GSTM1, GSTT1 and GSTP1 Ile105Val polymorphisms in outcomes of head and neck squamous cell carcinoma patients treated with cisplatin chemoradiation.

Cisplatin (CDDP) combined with radiotherapy (RT) is employed in head and neck squamous cell carcinoma (HNSCC) with variable toxicities and clinical response. Glutathione S-transferases (GSTs) participate in CDDP excretion from cells, and genes encoding GSTs, GSTM1, GSTT1and GSTP1, are polymorphic in humans. This prospective study aimed to evaluate the roles of GSTM1, GSTT1, and GSTP1 Ile105Val polymorphisms in outcomes of HNSCC patients treated with CDDP chemoradiation. Ninety patients were genotyped by multiplex PCR. Urinary CDDP measurements were performed by HPLC. Treatment side effects and response were analysed by conventional criteria. Patients with GSTT1 genes showed 7.23- and 5.37-fold higher likelihood of presenting vomiting and ototoxicity, lower glomerular filtration rate (GFR), and lower elimination of CDDP in urine relative to patients with deleted genes. Patients harbouring the GSTP1 IleVal or ValVal genotypes showed 4.28-fold higher likelihood of presenting grade 2 or 3 vomiting and lower GFR with treatment than those harbouring the IleIle genotype. In multivariate Cox analysis, patients with the GSTP1 105ValVal genotype had 3.87 more chance of presenting disease progression than those with the IleIle or IleVal genotype (p < 0.01). Our findings provide preliminary evidence that inherited abnormalities in CDDP metabolism, related to GSTT1 and GSTP1 Ile105Val polymorphisms, alter outcomes of HNSCC patients treated with CDDP and RT.

The Effect of Fibroblast Growth Factors in Grafted Fascia into the Vocal Fold of Rabbits

Abstract Introduction The human larynx is a very important organ for communication. Many conditions lead to scarring of the vocal folds, decreasing voice quality. Objective We aimed to determine whether fibroblast growth factors (FGFs) may influence tissue integration of grafted fascia into the vocal folds of an animal model. Methods This is an experimental animal study with 12 adult rabbits that were submitted to a grafting fragment obtained from superficial cervical fascia into the vocal fold lamina propria, bilaterally. The right vocal fold was injected with FGFs. The animals were sacrificed after 1 month or 12 months, depending on the group they were assigned to, and a histological analysis of their vocal folds was performed.We analyzed the histological changes (such as the presence of fibrosis and neovascularization) induced by the acute or chronic inflammatory reactions. Results The FGFs induced acute inflammatory changes in all animals after 1 month of the initial experiment. The presence of FGFs triggered more fibrosis than the expected due to the surgical procedure itself when compared with the control side of all animals after 12 months of the initial experiment. Conclusions Fibroblast growth factors alone do not represent a good therapeutic option in phonosurgery, since we observed higher levels of fibrosis in the vocal fold lamina propria. Further studies combining more substances may be necessary to elucidate the best option to be used in this kind of surgery. (AU)

The Effect of Fibroblast Growth Factors in Grafted Fascia into the Vocal Fold of Rabbits.

Introduction The human larynx is a very important organ for communication. Many conditions lead to scarring of the vocal folds, decreasing voice quality. Objective We aimed to determine whether fibroblast growth factors (FGFs) may influence tissue integration of grafted fascia into the vocal folds of an animal model. Methods This is an experimental animal study with 12 adult rabbits that were submitted to a grafting fragment obtained from superficial cervical fascia into the vocal fold lamina propria, bilaterally. The right vocal fold was injected with FGFs. The animals were sacrificed after 1 month or 12 months, depending on the group they were assigned to, and a histological analysis of their vocal folds was performed. We analyzed the histological changes (such as the presence of fibrosis and neovascularization) induced by the acute or chronic inflammatory reactions. Results The FGFs induced acute inflammatory changes in all animals after 1 month of the initial experiment. The presence of FGFs triggered more fibrosis than the expected due to the surgical procedure itself when compared with the control side of all animals after 12 months of the initial experiment. Conclusions Fibroblast growth factors alone do not represent a good therapeutic option in phonosurgery, since we observed higher levels of fibrosis in the vocal fold lamina propria. Further studies combining more substances may be necessary to elucidate the best option to be used in this kind of surgery.

