Primary Myelofibrosis in the Prefibrotic Stage Presenting as Portal, Splenic, and Superior Mesenteric Vein Thrombosis: A Case Report and Review of the Literature.

Introduction: Myeloproliferative neoplasms are the most common cause of splanchnic vein thrombosis in the absence of cirrhosis or nearby malignancy. Case Presentation: A 31-year-old male presented to the emergency department with epigastric pain associated with mild thrombocytosis and elevated levels of aminotransferases, lactate dehydrogenase, and C-reactive protein. Contrast-enhanced abdominal computed tomography revealed splanchnic venous thrombosis that involved the portal, splenic, and superior mesenteric veins, without signs of chronic liver disease. Anticoagulation with warfarin was immediately started. Diagnostic work-up was remarkable for the presence of the JAK2 V617T mutation and hypercellular bone marrow, with increased myeloid cells and atypical megakaryocytes, consistent with primary myelofibrosis in a prefibrotic stage. No other hypercoagulable conditions were identified. Discussion: We present a rare case of primary myelofibrosis in the prefibrotic stage presenting as portal-splenic-superior mesenteric vein thrombosis. This demonstrates that extensive splanchnic vein thrombosis may be the onset manifestation of myeloproliferative neoplasms, even in early stages and in the absence of concomitant hypercoagulable conditions. The presence of the JAK2 mutation is an important prothrombotic risk factor that can, per se, contribute to large venous thrombosis.

Introdução: As neoplasias mieloproliferativas constituem a causa mais comum de trombose venosa esplâncnica na ausência de cirrose hepatica ou neoplasia regional. Descrição do caso: Um homem de 31 anos apresentou-se no Serviço de Urgência com dor epigástrica associada a trombocitose ligeira e elevação das transamínases, desidrogenase láctica e proteína C-reactiva. Em tomografia computorizada abdominal com contraste, foi identificada trombose venosa esplâncnica envolvendo a veia porta, esplénica e mesentérica superior, sem sinais de doença hepática crónica. Foi de imediato iniciada anticoagulação com varfarina. Da investigação etiológica, destaca-se a presença da mutação JAK2 V617F e medula óssea hiper-celular com aumento das contagens de células mielóides e megacariócitos atípicos, consistente com mielofibrose primária em estadio pré-fibrótico. Não se identificaram distúrbios pro-trombóticos concomitantes. Discussão: Apresenta-se um raro caso de trombose da veia porta, esplénica e mesentérica superior, demonstrando que as neoplasias mieloproliferativas podem apresentar-se sob a forma de trombose venosa esplâncnica extensa, mesmo em estadios precoces e na ausência de distúrbios protrombóticos concomitantes. A presença da mutação JAK2 é um importante factor de risco pro-trombótico que pode por si só contribuir para a formação de tromboses venosas extensas.

Clinical Characteristics, Treatment and Evolution of Splenic and Nodal Marginal Zone Lymphomas-Retrospective and Multicentric Analysis of Portuguese Centers.

INTRODUCTION: Treatment of Splenic (SMZL) and Nodal (NMZL) Marginal Zone Lymphoma is not consensual. Histologic transformation (HT) to aggressive lymphoma is a poorly understood event, with an unfavorable outcome. OBJECTIVES: Describe the clinical characteristics, treatment, outcomes and incidence of HT. METHODS: Characteristics of patients with SMZL and NMZL consecutively diagnosed in 8 Portuguese centers were retrospectively reviewed. Endpoints were overall survival (OS), time to first systemic treatment (TTFST), frequency of HT and time to transformation (TTT). RESULTS: This study included 122 SMZL and 68 NMZL, most of them received systemic treatment: 55.4% and 76.5%, respectively. Splenectomy was performed in 58.7% of patients with SMZL. Different treatment protocols were used. OS or TTFST did not differ significantly according to treatments. Given the small sample size, no conclusion can be made concerning the role of Rituximab in the treatment of NMZL and SMZL based in these results. HT was documented in 18 patients, mainly in SMZL, with a cumulative incidence at 5 years of 4.2%. We confirmed that age is a prognostic factor. CONCLUSION: Randomized prospective trials are needed to standardize treatment in MZL. Patients with HT did appear to have shorter OS in comparison with those who did not experience HT (OS 5 years of 68.4% vs. 80.4%), but the number of HT was too small to reach statistical significance.

