Bevacizumab-Conjugated Quantum Dots: In Vitro Antiangiogenic Potential and Biosafety in Rat Retina.

Purpose: Disturbances that affect the inside of the eyeball tend to be highly harmful since they compromise the homeostasis of this organ. Alongside this, the eyeball has several anatomical barriers that prevent the entry of substances. This way, diseases that affect the retina are among those that present greater difficulty in the treatment. In many cases, abnormal proliferation of blood vessels (neovascularization) occurs from the lower layers of the retina. This process damages its structure physiologically and anatomically, causing the rapid and irreversible loss of visual capacity. This work aims to develop nanosuspensions of quantum dots (QDs) conjugated to bevacizumab. Methods: Two types of QDs were produced by aqueous route, stabilized with chitosan conjugated to bevacizumab. The antiangiogenic activity was evaluated in the chorioallantoic membrane model, in which results indicated discrete activity at the doses tested. Samples were assessed for their biosafety in animals, after intravitreal administration, by means of electroretinography (ERG), intraocular pressure (IOP) measurement, histological, morphometric, and immunohistochemical evaluation. Results: No significant alterations were detected in ERG that suggests damage to retinal function by the samples. No significant changes in IOP were also detected. The histological sections did not show signs of acute inflammation, although there was evidence of late retinal damage. The immunohistochemical analysis did not detect any apoptotic bodies. Conclusion: Preliminary results suggest that QDs present potential applicability in ocular therapy, and it is necessary to better characterize their in vivo behavior and to optimize their dosage.

Mast Cells and Blood Vessels Profile in Oral Carcinogenesis: An Immunohistochemistry Study.

BACKGROUND: The objectives of the present study were to evaluate angiogenesis and mast cell density in oral epithelial dysplasia and oral squamous cell carcinoma (OSCC). MATERIALS AND METHODS: This was an observational, retrospective and quantitative study. The samples consisted of 60 tissue specimens from patients with squamous cell carcinoma, epithelial dysplasia and controls (n=20/group). Immunohistochemistry was performed using an anti-tryptase antibody to mast cells and anti-CD31 and anti-CD34 for blood vessels and we count the number of mast cells and determine the percentage of CD31 and CD34 antibody staining (vascular density). RESULTS: The mast cells had lower density in OSCC compared to control and dysplasia (p = 0.009). In angiogenesis, the expression of CD31 showed a higher percentage of blood vessels in OSCC (p < 0.001), however, CD34 showed no difference between groups (p=0.092). The CD31 antibody presented as a high immunostaining in oral mucosa than CD34. CONCLUSIONS: The increased vascularity in squamous cell carcinoma suggests that angiogenesis begins when malignant transformation starts that seems to be inversely associated with the number of mast cells.

Sorafenib in Hepatopulmonary Syndrome: A Randomized, Double-Blind, Placebo-Controlled Trial.

The tyrosine kinase inhibitor sorafenib improves hepatopulmonary syndrome (HPS) in an experimental model. However, the efficacy and adverse effect profile in patients with HPS are unknown. We aimed to determine the effect of sorafenib on the alveolar-arterial oxygen gradient (AaPO2 ) at 3 months in patients with HPS. We performed a randomized, double-blind, placebo-controlled parallel trial of sorafenib in patients with HPS at 7 centers. A total of 28 patients with HPS were randomized to sorafenib 400 mg by mouth daily or a matching placebo in a 1:1 ratio. We found no statistically significant difference in the median change in AaPO2 from baseline to 12 weeks between the patients allocated to sorafenib (4.5 mm Hg; IQR, -3.8 to 7.0 mm Hg) and those allocated to placebo (-2.4 mm Hg; IQR, -4.8 to 8.2 mm Hg; P = 0.70). There was also no difference between the groups in terms of degree of intrapulmonary shunting by contrast echocardiography. Sorafenib significantly reduced circulating levels of angiogenic markers, including vascular endothelial growth factor receptors (P < 0.01) and TIE2-expressing M2 monocytes (P = 0.03), but it reduced the mental component scores of the Short Form 36 (P = 0.04), indicating a worse quality of life. In conclusion, sorafenib did not change the AaPO2 or other disease markers at 3 months in patients with HPS. Alternative antiangiogenic therapies or treatments targeting other pathways should be investigated.

