Liver transplantation in undifferentiated embryonal sarcoma of the liver in adults: a case report / Transplante hepático em sarcoma embrionário indiferenciado de fígado em adultos: relato de caso

Undifferentiated embryonal sarcoma of the liver (UESL) consists of a rare malignant neoplasm with a still poorly known etiopathogenesis, affecting mostly children between the ages of 6 and 10 years. It corresponds to 7% of primary liver tumors, and is the fourth most common liver cancer in pediatrics. The diagnosis of UESL is based on a set of imaging findings, age and level of alpha-fetoprotein (AFP), which is usually normal, as well as liver function tests. Early diagnosis is hampered by non-specific symptoms, such as abdominal pain, a rapidly growing palpable abdominal mass, fever, weight loss, and gastrointestinal symptoms. The most characteristic image finding is that of a large, unique, and well-defined mass. Ultrasonography shows a predominantly solid and echogenic mass. Computed tomography, on the other hand, shows a mass that takes on a mainly cystic characteristic. Histologically, myxoid tissue with spindle-shaped neoplastic cells is evidenced. Some immunohistochemical studies indicate UESL mesenchymal origin. The macroscopic aspect of the tumor appears as a large hepatic mass, with a predominantly solid component, with some cystic areas, hemorrhage, and necrosis in up to 80% of its surface. The best approach for the treatment of primary liver sarcoma is not yet well defined. Therapeutic options include surgical resection, chemotherapy, radiotherapy, and liver transplantation (LT). However, in cases of unresectable tumors, LT is an option that must be considered, since in this histological type both chemotherapy and radiotherapy have questionable benefits. This article aims to report a case of giant UESL, with vascular invasion, submitted to LT with good postoperative evolution and without signs of recurrence after nine months of LT.

O sarcoma embrionário indiferenciado de fígado (SEIF) consiste em uma neoplasia maligna rara com etiopatogenia ainda pouco conhecida, acometendo em sua maioria crianças na faixa etária entre 6 e 10 anos. Corresponde a 7% dos tumores primários de fígado, e é a quarta neoplasia hepática mais frequente na pediatria. O diagnóstico do SEIF se dá em um conjunto de achados de imagem, idade e nível de alfa-fetoproteína (AF), que geralmente está normal, assim como as provas de função hepática. O diagnóstico precoce é prejudicado pelos sintomas inespecíficos, como dor abdominal, massa abdominal palpável de rápido crescimento, febre, perda de peso e sintomas gastrintestinais. O achado de imagem mais característico é o de massa grande, única e bem-delimitada. A ultrassonografia mostra massa predominantemente sólida e ecogênica. Já a tomografia computadorizada evidencia uma massa que assume característica principalmente cística. Histologicamente é evidenciado tecido mixoide com células neoplásicas fusiformes. Alguns estudos imuno-histoquímicos indicam origem mesenquimal do SEIF. O aspecto macroscópico do tumor se apresenta como grande massa hepática, de componente sólido predominantemente, com algumas áreas císticas, hemorragia e necrose em até 80% de sua superfície. Ainda não é bem-definida a melhor abordagem para o tratamento do sarcoma primário de fígado. As opções terapêuticas incluem ressecção cirúrgica, quimioterapia, radioterapia e transplante hepático (TH). Porém, nos casos de tumores irressecáveis, o TH é uma opção que deve ser considerada, uma vez que nesse tipo histológico tanto quimioterapia como radioterapia têm benefício questionável. Este artigo tem por objetivo relatar um caso de SEIF gigante, com invasão vascular, submetido a TH com boa evolução pós-operatória e sem sinais de recidiva após nove meses de TH.

Islet transplantation in rodents. Do encapsulated islets really work?

CONTEXT: Diabetes mellitus type I affects around 240 million people in the world and only in the USA 7.8% of the population. It has been estimated that the costs of its complications account for 5% to 10% of the total healthcare spending around the world. According to World Health Organization, 300 million people are expected to develop diabetes mellitus by the year 2025. The pancreatic islet transplantation is expected to be less invasive than a pancreas transplant, which is currently the most commonly used approach. OBJECTIVES: To compare the encapsulated and free islet transplantation in rodents looking at sites of islet implantation, number of injected islets, viability and immunosuppression. METHODS: A literature search was conducted using MEDLINE/PUBMED and SCIELO with terms about islet transplantation in the rodent from 2000 to 2010. We found 2,636 articles but only 56 articles from 2000 to 2010 were selected. RESULTS: In these 56 articles used, 34% were encapsulated and 66% were nonencapsulated islets. Analyzing both types of islets transplantation, the majority of the encapsulated islets were implanted into the peritoneal cavity and the nonencapsulated islets into the liver, through the portal vein. In addition, the great advantage of the peritoneal cavity as the site of islet transplantation is its blood supply. Both vascular endothelial cells and vascular endothelial growth factor were used to stimulate angiogenesis of the islet grafts, increasing the vascularization rapidly after implantation. It also has been proven that there is influence of the capsules, since the larger the capsule more chances there are of central necrosis. In some articles, the use of immunosuppression demonstrated to increase the life expectancy of the graft. CONCLUSION: While significant progress has been made in the islets transplantation field, many obstacles remain to be overcome. Microencapsulation provides a means to transplant islets without immunosuppressive agents and may enable the performance of xenotransplantation. The use of alternative donor sources, fewer islets per capsule and the appropriate deployment location, such as the peritoneal cavity, may give a future perspective to the application of immunoprotective capsules and viability in clinical practice. A variety of strategies, such as genetic engineering, co-encapsulation, improvement in oxygen supply or the establishment of hypoxia resistance will also improve the islet transplantation performance. It remains to be determined which combination of strategies with encapsulation can fulfill the promise of establishing a simple and safe transplantation as a cure for diabetes.

