Afectación ocular en la enfermedad injerto contra huésped / Ocular damage in graft-versus-host disease

RESUMEN El trasplante alogénico de precursores hematopoyéticos está indicado en el tratamiento de diversos trastornos de la sangre, sobre todo en las neoplasias malignas. La enfermedad injerto contra huésped es la complicación principal de los trasplantes alogénicos de órganos hematopoyéticos. Es una enfermedad inmunológica provocada por la interacción entre el donante y el receptor, mediante respuestas innatas y adaptativas. Con gran frecuencia afecta la piel y el sistema gastrointestinal. Diferentes pueden ser las manifestaciones oculares, pero son las alteraciones de la superficie ocular las más frecuentes. Los cambios en la superficie ocular pueden provocar ceguera. El diagnóstico y el tratamiento precoz mejoran el pronóstico. Además del tratamiento general de la enfermedad es necesario instaurar medidas específicas para controlar las alteraciones oculares. Se realizó una revisión sobre los artículos publicados con el objetivo de conocer sobre la enfermedad injerto contra huésped y su afectación ocular(AU)

ABSTRACT Allogeneic transplantation of hematopoietic precursors is indicated in the treatment of various blood disorders, particularly malignant neoplasms. Graft-versus-host disease is the main complication of allogeneic transplants of hematopoietic organs. GVHD is an immunological condition caused by the interaction between the donor and the recipient manifested as innate and adaptive responses. It very often affects the skin and the gastrointestinal system. A variety of ocular manifestations may also occur, the most common of which are ocular surface alterations. Changes in the ocular surface may cause blindness. Early diagnosis and treatment improve prognosis. Besides the general treatment of the disease it is necessary to implement specific measures to control ocular alterations. A review was conducted of published papers on the topic to become acquainted with graft-versus-host disease and the ocular damage it causes(AU)

El trasplante alogénico haploidéntico: un traje hecho a la medida de nuestras condiciones y necesidades / Haploidentical allogeneic transplant: a tailored suit based on our conditions and needs

El trasplante de progenitores hematopoyéticos alogénico (TPHalo) es un tratamiento potencialmente curativo para muchos pacientes afectados por trastornos hematológicos, ya sean de naturaleza maligna o no. A pesar de ello, hallar al mejor donante posible en el momento apropiado para llevar a cabo el TPHalo se ha convertido progresivamente en uno de los problemas logísticos más difíciles de solventar para la realización de este proceder. Es en este contexto que se inserta la aplicación del TPHalo con el empleo de donantes haploidénticos. La forma que más fuerza toma para abordar este tipo de trasplante en la actualidad es la descrita por los investigadores de la Universidad Johns Hopkins, de Baltimore, Estados Unidos, en la cual se emplea un tratamiento condicionante no mieloablativo y una profilaxis de enfermedad de injerto contra huésped (EICH) que incluye la aplicación de altas dosis de ciclofosfamida los días +3 y +4. Se le señalan resultados muy alentadores en cuanto a la mortalidad no relacionada con la recaída, de ocurrencia de EICH, así como de probabilidades de recaída, sobrevida libre de progresión y sobrevida global. Por ello su realización está permitiendo acceder a numerosos y potenciales donantes. Su actual perfil en cuanto a resultados terapéuticos, accesibilidad, costos económicos y potenciales beneficios a un número superior de pacientes, lo convierte en una alternativa viable y significativa para Cuba(AU)

Allogeneic stem cell transplantation is a potentially curative treatment for many patients affected by haematological disorders, whether malignant or nonmalignant. In spite of this, finding the best donor possible at the appropriate time to carry out the transplantation has gradually become one of the most difficult logistic problems to be solved for this procedure. It is in this context where the application of the procedure is inserted with the use of haploidentical donors. The most forceful way to tackle this type of transplant today is the one described by researchers at Johns Hopkins University in Baltimore, USA, where a nonmyeloablative conditioning treatment and a prophylaxis of graft-versus-host disease (GVHD) are used, including the application of high doses of cyclophosphamide on the days +3 and +4. Results are very encouraging in terms of mortality not related to relapse, the occurrence of GVHD, as well as the probability of relapse, progression-free survival and overall survival. Therefore, its implementation is allowing access to many potential donors. Its current profile in terms of therapeutic results, accessibility, economic costs and potential benefits to a greater number of patients makes it a viable and significant alternative for a country with characteristics like ours(AU)

Outcomes of allogeneic stem cell transplantation among patients with acute myeloid leukemia presenting active disease: Experience of a single European Comprehensive Cancer Center / Resultados do transplante alogênico de células-tronco em doentes com leucemia mieloide aguda com doença ativa: experiência de um único Centro Oncológico Europeu

Summary Introduction: Allogeneic hematopoietic stem cell transplantation (ASCT) representes a potentially curative approach for patients with relapsed or refractory acute myeloid leukemia (AML). We report the outcome of relapsed/refractory AML patients treated with ASCT. Method: A retrospective cohort from 1994 to 2013 that included 61 patients with diagnosis of relapsed/refractory AML. Outcomes of interest were transplant-related mortality (TRM), incidence of acute and chronic graft-versus-host disease (GVHD), relapse incidence, progression-free survival (PFS) and overall survival (OS). Statistical significance was set at p<0.05. Results: The median age was 61 years (range 1 to 65). The cumulative incidence of 90 days, 1 year, and 3 years TRM were 60%, 26.7%, and 13.3%, respectively (p<0.001). The incidence of relapse was 21.7% at 1 year, 13% at 3 years, and 8.7% at 5 years. Median OS was estimated to be 8 months (95CI 3.266-12.734) and median PFS, 3 months (95CI 1.835-4.165). Conclusion: In our cohort, TRM in first years after ASCT remains considerable, but ASCT in this setting seems to be a good choice for AML patients with active disease. However, novel approaches are needed to reduce TRM and relapse in this set of patients.

