Treatment Of Skin Tumors Research Articles

Don't Delay Treatment of Skin Tumors in Children

Don't Delay Treatment of Skin Tumors in Children

Do basal cell carcinomas recur after complete conventional surgical excision?

For 1378 patients treated in the 11 years 1988-1998 by conventional excision of 1635 basal cell carcinomas, 1516 first index lesions were histologically completely excised. All patients having more than one BCC excised were identified from the data base from 1988 to 2003 to give minimum 5 years follow for last treated primary lesions in 1998. Measured clearance margins around the initial lesions at or near sites of presumptive recurrent lesions were noted and the lesions recorded photographically. All incompletely excised lesions whether or not re-excised were excluded. The median age for all patients was 70 years. Over minimum 5 years follow up, six patients developed nine subsequent lesions contiguous with the scar or graft repair of primary index lesion excision site (probable recurrences). The median interval to recurrence was 41 months (4 months-8 years 10 months), with median lateral clearance margin around the primary tumour of 2 mm (0.3-6.8 mm). A further nine patients developed 11 new lesions near (within 1cm of) the scar or graft of primary index lesion excision site (possible recurrences). The median interval to recurrence was 59 months (1 year-8 years 6 months). The median lateral clearance margin around the primary tumour was 4.1 mm (0.8-5.8 mm). For the two groups combined the maximum recurrence rate expressed as a percentage of index lesions was 1.3% (20/1516). Two thirds of possible and probable recurrences occurred in the temple and forehead, although these sites represented only 22% of all lesions, which may rather suggest new lesions in an area of field change as opposed to residual disease. The measured clearance margins reported here perhaps suggest that some original lesions may well have been completely excised primarily and many 'recurrences' were new primaries. These figures indicate there is a low order of probability for the incidence of recurrent basal cell carcinoma during minimum 5 years follow period after conventional surgical excision and conventional histological assessment of tumour resection margins.

The p73 Gene Is an Anti-Tumoral Target of the RARβ/γ-Selective Retinoid Tazarotene

Tazarotene, a member of the new class of acetylenic retinoids, has been shown to be effective in the treatment of several hyperproliferative skin diseases, including non-melanoma skin cancer. Its effectiveness is thought to rely on the ability to activate retinoic acid receptors beta and gamma and to induce a number of downstream anti-proliferative genes. Here, we show that the p53-related gene p73 is a target of tazarotene. Indeed, tazarotene modulates the expression of the p73 gene in immortalized keratinocyte cell lines by inducing the pro-apoptotic and anti-proliferative TAp73 isoforms and by repressing the anti-apoptotic and pro-proliferative DeltaNp73 isoforms. This occurs at the transcriptional level through a coordinated action on P1p73 and P2p73 promoters that control the expression of TA and DeltaN isoforms, respectively. The selective downregulation of DeltaNp73 expression by small interfering RNA led to an enhancement of tazarotene-induced bax activation and apoptosis, whereas the downregulation of both TA and DeltaN isoforms impairs tazarotene-mediated apoptosis. These results indicate the relevance of p73 gene products in tazarotene-induced growth inhibition and effectiveness in the treatment of skin tumors.

Historique, principes, analyse critique de l’efficacité et indications de la chirurgie micrographique de Mohs

To systematically review the literature for studies reporting on the role of Mohs' micrographic (MMS) surgery in the treatment of skin tumors. To show how it is performed in France. We reviewed with a quality grid all studies indexed in MEDLINE before 2003/01/01 and published in English or French. Data were extracted by two independent reviewers. Quality of clinical studies, recurrence rates, number of patients lost to follow-up. No randomized study was found among the 493 references found. Studies of lower quality, on procedures similar to MMS, or previous systematic reviews were therefore selected. In tumors such as basal (BCC) or spinous (SCC) cell carcinoma, microcystic adnexal carcinoma, dermatofibrosarcoma protuberans, and Merkel cell carcinoma, MMS commonly induced lower recurrence rates than figures reported for conventional treatments and/or reduced surgical margins. Studies on melanoma were of low quality. Although no evidence-based guidelines could be developed, MMS should be used mainly for larger, morphea, micronodular or infiltrative-type, or recurrent BCCs located in danger zones, but also (sometimes with a slightly modified procedure) in microcystic adnexal carcinomas, dermatofibrosarcoma protuberans, Merkel cell carcinoma, and in aggressive forms of SCC. Randomized, controlled studies should be performed.

