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Cancer Statistics
Population in 2008: 4.6m
People newly diagnosed with cancer (excluding NMSC) / yr: 12,900
Age-standardised rate, incidence per 100,000 people/yr: 196.0
Risk of getting cancer before age 75:19.6%
People dying from cancer /yr: 6,100
Data from IARC GlobalCan (2008)
Singapore Cancer Organisations and Resources
Latest Research Publications Related to Singapore

Singapore Cancer Organisations and Resources (6 links)

Latest Research Publications Related to Singapore

Lim JW, Yeap FS, Chan YH, et al.
Second Malignant Neoplasms in Childhood Cancer Survivors Treated in a Tertiary Paediatric Oncology Centre.
Ann Acad Med Singapore. 2017; 46(1):11-19 [PubMed] Related Publications
Introduction: One of the most feared complications of childhood cancer treatment is second malignant neoplasms (SMNs). This study evaluates the incidence, risk factors and outcomes of SMNs in a tertiary paediatric oncology centre in Singapore. Materials and Methods: A retrospective review was conducted on patients diagnosed with childhood cancer under age 21 and treated at the National University Hospital, Singapore, from January 1990 to 15 April 2012. Case records of patients with SMNs were reviewed. Results: We identified 1124 cases of childhood cancers with a median follow-up of 3.49 (0 to 24.06) years. The most common primary malignancies were leukaemia (47.1%), central nervous system tumours (11.7%) and lymphoma (9.8%). Fifteen cases developed SMNs, most commonly acute myeloid leukaemia/myelodysplastic syndrome (n = 7). Median interval between the first and second malignancy was 3.41 (0.24 to 18.30) years. Overall 20-year cumulative incidence of SMNs was 5.3% (95% CI, 0.2% to 10.4%). The 15-year cumulative incidence of SMNs following acute lymphoblastic leukaemia was 4.4% (95% CI, 0% to 8.9%), significantly lower than the risk after osteosarcoma of 14.2% (95% CI, 0.7% to 27.7%) within 5 years (P <0.0005). Overall 5-year survival for SMNs was lower than that of primary malignancies. Conclusion: This study identified factors explaining the epidemiology of SMNs described, and found topoisomerase II inhibitor use to be a likely risk factor in our cohort. Modifications have already been made to our existing therapeutic protocols in osteosarcoma treatment. We also recognised the importance of other risk management strategies, including regular long-term surveillance and early intervention for detected SMNs, to improve outcomes of high risk patients.

Chen TH, Yen AM, Fann JC, et al.
Clarifying the debate on population-based screening for breast cancer with mammography: A systematic review of randomized controlled trials on mammography with Bayesian meta-analysis and causal model.
Medicine (Baltimore). 2017; 96(3):e5684 [PubMed] Free Access to Full Article Related Publications
BACKGROUND: The recent controversy about using mammography to screen for breast cancer based on randomized controlled trials over 3 decades in Western countries has not only eclipsed the paradigm of evidence-based medicine, but also puts health decision-makers in countries where breast cancer screening is still being considered in a dilemma to adopt or abandon such a well-established screening modality.
METHODS: We reanalyzed the empirical data from the Health Insurance Plan trial in 1963 to the UK age trial in 1991 and their follow-up data published until 2015. We first performed Bayesian conjugated meta-analyses on the heterogeneity of attendance rate, sensitivity, and over-detection and their impacts on advanced stage breast cancer and death from breast cancer across trials using Bayesian Poisson fixed- and random-effect regression model. Bayesian meta-analysis of causal model was then developed to assess a cascade of causal relationships regarding the impact of both attendance and sensitivity on 2 main outcomes.
RESULTS: The causes of heterogeneity responsible for the disparities across the trials were clearly manifested in 3 components. The attendance rate ranged from 61.3% to 90.4%. The sensitivity estimates show substantial variation from 57.26% to 87.97% but improved with time from 64% in 1963 to 82% in 1980 when Bayesian conjugated meta-analysis was conducted in chronological order. The percentage of over-detection shows a wide range from 0% to 28%, adjusting for long lead-time. The impacts of the attendance rate and sensitivity on the 2 main outcomes were statistically significant. Causal inference made by linking these causal relationships with emphasis on the heterogeneity of the attendance rate and sensitivity accounted for the variation in the reduction of advanced breast cancer (none-30%) and of mortality (none-31%). We estimated a 33% (95% CI: 24-42%) and 13% (95% CI: 6-20%) breast cancer mortality reduction for the best scenario (90% attendance rate and 95% sensitivity) and the poor scenario (30% attendance rate and 55% sensitivity), respectively.
CONCLUSION: Elucidating the scenarios from high to low performance and learning from the experiences of these trials helps screening policy-makers contemplate on how to avoid errors made in ineffective studies and emulate the effective studies to save women lives.