Resumo Introdução: o transplante alogênico de células-tronco hematopoiéticas (TCTH-alo) representa uma abordagem potencialmente curativa para pacientes com leucemia mieloide aguda (LMA) recorrente ou refratária. Nosso trabalho apresenta o resultado de pacientes com recaída ou doença refratária tratados com TCTH-alo. Método: coorte retrospectiva incluindo 61 pacientes de 1994 a 2013 com diagnóstico de recidiva/LMA refratária. Os desfechos de interesse foram mortalidade relacionada ao transplante (MRT), incidência da doença aguda e crônica do enxerto contra hospedeiro (DECH), incidência de recaídas, sobrevida livre de progressão (PFS - progression-free survival) e sobrevida global (SG). A significância estatística foi considerada para p<0,05. Resultados: a média de idade foi de 61 anos (variação de 1 a 65). A incidência cumulativa de 90 dias, 1 ano e 3 anos de MRT foram de 60%, 26,7% e 13,3%, respectivamente (p<0,001). A incidência de recaída foi de 21,7% em 1 ano, 13% em 3 anos e 8,7% em 5 anos. A SG mediana foi estimada em 8 meses (IC 95% 3,266-12,734) e a mediana de PFS, em 3 meses (IC 95% 1,835-4,165). Conclusão: em nossa coorte, MRT no primeiro ano após o transplante permanece considerável, mas TCTH-alo nesse cenário parece ser uma boa opção para pacientes com LMA ativa. No entanto, novas abordagens são necessárias para reduzir MRT e recaída nesse conjunto de pacientes.

Ajuste de intensidad para el trasplante hematopoyético alogénico en leucemia aguda / Intensity adjustment of hematopoietic alogeneic transplantation in acute leukemia

Background: The intensity of conditioning chemotherapy and radiotherapy in hematopoietic stem cell transplantation (HSCT) varies according to several factors including the patient’s age, pre-existing conditions and performance status. Myeloablative conditioning (MA) increases transplant related mortality and reduces survival in older patients. Reduced intensity conditioning (RIC) is a good option for these patients. Aim: To report our experience with HSCT in patients of different ages with acute leukemia. Material and Methods: Retrospective analysis of 115 allogeneic HSCT performed in patients with acute myeloid or lymphoblastic leukemia. Results: We analyzed the cohort of patients in groups according to age at transplantation: younger than 40 years (n = 74), 41 to 50 years (n = 25) and older than 51 years of age (n = 16). Overall survival (OS), Disease free survival (DFS) and relapse at five years were similar in both groups of patients younger than 50 years (OS 40 and 44% respectively, DFS 38 and 42% respectively and relapse 40% and 34% respectively, p = NS). Patients over 51 years had a five years OS of 12%. However when we analyzed those patients by date and conditioning we found that patients who were treated with MA regimens in the first decade of the transplant program (before 2000) had lower OS compared to those treated after 2000 with RIC (five years OS 49% and 12% respectively, p < 0.01). No significant differences in terms of OS, recurrence or incidence of graft-versus-host disease were found when comparing groups under 40 years, between 41 and 50 years and older than 51 years treated only with RIC. Conclusions: RIC provides the possibility of HSCT in older patients with rates comparable to those obtained in younger patients successfully treated with MA conditioning.

Uso do enxerto ósseo alógeno de banco de tecidos para reconstrução extensa da maxila e reabilitação com prótese fixa aparafusada: controle clínico e radiográfico após oito anos / The use of tissue-bank allogeneic bone grafts for large maxillary reconstruction and rehabilitation with a complete fixed prosthesis: an 8-year clinical and radiographic follow-up

Este caso clínico relata uma reconstrução extensa na maxila de um paciente de 45 anos de idade, portador de prótese total superior e dentição natural inferior, feita com enxertos alógenos previamente à colocação de uma prótese total fixa parafusada. Inicialmente, peças corticoesponjosas de fíbula (4 mm x 15 mm), obtidas no mesmo bancos de ossos, foram colocadas na região anterior do rebordo. As membranas dos seios maxilares foram levantadas para colocação de osso particulado. Seis meses depois, implantes entre 13 mm e 15 mm de comprimento foram usados, sendo de largo diâmetro (5 mm) nas regiões posteriores. Após mais seis meses, a prótese definitiva foi colocada. O controle clínico e radiográfico de oito anos mostrou a estabilidade dos tecidos e ausência de complicações mecânicas na reabilitação.

