Advanced Stage Hepatocellular Carcinoma with Multiple Metastasis and Vascular Thrombosis: A Case of Complete Response to Sorafenib.

Sorafenib is a multi-targeted tyrosine kinase inhibitor, with antiangiogenic and antiproliferative properties, approved for the treatment of advanced hepatocellular carcinoma. It induces a significant increase in the median overall survival, despite a complete response to treatment being rare. We report a clinical case of a 60-year-old male with hepatic cirrhosis, Child-Pugh class A and performance status 0, and advanced hepatocellular carcinoma. The primary tumor measured 17 x 8 cm and had diffuse intrahepatic metastization, extensive lung and left adrenal invasion, as well as thrombosis of inferior vena cava, with projection to the right atrium. This patient showed a rapid and complete response to sorafenib, evaluated by mRECIST (modified Response Evaluation Criteria in Solid Tumors), that remains after three years of treatment.

O sorafenib, um inibidor de múltiplas cinases com propriedades antiangiogénicas e antiproliferativas foi aprovado para o tratamento de carcinoma hepatocelular em estádio avançado por induzir um prolongamento da sobrevivência global estatisticamente significativo, sendo a resposta completa rara. Relata-se o caso clínico de um homem de 60 anos com cirrose hepática classe A de Child-Pugh e performance status 0 e carcinoma hepatocelular em estádio avançado (com tumor primitivo medindo 17 X 8 cm, metastização intra-hepática difusa, pulmonar maciça e da suprarrenal esquerda e ainda trombose da veia cava inferior com extensão e projeção na c'mara da aurícula direita), que apresentou resposta completa com sorafenib, avaliada pelos critérios mRECIST (modified Response Evaluation Criteria in Solid Tumors). Esta resposta mantem-se após três anos de tratamento.

Oxidative stress and mitochondrial dysfunction play a role in myelodysplastic syndrome development, diagnosis, and prognosis: A pilot study.

The imbalance between reactive oxygen species (ROS) production and their elimination by antioxidants leads to oxidative stress. Depending on their concentration, ROS can trigger apoptosis or stimulate cell proliferation. We hypothesized that oxidative stress and mitochondrial dysfunction may participate not only in apoptosis detected in some myelodysplastic syndrome (MDS) patients, but also in increasing proliferation in other patients. We investigated the involvement of oxidative stress and mitochondrial dysfunction in MDS pathogenesis, as well as assessed their diagnostic and prognostic values. Intracellular peroxides, superoxide, superoxide/peroxides ratio, reduced glutathione (GSH), and mitochondrial membrane potential (Δψ(mit)) levels were analyzed in bone marrow cells from 27 MDS patients and 12 controls, by flow cytometry. We observed that all bone marrow cell types from MDS patients had increased intracellular peroxide levels and decreased GSH content, compared with control cells. Moreover, oxidative stress levels were MDS subtype- and risk group-dependent. Low-risk patients had the highest ROS levels, which can be related with their high apoptosis; and intermediate-2-risk patients had high Δψ(mit) that may be associated with their proliferative potential. GSH levels were negatively correlated with transfusion dependency, and peroxide levels were positively correlated with serum ferritin level. GSH content proved to be an accurate parameter to discriminate patients from controls. Finally, patients with high ROS or low GSH levels, as well as high superoxide/peroxides ratio had lower overall survival. Our results suggest that oxidative stress and mitochondrial dysfunction are involved in MDS development, and that oxidative stress parameters may constitute novel diagnosis and/or prognosis biomarkers for MDS.

[Hypovitaminosis D in patients admitted to an internal medicine ward]. / Hipovitaminose D em Doentes Internados num Serviço de Medicina Interna.

