Enhanced therapeutic efficacy of transarterial chemoembolisation treatment in hepatocelluar carcinoma (HCC) by mTOR inhibitor RAD001: implication for a novel treatment regimen in HCC

Oral Presentationpublished_or_final_versionThe 16th Medical Research Conference, Department of Medicine, the University of Hong Kong, Hong Kong, 22 January 2011. In Hong Kong Medical Journal, 2011, v. 17 n. 1, suppl. 1, p. 25, abstract no. 3

Inhibition of tumour growth by Raf265 via blockade of Raf/MEK/ERK pathway in colorectal cancer

published_or_final_versionThe 15th Annual Research Conference of the Department of Medicine, The University of Hong Kong, Hong Kong, 16 January 2010. In Hong Kong Medical Journal, 2010, v. 16, suppl. 1, p. 16, abstract no. 1

Anti-tumor efficacy of recombinant human arginase in combination with chemotherapeutic agents in human hepatocellular carcinoma

Poster Session 1: Translational & Clinical: no.41published_or_final_versionThe 16th Annual Research Conference of the Department of Medicine, The University of Hong Kong, Hong Kong, 22 January 2011. In Hong Kong Medical Journal, 2011, v. 17, suppl. 1, p. 23, abstract no. 2

Central Nervous System Inflammatory Demyelinating Disorders in the Hong Kong Chinese

Central nervous system inflammatory demyelinating disorders (CNS IDD) include classical multiple sclerosis, neuromyelitis optica (NMO) spectrum disorders, a single attack of/recurrent acute disseminated encephalomyelitis, a single attack of idiopathic acute transverse myelitis, optic neuritis (ON) and brainstem encephalitis. CNS IDD are potentially serious disorders with risks of mortality and significant disability. Typical relapsing forms of CNS IDD are relapsing remitting multiple sclerosis and relapsing NMO. Relapsing NMO is typified by recurrent longitudinally extensive transverse myelitis and severe unilateral or bilateral ON. Early diagnosis of CNS IDD is important as long-term treatment for different forms varies. Recognition of clinical, radiological and serological characteristics of different forms of CNS IDD facilitates early diagnoses. A significant proportion of NMO patients are seropositive for autoantibodies against aquaporin-4, the most abundant water channel in the CNS; this supports the hypothesis that NMO is an autoimmune disorder. Is NMO an autoantibody-mediated disorder sharing similar pathogenesis with myasthenia gravis (MG), a classical autoantibody-mediated autoimmune disease? An interesting observation is that paraneoplastic NMO associated various tumours is recognised recently, suggesting similarity with MG which is associated with thymoma in about 15 to 20% of patients.published_or_final_versio

Clinical and Pathological Findings in Women with Fabry Disease

Introduction. Fabry disease is a rare metabolic disorder caused by the genetic deficiency of the lysosomal hydrolase alpha-galactosidase A, located on chromosome X. Females with the defective gene are more than carriers and can develop a wide range of symptoms. Nevertheless, disease symptoms generally occur later and are less severe in women than in men. The enzyme deficiency manifests as a glycosphingolipidosis with progressive accumulation of glycosphingolipids and deposit of inclusion bodies in lysosomes giving a myelinlike appearance. Patients and Methods. Records of renal biopsies performed on adults from 1st January 2008 to 31st August 2011, were retrospectively examined at the Renal Pathology Laboratory. We retrieved biopsies diagnosed with Fabry disease and reviewed clinical and laboratory data and pathology findings. Results. Four female patients with a mean age of 49.3±4.5 (44-55) years were identified. The mean proteinuria was 0.75±0.3 g/24h (0.4-1.2) and estimated glomerular filtration rate (CKD EPI equation) was 71±15.7 ml/min/1.73m2 (48-83). Three patients experienced extra-renal organ involvement (cerebrovascular, cardiac, dermatologic, ophthalmologic and thyroid) with distinct severity degrees. Leukocyte α-GAL A activity was below normal range in the four cases but plasma and urinary enzymatic activity was normal. Light microscopy showed predominant vacuolisation of the podocyte cytoplasm and darkly staining granular inclusions on paraffin and plastic-embedded semi-thin sections. Electron microscopy showed in three patients the characteristic myelin-like inclusions in the podocyte cytoplasm and also focal podocyte foot process effacement. In one case the inclusions were also present in parietal glomerular cells, endothelial cells of peritubular capillary and arterioles. Conclusion. Clinical signs and symptoms are varied and can be severe among heterozygous females with Fabry disease. Intracellular accumulation of glycosphingolipids is a characteristic histologic finding of Fabry nephropathy. Since this disease is a potentially treatable condition, its early identification is imperative. We should consider it in the differential diagnosis of any patient presenting with proteinuria and/or chronic kidney disease, especially if there is a family history of kidney disease