Comparison of anterior segment optical coherence tomography angiography and fluorescein angiography for iris vasculature analysis.

PURPOSE: The aim of this study is to perform imaging of irises of different colors using spectral domain anterior segment optical coherence tomography angiography (AS-OCTA) and iris fluorescein angiography (IFA) and compare their effectiveness in examining iris vasculature. METHODS: This is a cross-sectional observational clinical study. Patients with no vascular iris alterations and different pigmentation levels were recruited. Participants were imaged using OCTA adapted with an anterior segment lens and IFA with a confocal scanning laser ophthalmoscope (cSLO) adapted with an anterior segment lens. AS-OCTA and IFA images were then compared. Two blinded readers classified iris pigmentation and compared the percentage of visible vessels between OCTA and IFA images. RESULTS: Twenty eyes of 10 patients with different degrees of iris pigmentation were imaged using AS-OCTA and IFA. Significantly more visible iris vessels were observed using OCTA than using FA (W = 5.22; p < 0.001). Iris pigmentation was negatively correlated to the percentage of visible vessels in both imaging methods (OCTA, rho = - 0.73, p < 0.001; IFA, rho = - 0.77, p < 0.001). Unlike FA, AS-OCTA could not detect leakage of dye, delay, or impregnation. Nystagmus and inadequate fixation along with motion artifacts resulted in lower quality images in AS-OCTA than in IFA. CONCLUSIONS: AS-OCTA is a new imaging modality which allows analysis of iris vasculature. In both AS-OCTA and IFA, iris pigmentation caused vasculature imaging blockage, but AS-OCTA provided more detailed iris vasculature images than IFA. Additional studies including different iris pathologies are needed to determine the most optimal scanning parameters in OCTA of the anterior segment.

Vascular endothelial growth factor as an angiogenesis biomarker for the progression of autosomal dominant polycystic kidney disease.

Autosomal dominant polycystic kidney disease (ADPKD) is a hereditary nephropathy characterized by abnormal growth of epithelial cells. Genetic factors, including the vascular endothelial growth factor (VEGF) gene, play an important role in its progression. The main aim of this study was to evaluate the influence of VEGF-C936T polymorphism in the development and progression of ADPKD. In total, 302 individuals were studied and divided into two groups: G1 (73 patients with ADPKD) and G2 (229 individuals without the disease). Among the patients, 46 (63%) progressed to end-stage renal disease (ESRD), and required hemodialysis and/or renal transplant. These patients were re-grouped into G1-A for progression analysis. A peripheral blood sample was obtained from all subjects; the DNA was extracted and the VEGF-C936T polymorphism analyzed using polymerase chain reaction/restriction fragment length polymorphism. The significance level was set at P < 0.05. The homozygous wild-type genotype (C/C) was predominant in G1 (78%) and G2 (79%; P = 0.9249). We observed a significant reduction in the mean age of patients with the risk allele (C/T + T/T = 44.3 ± 13.4 years) compared to the C/C genotype (52.2 ± 9.6 years; P = 0.047) in G1-A. In conclusion, the VEGF-C936T polymorphism does not discriminate patients from controls. However, the presence of the T allele appears to accelerate the progression of ADPKD, anticipating ESRD, thereby suggesting its importance in the prognosis of the disease. However, the importance role played by VEGF gene variants in different populations and larger sample sizes must be verified.