Anitha D, Thomas B, Jan KS, Subburaj K
Risk of vertebral compression fractures in multiple myeloma patients: A finite-element study.
Medicine (Baltimore). 2017; 96(2):e5825 [PubMed] Free Access to Full Article Related Publications
The purpose of this study was to develop and validate a finite element (FE) model to predict vertebral bone strength in vitro using multidetector computed tomography (MDCT) images in multiple myeloma (MM) patients, to serve as a complementing tool to assess fracture risk. In addition, it also aims to differentiate MM patients with and without vertebral compression fractures (VCFs) by performing FE analysis on vertebra segments (T1-L5) obtained from in vivo routine MDCT imaging scans. MDCT-based FE models were developed from the in vitro vertebrae samples and were then applied to the in vivo vertebrae segments of MM patients (n = 4) after validation. Predicted fracture load using FE models correlated significantly with experimentally measured failure load (r = 0.85, P < 0.001). Interestingly, an erratic behavior was observed in patients with fractures (n = 2) and a more gradual change in FE-predicted strength values in patients without fractures (n = 2). Severe geometric deformations were also observed in models that have already attained fractures. Since BMD is not a reliable parameter for fracture risk prediction in MM subjects, it is necessary to use advanced tools such as FE analysis to predict individual fracture risk. If peaks are observed between adjacent segments in an MM patient, it can be safe to conclude that the spine is experiencing regions of structural instability. Such an FE visualization may have therapeutic consequences to prevent MM associated vertebral fractures.

Yang MH, Chen KC, Chiang PW, et al.
Proteomic Profiling of Neuroblastoma Cells Adhesion on Hyaluronic Acid-Based Surface for Neural Tissue Engineering.
Biomed Res Int. 2016; 2016:1917394 [PubMed] Free Access to Full Article Related Publications
The microenvironment of neuron cells plays a crucial role in regulating neural development and regeneration. Hyaluronic acid (HA) biomaterial has been applied in a wide range of medical and biological fields and plays important roles in neural regeneration. PC12 cells have been reported to be capable of endogenous NGF synthesis and secretion. The purpose of this research was to assess the effect of HA biomaterial combining with PC12 cells conditioned media (PC12 CM) in neural regeneration. Using SH-SY5Y cells as an experimental model, we found that supporting with PC12 CM enhanced HA function in SH-SY5Y cell proliferation and adhesion. Through RP-nano-UPLC-ESI-MS/MS analyses, we identified increased expression of HSP60 and RanBP2 in SH-SY5Y cells grown on HA-modified surface with cotreatment of PC12 CM. Moreover, we also identified factors that were secreted from PC12 cells and may promote SH-SY5Y cell proliferation and adhesion. Here, we proposed a biomaterial surface enriched with neurotrophic factors for nerve regeneration application.

Janssen I, Wolf KI, Chui CH, et al.
Relevant Discordance Between 68Ga-DOTATATE and 68Ga-DOTANOC in SDHB-Related Metastatic Paraganglioma: Is Affinity to Somatostatin Receptor 2 the Key?
Clin Nucl Med. 2017; 42(3):211-213 [PubMed] Article available free on PMC after 01/03/2018 Related Publications
Pheochromocytomas/paragangliomas are somatostatin receptor 2-overexpressing tumors. Ga-DOTA-peptide imaging has recently shown excellent results in the detection of metastatic lesions in these tumors. However, currently used Ga-DOTA peptides show different somatostatin receptor affinities. Here, we report the remarkable differences in a patient who was imaged with Ga-DOTANOC and Ga-DOTATATE PET/CT within a 7-month period. The patient presented with a nearly negative Ga-DOTANOC PET/CT scan, whereas on Ga-DOTATATE PET/CT, multiple highly positive lesions were identified.

Hua Y, Ma X, Liu X, et al.
Identification of the potential biomarkers for the metastasis of rectal adenocarcinoma.
APMIS. 2017; 125(2):93-100 [PubMed] Related Publications
Rectal cancer is a common malignant tumor of the digestive tract, with a high incidence and high mortality. This study aimed to identify the potential biomarkers and therapeutic targets for rectal adenocarcinoma (RAC) metastasis. The expression profiling of RAC patients with metastasis and RAC patients without metastasis was downloaded from The Cancer Genome Atlas (TCGA) database. The datasets were used to identify the genes associated with RAC metastasis. Fifty up-regulated genes and seventeen down-regulated genes were identified in the primary tumor loci of RAC metastasis compared with non-metastasis. Sixty-seven dysregulated gens were conducted to construct the protein-protein network, and CCND3 was the hub protein. The dysregulated genes were significantly enriched in pancreatic secretion, cell adhesion molecules pathways, response to vitamin D of biological process, and retinoid binding of molecular function. Quantitative real-time polymerase chain reaction results demonstrated that CCND3, AQP3, PEG10, and RAB27B had the up-regulated tendency in RAC metastasis; ADCY1 had the down-regulated tendency in RAC metastasis. CCND3, AQP3, PEG10, RAB27B, and ADCY1 might play essential roles in the metastasis process of RAC through pancreatic secretion and cell adhesion molecules pathways. The five genes could be potential diagnosis biomarkers or therapeutic targets for RAC metastasis.