This clinical case reports a large maxillary reconstruction for a 45 years-old patient wearing a complete denture against a mandibular natural dentition, performed with allograft material before an implant-supported fixed prosthesis. First, cortico-medullary pieces (4 mm x 15 mm) from a bone tissue bank were adapted to the anterior edentulous ridge. Also, both sinus membranes were lifted to accomodate particulate bone chips. Six months later, dental implants having 13-15 mm in length were installed, being the most posterior of wider diameter (5 mm). After additional six months, the defnitive prosthesis was delivered. The 8-year clinical and radiographic controls demonstrated tissue stability and the lack of mechanical complications for the oral rehabilitation.

Recuperación temprana de linfocitos como factor pronóstico en el trasplante hematopoyético / Early lymphocyte recovery as a prognostic factor after hematopoietic stem cell transplantation

Introducción: la recuperación temprana de linfocitos es un factor pronóstico que está relacionado con una mayor supervivencia libre de eventos y supervivencia global en pacientes sometidos a trasplante hematopoyético. Objetivo: determinar el valor pronóstico del recuento absoluto de linfocitos (RAL). Métodos: se realizó un estudio observacional analítico, transversal, ambispectivo, en pacientes pediátricos con hemopatías malignas trasplantados en el Instituto de Hematología e Inmunología de La Habana, Cuba, entre 1986 y 2008. Se estudiaron 36 pacientes: 15 con leucemia linfoide aguda, 13 con leucemia mieloide aguda, 6 con leucemia mieloide crónica y 2 con linfoma no hodgkiniano. Veintitrés trasplantes fueron autólogos y 13 alogénicos; 22 de médula ósea y 14 de sangre periférica. Resultados : de los trasplantes antólogos, el 60,9 por ciento alcanzó un RAL el día + 15 (RAL-15) = 500 x mm3, mientras en los alogénicos este se alcanzó en el 53,8 por ciento. La sangre periférica tuvo un RAL-15 mayor que la médula ósea y se obtuvo en el 78,6 por ciento y el 45,4 por ciento de los enfermos, respectivamente (p = 0.049). Los factores pronósticos asociados a una peor supervivencia global fueron la sepsis (p <0.001), el RAL-15 < 500 x mm3 ( p= 0.001) y la recaída (p = 0.03). Las curvas de Kapplan-Meier mostraron una mejor supervivencia global y libre de eventos a los cinco años, en los pacientes con RAL-15 = 500 x mm3 (85 por ciento vs 15 por ciento; p <0.001). Conclusiones: el RAL-15 = 500 x mm3 es una herramienta simple y útil para predecir un mejor resultado en pacientes pediátricos sometidos a trasplante hematopoyético

Introduction: early lymphocyte recovery is a prognostic factor related to a higher event-free survival and overall survival in patients who have received hematopoietic transplantation. Objective: eo determine the prognostic value of absolute lymphocyte count (ALC). Method: a study in pediatric patients with hematological malignancies transplanted at the Institute of Hematology and Immunology from 1986 to 2011 was performed. The study group included 36 patients: 15 with acute lymphoid leukemia, 13 with acute myeloid leukemia, 6 with chronic myeloid leukemia and 2 with non Hodgkin lymphoma. Twenty transplants were autologous and 13 allogeneic. As stem cell source, bone marrow was used in 22 patients and peripheral blood in 14. Results : 60,9 percent of the autologous transplants reached an absolute lymphocyte count = 500 x mm3 on day 15 (ALC-15), whereas in the allogeneic this was achieved in 53,8 percent. Peripheral blood had a higher ALC-15 than bone marrow, 78,6 percent and 45,4 percent, respectively (p = 0.049). Prognostic factors associated to worse overall survival were sepsis (p <0.001), ALC-15 <500 x mm3 (p = 0.001) and relapse (p = 0.03). Kapplan-Meier curves showed better overall survival and event-free survival after five years in patients with ALC-15 = 500 x mm3 (85 percent vs. 15 percent, p <0.001). Conclusions: the ALC-15 = 500 x mm3 is a simple and useful tool to predict a better outcome in pediatric patients undergoing hematopoietic transplantation

Potencial osteoindutor de blocos de osso alógeno humano in vitro / Osteoinductive potential ot allogeneic human bone blacks in vitro

O enxerto alógeno apresenta diversas vantagens em relação ao enxerto autógeno, porém sua utilização é relativamente recente e cercada de incertezas em relação ao seu comportamento biológico/imunológico e eficácia como biomaterial. Alguns autores consideram-no estritamente osteocondutor, enquanto outros acreditam que ele pode ser osteoindutor. O objetivo deste trabalho foi estudar o potencial osteoindutor do osso alógeno analisando os efeitos dos extratos proteicos provenientes de blocos de aloenxerto sobre células pré-osteoblásticas humanas. As proteínas extraídas dos blocos ósseos foram incubadas em culturas de células pré-osteoblásticas, a fim de verificar o potencial de indução de proliferação celular. Foram utilizados os métodos do RT-qPCR, Vermelho de Alizarina e Von Kossa para avaliar o metabolismo das células ósseas e a formação de nódulos minerais contendo cálcio e fosfato, respectivamente. Também foi pesquisado se havia nos blocos ósseos a proteína morfogenética BMP-2. Foi possível observar, nos grupos experimentais, aumento na proliferação celular, do metabolismo das células ósseas e da produção de nódulos de cálcio e fosfato, em relação ao grupo controle. Foi possível detectar a presença de BMP-2 em seis dos nove blocos ósseos. Conclui-se que os blocos de aloenxerto mineralizado possuem proteínas com potencial osteoindutor quando testado seu comportamento in vitro em células osteoblásticas