Heart rate turbulence analysis in female patients with fibromyalgia

OBJECTIVE: Fibromyalgia is characterized by diffuse musculoskeletal pain and discomfort. There are several reports regarding autonomic nervous system dysfunction in patients with fibromyalgia. Heart rate turbulence is expressed as ventriculophasic sinus arrhythmia and has been considered to reflect cardiac autonomic activity. Heart rate turbulence has been shown to be an independent and powerful predictor of sudden cardiac death in various cardiac abnormalities. The aim of this study is to determine whether heart rate turbulence is changed in female patients with fibromyalgia compared with healthy controls. METHODS: Thirty-seven female patients (mean age, 40±11 years) with fibromyalgia, and 35 age- and sex-matched healthy female control subjects (mean age, 42±9 years) were included. Twenty-four hours of ambulatory electrocardiography recordings were collected for all subjects, and turbulence onset and turbulence slope values were automatically calculated. RESULTS: The baseline clinical characteristics of the two groups were similar. There were no significant differences in turbulence onset and turbulence slope measures between patients and control subjects (turbulence onset: −1.648±1.568% vs. −1.582±1.436%, p ϝ 0.853; turbulence slope: 12.933±5.693 ms/RR vs. 13.639±2.505 ms/RR, p ϝ 0.508). Although body mass index was negatively correlated with turbulence slope (r ϝ −0.258, p ϝ 0.046), no significant correlation was found between body mass index and turbulence onset (r ϝ 0.228, p ϝ 0.054). CONCLUSION: To the best of our knowledge, this is the first study to evaluate heart rate turbulence in patients with fibromyalgia. It appears that heart rate turbulence parameters reflecting cardiac autonomic activity are not changed in female patients with fibromyalgia. .

Transscleral delivery of Nd: YLF laser at 1,047 nm causes vascular occlusion in experimental pigmented choroidal melanoma.

PURPOSE: The aims of this study were to determine the scleral attenuation of focused neodymium: yttrium-lanthanum-fluoride laser at 1,047 nm applied transsclerally and whether transscleral delivery can close the vascular supply at the base of experimental choroidal melanoma in rabbits. METHODS: Fifty-two New Zealand albino rabbits were included. Scleral laser attenuation was measured across fresh sclera. B16F10 melanomas were established in the subchoroidal space of 49 rabbits. Twenty-one animals were killed immediately after transscleral treatment, 14 were followed for 2 weeks to 4 weeks, and 14 were followed without treatment. Ophthalmoscopy, fundus photographs, and fluorescein angiography were performed before treatment, immediately after, and weekly during the follow-up. Eyes were examined by light microscopy. RESULTS: Sclera attenuated laser energy by 31% ± 7%. Immediately after treatment, angiography showed diffuse hypofluorescence in 71% (15 of 21 rabbits). Light microscopy showed vascular occlusion extending at least two thirds of the tumor thickness from the base. Seven of the 14 tumors followed for 15 days ± 8 days were eradicated. There was no correlation between tumor height and eradication. CONCLUSION: Rabbit sclera attenuated 31% ± 7% of laser energy. A single transscleral treatment causes tumor vascular closure at the base and may serve as an adjuvant therapy to ensure destruction of deep and intrascleral tumor cells.

Sickle cell retinopathy: diagnosis and treatment.

Hemoglobinopathies are a group of inherited disorders characterized by quantitative or qualitative malformations of hemoglobin (Hb). Some of these diseases present vaso-occlusive phenomena that are responsible for high morbidity in clinical and/or ophthalmologic terms. Diagnosis of hemoglobinopathies is performed exclusively through hemoglobin electrophoresis. From the ophthalmologic perspective, the most important representative of this group of diseases is sickle cell retinopathy, which presents a wide spectrum of fundus manifestations and may even lead to irreversible vision loss if not properly diagnosed and treated. The aim of this review is to present the classification of sickle cell retinopathy and to describe current management and future perspectives for its treatment, taking into consideration the clinical management of these patients.

Sickle cell retinopathy: diagnosis and treatment / Retinopatia falciforme: diagnóstico e tratamento

Hemoglobinopathies are a group of inherited disorders characterized by quantitative or qualitative malformations of hemoglobin (Hb). Some of these diseases present vaso-occlusive phenomena that are responsible for high morbidity in clinical and/or ophthalmologic terms. Diagnosis of hemoglobinopathies is performed exclusively through hemoglobin electrophoresis. From the ophthalmologic perspective, the most important representative of this group of diseases is sickle cell retinopathy, which presents a wide spectrum of fundus manifestations and may even lead to irreversible vision loss if not properly diagnosed and treated. The aim of this review is to present the classification of sickle cell retinopathy and to describe current management and future perspectives for its treatment, taking into consideration the clinical management of these patients.

