Experimental Studies of Boronophenylalanine ((10)BPA) Biodistribution for the Individual Application of Boron Neutron Capture Therapy (BNCT) for Malignant Melanoma Treatment.

PURPOSE: Patients with the same histopathologic diagnosis of cutaneous melanoma treated with identical protocols of boron neutron capture therapy (BNCT) have shown different clinical outcomes. The objective of the present studies was to evaluate the biodistribution of boronophenilalanina ((10)BPA) for the potential application of BNCT for the treatment of melanoma on an individual basis. METHODS AND MATERIALS: The boronophenilalanine (BPA) uptake was evaluated in 3 human melanoma cell lines: MEL-J, A375, and M8. NIH nude mice were implanted with 4 10(6) MEL-J cells, and biodistribution studies of BPA (350 mg/kg intraperitoneally) were performed. Static infrared imaging using a specially modified infrared camera adapted to measure the body infrared radiance of small animals was used. Proliferation marker, Ki-67, and endothelial marker, CD31, were analyzed in tumor samples. RESULTS: The in vitro studies demonstrated different patterns of BPA uptake for each analyzed cell line (P<.001 for MEL-J and A375 vs M8 cells). The in vivo studies showed a maximum average boron concentration of 25.9 ± 2.6 µg/g in tumor, with individual values ranging between 11.7 and 52.0 µg/g of (10)B 2 hours after the injection of BPA. Tumor temperature always decreased as the tumors increased in size, with values ranging between 37 °C and 23 °C. A significant correlation between tumor temperature and tumor-to-blood boron concentration ratio was found (R(2) = 0.7, rational function fit). The immunohistochemical studies revealed, in tumors with extensive areas of viability, a high number of positive cells for Ki-67, blood vessels of large diameter evidenced by the marker CD31, and a direct logistic correlation between proliferative status and boron concentration difference between tumor and blood (R(2) = 0.81, logistic function fit). CONCLUSION: We propose that these methods could be suitable for designing new screening protocols applied before melanoma BNCT treatment for each individual patient and lesion.

Osteosarcoma of the jaw: an analysis of a series of 74 cases.

AIMS: To analyse a series of cases of osteosarcoma of the jaw. METHODS AND RESULTS: The study included 74 cases of osteosarcoma of the jaw. Their clinical, radiographic and histopathological features were analysed, and their frequency with respect to aggressive and malignant pathologies of the jaw was determined. Survival was assessed in 17 cases with available follow-up. Osteosarcoma of the jaw accounted for 10% of primary malignant and aggressive tumours of the jaw, and for 8% of all malignant lesions of the jaw, including metastatic and lymphoproliferative tumours. The mean age was 43 ± 18 years. Radiographic features varied greatly and were non-specific, with a predominance of mixed images. The dominant histological pattern was osteoblastic (48.4%), followed by chondroblastic (37.1%). The survival rate at 5 years was 68%. Females and patients with a predominantly chondroblastic pattern had lower survival rates. CONCLUSIONS: Osteosarcoma of the jaw was the most frequent primary malignant tumour of the jaw. Female gender and a predominantly chondroblastic pattern may be associated with a worse prognosis.

Oral mucosa tissue response to titanium cover screws.

BACKGROUND: Titanium is the most widely used metal in dental implantology. The release of particles from metal structures into the biologic milieu may be the result of electrochemical processes (corrosion) and/or mechanical disruption during insertion, abutment connection, or removal of failing implants. The aim of the present study is to evaluate tissue response of human oral mucosa adjacent to titanium cover screws. METHODS: One hundred fifty-three biopsies of the supra-implant oral mucosa adjacent to the cover screw of submerged dental implants were analyzed. Histologic studies were performed to analyze epithelial and connective tissue as well as the presence of metal particles, which were identified using microchemical analysis. Langerhans cells, macrophages, and T lymphocytes were studied using immunohistochemical techniques. The surface of the cover screws was evaluated by scanning electron microscopy (SEM). RESULTS: Forty-one percent of mucosa biopsies exhibited metal particles in different layers of the section thickness. Particle number and size varied greatly among specimens. Immunohistochemical study confirmed the presence of macrophages and T lymphocytes associated with the metal particles. Microchemical analysis revealed the presence of titanium in the particles. On SEM analysis, the surface of the screws exhibited depressions and irregularities. CONCLUSIONS: The biologic effects seen in the mucosa in contact with the cover screws might be associated with the presence of titanium or other elements, such as aluminum or vanadium. The potential long-term biologic effects of particles on soft tissues adjacent to metallic devices should be further investigated because these effects might affect the clinical outcome of the implant.