D2-40/podoplanin expression in chronic villitis of the placenta / Expressão de podoplanina/D2-40 em vilosite crônica placentária

ABSTRACT D2-40/podoplanin (D2-40/PDPN) is a multifunctional protein that can be expressed in lymphatic endothelium and immune cells. D2-40/ PDPN expression in chronic villitis (CV) has not been studied. In 22 cases of CV, we analyzed both D2-40/PDPN expression as well as its coexpression with immune cells markers, and the relationship with stromal cells. In the non-inflamed villi, the D2-40/PDPN positive plexiform pattern has a lymphatic-like conductive network. In the inflamed villi, the D2-40/PDPN expression, predominantly restricted to stromal cells forming a cellular network, is likely related to a phase of the inflammatory response, such as reorganization of the damaged tissue.

RESUMO Podoplanina/D2-40 (PDPN/D2-40) é uma proteína multifuncional que pode ser expressa no endotélio linfático e nas células imunes. Na vilosite crônica (VC), a expressão de PDPN/D2-40 ainda não foi estudada. Em 22 casos de VC, analisamos tanto a expressão de PDPN/D2-40 como sua coexpressão com marcadores de células imunes, além da relação com células estromais. Nas vilosidades não inflamadas, o padrão plexiforme PDPN/D2-40 positivo tem aspecto de rede condutora linfática. Nas vilosidades inflamadas, a expressão de PDPN/D2-40, com predominância restrita às células estromais, formando rede densa está, possivelmente, relacionada com uma fase da resposta inflamatória, como a reorganização do tecido danificado.

Evaluation of the Grafted Fascia in the Vocal Fold of Dogs: A Histologic Study.

INTRODUCTION: There is no consensus on the ideal graft for medialization surgery of the vocal folds in the literature. One of the most favorable proposals is the use of autologous fascia, which seems limited by the lack of information regarding the integration of grafted tissue. Our study aims to evaluate the degree of fully engrafted fascia integration in the vocal fold lamina propria of dogs. MATERIALS AND METHODS: Fourteen adult mongrel dogs that underwent intravenous general anesthesia were selected and kept under spontaneous ventilation. A fascia lata fragment of 4 cm2 was obtained from the right leg of each dog. The dogs underwent laryngoscopy; a 3 mm incision was made in the vocal process, next to the vestibular process, and the fascia was grafted into the right vocal fold. The left vocal fold was used as a control. The animals were divided into two groups: group A, evaluated after 2 months of the procedure, and group B, evaluated after 6 months of the procedure. Histologic analysis was made semiquantitatively regarding the presence of inflammatory reaction, fibrosis, and neovascularization. RESULTS: Our final studied group comprised 12 dogs. Microscopic examination of the larynx revealed the absence of any detectable inflammation in the incision site. The lamina propria of the grafted vocal fold showed identifiable compact, thick, and eosinophilic collagen bands. The surrounding tissue showed thin collagen bands with some organization, similar to the contralateral vocal fold. CONCLUSION: The grafted fascia integrates into the vocal fold lamina propria and seems not to cause inflammatory reaction response.

Hemangioendotelioma kaposiforme associado à síndrome de Kasabach-Merritt / Kaposiform hemangioendothelioma associated with Kasabach-Merritt

Objetivo: Descrever um caso de hemangioendotelioma kaposiforme, único tumor malígno de origem vascular específico da infância. Métodos: Relata-se o caso de lactente do sexo feminino com 40 dias de vida que apresentava um hemagioma gigante da face. O tumor evoluiu com crescimento rápido levando à compressäo da laringe com insuficiência grave. A criança tinha ainda uma coagulopatia trombocitopênica de consumo (síndrome de Kasabach-Merritt). Resultados: Ela foi admitica à UTI Pediátrica do Hospital das Clínicas da Universidade Estadual de Campinas e foi iniciada ventilaçäo mecânica. O tratamento durante dez dias com dexametasona levou à melhora por curto período. Foi inciado interferon alfa-2a na dose de 1,8 milhöes de unidades/m²/dia por via subcutânea, porém a paciente foi à óbito 4 dias após o início dessa terapia. A necrópcia revelou o diagnóstico de um hemangioendotelioma kapasiforme. Conclusäo: Discutem-se a evoluçäo fatal pouco freqüente de um hemangioma gigante e suas complicaçöes hematológicas.