Evaluation of the efficacy of photodynamic therapy for the treatment of actinic cheilitis.

INTRODUCTION: Actinic cheilitis (AC) is a lip intraepithelial neoplasia, whose cells present alterations similar to those presented by invasive squamous cell carcinomas (SCCs). OBJECTIVE: To conduct clinical and laboratory evaluation by histopathology and immunohistochemistry of the efficacy of actinic cheilitis treatment using photodynamic therapy (PDT) with methyl aminolevulinate (MAL) and noncoherent red light. MATERIALS AND METHODS: Patients with actinic cheilitis detected by histopathological examination were submitted to two sessions of photodynamic therapy with a two-week interval between them. They were examined immediately after the sessions, four, six, and twelve weeks after beginning treatment when a new biopsy was carried out. Clinical histopathological and immunohistochemical parameters were evaluated before and after treatment. RESULTS: Of the 23 patients who underwent biopsy, 16 completed two photodynamic therapy sessions and the material of one patient was insufficient for immunohistochemistry. Complete clinical response was achieved in 62.5% (10 of 16 patients) and 37.5% still remained with clinical evidence of AC. In spite of this, no case of cure by histopathological analysis was found. There was no significant statistical change among the values of Ki-67, survivin, and p53 observed before and after treatment. CONCLUSION: Photodynamic therapy, as carried out in this trial, was not an efficacious therapeutic option for treating patients with actinic cheilitis included in this sample.

Clinical and Histopathologic Assessment of Facial Melasma After Low-Fluence Q-Switched Neodymium-Doped Yttrium Aluminium Garnet Laser.

BACKGROUND: Melasma is a frequent and difficult to treat skin disorder. Results of laser therapy are inconsistent. OBJECTIVE: To determine the safety and efficacy of low-fluence Q-switched neodymium-doped yttrium aluminum garnet (QS Nd:YAG) laser for melasma treatment and assess recurrence rates and histopathologic findings before and after treatment. METHODS: Twenty patients were treated with 10 weekly sessions of low-fluence 1064-nm QS Nd:YAG laser at 1-week intervals. The modified Melasma Area and Severity Index (mMASI) score was evaluated at baseline; 1 week; and 1, 3, and 6 months after treatment. Epidermal melanin quantification was performed on 10 biopsy samples and compared before and after treatment. RESULTS: All patients showed improvement by mMASI scores, range (21%-75%) compared with that at baseline. No permanent side effects occurred. The recurrence rate was 81%. By histopathology, a slight, nonsignificant (p = .305) decrease in melanin deposition was seen in all layers of the epidermis 1 week after the laser treatments ended. CONCLUSION: The results confirm the safety and effectiveness of low-fluence QS Nd:YAG laser for treating melasma; however, the high recurrence suggests poor long-term results when the laser is used as a monotherapy.

Cutaneous field cancerization: clinical, histopathological and therapeutic aspects.

The concept of "field cancerization" was first introduced by Slaughter in 1953 when studying the presence of histologically abnormal tissue surrounding oral squamous cell carcinoma. It was proposed to explain the development of multiple primary tumors and locally recurrent cancer. Organ systems in which field cancerization has been described since then are: head and neck (oral cavity, oropharynx, and larynx), lung, vulva, esophagus, cervix, breast, skin, colon, and bladder. Recent molecular studies support the carcinogenesis model in which the development of a field with genetically altered cells plays a central role. An important clinical implication is that fields often remain after the surgery for the primary tumor and may lead to new cancers, designated presently as "a second primary tumor" or "local recurrence," depending on the exact site and time interval. In conclusion, the development of an expanding pre-neoplastic field appears to be a critical step in epithelial carcinogenesis with important clinical consequences. Diagnosis and treatment of epithelial cancers should not only be focused on the tumor but also on the field from which it developed. The most important etiopathogenetic, clinical, histopathological and therapeutic aspects of field cancerization are reviewed in this article.