Imiquimod as a dermatological therapy

Imiquimod is the first of a new class of drugs (immune response modifiers) to become commercially available. It is approved in many countries for the treatment of genital warts caused by the human papilloma virus infection. However, there are reports of its use in a variety of dermatological conditions, such as basal cell carcinomas, actinic keratoses, lentigo maligna, common warts and molluscum contagiosum. Its mechanism of action is through stimulation of the T helper cell Type 1 (Th1) immune response via activation of cell surface pathogen recognition receptors (mainly toll-like receptor 7). This activation stimulates the immune system’s own defence mechanism against both virally infected and tumour cells. Imiquimod and other analogues show promise in the prophylactic treatment of skin tumours in some patients, especially those who are immunocompromised.

Fluorescence detection of a new photosensitizer, PAD-S31, in tumour tissues and its use as a photodynamic treatment for skin tumours in dogs and a cat: a preliminary report

We describe here the detection by fluorescence of a new photosensitizer, PAD-S31, in tumours in dogs and cats and the effect of photodynamic therapy (PDT) by using PAD-S31 for skin tumours in two dogs and one cat. PAD-S31 is a hydrophilic photosensitizer that has two peaks at absorption wavelengths 406 and 665 nm in distilled water. In a preliminary experiment in mice transplanted with SCCVII and colon 26, PAD-S31 was retained in tumour tissues rather than in other organs. The tumours resected from dogs and cats after intravenous administration of PAD-S31 at a dose of 15 mg/kg emitted strong red fluorescence under light illumination of 402 nm wavelength. Animals given PAD-S31 showed no cutaneous photosensitivity under room light illumination. Irradiation at laser light 670 nm wavelength (fluence rate 150 mW/cm 2 and total light dosage 150 J/cm 2) on cutaneous mast cell tumours in dogs ( n=2) and a cutaneous basal cell tumour in a cat induced complete remission. These results suggest PAD-S31 could be a promising photosensitizer for use in a small animal veterinary practice.

Activation of two caspase cascades, caspase 8/3/6 and caspase 9/3/6, during photodynamic therapy using a novel photosensitizer, ATX-S10(Na), in normal human keratinocytes.

Photodynamic therapy (PDT) is a potent treatment for skin tumors. Although the therapeutic effect of PDT is supposed to be due to cellular cytotoxicity, the precise mechanism is still unknown. ATX-S10(Na) [13,17-bis(1-carboxypropionyl)carbamoylethyl-8-ethenyl-2-hydroxy-3-hydroxyiminoethylidene-2,7,12,18-tetramethylporphyrin sodium salt], a novel hydrophilic chlorin photosensitizer, shows good accumulation in tumors and is suitable for use in PDT. In this study, we investigated the mechanism of PDT-induced cell death using ATX-S10(Na). . Following ATX-S10(Na) treatment for 12 h, normal human keratinocytes (NHK) were irradiated using a diode laser. PDT-induced cell death and the activity of various caspases were measured. Activation of Fas antigen was also determined by immunoprecipitation analysis. The expression of Bax, cytochrome c, and apoptosis-inducing factor (AIF) was determined by Western blotting. ATX-S10(Na)-PDT had induced apoptosis of NHK by 2 h and the maximal effect was observed at 6 h following irradiation. The effect was suppressed by pretreatment of NHK with inhibitors of caspases 3, 6, 8 and 9. A caspase activity assay revealed the sequential activation of caspases 8, 3 and 6, and caspases 9, 3 and 6, respectively. Immunoprecipitation analysis indicated multimerization of Fas antigen without Fas ligand binding in ATX-S10(Na)-PDT-treated NHK. Western blotting revealed cytosolic release of cytochrome c and AIF accompanied by decreased Bax expression in the cytosol. ATX-S10(Na)-PDT induces apoptosis of NHK, and this was mediated by sequential activation of two caspase cascades, caspases 8, 3 and 6, and caspases 9, 3 and 6. This was accompanied by multimerization of Fas antigen and cytosolic release of cytochrome c and AIF.

Blue light inhibits the growth of skin tumors in the v-Ha-ras transgenic mouse.