Ploidy study in oral carcinomas: use of improved methodology to assess its clinical prognostic value.

OBJECTIVE: This study reports a ploidy analysis in oral squamous cell carcinomas (SCC) using methodologic adjustments to improve the accuracy of the measurements and derive numeric indices of aggressiveness of prognostic value. STUDY DESIGN: Sixty-seven SCC were assessed by DNA image cytometry in the areas of the histologic sections with most atypia. Five indices of aggressiveness were analyzed in relation to the clinical-pathologic data and evolution of the patients. RESULTS: The mean value of the index of deviation from the diploid value (2cDi) and malignancy index (Mi), taken as a cut-off value, defined 2 populations with statistically significant differences in survival. In patients with tumors in clinical stages III and IV (TNM classification), the Mi also exhibited prognostic value. CONCLUSIONS: The 2cDi and Mi can be used, under certain methodologic conditions, as an objective indicator of prognostic value of the degree of aggressiveness of oral SCC.

Expression of ezrin and metastatic tumor antigen in osteosarcomas of the jaw.

AIMS AND BACKGROUND: Ezrin is a membrane-cytoskeleton linker protein involved in regulation of the growth and metastatic behavior of cancer cells. Metastatic tumor antigen (MTA) is a potential metastasis-associated protein. The objective of this study was to evaluate the expression of ezrin and MTA and their correlation with clinicopathological features in osteosarcomas of the jaw. METHODS: We analyzed ezrin and MTA protein levels by immunohistochemistry in 31 osteosarcomas of the jaw. RESULTS: The mean age at diagnosis was 39 years and half of the patients were male. The mandible (n = 19) was more frequently involved than the maxilla (n = 12). The predominant histological type was chondroblastic (58.1%) and 24 patients (77.4%) were classified as having a high grade of malignancy. Immunoreactivity for ezrin was identified in 6 of 31 cases (19.4%), while 77.4% displayed expression of MTA. All ezrin-positive patients had high-grade tumors. The high-grade tumors (n = 24) had a higher rate of MTA expression (42.9% vs 87.5%). Expression of ezrin and MTA was not significantly different according to age, sex, tumor site, histological type, and tumor ploidy. Follow-up information was available for 13 patients, with a mean follow-up time of 26.7 months (range, 6-48 months). At the time of last follow-up, 5 (38.5%) patients had died of disease and 8 patients (61.5%) were alive with no evidence of disease. Expression of ezrin and MTA was not significantly different according to the follow-up data. CONCLUSIONS: In our study, high-grade tumors had a higher rate of ezrin and MTA expression. This expression pattern indicates that ezrin and MTA positivity can be additional prognostic markers in osteosarcoma of the jaw.

Ploidy studies of pleomorphic adenomas and minor salivary gland carcinomas of the palate.

Ploidy studies of tumors are a diagnostic and prognostic aid. The aim of the present study was to evaluate the DNA content of palate aggressive pleomorphic adenomas (PA) and adenocarcinomas of the salivary glands. Twelve cases of salivary gland tumors of the palate were selected from the archives of the Oral Pathology Department, Faculty of Dentistry, University of Buenos Aires (1966-2001). Six cases corresponded to aggressive pleomorphic adenomas (PA) and the remaining six to adenocarcinomas (AD). Myxoid and epithelial areas of PA were evaluated. The epithelial areas of the most aggressive cases of PA exhibited a high DNA content. The myxoid areas of same cases of PA had a 2C ploidy level. The difference in ploidy values between the myxoid and epithelial areas of PA would suggest the presence of different cell populations. DNA content and the detection of aneuploidy would be prognostic aids in palate salivary gland carcinomas.

Clinical features and evolution of oral cancer: A study of 274 cases in Buenos Aires, Argentina.

