MGMT gene promoter methylation correlates with tolerance of temozolomide treatment in melanoma but not with clinical outcome.

BACKGROUND: Despite limited clinical efficacy, treatment with dacarbazine or temozolomide (TMZ) remains the standard therapy for metastatic melanoma. In glioblastoma, promoter methylation of the counteracting DNA repair enzyme O(6)-methylguanine-DNA-methyltransferase (MGMT) correlates with survival of patients exposed to TMZ in combination with radiotherapy. For melanoma, data are limited and controversial. METHODS: Biopsy samples from 122 patients with metastatic melanoma being treated with TMZ in two multicenter studies of the Dermatologic Cooperative Oncology Group were investigated for MGMT promoter methylation. We used the COBRA (combined bisulphite restriction analysis) technique to determine aberrant methylation of CpG islands in small amounts of genomic DNA isolated from paraffin-embedded tissue sections. To detect aberrant methylation, bisulphite-treated DNA was amplified by PCR, enzyme restricted, and visualised by gel electrophoresis. RESULTS: Correlation with clinical data from 117 evaluable patients in a best-response evaluation indicated no statistically significant association between MGMT promoter methylation status and response. A methylated MGMT promoter was observed in 34.8% of responders and 23.4% of non-responders (P=0.29). In addition, no survival advantage for patients with a methylated MGMT promoter was detectable (P=0.79). Interestingly, we found a significant correlation between MGMT methylation and tolerance of therapy. Patients with a methylated MGMT promoter had more severe adverse events, requiring more TMZ dose reductions or discontinuations (P=0.007; OR 2.7 (95% CI: 1.32-5.7)). Analysis of MGMT promoter methylation comparing primaries and different metastases over the clinical course revealed no statistical difference (P=0.49). CONCLUSIONS: In advanced melanoma MGMT promoter, methylation correlates with tolerance of therapy, but not with clinical outcome.

Temozolomide plus pegylated interferon alfa-2b as first-line treatment for stage IV melanoma: a multicenter phase II trial of the Dermatologic Cooperative Oncology Group (DeCOG).

BACKGROUND: Combination of temozolomide (TMZ) with nonpegylated interferon alfa is associated with increased efficacy in terms of response rates compared with monotherapy. A multicenter phase II study was carried out to assess the activity and toxicity of TMZ plus pegylated interferon alfa-2b (peg-IFNalpha-2b), hypothesizing improved efficacy due to modified pharmacokinetic properties of the novel interferon (IFN) formulation. PATIENTS AND METHODS: In all, 124 patients with stage IV melanoma without prior chemotherapy and no cerebral metastases were treated with 100 mug peg-IFNalpha-2b s.c. per week and oral TMZ 200 mg/m(2) (days 1-5, every 28 days). Primary study end point was objective response, and secondary end points were overall and progression-free survival (PFS) and safety. RESULTS: In all, 116 patients were assessable for response: 2 (1.7%) had a complete response and 19 (16.4%) a partial response (overall response rate 18.1%). Of total, 25.0% achieved disease stabilization and 56.9% progressed. Overall survival was 9.4 months; PFS was 2.8 months. Grade 3/4 thrombocytopenia occurred in 20.7% and grade 3/4 leukopenia in 23.3%. CONCLUSIONS: The efficacy of TMZ plus peg-IFNalpha-2b in this large phase II study is moderate and comparable to published results of the combination of TMZ with non-peg-IFN. Likewise, the safety profile of peg-IFNalpha-2b seems to be similar to non-peg-IFN when combined with TMZ.

[Postoperative pyoderma gangrenosum of Cullen]. / Postoperatives Pyoderma gangraenosum Cullen.

The clinical picture in pyoderma gangrenosum varies but a typical medical history with resistance to antimicrobial treatment and worsening or first manifestation of disease because of surgical procedures are indications of this diagnosis. We describe the course of a woman patient who had a pyoderma gangrenosum for more than 1.5 years. After confirming the diagnosis an immunomodulating therapy was initiated until complete remission of the ulcers. Differential diagnosis and different clinicopathologic forms of pyoderma gangrenosum are discussed and an overview of the association with internal diseases is provided.