Cerebral Venous Thrombosis in Hematological Malignancy: Balancing the Risks.

BACKGROUND AND AIM: The coexistence of cerebral venous thrombosis (CVT) and hematological neoplasms is rare. Currently available therapeutic options raise problems concerning the balance of thrombotic and hemorrhagic risks. Our purpose is to characterize a series of cases of CVT and concomitant hematological malignancy, focusing on predisposing factors and treatment strategies. METHODS: We performed a descriptive retrospective analysis of the cases of CVT and hematological neoplasms diagnosed in a tertiary center from 2006 to 2015. RESULTS: From the 111 CVT cases diagnosed, only 7 coexisted with hematological malignancy (lymphoma, leukemia, multiple myeloma, and myelodysplastic syndromes). These included 4 women; median age was 44 years old. Median follow-up time was 72 days. The hematological condition was already known in 5 cases. Besides malignancy, we identified other prothrombotic conditions in all cases. Several anticoagulant strategies were used during the acute phase, after which 5 patients remained on warfarin indefinitely. One patient died due to cerebral hemorrhage during the acute phase. In the remaining 6 patients, there was no recurrence of CVT or other complications of anticoagulation. CONCLUSIONS: Although these results reiterate the role of hematological malignancy as predisposing factor to CVT, in all cases other factors contributed to CVT etiology, potentiating the risk. We report 1 death directly attributable to a fatal hemorrhagic complication of anticoagulation, evidencing the delicate balance of thrombotic and hemorrhagic risk. Nevertheless, most patients benefited of long-term anticoagulation, which proved a reasonable option. A multidisciplinary approach is paramount in making decisions regarding the time and type of anticoagulation.

Fractura mandibular parasinfisiaria y condilar intracapsular en paciente pediátrico manejado con placas reabsorbibles: reporte de un caso / Parasymphysial and intracapsular condylar fracture in a pediatric patient managed with resorbable plates: a case report

La fractura mandibular es uno de los tipos más comunes en el trauma maxilofacial pediá-trico. El principal objetivo del manejo de fracturas, es la restauración de forma y función del hueso. Las fracturas incompletas son más comunes, debido a la elasticidad del hueso; por lo que, usualmente el tratamiento de fracturas en niños es conservador.Debido al progreso en materiales de reparación ósea y la mejora tecnológica, actualmente la proporción de niños tratados con reducción abierta y fijación interna (RAFI) ha au-mentado; siendo el uso de miniplacas y minitornillos el tratamiento gold estándar para fijación semirrígida craneomaxilofacial. Una alternativa son los materiales reabsorbibles, lo cuales no requieren retiro y van degradándose gradualmente, ventaja considerable en el manejo de fracturas mandibulares en niños. Presentamos el caso de un paciente de 6 años, quién sufrió una fractura mandibular parasinfisiaria y condilar por caída de escale-ras. Al examen se evidencia limitación de apertura bucal, dolor moderado a la palpación; se solicitaron exámenes imagenológicos donde se evidencia trazo de fractura parasinfisia-ria y trazo a nivel intracapsular de cóndilo izquierdo, estas fracturas fueron manejadas con placas reabsorbibles y tratamiento conservador, respectivamente. El resultado fue óptimo. Palabras clave: Fracturas mandibulares; Reducción de fractura abierta; Fijación de frac-tura interna; Placa reabsorbible; Niños (fuente: DeCS BIREME).

The mandibular fracture is one of the most common types in pediatric maxillofacial trauma. The main objective of fracture management is the restoration of bone shape and function. Incomplete fractures are more common due to bone elasticity; so, usually the treatment of fractures in children is conservative. Due to the progress on materials bone reparation and technological improvement, currently the proportion of children treated with open reduction and internal fixation (RAFI) has increased. The use of mi-niplates and miniscrews are the gold standard treatment for craniomaxillofacial semirigid fixation. One alternative are the resorbable materials, which do not require the removal and are gradually degrade. This is a considerable advantage for the management of mandibular fractures in children. We present the case of a 6-year-old patient who suffered a parasympathetic mandibular and condylar fracture. The clinical examination showed limited oral opening and moderate pain on palpation. The radiological evaluation evi-denced parasymphyseal and intracapsular fracture traces on the left condyle. These frac-tures were managed with resorbable plates and conservative treatment, respectively. The result was optimal. Keywords: Mandibular fractures; Open fracture reduction; Fracture fixation internal; Biore-sorbable plate; Children (source: MeSH NLM).