Cutaneous field cancerization: clinical, histopathological and therapeutic aspects / Campo de cancerizacao cutaneo: implicacoes clinicas, histopatologicas e terapeuticas

The concept of "field cancerization" was first introduced by Slaughter in 1953 when studying the presence of histologically abnormal tissue surrounding oral squamous cell carcinoma. It was proposed to explain the development of multiple primary tumors and locally recurrent cancer. Organ systems in which field cancerization has been described since then are: head and neck (oral cavity, oropharynx, and larynx), lung, vulva, esophagus, cervix, breast, skin, colon, and bladder. Recent molecular studies support the carcinogenesis model in which the development of a field with genetically altered cells plays a central role. An important clinical implication is that fields often remain after the surgery for the primary tumor and may lead to new cancers, designated presently as "a second primary tumor" or "local recurrence," depending on the exact site and time interval. In conclusion, the development of an expanding pre-neoplastic field appears to be a critical step in epithelial carcinogenesis with important clinical consequences. Diagnosis and treatment of epithelial cancers should not only be focused on the tumor but also on the field from which it developed. The most important etiopathogenetic, clinical, histopathological and therapeutic aspects of field cancerization are reviewed in this article.

O conceito de campo de cancerização foi empregado, pela primeira vez, por Slaughter em 1953, estudando o tecido alterado peri-tumoral de carcinoma espinocelular, através da histopatologia. O conceito foi proposto para explicar o desenvolvimento de múltiplos tumores primários e recorrentes na mesma área onde já havia alterações histopatológicas. Os órgãos que apresentam campo de cancerização, até hoje descritos são: cavidade oral, orofaringe, pulmão, vulva, esôfago, cérvix uterino, pele, mama, cólon e bexiga. Os resultados obtidos a partir da biologia molecular sustentam o modelo de carcinogênese, onde um campo com células geneticamente alteradas têm papel fundamental. Uma importante implicação clínica é o fato de que campos com células mutadas geralmente permanecem após a cirurgia para a remoção de um tumor primário, podendo originar novos tumores, designados como segundo tumor primário ou recorrência local, dependendo do local exato e do intervalo entre a cirurgia e a detecção deste novo tumor. O desenvolvimento de campos com células mutadas é considerado uma etapa crítica na carcinogênese, com importante repercussão clínica. Assim, o diagnóstico e tratamento das lesões malignas epiteliais deve abordar não somente o tumor isolado mas sim, todo o campo onde se desenvolveu. Neste artigo, revisamos aspectos importantes da etiopatogenia, clínica, histopatologia e da terapêutica do campo de cancerização.

Pain in photodynamic therapy: mechanism of action and management strategies.

Photodynamic therapy involves administration of a photosensitizing drug and its subsequent activation by irradiation with a light source at wavelengths matching the absorption spectrum of the photosensitizer. In many countries around the world, topical photodynamic therapy has been approved for treatment of cutaneous oncologic conditions such as actinic keratosis, Bowen's disease, and superficial basal cell carcinoma. Multicenter, randomized, controlled studies have confirmed its efficacy and superior cosmetic outcomes compared to conventional therapies. Nevertheless, this therapeutic method presents some adverse effects, such as erythema, edema, pigmentation, pustules, and pain. There is no doubt that pain is the most severe of the adverse effects, being sometimes responsible for definitive treatment interruption. The pain mechanism has not yet been fully understood, which makes complete pain control a challenge to be conquered. In spite of that, this literature review presents some useful pain management strategies as well as the most important pain-related factors in photodynamic therapy.