Islet transplantation in rodents. Do encapsulated islets really work? / Transplante de ilhotas de Langerhans em modelos experimentais em roedores. Ilhotas encapsuladas realmente funcionam?

CONTEXT: Diabetes mellitus type I affects around 240 million people in the world and only in the USA 7.8 percent of the population. It has been estimated that the costs of its complications account for 5 percent to 10 percent of the total healthcare spending around the world. According to World Health Organization, 300 million people are expected to develop diabetes mellitus by the year 2025. The pancreatic islet transplantation is expected to be less invasive than a pancreas transplant, which is currently the most commonly used approach. OBJECTIVES: To compare the encapsulated and free islet transplantation in rodents looking at sites of islet implantation, number of injected islets, viability and immunosuppression. METHODS: A literature search was conducted using MEDLINE/PUBMED and SCIELO with terms about islet transplantation in the rodent from 2000 to 2010. We found 2,636 articles but only 56 articles from 2000 to 2010 were selected. RESULTS: In these 56 articles used, 34 percent were encapsulated and 66 percent were nonencapsulated islets. Analyzing both types of islets transplantation, the majority of the encapsulated islets were implanted into the peritoneal cavity and the nonencapsulated islets into the liver, through the portal vein. In addition, the great advantage of the peritoneal cavity as the site of islet transplantation is its blood supply. Both vascular endothelial cells and vascular endothelial growth factor were used to stimulate angiogenesis of the islet grafts, increasing the vascularization rapidly after implantation. It also has been proven that there is influence of the capsules, since the larger the capsule more chances there are of central necrosis. In some articles, the use of immunosuppression demonstrated to increase the life expectancy of the graft. CONCLUSION: While significant progress has been made in the islets transplantation field, many obstacles remain to be overcome. Microencapsulation provides a means to transplant islets without immunosuppressive agents and may enable the performance of xenotransplantation. The use of alternative donor sources, fewer islets per capsule and the appropriate deployment location, such as the peritoneal cavity, may give a future perspective to the application of immunoprotective capsules and viability in clinical practice. A variety of strategies, such as genetic engineering, co-encapsulation, improvement in oxygen supply or the establishment of hypoxia resistance will also improve the islet transplantation performance. It remains to be determined which combination of strategies with encapsulation can fulfill the promise of establishing a simple and safe transplantation as a cure for diabetes.

CONTEXTO: Diabetes mellitus tipo I afeta cerca de 240 milhões de pessoas no mundo e 7,8 por cento só nos EUA. Foi estimado que o custo de suas complicações fosse de 5 por cento-10 por cento dos custos mundiais em saúde. De acordo com a OMS (Organização Mundial de Saúde), espera-se que cerca de 300 milhões de pessoas desenvolvam o diabetes mellitus até o ano de 2025. É esperado que o transplante de ilhotas pancreáticas seja menos invasivo que o transplante pancreático, opção atual de maior uso. OBJETIVOS: Comparar as ilhotas encapsuladas e as ilhotas livres em roedores nos seguintes aspectos: local de implantação das ilhotas, número de ilhotas, viabilidade e imunossupressão. MÉTODOS: A pesquisa bibliográfica foi conduzida com o uso de citações do MEDLINE/PUBMED e SCIELO que apresentassem termos sobre transplante de ilhotas em roedores no período de 2000 a 2010. Foram achados 2.636 artigos, mas somente 56 desse período foram selecionados. RESULTADOS: Nos 56 artigos utilizados, 34 por cento eram encapsulados e 66 por cento eram não-encapsulados. Analisando ambos os tipos de transplante de ilhotas, a maioria delas encapsuladas, foi implantada na cavidade peritonial e as não-encapsuladas, através da veia porta, no fígado. A grande vantagem da cavidade peritonial como local de transplante era a oferta sanguínea. As células endoteliais e o fator de crescimento endotelial foram usados para estimular a angiogênese nas ilhotas, aumentando a vascularização rapidamente após a implantação. Foi também provada a influência das cápsulas, dado que quanto maior a cápsula maior era a chance de necrose central. Em alguns artigos, o uso de imunossupressão demonstrou aumento da expectativa de vida do enxerto. CONCLUSÃO: Enquanto algum progresso significativo não tenha sido obtido no campo de transplante de ilhotas, restam ainda muitos obstáculos a serem vencidos. A microencapsulação viabiliza o transplante de ilhotas sem o uso de imunossupressores, o que pode permitir o xenotransplante. O uso de fontes doadoras alternativas, menor quantidade de ilhotas por cápsula e local de implantação adequado, como a cavidade peritonial, podem dar melhor perspectiva na aplicação de cápsulas imunoprotegidas, aumentando viabilidade na prática clínica. Uma série de estratégias, como engenharia genética, coencapsulamento, melhora da oferta de oxigênio ou o estabelecimento de resistência à hipóxia também podem aprimorar os resultados do transplante de ilhotas. Deve-se determinar ainda qual a combinação de estratégias com relação ao uso de ilhotas encapsuladas que possam cumprir com as promessas de um transplante simples e seguro para a cura do diabetes.