As hemoglobinopatias são um grupo de doenças hereditárias caracterizadas por mal-formações quantitativas ou qualitativas da hemoglobina (Hb). Algumas destas doenças podem apresentar fenômenos vaso-oclusivos, responsáveis por alta morbidade do ponto de vista clínico e/ou oftalmológico. O diagnóstico das hemoglobinopatias é feito exclusivamente através da eletroforese de hemoglobinas. Do ponto de vista oftalmológico, a representante mais importante deste grupo de doenças é a retinopatia falciforme, que pode apresentar um amplo espectro de manifestações fundoscópicas, podendo, inclusive, levar à perda visual irreversível se não for corretamente diagnosticada e tratada. O objetivo desta revisão é apresentar a classificação desta doença, a conduta no tratamento atual, bem como suas perspectivas futuras de tratamento, considerando-se as particularidades no manejo clínico destes pacientes.

Assessment of vascular invasion in gastric cancer: a comparative study.

AIM: To evaluate and compare detection of lymphatic and blood vessel invasion (LVI and BVI) by hematoxylin-eosin (HE) and immunohistochemistry (IHC) in gastric cancer specimens, and to correlate with lymph node status. METHODS: IHC using D2-40 (a lymphatic endothelial marker) and CD34 (a pan-endothelial marker) was performed to study LVI and BVI in surgical specimens from a consecutive series of 95 primary gastric cancer cases. The results of the IHC study were compared with the detection by HE using McNemar test and kappa index. The morphologic features of the tumors and the presence of LVI and BVI were related to the presence of lymph node metastasis. A χ(2) test was performed to obtain associations between LVI and BVI and other prognostic factors for gastric cancer. RESULTS: The detection rate of LVI was considerably higher than that of BVI. The IHC study identified eight false-positive cases and 13 false-negative cases for LVI, and 24 false-positive cases and 10 false-negative cases for BVI. The average Kappa value determined was moderate for LVI (κ = 0.50) and low for BVI (κ = 0.20). Both LVI and BVI were statistically associated with the presence of lymph node metastasis (HE: P = 0.001, P = 0.013, and IHC: P = 0.001, P = 0.019). The morphologic features associated with LVI were location of the tumor in the distal third of the stomach (P = 0.039), Borrmann's macroscopic type (P = 0.001), organ invasion (P = 0.03) and the depth of tumor invasion (P = 0.001). The presence of BVI was related only to the depth of tumor invasion (P = 0.003). CONCLUSION: The immunohistochemical identification of lymphatic and blood vessels is useful for increasing the accuracy of the diagnosis of vessel invasion and for predicting lymph node metastasis.

Lack of prognostic significance of angiogenesis in canine melanocytic tumours.

The prognostic significance of angiogenesis in some canine tumours has been investigated, but little is known about its relevance in canine melanocytic tumours (MTs). The aim of this study was to evaluate the prognostic significance of angiogenesis in canine MTs. A total of 36 cutaneous melanocytomas (benign MTs), 40 cutaneous melanomas (malignant MTs) and 43 oral melanomas were studied. Survival data were available for a subset of 59 cases. Microvessel density (MVD) and endothelial area (EA) were determined by immunolabelling using an antibody specific for von Willebrand factor (vWF). Mean MVD (expressed as the number of microvessels per mm(2)) was 129 ± 14 in melanocytomas, 191 ± 16 in cutaneous melanomas and 208 ± 16 in oral melanomas. Mean EA (expressed as the percentage of the total area) was 1.5 ± 0.14 in melanocytomas, 2.6 ± 0.2 in cutaneous melanomas and 2.4 ± 0.3 in oral melanomas. The differences in MVD and EA between melanocytomas and melanomas were significant (P = 0.001 and P = 0.003, respectively). MVD and EA were significantly correlated between cutaneous and oral MTs (r = 0.54; P <0.001 and r = 0.63; P <0.001, respectively). MVD and EA were not related to survival in cutaneous and oral MTs. In conclusion, tumour vascularization was higher in melanomas than in melanocytomas, but it seemed to have no prognostic significance in these tumours.