UNLABELLED: Oral Squamous Cell Carcinoma has a low survival rate, 34 to 66% five-year survival after initial diagnosis, due to late diagnosis. OBJECTIVES: The aim of the present study was to examine the clinical features and evolution of oral cancer in the University of Buenos Aires. STUDY DESIGN: 274 patients with primary oral carcinoma, over the 1992-2000 period were included in the study. RESULTS: The survival rate of this population was 80% at 12 months, 60% at 24 months, 46% at 36 months, 40% at 48 months, and 39% at 60 months (5 years). The tumor localizations with worse prognosis were floor of mouth and tongue, with survival rates of 19% and 27% respectively. Sixty-five percent of the oral carcinomas evaluated were diagnosed at advanced stages (III and IV). CONCLUSIONS: The patients under study exhibited the lowest survival rate described for oral cancer (34% five-year survival after initial diagnosis). The population included in this study can be considered representative of the Argentine population. This bad prognosis would be mainly due to the large number of oral cancer cases that were diagnosed at advanced stages.

Ploidy studies of pleomorphic adenomas and minor salivary gland carcinomas of the palate

Los estudios de ploidía son usados como herramienta en el diagnóstico y pronóstico de tumores. El objetivo del presente estudio fue evaluar el contenido de ADN de adenomas pleomorfos (PA) y carcinomas de glándulas salivales de paladar.Se seleccionaron 12 casos de tumores de glándulas salivales de paladar de los archivos de la Cátedra de Anatomía Patológica de la Facultad de Odontología de la Universidad de Buenos Aires (1966-2001). Seis casos correspondieron a Adenomaspleomorfos y seis a adenocarcinomas. Se evaluaron las areas mixoides y epiteliales de los PA. En todos los casos de PA obtuvimos en los sectores epiteliales, un contenido elevado de DNAdel orden de 4C. En tanto las areas mixoides de los PA revelaron ploidas de 2C. Los resultados mostraron tres rangosdiferentes de contenidos de ADN. Laos sectores mixoides de los PA evidenciaron valores en el rango 2C, Llos sectores epiteliales de los PA fueron en un rango 4C y los adenocarcinomas mostraron valores anueploides. Se han encontradodiferencias en el contenido de DNA en los AP entre las áreas epiteliales y mixoides. Esto permitiría suponer la existencia de diferentes poblaciones celulares, con grado de agresividaddiferente. El contenido de ADN y su carácter aneuploide podrían ser de utilidad pronóstica en los carcinomas de glándulas salivales menores.

Evaluation of nucleolar organizer regions in maxillary osteosarcoma.

Maxillary osteosarcomas are a relatively frequent malignant tumor of the oral cavity. Similarly to other skeletal osteosarcomas, they exhibit different cellular differentiation patterns, i.e. chondroblastic, osteoblastic, or fibroblastic. Although their histological features resemble those of osteosarcomas of the long bones, their pattern of evolution usually differs. Morphometric variations in silver stained Nucleolar Organizer Regions (AgNOR) have proved of value to study the biology of several tumors. However, information on the analysis of AgNOR in maxillary tumors is scarce. The aim of the present study was to analyze the variations of different morphological parameters related to AgNOR in a series of 32 cases of maxillary osteosarcoma. In each case we analyzed 100 nuclei corresponding to the prevalent cellular differentiation type, selecting the most aggressive area. We employed software previously developed at our laboratory that yields information on different AgNOR-related parameters. The results were compared with those previously reported in a study on 12 cases of osteosarcoma of long bones. Six cases of oral mucosa squamous cell carcinoma were also included for comparative purposes. Single AgNOR volume proved to be the most discriminatory and informative parameter. The value of single AgNOR volume was considerably lower in mandible osteosarcomas than in osteosarcomas of the upper maxilla (p=0.02). The values were significantly lower in maxillary osteosarcomas than in long bone osteosarcomas and in oral carcinomas. This finding would suggest a slower rate of cell activity in maxillary osteosarcomas, associated in turn to its known lower degree of aggressiveness. The present results suggest that the analysis of AgNOR is a valuable and easily applicable marker to determine the degree of malignancy and biology of maxillary osteosarcomas.

Analysis of the epidemiological features of oral cancer in the city of Buenos Aires.

