Hemangioma: descrição de um caso clínico e sua importância no diagnóstico diferencial / Hemangioma: description of a clinical case and the importance in the differential diagnosis

O hemangioma infantil é um tumor vascular benigno que ocorre devido a uma proliferação anormal dos vasos sanguíneos. O quadro clínico apresenta três fases bem definidas: proliferativa, involutiva e involuída. O diagnóstico é realizado basicamente por meio da anamnese e do exame físico, e quando necessário preconiza-se avaliação histopatológica. O presente trabalho, descreve um caso clínico de um hemangioma presente em um bebê de 3 meses de idade que foi, de principio, diagnosticado como mucocele ou fibroma. A cirurgia excisional foi realizada eo material encaminhado para análise histopatológica, confirmando o diagnóstico de hemangioma. Nessas situações, vale ressaltar a importância do diagnostico diferencial, manobra cirúrgica adequada e a avaliação das características clínicas da lesão para evitar possíveis complicações cirurgicas.

The infantile hemangioma is a benign vascular tumor which occurs due to an abnormal proliferation of blood vessels. The clinical features three well-defined phases: proliferative, involution,and involuted. The diagnosis is made primarily by clinical history and physical examination, but when necessary, help to close the histopathological diagnosis. This paper describes a clinical case of a gift hemangioma in a baby three months old who was, in principle, diagnosed as mucocele or fibroma. The excisional surgery was performed and material sent for histopathological confirmation hemangioma. It is worth emphasizing the importance of differential diagnosis, appropriate surgical maneuver, assessment of clinical characteristics of the lesion to prevent potential surgical complications possible.

Inmunomodulación y antiangiogénesis en la terapéutica oncológica: De la investigación básica a la clínica / Immunomodulation and antiangiogenesis in cancer therapy: From basic to clinical research

La investigación básica y pre-clínica en oncología celular y molecular son pilares fundamentales en los que se apoyan la mayoría de los adelantos en la terapéutica del cáncer. Los hallazgos obtenidos y su aplicación en la práctica clínica constituyen la causa del avance sostenido en el tratamiento de la enfermedad neoplásica. El objetivo de este trabajo es resumir y discutir los resultados pre-clínicos en inmunomodulación y anti-angiogénesis para el tratamiento de diversos tipos de tumores, obtenidos en nuestro Instituto durante los últimos 15 años, y la posterior traslación y aplicación del conocimiento experimental en un Ensayo Clínico Fase I/II. Se describen los resultados que contribuyeron a descifrar los mecanismos de acción de la inmunomodulación antimetastásica con ciclofosfamida, la quimioterapia metronómica con diferentes drogas únicas o combinaciones, y finalmente el diseño y resultados preliminares de un ensayo clínico de quimioterapia metronómica para pacientes con cáncer de mama avanzado.

Basic and pre-clinic research in cellular and molecular oncology are the main supports accounting for the advancement in cancer therapeutics. The findings achieved, and their implementation in clinical practice are responsible for the permanent improvement in the treatment of the neoplastic disease. Our present objective is to summarize and discuss the pre-clinical findings in immunomodulation and anti-angiogenesis for the treatment of several types of tumors obtained in our Institute during the last 15 years, and the subsequent translation and application of the acquired experimental knowledge in a Phase I/II Clinical Trial. We present the results and mechanisms of action of antimetastatic immunomodulation with cyclophosphamide, the metronomic chemotherapy with different single drugs and their combinations, and finally the design and preliminary results of a clinical trial with metronomic chemotherapy for patients with advanced breast cancer.

Carcinogénesis

La división celular es controlada por una serie de sistemas que tienen efectos estimulantes o inhibitorios.El cáncer es de origen monoclonal, y para que una célula normal cambie su fenotipo y se convierta en una célula neoplásica deben ocurrir mutaciones genéticas en la misma.Dichas mutaciones genéticas ocasionan la modificación de los productos que en condiciones normales codificaría el gen y,finalmente,a un cáncer.El cáncer resultante puede ser hereditario (por mutaciones en uno o ambos alelos de las células germinales) o esporádico (por la acción de agentes mutágenos ambientales).A su vez, los mecanismos que pueden conducir a alteraciones en los genes pueden ser genéticos o epigenéticos; los primeros se presentan ante alteraciones estructurales del genoma y los restantes, epigenéticos, por alteraciones de las enzimas o de los sustratos de las mismas.La carcinogénesis consta de tres etapas:iniciación,promoción y progresión.La última de estas etapas,progresión,es exclusiva de la transformación maligna e implica la capacidad de invadir tejidos vecinos o a distancia. Para que se lleve a cabo el proceso metastásico, se requiere de una serie de mecanismos: angiogénesis, degradación de matrices, migración celular, evasión de la respuesta inmune del hospedero y colonización metastásica. Este artículo representa una revisión parcial de la bibliografía actualizada de los conceptos relacionados a la carcinogénesis y la información mínima necesaria para lograr un entendimiento de este complejo proceso.