Correlação da expressão do receptor do fator de crecimento do epitélio vascular (VEGRF1) e do KI-67, em pacientes com câncer de mama, com variáveis histopatológicas / Correlations of the expression of the receptor of vascular endothelial growth factor (VEGF) and ki-67 with phatological variables in breast cancer patients

Correlação da expressão do receptor do fator de crescimento do epitélio vascular - vascular endothelial growth factor (VEGF) e do KI-67, em pacientes com câncer de mama, com variáveis histopatológicas. Introdução: proteínas que influam na proliferação celular, como o VEGF e o KI-67, são alvo de estudos. O VEGF está implicado na angiogênese, que é necessária ao crescimento tumoral. Objetivo: Analisar a correlação do VEGF e do KI-67 com variáveis histopatológicas. Métodos: entre 15/03/2008 e 14/0412009, incluímos 41 pacientes com câncer de mama inicial, rumores T1 e T2, para estudo, usando a coloração H & E na análise do tumor, grau histológico e invasão vascular e a imunoperoxidade para a avaliação imuno-histoquímica com anticorpos específicos para os receptores de VEGF, KI-67, p53 e receptor de estrogênio (RE), usando escore qualitativo até 3+ na avaliação da intensidade da coloração e/ou quantitativo até 5+, para avaliar a expressão percentual das células coradas. O escore total, soma das duas, pode chegar ao máximo de 8+. Apenas o KI-67 foi categorizado pelo percentual de células coradas na IHQ e considerado positivo a partir de 20%. Resultados: O receptor do VEGFR1, tanto no escore intensidade de cor quanto no escore total, apresenta correlação positiva com os tumores T1 (p=.01), com o receptor estrogênico positivo (p=.01) e com a expressão negativa do KI-67 (p=.02). A expressão do KI-67 apresenta correlação positiva com p53 (p=.00) e com o receptor hormonal negativo (RE-) (p=.04) e correlação fraca com a invasão vascular (p=.09) e o grau histológico indiferenciado (G3) (p=.07). Discussão: A avaliação de marcadores tumorais que possam responder à terapia alvo é um objetivo a ser perseguido. A correlação positiva do VEGF com o status do RE ja foi relatada e está de acordo com nossos resultados. A expressão do KI-67 é associada à pobre evento. Os resultados controversos dos marcadores refletem a dificuldade em padronizar as avaliações (reagentes)...

Correlation of the expression of the receptor of vascular endothelial growth factor (VEGP) and KI-67 with pathological variables in breast cancer patients. Background: Many studies have been conducted on proteins that have action on cell proliferation, such as VEGP and KI-67. VEGP acts in the angiogenesis required for tumor growth. The KI-67 correlates with proliferation of tumor cells, probably reflecting its aggressiveness. Objective: To analyze the correlation of VEGPR1 and KI-67 with pathological variables. Methods: The study was approved by the Committee on Ethics in research, University Hospital of Porto Alegre (RS). Between March 2008 and April 2009 we included 41 patients with early breast cancer (T1 and T2). We used H & E staining for tumor analysis, histological grade and vascular invasion, and immunohistochemistry evaluation with antibodies specific for VEGP receptors, KI-67, p53, estrogen receptor (ER), using quality score until 3+ of the evaluation of intensity of stain and quantitative untiI 5+, to evaluate the expression percentage of stained cells. The total score, add either, can reach 8+ Only the KI-67 was categorized by percentage of stained cells in the IHC and considered positive above 20%. Statistics: correlation and pearson's chi square and, for the significant variables, used the multivariate analysis. Results: The receptor VEGPR1 in both color intensity score and the total score, correlated positively with T1 tumors (p=.01), with the estrogen receptor positive (p=.01) and negative expression of KI-67 (p=.02). The expression of KI-67 correlates positively with p53 (p=.00) and with estrogen receptor negative (p=.04) and weak correlation with vascular invasion (p=.09) and histological grade undifferentiated (p=.07). Discussion: evaluation of tumor markers that may respond to targeted therapy is a goal to be pursued. The positive correlation of VEGP with the status of ER has been reported and is consistent with our results...