Oral cancer comprises 0.6 to 5% of all human malignant tumors. It is accepted in the literature that the clinical evolution of oral cancer has a bad prognosis, i.e. the five year survival rate ranges from 34% to 56%. The aim of the present study was to present a metaanalysis of the most relevant publications on oral cancer in the city of Buenos Aires, including our own series. The publications reviewed herein include the following series: 517 cases (1950-1970), 243 cases (1961-1968), 336 cases (1972-1984), and 274 cases (1992-2000). The clinical end-points evaluated were: age, distribution by sex, tumor site, presence of metastatic adenopathies, and clinical stage. A comparative statistical evaluation of the clinical parameters assessed was performed. Survival was evaluated by the test of Kaplan-Meier. The male/female ratio was 7.1:1 for the 1950-1970 period, 4.3:1 for the 1961-1968 period; 2.3:1 for the 1972-1984 period; and 1.24:1 in our series (1992-2000). The most frequent tumor site (21 to 35% of the cases) was the tongue. At the time of diagnosis, 60-71% of the patients had advanced TNM clinical stages (III and IV). Our follow-up revealed a five-year survival rate after diagnosis of 39%. The overall analysis of all the cases corresponding to the 1950-2000 period revealed that the prevalence of oral cancer in women has risen alarmingly and that the percentage of patients with advanced stages of tumor development continues to be high.

Analysis of te epidemiological features of oral cancer in the city of Buenos Aires / Análisis de las características epidemiológicas del cáncer bucal en la ciudad de Buenos Aires

El cáncer de la cavidad bucal representa entre el 0.6 al 5 por ciento de los tumores malignos del cuerpo humano. La literatura coincide en que la evolución clínica es de mal pronóstico (sobrevida de 34 al 56 por ciento después de 5 años de diagnosticado). El objetivo de este trabajo es presentar un metaanálisis de los trabajos más relevantes publicados sobre cáncer bucal en la ciudad de Buenos Aires, incluyendo nuestro propia casuística. Los trabajos analizados incluyen las siguientes series: 517 casos (1950-1970), 243 casos (1961-1968), 336 casos (1972-1984) y 274 casos (1992-2000). Los parámetros clínicos analizados fueron edad, distribución or sexo, localización, tamaño tumoral, presencia de adenopatías metastásicas y estadio clínico. Se realizaron análisis estadísticos comparativos de los parámetros clínicos evaluados y se estudió la sobrevida mediante test de Kaplan y Meier. La relación sexo masculino/femenino para el período 1950-1970 fue de 7.1:1 durante el período 1961-1968 de 4.3:1; durante 1972-1984 de 2.3:1; y en nuestra casuística (1992-2000) de 1.24:1. La localización más frecuente (21 a 35 por ciento de los casos) fue la lengua. En el momento del diagnóstico entre el 60 y 71 por ciento de los pacientes presentaban estadíos clínicos TNM avanzados (III y IV). La sobrevida resultante de nuestro seguimiento para 5 años después del diagnósitoco fuel del 39 por ciento. Del análisis de la totalidad de casos correspondientes al intervalo de tiempo entre 1950-2000 se desprende que ha aumento progresivamente en forma alarmante la prevalencia del cáncer en las mujeres y se mantiene un elevado porcentaje de pacientes con diagnóstico en etapas avanzadas del tumor

Estudio radiografico de muestras de tejido oseo de cresta iliaca humana: su significado frente a la puncion osea para estudios metabolicos / Radiographic study of iliac crest bone tissue samples. Significance compared to bone puncture for metabolic studies

Introduccion: Las alteraciones del tejido oseo se estiman con diferentes metodologias: analisis del medio interno, estudios radiograficos simples o con doble longitud de onda para evaluar el contenido mineral y biopsia osea de cresta iliaca. En este trabajo presentamos un estudio radiografico con analisis de imagenes de 220 muestras de cresta iliaca con el objetivo de establecer parametros de densidad osea en una poblacion sin patologia evidente. Materiales y metodos: Se obtuvieron 220 muestras de cresta iliaca y de ri¤on de autopsias (48 correspondientes a mujeres y 172 a varones). Se radiografiaron con placas de alta resolucion y las imagenes se digitalizaron. Sobre esta imagen digitalizada se realizo el estudio densitometrico con un patron de tejido equivalente en cera virgen. Resultados: Este estudio demostro notables alteraciones del patron convencional densitometrico. Se detectaron importantes variaciones a nivel de la cortical y de la esponjosa. Conclusiones: Las importantes variaciones observadas podrian cuestionar el valor de la densidad osea a partir de la puncion osea metabolica convencional