Thymomatous myasthenia gravis

BACKGROUND: Myasthenia gravis (MG) is an autoimmune disorder targeting skeletal muscle acetylcholine receptor. Thymoma is associated with MG in some patients, the majority of whom present with symptoms of MG before detection of underlying thymoma. This study aimed to study clinical and serological characteristics of Chinese thymomatous MG patients …published_or_final_versio

Tolerance of high-intensity focused ultrasound ablation in patients with hepatocellular carcinoma

BACKGROUND: High-intensity focused ultrasound (HIFU) ablation is a relatively new, noninvasive way of ablation for treating hepatocellular carcinoma (HCC). Emerging evidence has shown that it is effective for the treatment of HCC, even in patients with poor liver function. There is currently no data on the safety limit of HIFU ablation in patients with cirrhosis. However, this information is vital for the selection of appropriate patients for the procedure. We analyzed HCC patients who had undergone HIFU ablation and determined the lower limit of liver function and other patient factors with which HCC patients can tolerate this treatment modality. METHODS: Preoperative variables of 100 patients who underwent HIFU ablation for HCC were analyzed to identify the risk factors in HIFU intolerance in terms of stress-induced complications. Factors that may contribute to postablation complications were compared. RESULTS: Thirteen (13 %) patients developed a total of 18 complications. Morbidity was mainly due to skin and subcutaneous tissue injuries (n = 9). Five patients had first-degree skin burn, one had second-degree skin burn, and three had third-degree skin burn. Four complications were grade 3a in the Clavien classification and 14 were below this grade. Univariate analysis showed that age (p = 0.022) was the only independent factor in HIFU intolerance. CONCLUSIONS: HIFU ablation is generally well tolerated in HCC patients with cirrhosis. It is safe for Child-Pugh A and B patients and selected Child-Pugh C patients. With this new modality, HCC patients who were deemed unsalvageable by other surgical means in the past because of simultaneous Child-Pugh B or C disease now have a new hope.published_or_final_versio

Survival analysis of transarterial radioembolization with yttrium-90 for hepatocellular carcinoma patients with HBV infection

Introduction: For patients with resectable hepatocellular carcinoma (HCC), hepatectomy remains one of the best treatment options to provide long-term survival. However, more than 50% of the patients have unresectable disease upon diagnosis even though there are no distant metastases. Transarterial chemoembolization (TACE) is a well-established treatment option that offers a palliative survival benefit for this group of patients. A better treatment for unresectable HCC has been sought after. There is some evidence that transarterial radioembolization (TARE) with the agent yttrium-90 produces encouraging outcomes, especially in patients with portal vein tumor thrombus. This study aims to analyze the outcomes of TARE at our center. Methods: From August 2009 to April 2013, 16 patients underwent TARE at our center. Sixteen patients with similar tumor characteristics were selected to undergo TACE alone for comparison. A retrospective analysis of the prospectively collected data of the patients was conducted. Only patients with newly diagnosed primary tumors were included in this study. Results: The median survival for patients having TARE was 19.9 versus 14.0 months in the TACE group (P=0.615). There was no difference in terms of tumor response according to the modified Response Evaluation Criteria in Solid Tumors (mRECIST) (P=0.632). The 1-, 2- and 3-year survival rates in the TARE group were 80.0%, 30.5% and 20.3% respectively. The 1-year survival in the TACE group was 58.3% (P=0.615). For patients who had major vascular invasion (eight in each group), the 1- and 2-year survival rates in the TARE group were 62.5% and 15.6% respectively, while the 1-year survival in the TACE group was 35.0% (P=0.664). Conclusions: The two groups showed similar results in terms of tumor response and overall survival benefit. TARE might provide a survival benefit for patients with major vessel invasion.published_or_final_versio

