Impact of allogeneic stem cell transplantation in childhood and adolescence on quality of adulthood life: A case-control study.

BACKGROUND: Allogeneic hematopoietic stem cell transplantation (allo-HSCT) is associated with late complications that can impair the quality of life (QoL) of patients for years after transplant. The purpose of the present study was to determine the difference in the QoL of adults that underwent allo-HSCT in childhood and adolescence compared with not transplanted adults. METHODS: In this prospective case-control cross-sectional study, we included patients aged ≥18 years that received an allo-HSCT during childhood or adolescence and subsequently survived at least 2 years after transplantation. The control group consisted of blood donors matched for age and sex. QoL assessment was performed using the Short Form-36 (SF-36) Health Survey, Portuguese version 2. RESULTS: Thirty-four transplanted patients and controls were included. 58.8% were male, and the median age at transplant was 13.5 years (range, 4-17 years). The median follow-up was 11.5 years (range, 2.0-23.0 years). The most common late effect was skeletally followed by endocrine complications. Patients with these late complications had the worst QOL in the following dimensions: physical functioning, role physical, bodily pain, general health, and mental health. When compared to the control group, patients had a lower score in two dimensions: physical functioning and role physical. CONCLUSIONS: Although skeletal and endocrine complications of transplant patients in childhood have an impact on physical functioning, most parameters of QoL of these patients in adulthood are similar to healthy individuals of the same age and gender. Early detection and long-term monitoring of late complications can prevent impairment of the QoL.

Keratoacanthoma of the Lip: Activation of the mTOR Pathway, Tumor Suppressor Proteins, and Tumor Senescence.

The PI3K-PTEN-mTOR is one of the most important pathways involved in cancer development and progression; however, its role in keratoacanthoma (KA) is poorly understood. In this study, we investigated the activation of key proteins in the PI3K-mTOR pathway in lip KA. We analyzed the activation of the PI3K-PTEN-mTOR pathway using human tumor samples stained for well-established protein markers in this pathway, including pS6 and pAKT phosphoproteins. We assessed proliferation using Ki-67 and performed additional morphological and immunohistochemical analysis using anti-PTEN and anti-p16 antibodies.We found that the majority of KA labeled to pS6 and not pAKT. PTEN expression was inversely correlated with Ki-67 expression. In addition to PTEN expression, KA cells were positive for p16 senescence marker. PI3K-PTEN-mTOR pathway is activated in lip KA, leading to downstream activation of mTORC1, but not mTORC2. This pathway plays an important role in KA progression by promoting proliferation and activation of oncogenic-induced senescence.

Histogenesis of keratoacanthoma: histochemical and immunohistochemical study.

OBJECTIVES: Keratoacanthoma (KA), a keratinocytic neoplasm, is associated with sun exposure and is often found in the head and neck area, including the lip. KA is thought to arise from hair follicle cells, but its origin is largely unknown. Keratins (Ks) and histochemical stains are of great value to characterize and identify normal and neoplastic cells. The objective of this study is to analyze a panel of Ks and periodic acid-Schiff (PAS) staining on KA. STUDY DESIGN: Using KA biopsies from the lips and normal skin samples, we performed immunohistochemical and histochemical profiling to determine which biomarkers are conserved between tumors and normal tissues. RESULTS: The normal hair follicle has multiple well-defined compartments. The outer root sheath (ORS) cells presented K6 and K14 and were also PAS positive. In addition, the infundibulum cells showed positive labeling to K10. Hair cortex keratin was observed in the cortical and precortical cells. Interestingly, KA tumor cells were positive for PAS, K6, K10, and K14 but not to hair cortex keratin. Lip and skin epithelium were negative for PAS and K6. CONCLUSIONS: Our results indicate that KA of the lip is derived from ORS cells, particularly those cells associated with the upper ORS.

Laser phototherapy triggers the production of reactive oxygen species in oral epithelial cells without inducing DNA damage.

Laser phototherapy (LPT) is widely used in clinical practice to accelerate healing. Although the use of LPT has advantages, the molecular mechanisms involved in the process of accelerated healing and the safety concerns associated with LPT are still poorly understood. We investigated the physiological effects of LPT irradiation on the production and accumulation of reactive oxygen species (ROS), genomic instability, and deoxyribose nucleic acid (DNA) damage in human epithelial cells. In contrast to a high energy density (20 J/cm²), laser administered at a low energy density (4 J/cm²) resulted in the accumulation of ROS. Interestingly, 4 J/cm² of LPT did not induce DNA damage, genomic instability, or nuclear influx of the BRCA1 DNA damage repair protein, a known genome protective molecule that actively participates in DNA repair. Our results suggest that administration of low energy densities of LPT induces the accumulation of safe levels of ROS, which may explain the accelerated healing results observed in patients. These findings indicate that epithelial cells have an endowed molecular circuitry that responds to LPT by physiologically inducing accumulation of ROS, which triggers accelerated healing. Importantly, our results suggest that low energy densities of LPT can serve as a safe therapy to accelerate epithelial healing.