Pain in photodynamic therapy: mechanism of action and management strategies / Dor na terapia fotodinâmica: mecanismo de ação e estratégias de manejo

Photodynamic therapy involves administration of a photosensitizing drug and its subsequent activation by irradiation with a light source at wavelengths matching the absorption spectrum of the photosensitizer. In many countries around the world, topical photodynamic therapy has been approved for treatment of cutaneous oncologic conditions such as actinic keratosis, Bowen's disease, and superficial basal cell carcinoma. Multicenter, randomized, controlled studies have confirmed its efficacy and superior cosmetic outcomes compared to conventional therapies. Nevertheless, this therapeutic method presents some adverse effects, such as erythema, edema, pigmentation, pustules, and pain. There is no doubt that pain is the most severe of the adverse effects, being sometimes responsible for definitive treatment interruption. The pain mechanism has not yet been fully understood, which makes complete pain control a challenge to be conquered. In spite of that, this literature review presents some useful pain management strategies as well as the most important pain-related factors in photodynamic therapy.

A terapia fotodinâmica consiste na administração de uma droga fotossensibilizante e sua subseqüente irradiação com uma fonte de luz de espectro correspondente ao do seu fotossensibilizador. Em diversos países do mundo, a terapia fotodinâmica tópica é aprovada para o tratamento de condições oncológicas cutâneas como queratoses actínicas, doença de Bowen e carcinoma basocelular superficial. Estudos multicêntricos controlados e randomizados confirmam sua eficácia e seus resultados cosméticos superiores em relação às terapias convencionais. No entanto, existem alguns efeitos adversos inerentes a esse método terapêutico, como eritema, edema, pigmentação, pústulas e dor. Essa última é, sem dúvida, a mais importante deles, chegando a ser responsável pela interrupção definitiva do tratamento em alguns casos. O mecanismo dessa dor permanece ainda não completamente entendido. Tal fato faz do controle total da dor durante a terapia fotodinâmica um desafio ainda a ser conquistado. Apesar disso, esta revisão apresenta algumas estratégias que podem ajudar os pacientes a tolerar melhor a terapia fotodinâmica, além de relacionar os principais fatores ligados à dor descritos na literatura.

Estudo da pele do campo cancerizável antes e após a terapia fotodinâmica através dos métodos clínicos, histopatológicos e imunohistoquímicos / Clinical, histopathological and immunohistochemical assessment of human skin field cancerization before and after photodynamic therapy

O conceito de campo de cancerização, em dermatologia, sugere que a pele fotodanificada tem maior potencial para o desenvolvimento de neoplasias cutâneas. A terapia fotodinâmica (TFD) é um método não invasivo para o tratamento de queratoses actínicas (QA) múltiplas, possibilitando a abordagem de todo o campo. Vinte e seis pacientes com múltiplas QAs na face foram submetidos a três sessões de TFD com metilaminolevulinato 16% (MAL) e luz vermelha, com intervalo de um mês. Biópsias foram realizadas antes e após três meses da última sessão e o material corado para hematoxilina-eosina e Weigert. O estudo imunohistoquímico foi feito para os marcadores: TP-53, pró-colageno I, Metaloproteinase-1 e Tenascina-C. A avaliação do fotoenvelhecimento global melhorou consideravelmente (p < 0,001) e a cura clínica das QAs foi de 89,5% ao final do estudo. Duas sessões mostraram ser equivalentes a três sessões de TFD. Diminuição significante do grau e extensão da atipia celular (p < 0,001), aumento das fibras colágenas (p = 0,001) e melhora do grau de elastose (p = 0,002) foram observadas. O estudo imunohistoquímico mostrou diminuição da expressão da TP-53 (p = 0,580), aumento de pró-colágeno I (p = 0,477) e de MMP-1 (p = 0,08), embora não houvesse diferença estatisticamente significante. Aumento significativo foi observado para Tenascina-C (p = 0,024). Múltiplas sessões de TFD com MAL induziram melhora clínica e histológica do campo de cancerização. A diminuição da severidade e extensão da atipia celular associada à menor expressão de TP-53 sugerem redução do potencial carcinogênico do campo.