Jiang H, Hu H, Lin F, et al.
S100P is Overexpressed in Squamous Cell and Adenosquamous Carcinoma Subtypes of Endometrial Cancer and Promotes Cancer Cell Proliferation and Invasion.
Cancer Invest. 2016; 34(10):477-488 [PubMed] Related Publications
S100P is known to affect tumor development and metastasis of various cancers, but its role in endometrial cancer is unclear. We reported that S100P expression was dramatically elevated in both endometrial squamous cell carcinoma and adenosquamous carcinoma, but not in adenocarcinoma and normal endometrial samples. Moreover, we revealed an oncogenic role of S100P promoting cell proliferation, invasion, and migration while reducing apoptosis, possibly via its upregulation and/or activation of receptors of advanced glycation end products and consequently the oncogenic PI3K-AKT and MAPK pathways. Therefore, S100P might be a specific biomarker and a potential drug target for squamous cell and adenosquamous carcinoma subtypes of endometrial cancer.

Allen JC, Nault JC, Zhu G, et al.
The transcriptomic G1-G6 signature of hepatocellular carcinoma in an Asian population: Association of G3 with microvascular invasion.
Medicine (Baltimore). 2016; 95(47):e5263 [PubMed] Article available free on PMC after 01/03/2018 Related Publications
In this study, a transcriptomic group classification based on a European population is tested on a Singapore cohort. The results highlight the genotype/phenotype correlation in a Southeast Asian population. The G1-G6 transcriptomic classification derived from hepatocellular carcinoma (HCC) resected from European patients, robustly reflected group-specific clinical/pathological features. We investigated the application of this molecular classification in Southeast Asian HCC patients.Gene expression analysis was carried out on HCC surgically resected in Singapore patients who were grouped into G1-G6 transcriptomic categories according to expression of 16 predictor genes (illustrated in Supplementary Table 1, http://links.lww.com/MD/B413 and Supplementary Fig. 1, http://links.lww.com/MD/B413) using quantitative reverse transcription polymerase chain reaction (RT-PCR). Univariate and multivariate polytomous logistic regression was used to investigate association between clinical variables and pooled transcriptomic classes G12, G3, and G456.HCC from Singapore (n = 82) were distributed (%) into G1 (13.4), G2 (24.4), G3 (15.9), G4 (24.4), G5 (14.6), and G6 (7.3) subgroups. Compared to the European data, the Singapore samples were relatively enriched in G1-G3 versus G4-G6 tumors (53.7% vs 46.3%) reflecting the higher proportion of hepatitis B virus (HBV) patients in Singapore versus Europe samples (43% vs 30%). Pooled classes were defined as G12, G3, and G456. G12 was associated with higher alpha-fetoprotein (AFP) concentrations (OR = 1.69, 95% CI: 1.30-2.20; P < 0.0001) and G3 with microvascular invasion (OR = 4.91, 95% CI: 1.06-24.8; P = 0.047).The European and Singapore cohorts were generally similar relative to associations between transcriptomic groups and clinical features. This lends credence to the G1-G6 transcriptomic classifications being applicable regardless of the ethnic origin of HCC patients. The G3 group was associated with microvascular invasion and holds potential for investigation into the underlying mechanisms and selection for therapeutic clinical trials.

Yeong J, Thike AA, Tan PH, Iqbal J
Identifying progression predictors of breast ductal carcinoma in situ.
J Clin Pathol. 2017; 70(2):102-108 [PubMed] Related Publications
Ductal carcinoma in situ (DCIS) refers to neoplastic epithelial cells proliferating within the mammary ducts of the breast, which have not breached the basement membrane nor invaded surrounding tissues. Traditional thinking holds that DCIS represents an early step in a linear progression towards invasive ductal carcinoma (IDC). However, as only approximately half of DCIS cases progress to IDC, important questions around the key determinants of malignant progression need to be answered. Recent studies have revealed that molecular differences between DCIS and IDC cells are not found at the genomic level; instead, altered patterns of gene expression and post-translational regulation lead to distinct transcriptomic and proteomic profiles. Therefore, understanding malignant progression will require a different approach that takes into account the diverse tumour cell extrinsic factors driving changes in tumour cell gene expression necessary for the invasive phenotype. Here, we review the roles of the tumour stroma (including mesenchymal cells, immune cells and the extracellular matrix) and myoepithelial cells in malignant progression and make a case for a more integrated approach to the study and assessment of DCIS and its progression, or lack thereof, to invasive disease.