The allogenic bone has several comparative advantages in relation to autograft bone, but its use is relatively recent and surrounded by uncertainties regarding the bioloqical/immunological behavior and effectiveness as a biomaterial. Some authors consider the material strictly osteoconductive, while others bel ieve that the materia I ca n a Iso possess osteoi nd uctive activitv Thus, we evaluated the osteoinductive potential of allograft bone by analyzing the effects of protein extracts from allograft blocks using human pre-osteoblastic cells. The protein extract from allograft block was incubated in cultures of pre-osteoblast cells in order to verify the cell proliferation potential. Moreover, it was employed the RT-qPCR, Alizarin and Von Kossa staining to evaluate the bone metabolism, as well as, the potential induction of calcium and phosphate nodule formation. Finally, it was quantified the morphogenetic protein BMP-2. It was possible to observe in the experimental group, an increase in the cell proliferation and cellular metabolism, as well as, a significant increase in the formation of nodules of calcium and phosphate in comparison to control group. It was possible to detect amounts of BMP-2 in six of nine total samples tested. It was possible to conclude that the mineralized allografts blocks have in vitro osteoinductive activity on osteoblastic cells

Trasplante alogénico de precursores hematopoyéticos de sangre de cordón umbilical de donante no emparentado: primera experiencia, en tres casos, con donantes del banco público chileno de células de cordón / Allogenic hematopoietic stem cell transplantation with unrelated cord blood: Report of three cases from the Chilean cord blood bank

Public cord blood banks are a source of hematopoietic stem cells for patients with hematological diseases who lack a family donor and need allogeneic transplantation. In June 2007 we started a cord blood bank with units donated in three maternity wards in Santiago, Chile. We report the first three transplants done with cord blood units form this bank. Cord blood units were obtained by intrauterine collection at delivery. They were depleted of plasma and red cells and frozen in liquid nitrogen. Tests for total nucleated cells, CD34 cell content, viral serology, bacterial cultures and HLA A, B and DRB1 were done. Six hundred cord blood units were stored by March 2012. Three patients received allogeneic transplant with cord blood from our bank, two with high risk lymphoblastic leukemia and one with severe congenital anemia. They received conditioning regimens according to their disease and usual supportive care for unrelated donor transplantation until full hematopoietic and immune reconstitution was achieved. The three patients had early engraftment of neutrophils and platelets. The child corrected his anemia and the leukemia patients remain in complete remission. The post-transplant course was complicated with Epstein Barr virus, cytomegalovirus and BK virus infection. Two patients are fully functional 24 and 33 months after transplant, the third is still receiving immunosuppression.

Osteointegración del aloinjerto crioconservado asociado a plasma enriquecido en plaquetas, en defectos óseos infectados. Estudio experimental / Osseointegration of cryopreserved allograft associated with platelet-rich plasma, in infected bone defects. Experimental study

El objetivo de este trabajo experimental es determinar si el agregado de plasma rico en plaquetas influye en la osteointegración del aloinjerto crioconservado con antibióticos, en fracturas infectadas, con pérdida ósea, en huesos largos de conejos. Materiales y métodos: Se evaluaron cuatro grupos de 7 conejos cada uno, a los cuales se les generó una fractura infectada del fémur derecho. En los cuatro grupos, se colocó aloinjerto molido con antibiótico local, en el grupo II y en el grupo IV, se agregó también plasma rico en plaquetas. Se sacrificó a los grupos I y II, a los 30 días, y a los grupos III y IV, a los 90 días. Se realizó una evaluación histológica y tomográfica. Resultados: Nueve conejos murieron en el período de estudio. No hubo diferencias estadísticamente significativas entre los grupos evaluados. En el grupo IV, con plasma rico en plaquetas, se observó neoformación ósea en tres de las cuatro muestras; se advirtieron sectores de acoplamiento entre el tejido receptor y el injertado, con consolidación en las imágenes tomográficas. Conclusiones: En este trabajo, hubo correlación entre los resultados histológicos y tomográficos. Pese a que no se hallaron diferencias estadísticamente significativas, el agregado de plasma rico en plaquetas, además de estimular la generación de nuevos tejidos, disminuyó la reabsorción del tejido injertado al análisis anatomopatológico, y mostró mayor neoformación ósea y consolidación en el grupo IV (75 por ciento) tratado con plasma rico en plaquetas que en el grupo III (25 por ciento) al que no se asoció plasma rico en plaquetas al aloinjerto óseo

The objective of this experimental work was to determine whether the addition of platelet-rich plasma influences the osseointegraton of cryopreserved allograft with antibiotics in infected fractures with bone loss, in long bones of rabbits.Methods: Four groups of 7 rabbits with generated infected fracture of the right femur. Milled allograft with local antibiotic was placed in the four groups; groups II and IV also received platelet-rich plasma. Rabbits in groups I and II were sacrificed at 30 days, and those of groups III and IV at 90 days. Histological and CT evaluation was performed.Results: Nine rabbits died during the study period. There were no statistically significant differences between groups. In group IV with platelet-rich plasma, bone formation was observed in three of the four samples, with noticeable areas of coupling between the receiver and the grafted tissue with consolidation in CT.Conclusions: In our study, there was no correlation between the histological and tomographic findings. Although we found no statistically significant differences, the addition of platelet-rich plasma stimulated the generation of new tissue, and also decreased reabsorption of the grafted tissue according to the pathologic analysis. Besides increased bone formation and consolidation was detected in group IV (75%) treated with platelet-rich plasma, compared to group III (25%) without platelet-rich plasma bone allograft.

