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Thiagarajan A.,National Cancer Center Singapore | Iyer N.G.,The Surgical Center
World Journal of Clinical Oncology | Year: 2014

With improved outcomes associated with radiotherapy, radiation-induced sarcomas (RIS) are increasingly seen in long-term survivors of head and neck cancers, with an estimated risk of up to 0.3%. They exhibit no subsite predilection within the head and neck and can arise in any irradiated tissue of mesenchymal origin. Common histologic subtypes of RIS parallel their de novo counterparts and include osteosarcoma, chondrosarcoma, malignant fibrous histiocytoma/sarcoma nitricoxide synthase, and fibrosarcoma. While imaging features of RIS are not pathognomonic, large size, extensive local invasion with bony destruction, marked enhancement within a prior radiotherapy field, and an appropriate latency period are suggestive of a diagnosis of RIS. RIS development may be influenced by factors such as radiation dose, age at initial exposure, exposure to chemotherapeutic agents and genetic tendency. Precise pathogenetic mechanisms of RIS are poorly understood and both directly mutagenizing effects of radiotherapy as well as changes in microenvironments are thought to play a role. Management of RIS is challenging, entailing surgery in irradiated tissue and a limited scope for further radiotherapy and chemotherapy. RIS is associated with significantly poorer outcomes than stagematched sarcomas that arise independent of irradiation and surgical resection with clear margins seems to offer the best chance for cure. © 2014 Baishideng Publishing Group Inc. All rights reserved.

Tan I.B.,National Cancer Center Singapore | Tan P.,National University of Singapore
Nature Reviews Clinical Oncology | Year: 2011

coloprint® is an 18-gene expression signature designed to predict disease relapse in patients with early-stage colorectal cancer (cRc). we discuss the potential impact of coloprint® on clinical practice, and its contribution to our knowledge of cRc molecular heterogeneity. © 2011 Macmillan Publishers Limited. All rights reserved.

Teo Y.L.,National University of Singapore | Ho H.K.,National University of Singapore | Chan A.,National University of Singapore | Chan A.,National Cancer Center Singapore
Cancer Treatment Reviews | Year: 2013

Introduction: Although existing evidence from clinical trials has demonstrated manifestation of hepatic adverse events (AEs) with the use of tyrosine kinase inhibitors (TKIs), overall risks have yet to be reported. Thus we conducted a meta-analysis to determine the risk of hepatotoxicity associated with the use of TKIs, by comparing the occurrence of hepatotoxicity of the TKI arms against that of comparison arms. Methods: A comprehensive literature search of randomized control trials involving TKIs was performed. Only randomized, double-blind and placebo-controlled phase 2 or phase 3 human trials were included. The included studies must involve the comparison of a TKI against placebo, or the comparison of TKI with chemotherapy agent against placebo with the same chemotherapy agent. Results: Twelve articles were included in the analysis. There was a significant overall increase in the odds of developing high-grade (grade 3 or above) hepatotoxicity with the use of TKIs compared to the control arms (Pooled OR 4.35, 95% CI 2.96-6.39). The odds of developing all-types all-grades (Pooled OR 2.42, 95% CI 1.52-3.85) and high-grade hepatotoxicity due to elevation in alanine transaminase (Pooled OR 5.22, 95% CI 2.88-9.46), aspartate transaminase (Pooled OR 6.15, 95% CI 3.09-12.25) and total bilirubin (Pooled OR 1.76, 95% CI 0.59-5.24) was higher with the use of TKI than compared to the controls. Discussion: This is the first meta-analysis to demonstrate a significantly increased risk of hepatic AEs associated with TKIs use. Clinicians should be aware of this risk and provide close monitoring in patients receiving these therapies. © 2012 Elsevier Ltd.

Krishna L.,National Cancer Center Singapore
Indian journal of medical ethics | Year: 2010

For the majority of patients at the end of life, their symptoms can be relieved through good palliative care. However, for an unfortunate few, these symptoms become intractable despite the best holistic interventions and in such cases terminal sedation is considered. The use of this intervention remains fraught with controversy, particularly around the subject of consent. A clinical scenario is used to propose that under such circumstances, given the physical and psychological stress to which these patients are subject, it is neither useful nor meaningful to ask for the patient's informed consent. Instead, physicians caring for such patients should act in the patient's best interests, in accordance with the Best Interest Principle, to alleviate such suffering.

Radha Krishna L.K.,National Cancer Center Singapore
BMJ Case Reports | Year: 2013

The concept of personhood is critical to the provision of holistic, patient-centred, palliative care yet no common definition of this term exists. Some characterise personhood by the presence of consciousness-related features such as self-awareness while others deem personhood present by virtue of Divine endowment or as a result of one's social relations. Efforts to appropriately delineate this concept come under scrutiny following suggestions that patients rendered deeply and irreversibly unconscious lack personhood and ought to be considered 'dead'. This case report studies the views of a family caring for a deeply sedated terminally ill patient, to appropriately site local views of personhood within the context of sedation at the end of life. The resultant Ring Theory of Personhood dispenses with concerns that personhood is solely dependent upon consciousness and distances sedative treatments of last resort such as continuous deep sedation from euthanasia. Copyright 2013 BMJ Publishing Group. All rights reserved.

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