Yeoh CJ, Ng SY, Goh BK
Pheochromocytoma Multisystem Crisis Triggered by Glucocorticoid Administration and Aggravated by Citrate Dialysis.
A A Case Rep. 2017; 8(3):58-60 [PubMed] Related Publications
Pheochromocytoma multisystem crisis is the most severe presentation of pheochromocytoma. We report on a 68-year-old survivor of pheochromocytoma multisystem crisis, whose clinical course was triggered inadvertently by a short innocuous course of oral dexamethasone to suppress inflammation and swelling after a left orbital floor fracture repair. He presented first with severe epigastric pain and headache, and subsequently experienced insults to neurological, cardiac, respiratory, hepatobiliary, renal, and immune system in his prolonged intensive care unit stay. We believe an episode of unexpected hypertensive crisis in the intensive care unit was set off iatrogenically during citrate protocol dialysis.

Williams JM, Arlinghaus LR, Rani SD, et al.
Towards real-time topical detection and characterization of FDG dose infiltration prior to PET imaging.
Eur J Nucl Med Mol Imaging. 2016; 43(13):2374-2380 [PubMed] Article available free on PMC after 01/12/2017 Related Publications
PURPOSE: To dynamically detect and characterize (18)F-fluorodeoxyglucose (FDG) dose infiltrations and evaluate their effects on positron emission tomography (PET) standardized uptake values (SUV) at the injection site and in control tissue.
METHODS: Investigational gamma scintillation sensors were topically applied to patients with locally advanced breast cancer scheduled to undergo limited whole-body FDG-PET as part of an ongoing clinical study. Relative to the affected breast, sensors were placed on the contralateral injection arm and ipsilateral control arm during the resting uptake phase prior to each patient's PET scan. Time-activity curves (TACs) from the sensors were integrated at varying intervals (0-10, 0-20, 0-30, 0-40, and 30-40 min) post-FDG and the resulting areas under the curve (AUCs) were compared to SUVs obtained from PET.
RESULTS: In cases of infiltration, observed in three sensor recordings (30 %), the injection arm TAC shape varied depending on the extent and severity of infiltration. In two of these cases, TAC characteristics suggested the infiltration was partially resolving prior to image acquisition, although it was still apparent on subsequent PET. Areas under the TAC 0-10 and 0-20 min post-FDG were significantly different in infiltrated versus non-infiltrated cases (Mann-Whitney, p < 0.05). When normalized to control, all TAC integration intervals from the injection arm were significantly correlated with SUVpeak and SUVmax measured over the infiltration site (Spearman ρ ≥ 0.77, p < 0.05). Receiver operating characteristic (ROC) analyses, testing the ability of the first 10 min of post-FDG sensor data to predict infiltration visibility on the ensuing PET, yielded an area under the ROC curve of 0.92.
CONCLUSIONS: Topical sensors applied near the injection site provide dynamic information from the time of FDG administration through the uptake period and may be useful in detecting infiltrations regardless of PET image field of view. This dynamic information may also complement the static PET image to better characterize the true extent of infiltrations.