Our experience of fibrin sealant-assisted implantation of Ahmed glaucoma valve.

Aim: To report our experience with the fibrin sealant as a suture substitute for securing the human scleral patch graft during implantation of Ahmed glaucoma valve (AGV). Materials and Methods: A retrospective, non-comparative study of 12 eyes of 12 patients who underwent an AGV implantation with fibrin sealant for part of the procedure during June 2009 to September 2010. Results: The mean patient age was 21.5 ± 20.6 years. Male: Female ratio was 2 : 1. Seven (58.3%) patients were monocular. The indications for AGV were varied. The mean number of intra-ocular surgeries prior to an implantation of AGV was 1.8. The mean follow-up duration was 24.5 ± 17.9 weeks. There was a statistically significant reduction in the mean IOP and in the mean number of anti-glaucoma medications at the final visit compared to the pre-operative values (P < 0.01, paired t test). Conjunctival retraction was seen in 1 (8.3%) case. The scleral patch graft was retracted posteriorly in another (8.3%) case. There was no case of AGV tube exposure, tube-cornea touch, or conjunctival erosion. Vision threatening complication viz. late post-operative rhegmatogenous retinal detachment, unlikely to be related to the use of the fibrin sealant, occurred in 2 (16.6%) eyes. Conclusion: The fibrin sealant offers the advantages of safety and convenience to the placement of a scleral patch graft during an AGV implantation.

Comparative study and histomorphometric analysis of bone allografts lyophilized and sterilized by autoclaving, gamma irradiation and ethylene oxide in rats

PURPOSE: To compare three sterilization methods (autoclave, gamma irradiation and ethylene oxide) over non demineralized lyophilized bone allografts. METHODS: Bone allografts were implanted on paravertebral muscles of 21 rats. After 30 days animals were sacrificed and grafts underwent comparative analysis regarding histomorphometric and macroscopic parameters. RESULTS: Allografts that underwent the three sterilization methods presents similar weight gain, cortical thickness similar to control group, and less fibrosis than the control group. Grafts that underwent sterilization in autoclave presented less presence of multinucleated giant cells, although not statistically significant. There was also no statistically significant difference regarding mineralization on the three groups. CONCLUSION: The three sterilization methods cause similar effects on bone allografts regarding macroscopic and histomorphometric parameters.

Análise comparativa entre o aloenxerto ósseo liofilizado, aloenxerto ósseo congelado e enxerto autógeno: estudo histológico em coelhos / Comparative analysis of demineralized freeze-dried bone, fresh frozen bone allograft and autogenous bone graft: a histologic study in rabbits

Considerando as diferentes aplicações clínicas dos enxertos ósseos nas reconstruções alveolares e a dificuldade de se obter ganhos ósseos em altura, o presente estudo avaliou do ponto de vista histológico a integração do enxerto autógeno (AU), do aloenxerto ósseo liofilizado desmineralizado (ALD), do aloenxerto ósseo congelado mineralizado (ACM) e do coágulo sanguíneo (CO) em um modelo de regeneração óssea vertical. Foram utilizados nove coelhos, sendo um animal doador primário de enxertos ósseos e oito animais submetidos a um modelo de regeneração óssea guiada (ROG), onde 32 cilindros de titânio foram fixados na calota craniana e preenchidos aleatoriamente com AU, ALD, ACM e CO. Após 13 semanas, os animais sofreram eutanásia e o conteúdo dos cilindros submetido à avaliação histológica e histomorfometrica para quantificar a área total de tecido neoformado (AT), o osso neoformado (ON) e o remanescente do material enxertado (MR). Os dados foram submetidos aos testes t-Student e Mann-Whitney com nível de significância de 5%. Os resultados mostraram que em relação à AT os valores médios foram significantes para ACM e ALD e seguiram a seguinte relação: ACM = ALD > AU > CO. Para a variável neoformação óssea as intervenções ALD e ACM mostraram maior quantidade de tecido ósseo formado do que as que empregaram osso autógeno ou coágulo. Já em relação à MR, a média da variável obedeceu à relação: ACM > ALD = AU = CO (valores-p < 5%). Todas as intervenções apresentaram médias mais significativas de crescimento tecidual nas regiões mais próximas ao leito receptor. Foi possível concluir que os aloenxertos podem ser considerados soluções adequadas para o crescimento ósseo vertical.

