A Review of Topical Sirolimus for the Treatment of Facial Angiofibromas in Tuberous Sclerosis Complex.

OBJECTIVE: This article assesses the efficacy, safety, pharmacology, and clinical applications of topical sirolimus 0.2% gel for the treatment of tuberous sclerosis complex (TSC)-associated facial angiofibromas. DATA SOURCES: A review of the literature was conducted using the Medline (PubMed) and EMBASE databases using the keywords topical sirolimus, rapamycin, Hyftor, and tuberous sclerosis. STUDY SELECTION AND DATA EXTRACTION: Articles written in English and relevant to the topic were included. DATA SYNTHESIS: In the phase 2 trial, the mean improvement factor, a composite measure of improved tumor size and redness, was achieved in all patient groups (P < 0.001) with significant responses among the adult and pediatric subgroups at week 12. There were no serious adverse events recorded. In the phase 3 trial, 60% of participants responded to treatment in the sirolimus group compared with 0% in the placebo group with different response rates between the adult and pediatric subgroups at week 12. Sirolimus gel had no serious adverse events, and dry skin was the most common adverse reaction. Patients who had completed the 12-week trials were then enrolled in a long-term trial; angiofibromas had response rates of 78.2% to 0.2% sirolimus gel. RELEVANCE TO PATIENT CARE AND CLINICAL PRACTICE IN COMPARISON TO EXISTING DRUGS: Topical sirolimus 0.2% is a first-in-class, newly Food and Drug Administration (FDA)-approved, mammalian target of rapamycin (mTOR) inhibitor that is a promising and safe, noninvasive alternative to surgical procedures for TSC-associated angiofibromas. CONCLUSIONS: Topical sirolimus 0.2% gel is a moderately effective treatment for TSC-associated facial angiofibromas with an adequate safety profile.

Topical rapamycin in the treatment of facial angiofibromas in tuberous sclerosis: a systematic review based on evidence.

INTRODUCTION: facial angiofibromas of tuberous sclerosis are the most prevalent cutaneous manifestation, affecting 80% of patients, which cause facial lesions with negative psychosocial consequences. Newly, topical rapamycin has been established as an effective and safe therapy for this skin condition. PURPOSE: to analyze the available scientific evidence about the effectiveness and safety of topical sirolimus in the treatment of facial angiofibromas in tuberous sclerosis. METHODS: a literature search was conducted in PubMed and Cochrane. Effectiveness and safety were analyzed along with the main characteristics of each formulation in all included studies. RESULTS: thirty studies were included involving a total of 508 patients, developed in the last 20 years. Four randomized clinical trial, 17 case series and 9 single case reports were founded. Multiple topical rapamycin concentrations (0.003-1%) and formulations (gel, ointment, solution) were found in literature. Rapamycin demonstrated its effectiveness in all studies included, except for 5 patients in a 1 b study. Rapamycin was shown to be safe for the treatment of FA. CONCLUSIONS: Topical sirolimus can be considered an effective and safety option for the treatment of facial angiofibromas in tuberous sclerosis. However, further long-term studies need to establish an evidence-based therapeutic protocol.KEY MESSAGEUpdated review to date in topical rapamycin for facial angiofibromas, allowing support in therapeutic decisions.

Facial intramuscular lipoma occurrence following topical cosmetic injection with a mixture of basic fibroblast growth factor: A report of two cases.

Growth factors and cytokines control cell growth, proliferation and differentiation via a network of inter- and intracellular signalling pathways, and are involved in skin self-renewing and wound healing. In recent years, topical and injectable growth factors and cytokines have emerged as an intriguing therapeutic modality that can be harnessed for aesthetic purposes. However, very little data are available on their long-term safety and tolerability. In this report, we describe two cases of patients, who developed intramuscular lipoma of the chin following topical injection with a mixture of basic fibroblast growth factor as the main ingredients for chin augmentation. Biopsies in the two cases were performed at our department, and revealed intramuscular lipoma. Our report indicates that the topical injection of growth factors can lead to tumorigenesis, so health care providers need to be aware of its potential consequences.

Rapidly-growing squamous cell carcinoma shortly after treatment with ingenol mebutate for actinic keratoses: report of two cases.

Actinic keratoses (AKs) are defined as cutaneous areas of atypical squamous transformation that are regarded as an early step in the continuum of alterations leading from normal skin to invasive and metastatic squamous cell carcinoma (SCC). AKs are classified as precancerous lesions by some authors and in situ SCC by others. The rate of evolution of a given AK to an invasive SCC has been estimated as 0·075-0·096% per lesion per year. These rates are similar to those estimated for gynaecological intraepithelial neoplasia. We describe two cases of SCC with rapid onset that developed after the application of ingenol mebutate gel for the treatment of AKs.