INTRODUCTION: Hypovitaminosis D (hypoD) is a vitamin deficiency that has been rising in the developed countries, due not only to inappropriate eating habits, but also because of lower sun exposure and lack of exercise. OBJECTIVE: To determine the prevalence of vitamin D deficiency and to analyze associated factors, in patients admitted to an Internal medicine Ward. METHODS: Cross-sectional study which included 123 hospitalized patients admitted to an Internal Medicine Ward between April and May. Serum levels of vitamin D [25-hydroxyvitamin D, 25(OH)D] were determined and the sample divided into three groups based on 25(OH)D levels: severe hypoD (<10ng/mL), moderate deficiency of 25(OH)D (>10ng/mL and <20ng/mL) and third group with normal levels of 25(OH)D (>20ng/mL). Demographic variables were recorded as were factors potentially related to vitamin D deficiency. RESULTS: In this sample (52.0% women) the average age was 71 ± 17 years, 67.5% of patients had severe hypoD, 25.2% moderate deficiency and 7.3% normal levels of vitamin D. The patients in the group with severe hypoD were older (p=0.027). In the same group there was a higher percentage of patients in the bedridden state (p=0.022), with higher impaired functional capacity (p=0.009) and with chronic renal insufficiency (p=0.011). In multivariate logistic regression analysis, factors associated with an increased likelihood of severe hypoD were: furosemide treatment [OR=3.673 (1.232-10.956) p=0.020] and albumin ≤3.25 [OR=5.617 (2.257-13.981) p<0.001]. CONCLUSION: The high prevalence of hypoD (67.5%) in this sample expresses the need for systematic evaluation of serum levels of 25(OH)D, in order to initiate early treatment in patients with inadequate levels. Furosemide treatment and hypoalbuminaemia present an increased likelihood of being associated with severe hypoD. Treatment of this hypovitaminosis is warranted not only because of the clinical consequences related to bone loss, but also because of its relationship with hypoalbuminemia which is associated with a poorer prognosis in hospitalized patients.

Churg-Strauss syndrome: case series.

Churg-Strauss syndrome (CSS) is a systemic necrotizing vasculitis of the small and medium vessels, associated with extravascular eosinophilic granulomas, peripheral eosinophilia and asthma. This is a rare syndrome of unknown etiology, affecting both genders and all age groups. CSS patients usually respond well to steroid treatment, although relapses are common after it ends. Timely diagnosis and treatment generally lead to a good prognosis with a 90% survival rate at one year. A brief review of CSS is presented, with particular attention to diagnosis, therapy and recent developments in this area. The authors then report and discuss the clinical, laboratory and imaging characteristics of four patients admitted to an Internal Medicine Department with this diagnosis. The treatment, response and follow-up of the cases are also described.

[Digital ulcers in systemic sclerosis: use of endotheline antagonists]. / Úlceras digitais na esclerodermia: papel dos antagonistas dos receptores da endotelina na terap êutica.

INTRODUCTION: Systemic sclerosis (SSc) is a systemic disease, characterized by fibrosis and vasculopathy, with variable internal organ involvement. Skin is very often involved, namely digital ulcers (DU), seldom treatment resistant, responsible for important functional limitation. The DU can evolve from sclerodactily with superficial ulcers, isquemic lesions, deep necrosis, gangrene, loss of tissue, and consequently, to finger amputation. METHODS: The authors describe the case of a 36 year old female patient, with SSc diagnosed 6 years previously, with skin, lung and gut manifestations. The patient showed uncontrolled Raynaud's phenomenon (RF), despite the adequate treatment using nifedidpine and general local warming measures, with progressively worsening DU and isquemia, especially in cold seasons. Bosentan, 62.5 mg twice daily was started, and a significant improvement in the peripheral isquemic lesions was achieved. The ulcers' healing was fast, the patient totally recovered function and regained quality of life, and no further lesions developed. CONCLUSION: The authors review the RF and DU in SSc, as well as the use of bosentan, an endotheline receptor antagonist, and its indications. Although it is not formally approved, the use of bosentan in SS has shown benefits in reducing the incidence of DU, and despite no influence in the healing process, this drug prevents the development of new lesions.

[Undifferentiated osteoclastic-type giant cell carcinoma]. / Carcinoma pancreático de células gigantes de tipo osteoclástico.

Initially described 40 years ago (Rosai), the undifferentiated osteoclastic-type giant cell carcinoma (IOGCC) is a variant of ductal adenocarcinoma and accounts for less than 1% of exocrine pancreatic tumors. Its extreme rarity, with consequent existence of few reports and clinical experience, leads to the arousal of doubts with regard to its histogenesis, types of approach and therapeutical attitudes. It is important to note that in Portugal no similar case is registered in medical literature. A 61 year old patient admitted to the Internal Medicine Ward 3 at Coimbra University Hospital presents with a voluminous intra-abdominal mass in the left hypochondrium and microcytic anemia. During the investigation, a pancreatic neoplasm was identified, and the patient was submitted to surgical resection, the anatomo-pathological study of the tumor having revealed IOGCC. The particularities of the case, current available therapeutical options and its evolution are discussed, as well as a revision of the existing literature.