Regarding different clinical applications for bone grafts in alveolar reconstructions and difficulties on achieving vertical osseous increase the present study performed a comparative histological evaluation of demineralized freeze-dried bone allograft (DFDBA), of fresh frozen bone allograft (FFBA), autogenous graft (AU) and blood clot (CO) on vertical guided bone regeneration (GBR) in rabbit calvarium. Nine rabbits were used, with one as the primary bone graft donor and eight that were subjected to a model of GBR, whereby 32 titanium cylinders were fixed to the calvaria and randomly filled with DFDBA, FFBA, AU, or CO. The animals were sacrificed 13 weeks later, and the content of the cylinders was subjected to hitomorphological and histomorphometric analysis to quantify the total area of neoformed tissue (AT), the new bone tissue (NB) and residual graft particles (RG). The results showed that mean values for AT were significant to DFDBA and FFBA and followed the relation DFDBA = FFBA > AU > CO. Considering new bone formation DFDBA and FFBA showed better results than the AU and CO. The amount of residual bone particles was larger in the DFDBA and followed the relation FFBA > DFDBA = AU = CO (pvalues < 5%). All interventions showed greater new tissue formation nearby the receptor site. It was possible to conclude that allografts DFDBA and FFBA can be considered good strategies for new bone formation in vertical increasing bone.

Reconstrução de extremidades com retalho livre de fíbula após ressecções oncológicas / Extremity reconstruction using a free fibula flap after oncological resection

INTRODUÇÃO: O tumor primário de ossos longos é raro, correspondendo de 0,2% a 1% dos tumores malignos. No passado, a amputação era o tratamento padrão, ocasionando grande impacto na morbidade e na mortalidade desses pacientes. Com o avanço das técnicas cirúrgicas e o envolvimento multidisciplinar, a cirurgia conservadora dos membros tornou-se o tratamento de escolha, sendo a reconstrução com retalho microcirúrgico de fíbula a mais utilizada. Este trabalho tem como objetivo apresentar a experiência do Instituto Nacional de Câncer (INCA) nas reconstruções de membros com retalho microcirúrgico de fíbula após ressecções de tumores de ossos longos. MÉTODO: Foi realizada análise retrospectiva de 7 casos de retalho livre de fíbula operados no INCA, no período de 1997 a 2009, para reconstrução de defeitos de extremidades após ressecções de tumores ósseos. Foram avaliados os seguintes parâmetros: sexo, idade, diagnóstico, localização do tumor, tipo e tamanho da ressecção, tipo e tamanho da reconstrução, vasos utilizados para anastomose, complicações pós-operatórias, estado da doença na última consulta, seguimento e tempo até deambulação. RESULTADOS: No total, 7 pacientes com média de idade de 11,8 anos (variando de 5 anos a 14 anos) foram submetidos a reconstrução de extremidades com retalho livre de fíbula, com 100% de viabilidade e consolidação óssea. As lesões eram localizadas em fêmur, tíbia ou úmero. O tumor mais comum foi o osteossarcoma. O tempo médio de retorno à deambulação foi de 14,7 meses. CONCLUSÕES: O uso do retalho livre de fíbula é uma excelente alternativa para reconstrução de membros, apresentando alta taxa de consolidação óssea, deambulação precoce, boa funcionalidade e baixa taxa de complicações.

BACKGROUND: Primary tumors of the long bones are rare, accounting for 0.2-1% of malignant tumors. In the past, amputation was the standard treatment and had a large impact on patient morbidity and mortality. With advances in surgical techniques and multidisciplinary involvement, conservative surgery of the limbs has become the treatment of choice, and reconstruction using a microsurgical fibula flap is the most commonly used technique. In this study, we aimed to present the experience of the National Cancer Institute (INCA) with limb reconstruction using a microsurgical fibula flap following tumor resection from the long bones. METHODS: We retrospectively analyzed 7 cases of free fibular flap surgery at the INCA from 1997 to 2009 for the reconstruction of defects of the extremities after bone tumor resection. We evaluated the following parameters: gender, age, diagnosis, tumor location, resection size and type, reconstruction size and type, vessels used for the anastomosis, postoperative complications, disease status at the last visit, follow-up, and time to ambulation. RESULTS: Seven patients with a mean age of 11.8 years (range, 5-14 years) underwent extremity reconstruction with a free fibula flap with 100% bone viability. The lesions were located within the femur, tibia, or humerus. Osteosarcoma was the most common tumor type. The average return to ambulation was 14.7 months. CONCLUSIONS: The use of a free fibula flap is an excellent alternative for limb reconstruction and features a high bone healing rate, early ambulation, good functionality, and a low complication rate.

Artrodesis de radio distal con autoinjerto masivo de cresta iliaca en tumor de células gigantes: reporte de un caso / Arthrodesis of the distal radio with massive iliac crest bone autograft in a giant cell tumor: a case report

El tumor de células gigantes se presenta en cerca del 5% de todos los tumores óseos benignos en adultos; es un tumor que a pesar de su naturaleza benigna, la mayoría de las veces tiene un comportamiento agresivo, lo cual causa severa incapacidad y limitación funcional. Existen técnicas descritas para manejo de este tipo de tumor en el radio distal, mediante resección, aplicación de aloinjerto, curetaje intralesional y aumentación con cemento. En este artículo reportamos el caso de una mujer con un tumor de células gigantes del radio distal tratado mediante resección ampliada de la lesión y reconstrucción con un autoinjerto masivo de cresta iliaca. Se describe la técnica y se reporta el resultado funcional.