12-O-Tetradecanoylphorbol-13-acetate (TPA) was applied to the back skin of v-Ha-ras (TG-AC) female transgenic mice at a dose of 2.5 microg/200 microl twice a week for 9 weeks. The back skin was then exposed to blue light (wavelength, 470 nm; irradiance, 5.7 mW/cm2) for 1 h daily for 9 weeks. The mice to which TPA was applied developed skin tumors at 6 weeks after the start of application. The tumor incidence rates at 6, 7, 8 and 9 weeks after the start of application were 70%, 80%, 100% and 100%, respectively, and the numbers of tumors 1 mm or more in diameter were 1, 5, 10 and 19, respectively. In the mice that were exposed to blue light after TPA application, the tumor incidence rates were 10%, 40%, 60% and 80%, respectively, and the numbers of tumors 1 mm or more in diameter were 0, 2, 5 and 9, respectively. Histopathological examination of the skin revealed that TPA application induced diffuse hyperplasia, exaggerated keratinization, and papillomas in all 10 mice. A localized form of epidermal hyperplasia was also observed in 4 mice. The incidence rate of papillomas in the mice that were exposed to blue light after TPA application was lower and the degree of exaggerated keratinization was greater. Exaggerated keratinization was considered to represent a regressive change following exposure. These findings suggest that exposure to blue light may be a promising new approach in the treatment of skin tumors.

Inhibition of skin tumor growth and angiogenesis in vivo by activation of cannabinoid receptors.

Nonmelanoma skin cancer is one of the most common malignancies in humans. Different therapeutic strategies for the treatment of these tumors are currently being investigated. Given the growth-inhibiting effects of cannabinoids on gliomas and the wide tissue distribution of the two subtypes of cannabinoid receptors (CB(1) and CB(2)), we studied the potential utility of these compounds in anti-skin tumor therapy. Here we show that the CB(1) and the CB(2) receptor are expressed in normal skin and skin tumors of mice and humans. In cell culture experiments pharmacological activation of cannabinoid receptors induced the apoptotic death of tumorigenic epidermal cells, whereas the viability of nontransformed epidermal cells remained unaffected. Local administration of the mixed CB(1)/CB(2) agonist WIN-55,212-2 or the selective CB(2) agonist JWH-133 induced a considerable growth inhibition of malignant tumors generated by inoculation of epidermal tumor cells into nude mice. Cannabinoid-treated tumors showed an increased number of apoptotic cells. This was accompanied by impairment of tumor vascularization, as determined by altered blood vessel morphology and decreased expression of proangiogenic factors (VEGF, placental growth factor, and angiopoietin 2). Abrogation of EGF-R function was also observed in cannabinoid-treated tumors. These results support a new therapeutic approach for the treatment of skin tumors.

Clinical Snippets

Hair regrowth after chemotherapy or alopecia areata commonly results in white hair. In mice treated with cyclophosphamide, Sharvov et al (p. 27) showed Fas ligand mediated melanocyte apoptosis. Melanocyte migration accompanied the recovery phase, suggesting new paradigms for treating disorders with hypopigmentation. These studies also suggest a mechanism for the hyperpigmentation of the nail bed seen with antimetabolite therapy. Endemic pemphigus foliaceus in Brazil, Fogo Selvagem, is associated with IgG antibodies against desmoglein-1 in all affected individuals and, surprisingly, half of the normal subjects living in endemic regions (Warren et al, p. 104). The clinically affected individuals and those only with antibodies differed from those with the disease by having an increased anti-desmoglein1 IgG4 level. This two-stage model for disease suggests that preventing the IgG1 to IgG4 conversion might prevent clinical disease. From Star Wars to skin tumor treatment, lasers are usually destructive devices. Yu and co-workers (p. 56) emphasize the “biostimulation” of the low energy Helium–Neon (632.8nm) laser. Basic fibroblast growth factor was induced from fibroblasts and keratinocytes and media from these irradiated cells stimulated melanocyte proliferation and migration. Thirty patients with segmental vitiligo were treated with the laser and 60% of those treated had greater than 50% repigmentation. Further studies of this treatment, especially in those recalcitrant to other forms of treatment, will be of interest. In Doctor's Dilemma, one of Shaw's characters spouts, “Stimulate the phagocytes”; some day we may shout “stimulate the melanocytes”. Prudent sunbathers – possibly an oxymoron – can avoid acute sunburn but have immunosuppression. Kelly and colleagues (p. 65) studied unexposed buttock skin of 119 white-skinned volunteers from 18–35 years for both sun-protective factor responses and the ability to be immunized with dinitrochlorobenzene. Sun Protection Factors (SPF) and Immune Protective Factors (IPF) were calculated. Although the acute sunburn response from simulated sunlight could be suppressed with commercial sunscreen, there was still immunosuppression – possibly due to unfiltered UVA. This study has important implications for the health of the public and those concerned with optimum sunscreen composition and usage and understanding the epidemiology of skin malignancies. Beta-endorphin, a peptide, is the endogenous ligand for the alpha-opiate receptor that stimulates the production of cytokeratin 16, a cytokeratin associated with wound healing and epidermal proliferation in organ culture (Bigliardi et al, p. 145). Beta-endorphins induced fibroblast and capillary proliferation in animal models. These peptides, opiates themselves and modulators of the receptors, may lead to new treatments for chronic wounds. Opiate antagonists might have roles in treating keloids or preventing hypertrophic scars. Watch Fido jump.