The field cancerization concept suggests that photodamaged skin has an increased risk for the development of malignant lesions. Topical photodynamic therapy (PDT) is a non-invasive therapeutic method for multiple actinic keratosis (AK), allowing the possibility of treating the entire surface. Twenty-six patients with photodamaged skin and multiple AKs on the face were submitted to three consecutive sessions of PDT with mehtylaminolevulinate 16% (MAL) and red light, one month apart. Biopsies were performed before and three months after the last treatment session, and stained for hematoxilin-eosin and Weigert. Immunohistochemestry study was performed for TP-53, pro-collagen I, Metalloproteinase-1 and Tenascin-C. The global score for photodamage improved considerably in all patients (p < 0.001). The AK clearance rate was 89.5% at the end of the study. Two treatments were similar to three MAL-PDT sessions. A significant decrease in keratinocytes atypia grade and amount was observed (p < 0.001). A significant increase in collagen deposition (p = 0.001) and improvement of solar elastosis (p = 0.002) were noticed. Immunohistochemical study showed decreased TP-53 expression although not statistically significant (p = 0.580), increased pro-collagen I and MMP-1 expressions (p = 0.477 and p = 0.08) again not statistically significant and a increased expression of Tenascin-C (p = 0.024), which was statistically significant. In conclusion, multiple sessions of MAL-PDT induced clinical and histological improvement of field cancerization. The decrease in severity and extension of keratinocytes atypia associated with a decreased expression of TP-53 suggest a reduced carcinogenic potential of the altered field.

Fractional photothermolysis for the treatment of hypertrophic scars: clinical experience of eight cases.

BACKGROUND: Hypertrophic scars are common problems and represent a challenging condition to treat. Fractional photothermolysis has been effective at resurfacing photodamaged skin, acne scars, and atrophic scars, but there are few reports on its use for hypertrophic scars. OBJECTIVE: To evaluate the safety and efficacy of 1,550-nm erbium-doped fiber laser treatment of hypertrophic scars in eight patients. METHODS: Eight patients (skin phototypes II-IV) with hypertrophic scars received monthly treatments with a 1,550-nm erbium-doped fiber laser. Energy settings ranged from 35 to 50 mJ, and eight to 10 passes were applied with treatment levels 6 to 8. An independent physician evaluator assessed the treatment response by comparing pre- and posttreatment clinical photographs using a quartile grading scale (grade 1, < or =25%=minimal to no improvement; grade 2, 26-50%=moderate improvement; grade 3, 51-75%=marked improvement; grade 4, >75%=near total improvement. RESULTS: At four weeks after the last treatment session, a mean grade of 2.4 was achieved based on an independent physician's clinical assessment. Improvement in pigmentation occurred in all hyperpigmented scars. CONCLUSION: Hypertrophic scars can be effectively and safely improved with 1,550-nm erbium-doped fiber laser treatment.

Laser no rejuvenescimento facial / Lasers on facial rejuvenescence

Os primeiros lasers usados para o rejuvenescimento foram o CO2 10.600nm e o Erbium 2.940nm, com resultados surpreendentes pela grande capacidade de estimular o colágeno. Por serem abativos, o pós-operatório é muito difícil e demorado, com complicações importantes. No intuito de minimizar estes efeitos indesejados, lasers não ablativos com diferentes comprimentos de onda foram introduzidos (840nm, 1.320nm, 1.640nm pulso longo entre outros) e apresentaram um pós-operatório muito leve, porém com capacidade muito limitada de promover neocolagênese. Novas pesquisas trazem os fracionados não ablativos (1.440nm, 1.540nm e 1.550nm) com uma ação diferente: fazem colunas de coagulação dermo-epidérmicas, têm um pós-operatório moderado e uma capacidade razoável de estimular as fi bras colágenas com risco mínimo de efeitos colaterais. São, porém, limitados para fotoenvelhecimento severo. Para suprir esta lacuna, novos aparelhos de CO2 10.600nm e de Erbium 2.940nm, agora fracionados, foram introduzidos. Houve redução dos efeitos colaterais e do resultado fi nal, que são menores quando comparados aos mesmos usados sem o fracionamento dos raios. São uma boa opção para tratamento de peles com fotoenvelhecimento acentuado.