Giant cell tumors appear in approximately 5% of all benign bone tumors in adults; despite its benignity, it is usually aggressive, leading to severe functional disability and limitations. Techniques have been described for the management of this type of tumor in the radio distal using surgical resection, application of allograft, intralesional curettage and cement augmentation. In this article we report on the case of a female patient with a giant cell tumor in the radio distal treated with wide resection of the lesion and reconstruction with massive iliac crest bone autograft. The technique is described and a report is provided on the functional result.

Enteral nutrition during bone marrow transplantation in patients with pediatric cancer: a prospective cohort study / Nutrição enteral durante o transplante de medula óssea em pacientes com câncer infanto-juvenil: estudo prospectivo de coorte

CONTEXT AND OBJECTIVE: Cancer patients undergoing bone marrow transplantation (BMT) often require nutritional therapy due to treatment toxicities. The aim here was to evaluate the use of tube feeding and its applicability, indications, contraindications and complications in these patients. DESIGN AND SETTING: Prospective observational study conducted at a public university in São Paulo between January 2002 and August 2007. METHODS: The patients were followed up daily in the BMT unit by a research dietitian. Tube feeding was indicated when oral supplementation proved to be insufficient, when the patient had severe malnutrition or there was an impediment to use of oral feeding. It was contraindicated in the presence of gastrointestinal toxicity of grade 3 and 4 or other conditions that implied a risk or hindered its use or placement. Complications of tube feeding were divided into minor and major, according to whether they had life-threatening implications. RESULTS: Forty-two (47.2%) patients had indications for tube feeding: the main reasons were transplantation inadequate food and supplement intake, insufficient intake with malnutrition or weight loss, severe malnutrition or need for oral fasting. Thirty-one (73.8%) received tube feeding: 11 autologous and 20 allogenic patients (P = 0.04). The main contraindications were severe gastrointestinal toxicities and sinusitis. Minor complications from tube feeding were more prevalent in patients with allogenic BMT, but no major complications were observed. CONCLUSION: Enteral nutrition is a feasible procedure in patients undergoing BMT and should be encouraged. The main difficulty in BMT patients, in relation to tube feeding, is gastrointestinal toxicities.

CONTEXTO E OBJETIVO: Pacientes com câncer submetidos ao transplante de medula óssea (TMO) frequentemente necessitam de terapia nutricional devido às toxicidades do tratamento. O objetivo foi avaliar uso de sonda enteral, aplicabilidade, indicações, contraindicações e complicações nesses pacientes. TIPO DE ESTUDO E LOCAL: Estudo observacional prospectivo, conduzido de janeiro de 2002 a agosto de 2007 em uma universidade pública em São Paulo. MÉTODOS: Os pacientes foram acompanhados diariamente na unidade de TMO por uma nutricionista da pesquisa. Indicações de sonda: suplementação oral insuficiente, desnutrição grave, ou alguma contraindicação para alimentação via oral. A contraindicação da sonda ocorreu na presença de toxicidades gastrintestinais de grau 3 e 4 ou outras condições que implicassem em risco ou impedissem seu uso ou passagem. As complicações da sonda foram divididas em menores e maiores, de acordo com implicações para o risco de vida. RESULTADOS: Quarenta e dois (47,2%) pacientes tiveram indicações de nutrição por sonda: os principais motivos foram: ingestão alimentar e de suplemento inadequada, ingestão insuficiente com desnutrição ou perda de peso, desnutrição grave ou necessidade de jejum. Trinta e um (73,8%) pacientes usaram sonda: 11 com transplantes autólogos e 20 alogênicos (P = 0,04). As principais contraindicações foram toxicidades gastrintestinais graves e sinusite. Complicações leves com a sonda foram mais prevalentes nos pacientes em TMO alogênico, mas nenhuma complicação grave foi observada. CONCLUSÃO: O uso de sonda enteral é um procedimento factível em pacientes durante o TMO e deve ser encorajado. A principal dificuldade nesse grupo em relação ao uso de sonda foi a toxicidade gastrintestinal.

Pseudoartrosis por defecto de radio tratada con aloinjerto óseo estructurado de cadáver: reporte de un caso / Radial`s by default nonunion treated with structured bone allograft: a case report

La pérdida de masa ósea continúa siendo un gran reto para los Cirujanos Traumatólogos y Ortopedistas. Los Aloinjertos Estructurales Óseos (AEO), se usan para rellenar o sustituir defectos tras grandes fracturas o pseudoartrosis. Los AEO Intercalares se usan en defectos diafisiarios o metafisiarios. Casi siempre precisan fijación estable bien sea con placas, enclavados intramedulares o ambos. Se presenta el caso de un paciente masculino de 23 años, quien presentó fractura abierta de radio y cúbito izquierdo secundario a herida por arma de fuego en 2011 con importante compromiso de las partes blandas, posteriormente complicada con pseudoartrosis por un defecto de 6 cm en el cúbito. Una vez controlada la infección y logrado cobertura cutánea, se resuelve en julio del mismo año mediante osteosíntesis y aloinjerto estructurado óseo de cadáver. Se presenta su evolución clínica y radiológica