Fast-growing cutaneous squamous cell carcinoma in a patient treated with vismodegib.

BACKGROUND: Vismodegib therapy achieves a breakthrough in patients with locally advanced basal cell carcinoma (BCC). Yet, long-term safety of hedgehog pathway inhibitors remains to be established, while drug resistance is becoming a new challenging issue. CASE REPORT: We report the case of a 90-year-old male initially referred for a locally advanced BCC of the nose. He had been previously treated by topical 5-fluorouracil for an adjacent microinvasive squamous cell carcinoma (SCC), with complete clinical response. Afterwards, vismodegib was initiated to treat his BCC. At week 16, both tumor and tumor ulceration obviously progressed. Palliative rhinectomy was performed. Histological examination found a deeply invasive SCC. CONCLUSION: Although our case must be interpreted with caution, a role of vismodegib as a promoter of cutaneous SCC should be considered, consistently with recently published evidence. Physicians should perform new biopsies whenever in doubt about new and/or progressive skin lesions in patients receiving hedgehog pathway inhibitors.

Multiple miliary osteoma cutis of the face after initiation of alendronate therapy for osteoporosis.

A 62-year-old Asian woman presented with multiple small, rock-hard papular lesions on her face (Figure). She had no previous history of acne vulgaris or cutaneous malignancy. She had been diagnosed with breast cancer in 1995 and was treated with left lumpectomy followed by combination chemotherapy consisting of cyclophosphamide, 5-fluorouracil, and methotrexate. In 1995, at age 50, she also began therapy with systemic alendronate to treat osteoporosis. Within 1 year, she noticed the development of asymptomatic indurated dermal papules on her cheeks. Topical treatment with 12% lactic acid lotion did not improve her condition. Clinical examination revealed numerous 1- to 2-mm, brown dermal nodules on the malar cheeks bilaterally. Normal laboratory data included complete blood cell count, alkaline phosphatase, serum calcium, and serum phosphate. A lesional punch biopsy from the left cheek revealed lamellar bone within the dermis. Correlation of the clinical presentation, laboratory data, and pathology established the diagnosis of multiple miliary osteoma cutis of the face.

[Multiple miliary osteomas of the face]. / Multiple miliare Osteome des Gesichts.

Osteoma cutis is a single or multiple ectope calcification with development of bony structures in the skin. We distinguish between primary and secondary ossification. Multiple miliary osteoma in the face has mostly been described secondary to preexisting acne vulgaris. We present a 62-year-old woman who developed multiple miliary osteoma in the face together with repeated doses of estrogen and discuss pathogenesis and therapeutic possibilities.

Occupationally related tumors in tar refinery workers.

BACKGROUND: The study comprised 606 workers with tar-induced dermatosis employed in a German tar refinery. During the period from 1946 to 1996 they were recognized as having an occupational disease. OBJECTIVE: The aim of this study was to characterize the histologic findings and the localization of the occupational dermatosis and to determine the latency period of the carcinomas from the beginning of exposure in the tar refinery to the first occurrence of malignant skin tumors. Furthermore, the study aimed to check whether other skin changes were frequently diagnosed in addition to known tar-induced tumors. METHODS: The data were collected retrospectively from the documents of the Employer's Liability Insurance Association. RESULTS: Surgical removal of 4754 skin tumors was documented up to the end of 1996 in the study. In 90% of cases the histologic diagnosis was confirmed. Among other conditions, this yielded 2490 precancerous stages, 380 squamous cell carcinomas, 218 basal cell carcinomas, and 182 keratoacanthomas. The skin tumors were found mainly in the facial area, as well as on the forearms and hands. Latency from the first exposure in the tar refinery until manifestation of tar-induced dermatosis covered a period of 57 years. CONCLUSION: In comparison to the general population, the ratio of squamous cell to basal cell carcinomas was shifted toward the squamous cell carcinomas (1.7:1). Sunlight is known to be a cofactor in the pathogenesis of keratosis, squamous cell carcinomas, and basal cell carcinomas. However, the difference in location of these tumors shows that the role sunlight plays in the pathogenesis of precancerous lesions and squamous cell carcinomas may be overvalued. The latency period from the beginning of exposure to the manifestation of squamous cell carcinomas could not be evaluated because of an intervention bias as a result of preventive excisions of precancerous lesions. The frequent occurrence of keratoacanthomas (in 18.7% of the workers) and the early age at which this disease became manifest relative to the general population (median, 55 years) indicate that employment in a tar refinery can primarily or secondarily cause keratoacanthomas.

The inhibition of DMBA-induced carcinogenesis by neoxanthin in hamster buccal pouch.