Pulmonary aspergillosis diagnosed by endoscopic ultrasound fine-needle aspiration.

Pulmonary aspergillosis generally occurs in patients with prolonged neutropenia or immunosupression. Definitive diagnosis depends on the demonstration of the organism in tissue, as positive culture result from sputum, needle biopsy, or bronchoalveolar lavage fluid. Even though endoscopic ultrasound (EUS) fine needle aspiration (FNA) of paraesophageal/mediastinal lesions has been used numerous times, this is the first case that reports an aspergilloma diagnosed by EUS-FNA, allowing us to reach a definitive diagnosis. We present a patient with a nodular lesion located in the right upper lobe lung, with ground-glass opacity. Upper EUS revealed an ill-defined hypoechoic paraesophageal lesion with a central annular image. Culture results from EUS-FNA were positive for Aspergillus fumigatus. There are no previous reports of EUS imaging features of pulmonary aspergillosis. We believe that this central annular image in an ill-defined hypoechoic paraesophageal lesion may be a characteristic feature.

Aggressive mature natural killer cell neoplasms: report on a series of 12 European patients with emphasis on flow cytometry based immunophenotype and DNA content of neoplastic natural killer cells.

We report 12 cases of aggressive natural killer (NK) cell neoplasms diagnosed in Portugal, with emphasis on flow cytometry. Ten patients had extranodal NK/T cell lymphoma, nasal type and two had aggressive NK cell leukemia, and seven were men and five were women, with a median age of 50 years. NK cells brightly expressed the CD56 adhesion molecule and CD94 lectin type killer receptor and had an activation-related HLA-DR+ CD45RA+ CD45RO+ immunophenotype, in most cases. In contrast, dim CD16 expression was found in a minor proportion of cases, whereas CD57 and the CD158a and CD158e1 killer immunoglobulin-like receptors were negative. One-third of cases showed a hyperploid DNA content and nearly all had a very high S-phase proliferative rate. The phenotypic features of the neoplastic NK cells would suggest that they represent the transformed counterpart of the CD56 + bright NK cells that circulate in normal blood.

What determines therapeutic choices for elderly patients with DLBCL? Clinical findings of a multicenter study in Portugal.

BACKGROUND: Age is a negative prognostic factor in lymphomas, and elderly patients are often undertreated because of toxicity concerns. The pattern of treatment in elderly patients with diffuse large B-cell lymphoma (DLBCL) in Portugal has not been previously described. PATIENTS AND METHODS: We conducted a multicenter retrospective study including 378 elderly patients with DLBCL receiving alkylating agent-containing regimens between 2003 and 2010. We compared the outcome of patients aged 60 to 79 years with patients > 79 years and analyzed the second group according to treatment. RESULTS: R-CHOP (rituximab, cyclophosphamide, doxorubicin [hydroxydaunorubicin], vincristine [Oncovin], prednisolone) was prescribed in only 60% of patients and was prescribed significantly less in patients > 79 years, despite no significant differences being found in comorbidities between the 2 age groups. Similarly, dose reductions frequently were instituted because of chronologic age and not always because of toxicity. When different regimens were compared, multivariate analysis showed an independent beneficial effect of R-CHOP in treatment outcomes. Additionally, treatment with anthracyclines and rituximab predicted a better progression-free survival (PFS) and time to progression (TTP) in patients > 79 years. CONCLUSION: This was the first characterization of the clinical care of elderly Portuguese patients with DLBCL. We showed that R-CHOP is effective even in patients > 79 years, emphasizing that treatment decisions based on age alone can compromise treatment efficacy and outcome in fit patients.

[Biosimilars in oncology]. / Biossimilares em oncologia.