The 10,600-nm CO2 and 2940-nm Erbium lasers were the fi rst ones used for rejuvenescence, with surprising results due to their ability stimulate collagen. Since they are ablative lasers, the postoperative period is diffi cult and prolonged, and with important complications. To minimize those undesirable effects, non-ablative lasers with different wavelengths were introduced (840nm, 1,320nm, long pulse 1,640nm, among others), with a very mild postoperative period, but with a very limited capacity to promote neocollagenesis. New studies were responsible for non-ablative fractional lasers (1,440nm, 1,540nm, and 1,550nm) with a different action: they promote dermal-epidermal coagulation columns, have a moderate postoperative period, and a reasonable capacity to stimulate collagen fi bers with a negligible risk of side effects. However, they are very limited in severe photoaging. To fi ll this gap, new fractional 10,600-nm CO2 and 2,940-nm Erbium lasers were introduced. This reduced the incidence of side effects, but also reduced the fi nal effect, which is not as good when compared with the same, non-fractional, lasers. They represent a good option for the treatment of severe photoaging.

Angioma em tufos: relato de um caso tratado com laser corante pulsado / Tufted angioma: a case report treated with pulsed-dye laser

O angioma em tufos é quadro raro, benigno, de proliferação cutânea angiomatosa. Acomete mais crianças e clinicamente caracteriza-se por lesões em placas, vermelho-violáceas, dolorosas e mais freqüentes no tronco. Quando não regride espontaneamente, os tratamentos propostos (cirurgia convencional, corticoterapia, interferon e laser) alcançam pouco sucesso. Descreve-se o caso de uma menina de 11 anos, com angioma em tufos no tronco, tratada com laser corante pulsado que mostrou alívio importante da dor local e redução discreta do tamanho da lesão. A raridade de casos relatados no Brasil e a tentativa terapêutica com laser corante pulsado motivaram a divulgação do caso.

Tufted angioma is a rare, benign, cutaneous angiomatous proliferation. It is more common in children and is clinically characterized by red-purple painfull plaques, more common in trunk. When spontaneous regression does not occur, proposed treatments (conventional surgery, steroid therapy, interferon and laser) achieve little success. We describe a case of a 11-year-old girl with a tufted angioma located in the trunk treated with pulsed-dye laser, showing important relief of local pain, and small reduction in lesion size. We have been motivated to describe this case due to the small number of such reports in Brazil and by the attempt to treat it with pulsed-dye laser.

Laser em dermatologia: princípios físicos, tipos e indicaçöes / Laser in dermatology: phisycal principles, types and indications

O uso de laser em dermatologia tem se expandido muito nos últimos anos. O avanço tecnológico, em mais de 30 anos, permite que a eficácia e as respostas terapêuticas sejam cada vez melhores. Porém, mais complexos tornam-se a compreensäo do seu uso e suas indicaçöes em dermatologia

Needle liver biopsy: relationship between sampling and degree of conclusiveness of the histopathological diagnoses

A biópsia hepática por agulha é um importante procedimento no diagnóstico de doenças hepatobiliares. quantidade adequada de tecido é necessária para uma correta interpretaçäo. Neste estudo, 1873 biópsias hepáticas foram analisadas e os espécimes divididos em cinco subgrupos de acordo com o tamanho e aspectos macroscópicos. Os diagnósticos histopatológicos foram classificados em conclusivo, sugestivo e inconclusivo. Observou-se que os diagnósticos conclusivos predominaram nos grupos onde os espécimes eram maiores do que 0.5 cm. Por outro lado, os diagnósticos sugestivos e inconclusivos predominaram nos grupos com menos do que 0.5 cm. Diferenças estatísticas altamente significantes entre os grupos validaram estes achados. Estes resultados säo de grande importância para todos aqueles que realizam biópsias hepáticas e mostram que a eficácia do procedimento depende de uma mostra de tecido adequada