Cell division is controlled by stimulatory and inhibitory systems.The origin of cancer is monoclonal, and in order that a normal cell switches its phenotype and becomes a neoplastic cell, genetic mutations must occur on it.These genetic mutations modify the products that in normal conditions the gene would codify and, finally, cause cancer. Cancer may be hereditary (due to mutations in one or both of germinal cells alleles) or sporadic (due to action of environmental mutagenic agents).The mechanisms that may cause alterations on genes may be genetic or epigenetic. Genetic mechanisms occur when structural alterations of genome are present and the epigenetic processes occur due to enzymatic alterations or alterations on its substrates. Carcinogenesis has three stages: initiation, promotion and progression.The last of these stages, progression, is exclusive of malignant transformation and implies the capacity to invade surrounding or distant tissues. For metastasis to take place, many mechanisms are required: angiogenesis, matrix degradation, cell migration, evasion of host immune response and metastatic colonization. This article presents a partial review of current bibliography about concepts related to carcinogenesis and conveys the minimum necessary information to achieve an understanding of this complex process.

[Angiogenesis and tumor]

Angiogenesis, the process of new blood vessel formation from existing ones, plays an important role in the physiologic circumstances such as embryonic development, placenta formation, and wound healing. It is also crucial to progress of pathogenic processes of a variety of disorders, including tumor growth and metastasis. In general, angiogenesis process is a multi-factorial and highly structured sequence of cellular events comprising migration, proliferation and differentiation of endothelial cells and finally vascular formation, maturation and remodeling.Thereby, angiogenesis inhibition as a helping agent to conventional therapies such as chemotherapy and radiation has attracted the scientists' attentions studying in this field

Estimation of Radiation Exposure of 128-Slice 4D-Perfusion CT for the Assessment of Tumor Vascularity

OBJECTIVE: We aimed to estimate the effective dose of 4D-Perfusion-CT protocols of the lung, liver, and pelvis for the assessment of tumor vascularity. MATERIALS AND METHODS: An Alderson-Rando phantom equipped with thermoluminescent dosimeters was used to determine the effective dose values of 4D-Perfusion-CT. Phantom measurements were performed on a 128-slice single-source scanner in adaptive 4D-spiral-mode with bidirectional table movement and a total scan range of 69 mm over a time period of nearly 120 seconds (26 scans). Perfusion measurements were simulated for the lung, liver, and pelvis under the following conditions: lung (80 kV, 60 mAs), liver (80 kV/80 mAs and 80 kV/120 mAs), pelvis (100 kV/80 mAs and 100 kV/120 mAs). RESULTS: Depending on gender, the evaluated body region and scan protocol, an effective whole-body dose between 2.9-12.2 mSv, was determined. The radiation exposure administered to gender-specific organs like the female breast tissue (lung perfusion) or to the ovaries (pelvic perfusion) led to an increase in the female specific dose by 86% and 100% in perfusion scans of the lung and the pelvis, respectively. CONCLUSION: Due to a significant radiation dose of 4D-perfusion-CT protocols, the responsible use of this new promising technique is mandatory. Gender- and organ-specific differences should be considered for indication and planning of tumor perfusion scans.

Arterial reconstructions associated with the resection of malignant tumors

OBJETIVO: Quando há acometimento de artérias tronculares por neoplasias malignas e o tratamento cirúrgico é empregado para realização de ressecções tumoral e arterial, a reconstrução vascular deve ser imediata, para evitar a isquemia de tecidos nobres. O objetivo desse trabalho é analisar os resultados do tratamento de pacientes portadores de neoplasias malignas submetidos a ressecções tumoral e vascular associada à reconstrução arterial, avaliando a perviedade primária das reconstruções, as complicações arteriais e a sobrevida dos pacientes. MÉTODOS: Foram acompanhados 36 pacientes com neoplasias em regiões cervical, abdominal ou extremidades inferiores, operados eletivamente no período de setembro de 1997 a setembro de 2004 no Hospital do Câncer A.C.Camargo em São Paulo. Os pacientes foram divididos em três grupos de acordo com a localização das neoplasias: Cervical (14), Extremidade (13) e Abdome (9). Foram realizadas 38 reconstruções arteriais nos 36 pacientes. RESULTADOS: Houve cinco complicações arteriais, sendo duas precoces e três tardias. Entre as precoces, houve uma oclusão carotídea sintomática com seqüelas e uma rotura de enxerto femoral sem seqüelas. Entre as tardias, houve uma oclusão carotídea sintomática, uma oclusão de enxerto carotídeo-axilar e uma oclusão de ramo de enxerto aorto-bifemoral, todas sem sequelas. Não houve diferença entre os índices de perviedade arterial primária . Todos os óbitos (22) ocorreram devido à evolução da doença neoplásica. CONCLUSÕES: As reconstruções arteriais associadas à ressecção de neoplasias malignas em segmentos cervical, abdominal ou extremidades inferiores podem ser realizadas com baixos índices de morbi-mortalidade. Não houve diferença entre os índices de perviedade primária das reconstruções.