Hortobagyi GN, Stemmer SM, Burris HA, et al.
Ribociclib as First-Line Therapy for HR-Positive, Advanced Breast Cancer.
N Engl J Med. 2016; 375(18):1738-1748 [PubMed] Related Publications
Background The inhibition of cyclin-dependent kinases 4 and 6 (CDK4/6) could potentially overcome or delay resistance to endocrine therapy in advanced breast cancer that is positive for hormone receptor (HR) and negative for human epidermal growth factor receptor 2 (HER2). Methods In this randomized, placebo-controlled, phase 3 trial, we evaluated the efficacy and safety of the selective CDK4/6 inhibitor ribociclib combined with letrozole for first-line treatment in 668 postmenopausal women with HR-positive, HER2-negative recurrent or metastatic breast cancer who had not received previous systemic therapy for advanced disease. We randomly assigned the patients to receive either ribociclib (600 mg per day on a 3-weeks-on, 1-week-off schedule) plus letrozole (2.5 mg per day) or placebo plus letrozole. The primary end point was investigator-assessed progression-free survival. Secondary end points included overall survival, overall response rate, and safety. A preplanned interim analysis was performed on January 29, 2016, after 243 patients had disease progression or died. Prespecified criteria for superiority required a hazard ratio of 0.56 or less with P<1.29×10(-5). Results The duration of progression-free survival was significantly longer in the ribociclib group than in the placebo group (hazard ratio, 0.56; 95% CI, 0.43 to 0.72; P=3.29×10(-6) for superiority). The median duration of follow-up was 15.3 months. After 18 months, the progression-free survival rate was 63.0% (95% confidence interval [CI], 54.6 to 70.3) in the ribociclib group and 42.2% (95% CI, 34.8 to 49.5) in the placebo group. In patients with measurable disease at baseline, the overall response rate was 52.7% and 37.1%, respectively (P<0.001). Common grade 3 or 4 adverse events that were reported in more than 10% of the patients in either group were neutropenia (59.3% in the ribociclib group vs. 0.9% in the placebo group) and leukopenia (21.0% vs. 0.6%); the rates of discontinuation because of adverse events were 7.5% and 2.1%, respectively. Conclusions Among patients receiving initial systemic treatment for HR-positive, HER2-negative advanced breast cancer, the duration of progression-free survival was significantly longer among those receiving ribociclib plus letrozole than among those receiving placebo plus letrozole, with a higher rate of myelosuppression in the ribociclib group. (Funded by Novartis Pharmaceuticals; ClinicalTrials.gov number, NCT01958021 .).

Hsieh KH, Tan Hwei Ching G, Chong Phek Yoon A, Teo M
Metastatic prostate adenocarcinoma presenting as a large right supraclavicular and anterior chest wall mass.
BMJ Case Rep. 2016; 2016 [PubMed] Related Publications
Left-sided cervical lymphadenopathy as first presentation of metastatic prostate carcinoma is not a novel observation. Here, we discuss a case of metastatic prostate primary carcinoma with an initial presentation of a right supraclavicular mass with extension into the anterior chest wall, which on radiological investigation was suggestive of a sarcomatous tumour; however, was confirmed to be pervasive metastatic prostatic adenocarcinoma. This is the second case in literature, which reports a prostatic primary cancer presenting as a right-sided supraclavicular and anterior chest wall mass.

Chiang B, Cheng S, Seow CJ
Commonly forgotten complication of Hashimoto's thyroiditis.
BMJ Case Rep. 2016; 2016 [PubMed] Related Publications
Hashimoto's thyroiditis (HT) is a frequently encountered condition in clinical practice and management is generally uncomplicated with patients on a stable dose of thyroxine supplementation. However, complications of thyroid lymphoma can develop, though it is rare and hence commonly forgotten by physicians. We present a case of a patient with HT who developed thyroid lymphoma. A 61-year-old woman presented with an enlarged goitre complicated by compressive symptoms and was diagnosed with HT. She was treated with stable dose of thyroxine but her constitutional symptoms of weight loss prompted further investigations and diagnosis of diffuse large B-cell lymphoma was eventually made. She underwent chemotherapy and adjuvant radiotherapy and is currently in remission 1 year post-treatment. There should be an increased index of suspicion of primary thyroid lymphoma in patients with HT for early diagnosis and treatment for better outcomes.

Martin RC, Durham AN, Besselink MG, et al.
Irreversible electroporation in locally advanced pancreatic cancer: A call for standardization of energy delivery.
J Surg Oncol. 2016; 114(7):865-871 [PubMed] Related Publications
Irreversible Electroporation (IRE) is used to treat locally advanced cancers, commonly of the pancreas, liver, kidney, and other soft tissues. Precise eligibility for IRE should be established in each individual patient by a multidisciplinary team based on comprehensive clinical, imaging, and laboratory assessment. Standardization of IRE technique and protocols is expected to improve safety, lead to reproducible outcomes, and facilitate further research into IRE. The present article provides a set of technical recommendations for the use of IRE in the treatment of locally advanced pancreatic cancer. J. Surg. Oncol. 2016;114:865-871. © 2016 2016 Wiley Periodicals, Inc.