The bone loss remains a major challenge for trauma surgeons and orthopedists. Structural Bone Allografts (SBA) are used to fill or replace large defects after fracture or nonunion. The Intercalary SBA is used in diaphyseal or metaphyseal defects. Almost always require either stable fixation with plates, intramedullary nailing, or both. We report the case of a 23 years male patient, who presented left radius and ulna open fracture due to firearm injury in 2011 with significant soft tissue compromise, later complicated by a radial bone defect of 6 cm. After controlling the infection and skin coverage achieved, is resolved in July of that year by fixation and structured cadaver bone allograft. We present the clinical and radiological evolution

Histological evaluation of bone regeneration means freeze dried bone allograft (FDBA) in post exodontia sockets / Evaluación histológica de la regeneración ósea en alvéolos post exodoncia mediante uso de freeze dried bone allograft (FDBA)

Within oral rehabilitation alveolar ridge preservation following extraction is important. This research study shows a histological, histochemical and histomorphometrical evaluation in two cases of post extraction ridge-socket preservation performed with FDBA. In two patients dental extraction procedures were performed and sockets were immediately filled with FDBA. Six months later a biopsy of grafted area was obtained and rehabilitated through dental implant. Grafted bone samples were treated for histological and histochemical analysis. Bone tissue area was measured. Laboratory analysis of three samples showed inactive bone surfaces, neither osteoblasts nor osteoclasts were found, only osteocyte and osteogenous cells were observed. These findings do not mean that tissue is metabolically inactive, rather bone genesis develop from a tissue matrix with the potential to generate undifferentiated osteocytes, and a micro environment with proteins such as bone morphogenetic proteins (BPM). Inactive biomaterial particles were not observed. Samples showed 0 percent and 30 percent bone tissue respectively. Considering histological differences between this and other research studies, it is necessary to develop further investigation to increase knowledge of processes involved in bone regeneration as well as bone quality, considering the variability that could be seen in each patient.

Dentro de la rehabilitación oral, es importante preservar el reborde alveolar post exodoncia. Se expone un análisis histológico, histoquímico e histomorfométrico de dos casos clínicos de terapias de regeneración ósea de alvéolos post extracción mediante FDBA. En dos pacientes se extrajeron piezas dentarias destruidas y se indujo regeneración ósea mediante FDBA. Seis meses después, se obtuvo una biopsia del injerto y mediante un implante de titanio fue rehabilitado. Para el análisis Histológico e Histomorfométrico, las muestras fueron tratadas con las técnicas Hematoxilina-Eosina, Azul de Alcián, Masson, Von Kossa y colorante Picrosirius de Junqueira.Se midió el área total de tejido, así como el área de tejido óseo. Las superficies de hueso de las muestras se observaron inactivas, no fueron encontrados osteoblastos ni osteoclastos, sólo osteocitos y células osteógenas, lo que no significa que el hueso esté en estado quiescente, sino mas bien a que su génesis ocurre a partir de la matriz de tejido donde se encuentran células con potencialidad de formar osteocitos indiferenciados y un microambiente con proteinas de la familia de factor de crecimiento transformante beta. No fueron encontradas partículas de biomaterial inactivo. En las muestras se cuantificó 0 por ciento y 30 por ciento de hueso mineralizado. Dadas las diferencias histológicas encontradas con otros estudios, es necesario profundizar el conocimiento en los procesos involucrados en la regeneración ósea dependiendo del biomaterial utilizado, y la calidad ósea resultante en cada procedimiento en particular sin perder de vista la variabilidad que puede presentarse dependiendo de cada caso clínico.

The Decellularized Vascular Allograft as an Experimental Platform for Developing a Biocompatible Small-Diameter Graft Conduit in a Rat Surgical Model

PURPOSE: The present study was aimed to assess the feasibility of using decellularized aortic allograft in a rat small animal surgical model for conducting small diameter vascular tissue engineering research. MATERIALS AND METHODS: Decellularized aortic allografts were infra-renally implanted in 12 Sprague-Dawley (SD) adult rats. The conduits were harvested at 2 (n = 6) and 8 weeks (n = 6), and assessed by hematoxylin and eosin (H&E), van Gieson, Masson Trichrome staining, and immunohistochemistry for von Willebrand factor, CD 31+, and actin. RESULTS: Consistent, predictable, and reproducible results were produced by means of a standardized surgical procedure. All animals survived without major complications. Inflammatory immune reaction was minimal, and there was no evidence of aneurysmal degeneration or rupture of the decellularized vascular implants. However, the aortic wall appeared thinner and the elastic fibers in the medial layer showed decreased undulation compared to the normal aorta. There was also minimal cellular repopulation of the vascular media. The remodeling appeared progressive from 2 to 8 weeks with increased intimal thickening and accumulation of both collagen and cells staining for actin. Although the endothelial like cells appeared largely confluent at 8 weeks, they were not as concentrated in appearance as in the normal aorta. CONCLUSION: The results showed the present rat animal model using decellularized vascular allograft implants to be a potentially durable and effective experimental platform for conducting further research on small diameter vascular tissue engineering.