Laser phototherapy accelerates oral keratinocyte migration through the modulation of the mammalian target of rapamycin signaling pathway.

Keratinocytes play a central role in wound healing by responding to tissue injury through the activation of cellular proliferation and migration. Current clinical evidence suggests that the laser phototherapy (LPT) accelerates wound healing in a variety of oral diseases; however, the molecular mechanisms involved in response to LPT are not fully understood. Oral keratinocytes (NOK-SI) maintained under nutritional-deficit culture medium (2% fetal bovine serum) were irradiated with InGaAlP laser (660 nm; 40 mW; 0.04 cm2 spot size) in punctual and contact modes. The energy densities used were 4 and 20 J/cm2 corresponding to 4 and 20 s of exposure times and 0.16 and 0.8 J of energy per point, respectively. Three sessions of irradiations were applied with 6-h intervals. Further, the impact of LPT over cellular migration, proliferation, and activation of the mammalian target of rapamycin (mTOR) pathway, known to play a major role in epithelial migration and wound healing, was analyzed. Compared with control cells, the LPT-treated cells showed accelerated cellular migration without any changes in proliferation. Furthermore, LPT resulted in an increase in the phospho-S6 ribosomal protein, indicating activation of the mTOR signaling pathway. Collectively, these findings suggest that the LPT activates mTOR signaling pathway, promotes epithelial cell migration, and accelerates healing of oral mucosa.

Efficacy of laser phototherapy in comparison to topical clobetasol for the treatment of oral lichen planus: a randomized controlled trial.

Oral lichen planus (OLP) is a relatively common chronic mucocutaneous inflammatory disease and a search for novel therapeutic options has been performed. We sought to compare the efficacy of laser phototherapy (LPT) to topical clobetasol propionate 0.05% for the treatment of atrophic and erosive OLP. Forty-two patients with atrophic/erosive OLP were randomly allocated to two groups: clobetasol group (n=21): application of topical clobetasol propionate gel (0.05%) three times a day; LPT group (n=21): application of laser irradiation using InGaAlP diode laser three times a week. Evaluations were performed once a week during treatment (Days 7, 14, 21, and 30) and in four weeks (Day 60) and eight weeks (Day 90) after treatment. At the end of treatment (Day 30), significant reductions in all variables were found in both groups. The LPT group had a higher percentage of complete lesion resolution. At follow-up periods (Days 60 and 90), the LPT group maintained the clinical pattern seen at Day 30, with no recurrence of the lesions, whereas the clobetasol group exhibited worsening for all variables analyzed. These findings suggest that the LPT proved more effective than topical clobetasol 0.05% for the treatment of OLP.

Prevenção de intercorrências estomatológicas em oncologia pediátrica / Prevention of stomatological complications in pediatric oncology

Objetivo: este artigo visa demonstrar por meio da Revisão de literatura e do relato de dois casos a importância da aplicação de protocolos de adequação do meio bucal em crianças submetidas a tratamento oncológico. As neoplasias em crianças e adolescentes estão entre 1% e 3% de todos os tumores malignos na maioria da população. Representam a principal causa de morte a partir dos 5 anos de idade. Para tratar essas doenças, os pacientes são submetidos à quimioterapia e à radioterapia, tratamentos que podem ocasionar alterações na integridade e na função dos tecidos da cavidade bucal. A toxicidade das drogas quimioterápicas pode ser direta ou indireta, aguda ou tardia, causando impacto na saúde e na qualidade de vida dos pacientes. Relato de casos: neste artigo são relatados dois casos de crianças diagnosticadas com neoplasias. Em uma delas, foi realizada a adequação do meio bucal antes do tratamento oncológico para prevenir intercorrências estomaológicas e, na outra, cujas condições de saúde bucal eram favoráveis, mas que desenvolveu mucosite durante o tratamento oncológico, foi instituído um protocolo para tratar as lesões. Considerações finais: as inadequadas condições de saúde bucal prévias ao tratamento oncológico influenciam diretamente nas intercorrências estomatológicas, aumentando os riscos de infecção local e sistêmica, prejudicando a alimentação e a recuperação do paciente e, dessa forma, aumentando o uso de analgésicos e de dias de internação hospitalar. A avaliação, o tratamento odontológico e o condicionamento bucal, previamente ao tratamento oncológico, tem sido importante na prevenção de sequelas para os pacientes pediátricos.