Tan GH, Wong JS, Quek R, et al.
Role of upfront surgery for recurrent gastrointestinal stromal tumours.
ANZ J Surg. 2016; 86(11):910-915 [PubMed] Related Publications
BACKGROUND: Gastrointestinal stromal tumours (GISTs), despite complete surgical cytoreduction, are associated with recurrence rates of up to 50% at 2 years. At recurrence, tyrosine kinase inhibitor (TKI) therapy is recommended, conferring a survival of up to 55 months. Several studies have shown that patients with TKI-responsive recurrent GIST benefit from surgery. However, no studies have compared upfront surgery versus TKI alone.
METHODS: Data were retrospectively collected from patients with recurrent GIST treated at Singapore General Hospital and National Cancer Centre Singapore over a 12-year period. Our primary end points were disease-free and overall survival (OS).
RESULTS: A total of 186 patients underwent curative surgery for GIST between January 2000 and June 2012. Fifty-six (30%) patients experienced recurrence, of which 30 (54%) had resectable recurrent disease. Twenty-four patients underwent upfront surgery for their recurrence while the remaining six patients opted for non-surgical management. The median OS for all patients with recurrent GIST was 5.3 years (95% confidence interval (CI) 3.2-8.4). It was not reached for patients who underwent curative surgery for their recurrence, and was 3.9 years (95% CI 2.4-7.0) for patients who had palliative TKI and conservative management. There were significant differences in OS and disease-specific survival between patients who underwent curative surgery for recurrence compared with those who had not.
CONCLUSION: Our study shows that upfront surgery is a reasonable treatment strategy for selected patients with recurrent GIST.

Ang SY, Ng VW, Kumar SD, Low SY
Cryptococcosis mimicking lung carcinoma with brain metastases in an immunocompetent patient.
J Clin Neurosci. 2017; 35:73-75 [PubMed] Related Publications
Cryptococcosis is a fungal infection caused by Cryptococcus spp. that enters the body via inhalation. This ubiquitous yeast has gained notoriety as an opportunistic pathogen in the immunosuppressed population. The authors report a case of a previously-well adult male presented with left-sided weakness. Imaging demonstrated a pulmonary mass and 2 contrast-enhancing intracranial lesions-all features suggestive of a primary lung carcinoma with brain metastases. However, further investigations confirmed disseminated cryptococcosis, without evidence of malignancy. The patient was successfully treated with a course of antifungals. To the authors' knowledge, this is the first reported case of dissemintated cryptococcosis in an immunocompetent adult male, simulating as primary lung carcinoma with brain metastases.

Khng JN, Woo IM, Fan G
Experiential group work for cancer patients shaped by experiences of participants during group intervention.
Future Oncol. 2016; 12(24):2817-2822 [PubMed] Related Publications
Cancer tends to have an impact on a person's psychological and social well-being. Group work is one approach that can help manage the psychosocial impact of cancer. Group interventions for people living with cancer have existed for a number of decades with a majority of them adopting the cognitive-behavioral approach. While this approach has been found to be efficacious, it may be limited for people who prefer acts of service and metaphors. This article describes an experiential approach to group intervention, an alternative to cognitive-behavioral groups. The group intervention featured is designed for participants of Enreach Retreat, a retreat for people living with cancer and their caregivers, by the Department of Psychosocial Oncology, National Cancer Centre Singapore.

Richardson JS, Sethi G, Lee GS, Malek SN
Chalepin: isolated from Ruta angustifolia L. Pers induces mitochondrial mediated apoptosis in lung carcinoma cells.
BMC Complement Altern Med. 2016; 16(1):389 [PubMed] Article available free on PMC after 01/12/2017 Related Publications
BACKGROUND: Cancer has been one of the leading causes of mortality in this era. Ruta angustifolia L. Pers has been traditionally used as an abortifacient, antihelmintic, emmenagogue and ophthalmic. In Malaysia and Singapore, the local Chinese community used it for the treatment of cancer.
METHODS: In this study, the methanol and fractionated extracts (hexane, chloroform, ethyl acetate and water) of R. angustifolia were tested for its cytotoxicity using the sulforhodamide (SRB) cytotoxicity assay against HCT-116, A549, Ca Ski and MRC5 cell lines. Chemical isolation was carried out by using the high performance liquid chromatography (HPLC) and the isolated compounds were tested for its cytotoxicity against A549 cell line. Cellular and nuclear morphological changes were observed in the cells using phase contrast microscopy and Hoechst/PI fluorescent staining. The externalisation of phosphatidylserine was observed through FITC-labelling Annexin V/PI assay whilst DNA fragmentation was observed through the TUNEL assay. Other indication of apoptosis occuring through the mitochondrial pathway were the attenuation of mitochondrial membrane potential and increase in ROS production. Activation of caspase 9 and 3 were monitored. Western blot analysis was done to show the expression levels of apoptotic proteins.
RESULTS: The chloroform extract (without chlorophyll) exhibited the highest cytotoxic activity with IC50 of 10.1 ± 0.15 μg/ml against A549 cell line. Further chemical investigation was thus directed to this fraction which led to the isolation of 12 compounds identified as graveoline, psoralen, kokusaginine, methoxysalen, bergapten, arborinine, moskachan B, chalepin, moskachan D, chalepensin, rutamarin and neophytadiene. Among these compounds, chalepin exhibited excellent cytotoxicity against A549 cell line with an IC50 value of 8.69 ± 2.43 μg/ml (27.64 μM). In western blot analysis, expression of p53, truncated Bid, Bax and Bak while the anti-apoptotic proteins Bcl-2, survivin, XIAP, Bcl-XL,cFLIP decreased in a time-dependent manner when A549 cells were treated with 36 μg/ml of chalepin. In addition, the level of PARP was found to decrease.
CONCLUSION: Hence these findings indicated that chalepin-induced cell death might involve the intrinsic mitochodrial pathway resulting in the upregulation of pro-apoptotic proteins and downregulation of anti-apoptotic proteins. Thus, chalepin could be an excellent candidate for the development of an anticancer agent.