570 Poster High-dose rate moulds in the treatment of skin tumors

570 Poster High-dose rate moulds in the treatment of skin tumors

Management of patients taking anticoagulant, aspirin, non-steroidal anti-inflammatory and other anti-platelet drugs undergoing dermatological surgery.

An increasing number of patients who require surgical treatment for skin tumours also take anticoagulants or anti-platelet drugs to prevent thromboembolic events. Stopping therapy places the patient at risk from a thromboembolic event, whilst continuing treatment places them at risk from bleeding complications during surgery. We have reviewed all of the published studies of the effects of warfarin, aspirin, non-steroidal anti-inflammatory and other anti-platelet drugs on surgical outcome in patients having skin surgical procedures. There is little evidence that continuing with treatment is harmful in any of these groups with the exception of warfarin therapy, where the risk of haemorrhagic complications is presumably dependent on the degree of anticoagulation.

Led enhancement in mitochondrial oxidative phosphorylation for hepatectomized rats

Recently, the LED (light emitting diode) developed by the Optics Group of IFSC-USP has been used instead of laser for the treatment of skin tumors by the PDT (Photodinamic Therapy) because of its low operational cost compared to the use of a laser. In this paper we investigate the effect of LED light on oxidative phosphorylation during liver regeneration after partial hepatectomy. Twenty-four male Wistar rats (250 g) were kept in identical housing units on a 12-hour light/12 hour dark cycle. The LED 10 group was exposed to LED at 638 nm (10 J/cm2 for 3 minutes). Seventy percent partial hepatectomy was performed in the LED 10 and HPC (Partial Hepatectomy-Control). A sham-operated group (C) was used for control. Twenty four hours after the procedure, LED 10, HPC and control animals were sacrificed. Samples of liver tissue were used for the mitochondrial respiration assay. Statistical comparisons of the groups were performed by analysis of variance (ANOVA), followed by the Bonferroni post-test. Probability values less than 0.05 were considered to be statistically significant. the phosphorylation index (FI) for the LED 10 group was higher than that for the HPC group and for the sham group (p 0.05). In the present study we noted an effective interaction between LED light and hepatic mitochondria, with an increased phosphorylation rate for the latter.

Radiotherapy and skin tumors

Radiotherapy plays an important role in the treatment of skin tumours. For skin carcinomas, external irradiation (kilovoltage X-rays or electrons according to clinical characteristics) is more valuable than interstitial brachytherapy, which is recommended for tumours of the lip and of the nasal vestibule. In mycosis fungoides, total cutaneous electron beam radiation therapy is efficient for patients with limited superficial plaques. In the classical form of Kaposi's sarcoma, radiotherapy can achieve local control whereas it obtains good palliative results in the epidemic form.

Skin cancers in transplant patients.

Skin tumors are frequent in transplant patients, and their potential for progression (locoregional recurrences, metastases) is much greater than in the general population. The viral element with HPV probably represents one of the etiologic factors, although other only partially known factors play a role, including the sun and genetic factors. The high frequency of these skin tumors in transplant patients and their potential for progression require preventive and therapeutic measures: regular examination of the skin, strict advice about protection from sun exposure, excision of any suspect lesion, and treatment of warts that might be conducive to the development of skin cancers. Finally, it must be decided whether immunosuppression should be reduced or stopped during treatment of skin tumors with a high risk of progression.