Computational Analysis of Tumor Angiogenesis Patterns Using a Two-dimensional Model

Tumor angiogenesis was simulated using a two-dimensional computational model. The equation that governed angiogenesis comprised a tumor angiogenesis factor (TAF) conservation equation in time and space, which was solved numerically using the Galerkin finite element method. The time derivative in the equation was approximated by a forward Euler scheme. A stochastic process model was used to simulate vessel formation and vessel elongation towards a paracrine site, i.e., tumor-secreted basic fibroblast growth factor (bFGF). In this study, we assumed a two-dimensional model that represented a thin (1.0mm) slice of the tumor. The growth of the tumor over time was modeled according to the dynamic value of bFGF secreted within the tumor. The data used for the model were based on a previously reported model of a brain tumor in which four distinct stages (multicellular spherical, first detectable lesion, diagnosis, and death of the virtual patient) were modeled. In our study, computation was not continued beyond the 'diagnosis' time point to avoid the computational complexity of analyzing numerous vascular branches. The numerical solutions revealed that no bFGF remained within the region in which vessels developed, owing to the uptake of bFGF by endothelial cells. Consequently, a sharp declining gradient of bFGF existed near the surface of the tumor. The vascular architecture developed numerous branches close to the tumor surface (the brush-border effect). Asymmetrical tumor growth was associated with a greater degree of branching at the tumor surface.

Angiogenesis and cancer: recent advances

Recent studies have shown the possibility to treat cancer with drugs that affect the formation of new blood vessels instead of attacking directly the malignant cell. This relatively new field in the area of oncology on angiogenesis inhibition has expanded the therapeutic option for malignant diseases. We will discuss several antiangiogenesis drugs in clinical development and their mechanism of action. Some of these drugs include: angiostatin, metalloproteinase inhibitors, thalidomide, tamoxifen, interferons and others. The use of antiangiogenic agents, both in combination with other treatment modalities in the acute setting as well as long-term maintenance or prevention of cancer, is at present one of the better promises in the war against cancer.

clinical implications of angiogenesis in the treatment of cancer

Angiogenesis, the formation of new blood vessels from pre-existing ones, is a very well controlled multistep process under physiologic conditions. It involves a balance between several positive and negative regulators. Pathologic angiogenesis, both-excessive and insufficient, plays a role in the pathophysiology of many diseases including cancer. It has been proven that tumor growth and metastasis are angiogenesis-dependent. Endothelial cells and tumor cells also provide a mutual support to each other via the secretion of several substances. Targeting tumor blood vessels is a new approach to the treatment of cancer. Clinical trials are currently underway and the results appear to be very promising

Tumor angiogenesis.

Tumor angiogenesis is the growth of new blood vessels which is required for tumor growth and progression. Vascularization of the tumor occurs through a series of sequential steps before or during the multistep progression to neoplasia. Several events occur during the formation of new vessels including production of protease enzymes, unregulation of positive regulators of angiogenesis, and down regulation of negative regulators. In addition, tumor associated macrophage also influence angiogenesis by secreting enzymes, enzymes inhibitors and cytokines. Recent knowledge in tumor angiogenesis may have clinical implications in diagnosis and treatment. Quantification of microvessel density in tumor specimen correlates either metastasis or recurrence in many malignancies such as breast cancer and lung cancer. Therefore, assessment of tumor angiogenesis may serve as prognostic factors. Therapeutic applications include the development of new agents with antiangiogenic properties, vascular targeting drugs, antibody-based therapy, and gene therapy. Combination of antiangiogenic therapy with cytotoxic drugs may enhance antitumor activity. Moreover, the role of antiangiogenic therapy in adjuvant setting may provide and alternative approach to better cancer treatment in the near future.

Vena cava filter insertion as a primary therapy for deep venous thrombosis in patients with malignant disease

Anticoagulation therapy in patients with malignant disease and deep venous thrombosis [DVT] carries a high hemorrhagic complication rate. Pulmonary showers may also not be properly controlled on anticoagulation. Accordingly, a policy of placing Greenfield vena cava filters [GFs] was established, as a primary therapy instead of anticoagulation whenever this was possible. Since 1988 till present, 40 patients with malignant disease [blood or visceral] and DVT, were treated. 15 patients had GFs as a primary therapy and 25 patients underwent anticoagulation therapy at their own request after explaining both modalities of treatment. The purpose of this study was to compare the result of anticoagulation versus GFs insertion in these two groups of patients. The anticoagulation group A showed a significantly higher number of major complications than GFs group B. Massive pulmonary embolism [PE] occurred in 2 patients despite adequate anticoagulation both resulted in death of the patients. 4 major bleeding episodes occurred, 3 of those were gastrointestinal and one intracerebral. The patients with intracerebral bleeding developed a major stroke and subsequently died. The 3 patients with gastrointestinal bleeding required transfusion of more than 4 units of blood and all received platelet transfusions and one of them subsequently died. Although this study is a small nonrandomized one, the data indicate that GF placement is safer than anticoagulation in patients with malignant disease and DVT