[Cutaneous botryomycosis. A rarely diagnosed bacterial infection of the skin]. / Kutane Botryomykose. Eine selten diagnostizierte bakterielle Infektion der Haut.

Botryomycosis is a rare chronic bacterial infection, which can involve the skin as well as internal organs. Clinically and histologically it resembles actinomycosis and deep fungal infections. The most common causative organisms described are Staphylococcus aureus, Escherichia coli and Pseudomonas aeruginosa, but the pathogenesis of botryomycosis is still poorly understood. A 16-year-old girl presented with multiple erythematous solid and partly purulent nodules which were extremely resistant to therapy. In this case we could diagnose a botryomycosis caused by Staphylococcus aureus.

[Cutaneous variant of Langerhans cell histiocytosis in early childhood]. / Kutane Varianten der Langerhans-Zell-Histiozytose im frühen Kindesalter.

The term Langerhans cell histiocytosis (LCH) has been endorsed to describe a group of rare entities, a highly variable spectrum of clinical presentations which are all characterized by localized or generalized proliferation of pathological Langerhans cells. We describe two infants with LCH who had very distinct cutaneous lesions. A two month-old infant developed discrete, disseminated red-brown nodules and plaques. In contrast, a second child at the age of nine months presented with brown aggregated scaling, crusted and ulcero-necrotic papules mainly restricted to the abdomen. In both patients, dermatohistopathology showed characteristic proliferation of pathologic Langerhans cells, and staging procedures revealed involvement of lung and bones. These two cases illustrate the marked variability of clinical presentation and disease course of LCH. In addition, important aspects and current concepts of LCH are discussed reviewing relevant and recent literature.

Er:YAG laser-assisted hair transplantation in cicatricial alopecia.

BACKGROUND: Autologous hair transplantation and its combination with flap or reduction procedures is a common surgical approach to cover defects in cicatricial alopecias. Due to the poor recipient conditions present in scar tissue, it is crucial to minimize the trauma exerted on implantation holes in order to achieve good transplantation results. OBJECTIVE: We sought to evaluate the "cold"-ablative properties of the Er:YAG laser for the generation of recipient holes in cicatricial alopecia. METHODS: Patients with cicatricial alopecia of diverse etiology were treated with Er:YAG laser-assisted hair transplantation. Mini- or micrografts were inserted into recipient holes ablated with a pulse energy of 900-1200 mJ and a spot size of 1.0-1.6 mm. RESULTS: A fluence of 80-120 J/cm2 and 8-12 pulses gave an almost ideal combination of minimal thermal damage and tissue ablation down to the subcutis. With an apparent mini- and micrograft survival of 95% we achieved good cosmetic results after two to five transplant sessions in all patients. CONCLUSION: The Er:YAG laser is a novel effective tool to ablate recipient holes for autologous hair transplantation in cicatricial alopecia.

Intralesional methotrexate as effective treatment in solitary giant keratoacanthoma of the lower lip.

When size and location of a keratoacanthoma along with patient-related factors argue against surgical treatment, intralesional methotrexate shows to be an effective, easy and inexpensive alternative. The case report presented validates this treatment modality.

PUVA-cream photochemotherapy for the treatment of localized scleroderma.

BACKGROUND: The efforts to treat localized scleroderma, including therapies with potentially hazardous side effects, are often unsatisfactory. Recently, PUVA-bath photochemotherapy has been proven highly effective in the treatment of localized scleroderma. Another form of topical PUVA therapy, 8-methoxypsoralen (8-MOP) containing cream or gel preparations, has been proven to be as effective as PUVA-bath therapy for palmoplantar dermatoses. OBJECTIVE: We sought to assess the efficacy of PUVA-cream photochemotherapy in patients with localized scleroderma. METHODS: Four patients with localized scleroderma were included in the study. Diagnosis was confirmed by 20 MHz ultrasound assessment as well as pretreatment skin biopsy specimens from lesional skin. PUVA-cream therapy was performed 4 times a week; all patients received 30 treatments. RESULTS: PUVA-cream photochemotherapy induced significant clinical improvement or clearance of localized scleroderma in all patients. Clearance was documented by clinical features as well as by 20 MHz ultrasound and histopathologic analysis. CONCLUSION: PUVA-cream phototherapy can be highly effective in patients with localized scleroderma even if previous therapy was unsuccessful.