Neoxanthin, a major carotenoid pigment of spinach, is found in the Chloroplast membrane and has an unknown function in plants. Neoxanthin inhibited the production of superoxide anions in an artificial xanthine and xanthine oxidase system and depressed DNA synthesis in methylcholanthrene (MCA)-initiated C3H10T1/2 fibroblasts. in two-stage carcinogenesis experiments, neoxanthin at 0.2 micrograms/0.2 ml inhibited the formation of tumors that were induced sequentially by 7,12-dimethylbenz[a]anthracene (DMBA) and 12-O-tetradecanoylphorbol-13-acetate (TPA) in the buccal pouch of Syrian Golden hamsters. To assess the ongoing process of carcinogenesis, the activity of ornithine decarboxylase (ODC), required for cell proliferation, was analyzed. Neoxanthin inhibited the activity of ODC when animals were treated with neoxanthin one hour before the application of TPA in two-stage carcinogenesis. However, neoxanthin did not inhibit ODC activity when animals were treated with neoxanthin one hour before the application of DMBA in two-stage carcinogenesis, and there was no subsequent tumor formation. In a short-term anti-initiation experiment, neoxanthin inhibited the covalent binding of isotope-labeled DMBA to DNA by 53%. These results indicate that neoxanthin inhibits the initiation stage and the promotion stage in two-stage carcinogenesis. This suggests that neoxanthin may act as a potential chemopreventive agent.

Desarrollo de un melanoma maligno facial durante la administración de L-Dopa / Development of a facial malignant melanoma during L-Dopa administration

En un hombre de 80 años de edad que padece del mal de Parkinson, se desarrolla un melanoma malignoen la cara durante la administración de L-Dopa. Aunque exista una relación casual entre el crecimiento del tumor y la administración de la droga, puede ser sospechada tal posibilidad la cual debe ser considerada cuando se use este medicamento. Se realiza una revisión sobre el tema

A case-control study of cancer among du pont employees with potential for exposure to dimethylformamide.

This case-control study was undertaken to determine whether the risk of developing cancers of the buccal cavity and pharynx (N = 39), liver (N = 6), prostate (N = 43), testis (N = 11), or malignant melanoma of the skin (N = 39) is related to exposure to dimethylformamide (DMF). Case and control subjects were obtained from four Du Pont plants. DMF is produced at one plant and used at the other three. Cancer cases identified from the company Cancer Registry comprise those reported among active male employees at the study plants during 1956 to 1985. For each case, two control subjects were selected, matched on sex, payroll class (wage or salary), birth year, and plant. To determine whether an employee could have been exposed to DMF during his career at the plant, all jobs with potential for exposure to DMF were identified. Each job was assigned an exposure ranking based on DMF industrial hygiene air monitoring, DMF metabolite (measured as N-methylformamide in urine) monitoring, and knowledge of the evolution of manufacturing processes and workplace exposure controls. Each employee's DMF exposure pattern was then characterized as (a) ever v never having been exposed to DMF and (b) highest DMF exposure experienced. Summary analyses for all plants combined showed no statistically significant association between ever having been exposed to DMF and subsequent development of cancers of the buccal cavity and pharynx, liver, malignant melanoma, prostate, and testis. Examined by plant site, prostate cancer at one plant was significantly elevated, based on three case subjects exposed out of four.(ABSTRACT TRUNCATED AT 250 WORDS)

Carcinogenicity of 2,3,7,8-tetrachlorodibenzo-p-dioxin in the Syrian golden hamster.

The carcinogenic potential of 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) was examined in Syrian golden hamsters, at different dose levels. Twenty-one percent of the hamsters that received a total of 600 micrograms/kg body weight of TCDD either by the s.c. or i.p. route developed squamous cell carcinomas of the skin of facial region within 12-13 months from the beginning of the experiment. Neoplasms were not observed in any other organs. These studies suggest that TCDD may be a complete carcinogen in hamsters, the species most resistant to the toxic effect of this compound.

Osteoma cutis: a case of probable exacerbation following treatment of severe acne with isotretinoin.

A florid case of osteoma cutis was observed following isotretinoin treatment of severe cystic acne in which a few scattered osteomata of the skin were observed prior to the treatment with isotretinoin.

[Simulation of malignant tumors by undeclared polyvinylpyrrolidone in drugs]. / Vortäuschung maligner Tumoren durch nicht deklariertes Polyvinylpyrrolidon in Arzneimitteln.

Numerous drugs are available containing polyvinylpyrrolidone as a carrier and retard substance. Repeated intramuscular or subcutaneous injections of polyvinylpyrrolidone over a long time can lead to tumor-like foreign body reactions mimicking true malignant tumors by clinical and histological features. Additionally, a storage of polyvinylpyrrolidone in visceral organs is possible in such patients.