Treatment of skin tumors of the inner canthal region--reconstructing the medial canthal area: a dilemma between doing too much and an aesthetic outcome.

Treatment of skin tumors of the inner canthal region--reconstructing the medial canthal area: a dilemma between doing too much and an aesthetic outcome.

Determination of the maximal tumor/normal skin ratio after HpD or m-THPC administration in hairless mouse (SKh-1) by fluorescence spectroscopy--a non-invasive method.

Two major steps in our study on the treatment of skin tumors by photochemotherapy (PCT) were the development of a skin tumor model in hairless mice by chemical carcinogenesis and by the use fluorescence spectroscopy, a semi-quantitative and non-invasive method, to determine the time after i.p. injection of photosensitizer when the tumor/normal skin ratio is the highest. Carcinogenesis provided mice bearing many benign papillomas and these were used to determine the tumor/normal skin ratios of two photosensitizers by fluorescence spectroscopy. Hematoporphyrin derivative (HpD) (5 mg/kg body weight) and m-tetra(hydroxyphenyl)-chlorin (m-THPC) (0.3 mg/kg body weight) were injected, and fluorescence measured at 4, 8, 24, 48, 72 and 96 h after injection. The tumor/normal skin ratio was 6.2 for HpD and 5.1 for m-THPC. The times required to reach these ratios were 48 h for HpD and 72 h for m-THPC. Published reports indicate that m-THPC gives a much higher tumor/normal skin ratio than HpD. These results must be confirmed by organic extraction. Photodynamic therapy with the same doses of HpD and m-THPC used in this pharmacokinetic study must also be carried out to compare the toxicities of the two photosensitizers and to determine which is best for this type of tumor.

The importance of Mohs surgery in the treatment of skin tumors localized in a critical sites

The importance of Mohs surgery in the treatment of skin tumors localized in a critical sites

High dose-rate microselectron molds in the treatment of skin tumors

Purpose : The feasibility of high dose rate iridium afterloaded molds in the treatment of skin tumors. Methods and Materials : Expanded silicone rubber and bronchial applicator tubes were used in the construction of various molds. The number of tubes used and the separation between them depends on the size and area to be treated. Source dwell position and time are set to follow Paterson—Parker rules. Single plane expanded silicone rubber molds between 15 × 15 mm and 60 × 70 mm were used in 120 different sites, and of the others, seven were perspex double molds, two were cylindrical applicators, and one was a partially shielded intranasal applicator. One hundred and thirty lesions of various site and histology were treated in all. After exclusion of treatments that were combined with either external beam or chemotherapy, 106 lesions (76 patients) were evaluated. Results : Full response was obtained in all but four basal cell carcinomas. The acute reaction ranged from moist desquamation (27 sites) to erythema only. Follow-up at 5 or more months revealed no changes whatever in 47 sites; 53 showed an excellent cosmetic outcome, although slight changes in pigmentation or minimal atrophy was demonstrable and 6 sites became noticeably atrophic with patchy pigmentation. For 9.6 months of average follow-up time, no recurrences have been observed. Conclusion : The high-dose-rate iridium-loaded skin applicators offer the possibility of improved therapeutic ratio in the treatment of superficial skin tumors. With the availability of a high-dose-rate afterloader this technique is simple and straightforward.

Laser therapy of skin tumors.

Malignant skin tumors can be treated by CO2 laser excision or vaporization, neodymium: yttrium aluminum garnet (Nd:YAG) laser coagulation, and systemic or topical photodynamic therapy (PDT). Possible indications for CO2 laser vaporization include superficial basal cell carcinomas, actinic keratoses, Bowen's disease, actinic cheilitis, and leukoplakias. The Nd:YAG laser may be used for coagulation of basal cell carcinomas, squamous cell carcinomas, Kaposi's sarcoma, and metastatic skin tumors. Systemic and topical PDT is still an experimental modality and is mostly applied for treatment of basal cell carcinomas. However, laser treatment of skin tumors is not yet considered as standard therapy and should be confined to selected patients. Further clinical studies are necessary to determine the role of laser therapy in this special indication.