Sobre - expresión del factor endotelial de crecimiento vascular en blastos leucemicos e implicaciones para el tratamiento de la leucemia mieloide aguda. / Over expression of vascular endothelial growth factor in leukaemic blasts and implication for the treatment of acute myeloid leukaemia

Antecedentes: El factor endotelial de crecimiento vascular (VEGF) y su receptor celular VEGFR-2 ya han sido implicados en la via endotelial principal necesaria para la neovascularización tumoral. Aún así, la importancia del sistema VEGF/VEGFR-2 en angiogenesis en tumores hematológicos como la leucemia mieloide aguda (LMA) no ha sido dilucidado. Pacientes y métodos: Evaluación de 32 pacientes con diagnóstico nuevo y no tratado de LMA, mediante inmunohistoquímica de biopsias de médula osea, se hizo comparación con 10 pacientes control. Resultados: La expresión de VEGF y VEGFR-2 fue significantemente mayor en pacientes con mayor grado de densidad microvascular comparado con aquellos con bajo grado (VEGF: p= 0.024; VEGFR-2: p= 0.040) y también mayor que en los controles (P>0.001), mostrando correlación con la densidad microvascular de médula osea. Los pacientes que alcanzaron una remisión completa después de quimioterapia mostraron niveles bajos normales de VEGFR-2. Conclusión: Se encontró evidencia sobre la aumentada expresión de VEGF/VEGFR-2 en blastos leucémicos, así como la correlación con angiogenesis de pacientes con LMA. Esto sugiere que el sistema VEGF/VEGFR-2 puede ser utilizado como objetivo prometedor en las estrategias de terapia antiangiogénica y antileucémica en LMA...(AU)

Sobre-expresión del factor endotelial de crecimiento vascular en blastos leucemicos e implicaciones para el tratamiento de la leucemia mieloide aguda / Over expression of vascular endothelial growth factor in leukaemic blasts and implication for the treatment of acute myeloid leukaemia

Antecedentes: El factor endotelial de crecimiento vascular (VEGF) y su receptor celular VEGFR-2 ya han sido implicados en la via endotelial principal necesaria para la neovascularización tumoral. Aún así, la importancia del sistema VEGF/VEGFR-2 en angiogenesis en tumores hematológicos como la leucemia mieloide aguda (LMA) no ha sido dilucidado. Pacientes y métodos: Evaluación de 32 pacientes con diagnóstico nuevo y no tratado de LMA, mediante inmunohistoquímica de biopsias de médula osea, se hizo comparación con 10 pacientes control. Resultados: La expresión de VEGF y VEGFR-2 fue significantemente mayor en pacientes con mayor grado de densidad microvascular comparado con aquellos con bajo grado (VEGF: p= 0.024; VEGFR-2: p= 0.040) y también mayor que en los controles (P>0.001), mostrando correlación con la densidad microvascular de médula osea. Los pacientes que alcanzaron una remisión completa después de quimioterapia mostraron niveles bajos normales de VEGFR-2. Conclusión: Se encontró evidencia sobre la aumentada expresión de VEGF/VEGFR-2 en blastos leucémicos, así como la correlación con angiogenesis de pacientes con LMA. Esto sugiere que el sistema VEGF/VEGFR-2 puede ser utilizado como objetivo prometedor en las estrategias de terapia antiangiogénica y antileucémica en LMA...

Immunostaining with D2-40 improves evaluation of lymphovascular invasion, but may not predict sentinel lymph node status in early breast cancer.

BACKGROUND: Sentinel lymph node (SLN) biopsy is a widely used diagnostic procedure in the management of early breast cancer. When SLN is free of metastasis, complete axillary dissection may be skipped for staging in clinically N0 patients, allowing a more conservative procedure. Histological tumor features that could reliably predict SLN status have not yet been established. Since the degree of tumor lymphangiogenesis and vascularization may theoretically be related to the risk of lymph node metastasis, we sought to evaluate the relationship between lymph vessel invasion (LVI), lymphatic microvascular density (LVD), microvascular density (MVD) and VEGF-A expression, with SLN status and other known adverse clinical risk factors. METHODS: Protein expression of D2-40, CD34, and VEGF-A was assessed by immunohistochemistry on paraffin-embedded sections of primary breast cancer specimens from 92 patients submitted to SLN investigation. The presence of LVI, the highest number of micro vessels stained for D2-40 and CD34, and the protein expression of VEGF-A were compared to SLN status, clinicopathological features and risk groups. RESULTS: LVI was detected in higher ratios by immunostaining with D2-40 (p < 0.0001), what would have changed the risk category from low to intermediate in four cases (4.3%). There was no association between LVI and other angiogenic parameters determined by immunohistochemistry with SLN macrometastases, clinical features or risk categories. CONCLUSION: Assessment of LVI in breast carcinoma may be significantly increased by immunostaining with D2-40, but the clinical relevance of altering the risk category using this parameter may not be advocated according to our results, neither can the use of LVI and LVD as predictors of SLN macrometastasis in early breast cancer.

