamic therapy in seven patients,including two children: interest of tumescent anesthesia for pain control in children

Objective To report our experience of methylaminolevulinate photodynamic therapy (MAL‐PDT) in the treatment of multiple basal cell carcinoma (BCC) in adults and children with Gorlin syndrome (GS). Design Report of cases. Setting University of Montpellier, Department of Dermatology. Patients Seven Gorlin patients (41 superficial or nodular carcinomas), including two children. Interventions Prior superficial curettage for superficial BBCs or debulking for nodular BCCs was systematically performed. Methylaminolevulinic acid was applied topically to lesions 3 h before illumination with 635 nm red light for 10 min (37 J/cm²). To prevent treatment discomfort, analgesics and/or cooling by sprayed water were most often provided, and occasionally 1% lidocaine local anesthesia. A ropivacaine‐lidocaine tumescent anesthesia was performed on the youngest patient. Main outcome measures The initial response rate; tolerance, particularly in children; cosmetic outcome. Results Overall clearance in patients was 60% after one session of MAL‐PDT and 78% after three sessions. Resolution of the lesions was accompanied by an excellent cosmetic outcome in all patients. Treatments were well tolerated in adults with moderate pain sensation during illumination. In a child, tumescent anesthesia assured excellent tolerance in all treatment stages. Conclusion We add our experience to previous articles that consider PDT as an interesting option in the treatment of GS. To our knowledge, this study is the first report of MAL‐PDT in GS children using tumescent anesthesia. Specific guidelines for adult and pediatric patients remain to be established.     

High and sustained efficacy after two sessions of topical 5-aminolaevulinic acid photodynamic therapy for basal cell carcinoma: a prospective, clinical and histological 10-year follow-up study

Background Prolonged follow‐up data on topical photodynamic therapy (PDT) in basal cell carcinoma (BCC) are necessary for a full evaluation of its effect and for comparison with conventional treatment methods. Objectives To assess 10‐year long‐term PDT efficacy in primary and recurrent BCC and to evaluate clinical and histopathological factors which may be associated with treatment failure. Methods We performed a longitudinal study on 60 histologically verified BCCs in 44 patients treated with curettage and one or two sessions of dimethylsulphoxide (DMSO)‐supported topical 5‐aminolaevulinic acid (ALA)‐based PDT. Treated lesions were investigated by clinical and histopathological examination at regular intervals. The main outcomes were 10‐year lesion complete response rate using a time‐to‐event analysis, histological treatment failure and cosmesis. Results Overall complete response rate for all lesions was 75% (95% confidence interval 64–87%); 60% after one and 87% after two treatment sessions. The response rate was 78% for primary lesions; 63% after one and 90% after two sessions. The cosmetic outcome was rated as good or excellent in 91–100% of evaluated cases. Treatment failure was documented in 15 (25%) of 60 lesions; clinical investigation identified 14 of them. All failures were noted within 3 years of treatment. Male gender, recurrent tumour and one treatment session were factors significantly associated with treatment failure. The only lesion larger than 2·0 cm relapsed. Conclusions Two sessions of DMSO‐supported topical ALA‐PDT and curettage can provide long‐term effective treatment results with favourable cosmetic outcome in primary, small BCC.     

Giant and large basal cell carcinoma treated with topical photodynamic therapy

Basal cell carcinoma (BCC) is the most common cancer affecting Caucasians and, due to its large size or to the poor condition of the patient, it can be difficult to treat it with conventional therapies: in these cases photodynamic therapy with methyl aminolevulinate (MAL-PDT) may represent a good option. A retrospective non-comparative follow-up study was performed to test the response of giant and large BCC to MAL-PDT. Twelve patients with 14 giant BCC (> or = 5 cm) and 5 patients with 5 large BCC (4-5 cm) were treated with MAL-PDT; they were evaluated 6 months after the end of the treatment to define the initial cure rate, and then at 12 and 36 months for the follow-up. At 6 months the initial cure rate for the 19 BCCs was 95% and at 36 months the overall long-term cure rate was 66%. The follow-up will last up to 5 years. MAL-PDT is a valid option for the treatment of giant and large BCC.     

Efficacy of imiquimod for the expression of Bcl-2, Ki67, p53 and basal cell carcinoma apoptosis

BACKGROUND: Imiquimod is a modifier of the immune response that has been proven to be an effective treatment for basal cell carcinoma (BCC). However, its mechanism of action is still unknown. OBJECTIVES: To determine whether imiquimod modifies the expression of proteins such as Bcl-2, Ki67, p53 and the BCC apoptotic index. PATIENTS AND METHODS: Thirty caucasian patients with primary BCCs larger than 8 mm in diameter were included in a double-blind randomized clinical and immunohistochemical study which was designed in a reference university hospital. The 30 BCCs were randomized in two treatment arms between September 2001 and February 2002. Twenty-four BCCs were treated with imiquimod 5% cream and six BCCs with Aldara (3M Pharmaceuticals) excipient. Histological samples were obtained before treatment and on days 8 and 15 during the course of treatment. The BCC expression of Bcl-2, Ki67 and p53 was determined in paraffin samples and the apoptotic index of the BCC was studied using the TUNEL technique (terminal deoxynucleotidyl transferase-mediated deoxyuridine triphosphate biotin nick end labelling) in frozen samples. All variables were evaluated quantitatively in fields with a magnification x 400. RESULTS: The BCCs treated with imiquimod showed a decrease in the expression of Bcl-2 (88.7% before treatment, 61.4% day 15, P = 0.01) and an increase in the apoptotic index (0.53% before treatment, 1.66% day 15, P = 0.002), which were not observed in the BCCs treated with the excipient. Ki67 and p53 did not show significant changes in any group. CONCLUSIONS: Imiquimod reduces the expression of Bcl-2 in the BCC cells and increases the BCC apoptotic index.