Cheo T, Ng I, Ooi KH, Ai Choo B
Long-term remission after low dose radiotherapy in patient with extensive squamous cell carcinoma of the hand: A case report.
Medicine (Baltimore). 2016; 95(39):e5013 [PubMed] Article available free on PMC after 01/12/2017 Related Publications
RATIONALE FOR CASE REPORT: Cutaneous Squamous Cell Carcinoma (cSCC) of the hand is uncommon and tends to have poorer outcomes. Surgical resection with wide margins around the tumor is recommended as the treatment of choice, and radiotherapy is considered second-line treatment. Nodal evaluation involves dissection necessitating some morbidity. The role of less invasive modalities of nodal evaluation is not well established.
CASE PRESENTATION: We report a case of locally advanced case of hand cSCC. Positron emission tomography-computed tomography (PET-CT) showed disease involving full thickness of the hand as well as the ipsilateral axillary node. To achieve adequate surgical margins would have necessitated amputation at the wrist, which the patient did not consent to. Instead, he was given a two-and-a-half week course radiotherapy to the hand without axillary radiation. With the radiotherapy treatment, he managed to achieve complete remission of disease while retaining full function of the hand, which was maintained at 22 months post-treatment.
MAIN LESSONS: CSCC of the hand is uncommon and challenging to treat. Radiotherapy is a highly effective treatment modality which is able to achieve functional preservation. Care should be taken when evaluating nodal status using PET-CT.

Zhang JW, Chen ZJ, Gopinathan A
Focal Nodular Hashimoto's Thyroiditis: Comparison of Ultrasonographic Features with Malignant and Other Benign Nodules.
Ann Acad Med Singapore. 2016; 45(8):357-63 [PubMed] Related Publications
INTRODUCTION: Hashimoto's thyroiditis (HT) can present as focal nodular disease. This study aimed to determine the distinguishing sonographic features of nodules in biopsy-proven focal HT.
MATERIALS AND METHODS: The study included 388 thyroid nodules from 310 patients who underwent ultrasound-guided fine-needle aspiration biopsy (FNAB). There were 28 focal HT, 27 malignant and 333 other benign nodules. Sonographic features of focal HT nodules on prebiopsy ultrasound were compared with malignant nodules and other benign nodules using multinomial logistic regression adjusting for the correlation between multiple nodules obtained from the same patient.
RESULTS: Most focal HT nodules were purely solid (92.8%), iso-hyperechoic (70.4%), had regular margins (75.0%) and central vascularity (85.7%). Hypoechogenicity (29.6% vs 42.3%; P = 0.017) and microcalcifications (3.6% vs 44.4%; P = 0.003) were significantly less common in focal HT than malignant nodules. None of the focal HT nodules demonstrated marked hypoechogenicity, irregular margins or cervical lymphadenopathy, which are traditionally associated with malignancy. Compared to other benign nodules, focal HT nodules were significantly more likely to be purely solid (92.8% vs 49.0%; P = 0.016), ill-defined (25.0% vs 7.0%; P = 0.004) and lack comet-tail artefacts (92.9% vs 66.1%; P = 0.012), which in combination were 17.9% sensitive and 94.6% specific for focal HT.
CONCLUSION: Awareness of the above-described sonographic appearances of focal HT may aid in differentiating them from malignant nodules and risk-stratify for FNAB. While there is substantial overlap with other benign nodules, a combination of the above-mentioned 3 ultrasound features is highly specific for focal HT and can prompt further serological evaluation in clinically unsuspected HT.