Epigenetic regulation of pluripotent genes mediates stem cell features in human hepatocellular carcinoma and cancer cell lines

Activation of the stem cell transcriptional circuitry is an important event in cancer development. Although cancer cells demonstrate a stem cell-like gene expression signature, the epigenetic regulation of pluripotency-associated genes in cancers remains poorly understood. In this study, we characterized the epigenetic regulation of the pluripotency-associated genes NANOG, OCT4, c-MYC, KLF4, and SOX2 in a variety of cancer cell lines and in primary tumor samples, and investigated the re-activation of pluripotency regulatory circuits in cancer progression. Differential patterns of DNA methylation, histone modifications, and gene expression of pluripotent genes were demonstrated in different types of cancers, which may reflect their tissue origins. NANOG promoter hypomethylation and gene upregulation were found in metastatic human liver cancer cells and human hepatocellular carcinoma (HCC) primary tumor tissues. The upregulation of NANOG, together with p53 depletion, was significantly associated with clinical late stage of HCC. A pro-metastatic role of NANOG in colon cancer cells was also demonstrated, using a NANOG-overexpressing orthotopic tumor implantation mouse model. Demethylation of NANOG promoter was observed in CD133+high cancer cells. In accordance, overexpression of NANOG resulted in an increase in the population of CD133+high cells. In addition, we demonstrated a cross-regulation between OCT4 and NANOG in cancer cells via reprogramming of promoter methylation. Taken together, epigenetic reprogramming of NANOG can lead to the acquisition of stem cell-like properties. These results underscore the restoration of pluripotency circuits in cancer cells as a potential mechanism for cancer progression. © 2013 Wang et al.published_or_final_versio

Estudo de caso: Gestão do risco operacional ligado às reclamações dos clientes na indústria hoteleira

Cada vez é mais difícil fidelizar os clientes, o desafio para os hotéis continua a ser a diminuição do número de reclamações e a melhoria da satisfação dos hóspedes. A indústria hoteleira já implementou processos para ter uma regularidade na qualidade do serviço. Contudo, no dia a dia os clientes continuam a reclamar quando existe uma falha no serviço. É aqui que entra o conceito do risco operacional, um conceito mais conhecido no setor da banca e pouco estudado na literatura para a indústria do Turismo e da Hotelaria. O relatório de estágio inclui um estudo de caso, criado de maneira a simular as estadias de um casal que vem com regularidade ao Hotel cinco estrelas Penha Longa Ritz-Carlton. Cada reclamação foi resolvida da melhor maneira para satisfazer novamente os hóspedes e o custo associado foi simulado com o objetivo de medir o impacto do risco operacional na rendibilidade. Em conclusão, o risco operacional tem de ser medido com cuidado, mesmo que não seja suposto gerir perdas financeiras significativas, o seu custo tem um impacto na rendibilidade. Existem várias formas de gerir o risco operacional, antecipando processos bem definidos no papel até à gestão das reclamações.As it becomes more complicated to build up customer loyalty, the challenge for hotels continues to be the reduction of customer complaints and the improvement of customer satisfaction. The Hotel industry already implemented processes to assure a regularity in the service quality. However, customers are still complaining on a daily basis when they are victim of a service failure. The operational risk is a concept known in the bank sector and few studies exist for tourism and Hotel industry. The internship report includes a case study, created in a way to simulate various stays of a couple that comes regularly in the five stars Hotel Penha Longa Ritz-Carlton. Each complaint was solved in the best way to satisfy the client and the cost was simulated in order to measure the impact of operational risk on profitability. To conclude, operational risk has to be considered carefully, even if it is not supposed to generate important loss, the cost has impact on profitability. It exists various ways to manage the operational risk, from the anticipation with well-defined processes until the complaints management