The development of biotechnology drugs represents one of the great advances in medical therapy and it was observed an exponential growth in its use. The resource to these drugs in Oncology and Hematology is no exception and it soon became an essential element of an integrated and directed therapy strategy. The expiry of the first biotechnology drugs patents has opened the door for the development and marketing of biosimilars, which entry in the Portuguese market was recently approved. This article was built on the analysis of the available state-of-the-art information on biotechnology drugs, biosimilars and current legislation and it expresses the opinion of Oncology and Hematology experts about the substituition of biological drugs by biosimilars in clinical practice.

[Use of granulocyte growth factors: recommendations of the Portuguese Society of Hematology]. / Uso de factores de crescimento de granulócitos: recomendações da Sociedade Portuguesa de Hematologia.

The administration of cytotoxic chemotherapy may be complicated by the emergence of neutropenia and febrile neutropenia, frequently determining hospital admission and intravenous treatment with broad spectrum antibiotics. Frequently, it is necessary to reduce the dose or to delay the administration of the cytotoxic drugs reducing the relative dose intensity of the chemotherapy regimen. Granulocyte growth factors stimulate the proliferation and differentiation of neutrophils and reduce the number of days of severe neutropenia and febrile neutropenia associated with cytotoxic chemotherapy. They are also indicated for the collection of hematopoietic progenitors for autologous and allogeneic transplantation, as well as in non malignant diseases associated with chronic neutropenia. This article reviews the evidence supporting the use of granulocyte growth factors in Hematology.

Photodynamic damages induced by a monocationic porphyrin derivative in a human carcinoma cell line.

The photokilling activity of 5-(4-trimethylammoniumphenyl)-10,15,20-tris(2,4,6-trimethoxyphenyl)porphyrin (CP) was evaluated on a Hep-2 human larynx-carcinoma cell line. Cell treatment was carried out with 5 microM CP incorporated into liposomal vesicles. Under violet-blue exciting light, the red fluorescence of CP was mainly detected as a filamentous pattern characteristic of mitochondrial localization. Similar pattern was also observed using rhodamine 123 in Hep-2 cells. No dark cytotoxicity was observed using 5 microM CP concentration and long incubation time (24 h). Using Hoechst-33258 and caspase-3 immunostaining methods, cell cultures treated for 24 h with CP and exposed to light for 7.5 min (27 J/cm2) showed a great amount of apoptotic cells (40%). In contrast, necrotic cells (58%) were observed using the same drug concentration but irradiated for 15 min (54 J/cm2). The results show that CP can induce different mechanisms of cell death depending on irradiation doses in the photodynamic treatments, which makes this agent an interesting sensitizer with potential application in photodynamic tumor therapy.

Pharmacokinetic and phototherapeutic studies of monocationic methoxyphenylporphyrin derivative.

BACKGROUND AND OBJETIVE: Photodynamic therapy, a novel treatment for cancer, works through photoactivation of a tumor-localized photosensitive drug, and localized through oxidative damage to kill cells and ablate tumors. Pharmacokinetic and phototherapeutic properties of a cationic porphyrin were assayed in a Balb/c mouse cancer model in order to evaluate its efficiency as photosensitizer. METHODS: Biodistribution studies were carried out by intraperitoneal injection of 5mg/kg CP incorporated into a liposome solution. CP was recovered from serum and organs at various times after treatment. The serum biochemical parameters and histological studies were used to test hepatic and renal functionality. For phototherapeutic studies, the light source used was a slide projector (360J/cm(2)). The efficiency of CP was evaluated by following tumor growth curves for 10 days after PDT doses. Immunohistochemical detection was carried out to evaluate caspase-3 activation in CP-PDT-treated tumors. RESULTS AND CONCLUSIONS: The photosensitizer distribution suggests that CP is mainly eliminated from the organism via the bile-gut pathway, and that neurotoxic and cutaneous photosensitivity effects are reduced or absent. The porphyrin distribution from bloodstream to tissue began at 24h of drug administration. CP did not affect the hepatic and renal functionality, as was demonstrated by the physiological parameters. PDT-treated tumors showed delay in growth rate as compared to untreated control mice. Biochemical studies showed that the efficient tumor regression is dependent on caspase-3 activity signaling response associated with apoptosis. The results obtained suggest that the porphyrin CP may be a promising candidate for further use in PDT treatments.