Comparison of acquired cholesteatoma between pediatric and adult patients.

The quantification of angiogenesis and metalloproteinases may be useful in cholesteatoma behavior assessment as markers of its aggressiveness. The objective of this study is to compare markers CD31, MMP2 and MMP9 in pediatric and adult patients. This study is based on cross-sectional studies of pediatric (or=19 years old). Samples of 120 cholesteatomas were fixed in 10% formol, prepared on five slides of each sample through habitual histological techniques, and number of blood vessels (CD31), marking with MMP2 and MMP9, number of matrix cells and thickness at perimatrix cell were observed. Data were analyzed through SPSS using Spearman and Mann-Whitney coefficients. Cholesteatomas were equally distributed: 60 in pediatric patients (11.77 +/- 3.57 years); 60 in adult patients (38.29 +/- 14.51 years). When correlating the number of blood vessels and metalloproteinases with perimatrix thickness, we obtained the following values: pediatric CD31, 7 (4-11); adult CD31, 4 (0-10) (P = 0.044); pediatric cytoplasmatic MMP2, 1 (0-3); adult cytoplasmatic MMP2, 0 (0-1) (P = 0.006); pediatric nuclear MMP2, 0 (0-1); adult nuclear MMP2, 0 (0-1) (P = 0.056); pediatric MMP9, 2 (0-4); adult MMP9, 0 (0-4) (P = 0.049). In conclusion, pediatric cholesteatomas present a more exacerbated inflammatory degree, produce more metalloproteinases, factors that, when combined, could characterize pediatric cholesteatomas as more aggressive than adult cholesteatomas.

Clinico-pathological and immunohistochemical characteristics associated to recurrence/regrowth of craniopharyngiomas.

BACKGROUND: Craniopharyngioma is a rare, benign epithelial brain tumor of the suprasellar region with a high rate of recurrence. Clinical and histopathological features that might be predictors of recurrence/regrowth have not been clearly delineated. METHODS: We compared recurrence/regrowth of the tumors with the clinico-pathological characteristics, vascular density, cell proliferation index, and immunohistochemical profile (cytokeratins, epithelial membrane antigen [EMA], carcinoembrionary antigen [CEA], and laminin) of 47 patients with craniopharyngioma followed for more than 5 years. RESULTS: Tumors were adamantinomatous in 42 cases (89%) and papillary squamous in 5 cases (11%). Immunoreactivity for cytokeratin 8/18/19 was positive in 64%; cytokeratin 5 in 42%; laminin 8 in 62%; and CEA in 21%. The cell proliferation index and vascular density were greater in adamantinomatous than in papillary tumors (22+/-6 versus 17+/-3, p=0.05; and 21+/-3 versus 17+/-3, p=0.037, respectively); they were neither related to recurrence nor to regrowth. No significant differences were found between adamantinomatous and papillary tumors regarding the presence of cytokeratin, laminin, CEA or glial fibrillary acidic protein (GFAP). Recurrence rate at 5 years was 59%. No relation was found between recurrence and adjuvant radiotherapy (AR). Residual tumor after surgery, whorl-like arrays (p=0.04) and immunoreactivity for p53 (p=0.022) were significantly related to recurrence/regrowth. CONCLUSIONS: Residual tumor after surgery, immunoreactivity to p53 and presence of whorl-like arrays are associated to recurrence/regrowth of craniopharyngioma.