Zhong FL, Mamaï O, Sborgi L, et al.
Germline NLRP1 Mutations Cause Skin Inflammatory and Cancer Susceptibility Syndromes via Inflammasome Activation.
Cell. 2016; 167(1):187-202.e17 [PubMed] Related Publications
Inflammasome complexes function as key innate immune effectors that trigger inflammation in response to pathogen- and danger-associated signals. Here, we report that germline mutations in the inflammasome sensor NLRP1 cause two overlapping skin disorders: multiple self-healing palmoplantar carcinoma (MSPC) and familial keratosis lichenoides chronica (FKLC). We find that NLRP1 is the most prominent inflammasome sensor in human skin, and all pathogenic NLRP1 mutations are gain-of-function alleles that predispose to inflammasome activation. Mechanistically, NLRP1 mutations lead to increased self-oligomerization by disrupting the PYD and LRR domains, which are essential in maintaining NLRP1 as an inactive monomer. Primary keratinocytes from patients experience spontaneous inflammasome activation and paracrine IL-1 signaling, which is sufficient to cause skin inflammation and epidermal hyperplasia. Our findings establish a group of non-fever inflammasome disorders, uncover an unexpected auto-inhibitory function for the pyrin domain, and provide the first genetic evidence linking NLRP1 to skin inflammatory syndromes and skin cancer predisposition.

Parameswaran R, Shulin Hu J, Min En N, et al.
Patterns of metastasis in follicular thyroid carcinoma and the difference between early and delayed presentation.
Ann R Coll Surg Engl. 2017; 99(2):151-154 [PubMed] Related Publications
Introduction Follicular thyroid cancer (FTC) has a good prognosis if treated early. The aim of this study was to look at the difference in outcomes in those who presented with metastasis early or late in their disease. Methods A retrospective cohort study was conducted of patients diagnosed with FTC (n=91) treated between 2000 and 2013. Demographic, laboratory, pathological and survival data were collected and analysed. Results Metastatic FTC was diagnosed in 20 cases (22%). The median age at diagnosis was 65 years (range: 17-86 years) and 65% of the patients were female. Twelve patients (60%) were diagnosed with metastatic disease at presentation, with the bones being the most common site (75%). In the remaining eight cases (40%), metastasis developed at a median of 4.5 years (range: 2-8 years) after initial thyroid surgery, lungs being the most common site (50%). Eighteen patients (90%) underwent surgical intervention for the primary disease. Sixteen patients (80%) received adjuvant radioactive iodine and eight (40%) received external beam radiotherapy. Widely invasive follicular cancer was the predominant histological diagnosis (90%). No prognostic association was observed with any of the parameters studied. The overall disease specific mortality rate was 40%. There was no significant difference in mortality between those who presented with metastatic disease and those who developed metastasis during the follow-up period (33% vs 50%, p=0.61). Conclusions The clinical outcome and prognosis for cases with metastatic disease is generally poor. Despite this, almost half of the patients in our study were still alive at a median follow-up of 5.5 years, regardless of whether they were diagnosed with metastatic disease on initial presentation or whether they developed metastasis after initial thyroid surgery.

Malhotra C, Bilger M, Liu J, Finkelstein E
Barriers to Breast and Cervical Cancer Screening in Singapore: a Mixed Methods Analysis.
Asian Pac J Cancer Prev. 2016; 17(8):3887-95 [PubMed] Related Publications
BACKGROUND: In order to increase breast and cervical cancer screening uptake in Singapore, women's perceived barriers to screening need to be identified and overcome. Using data from both focus groups and surveys, we aimed to assess perceived barriers and motivations for breast and cervical cancer screening.
MATERIALS AND METHODS: We conducted 8 focus groups with 64 women, using thematic analysis to identify overarching themes related to women's attitudes towards screening. Based on recurring themes from focus groups, several hypotheses regarding potential barriers and motivations to screen were generated and tested through a national survey of 801 women aged 25-64.
RESULTS: Focus group participants had misconceptions related to screening, believing that the procedures were painful. Cost was an issue, as well as efficacy and fatalism.
CONCLUSIONS: By identifying barriers to and motivators for screening through a mixed-method design that has both nuance and external validity, this study offers valuable suggestions to policymakers to improve breast and cervical cancer screening uptake in Singapore.

Holzapfel BM, Wagner F, Martine LC, et al.
Tissue engineering and regenerative medicine in musculoskeletal oncology.
Cancer Metastasis Rev. 2016; 35(3):475-87 [PubMed] Related Publications
Currently used surgical techniques to reconstruct tissue defects after resection of musculoskeletal tumours are associated with high complication rates. This drives a strong demand for innovative therapeutic concepts that are able to improve the clinical outcomes of patients suffering from bone and soft tissue tumours. Tissue engineering and regenerative medicine (TE&RM) provides a technology platform based on biochemical, molecular, cellular and biomaterials modules to selectively direct tissue healing processes for improved defect regeneration. At the same time, precautionary measures have to be taken when these instruments are used in cancer patients to prevent any promotion of tumour growth or metastatic spread. On the other hand, several innovative TE&RM tools are being developed such as multi-functionalized biomaterials, drug-delivering nanomaterials or genetically engineered stem cells that per se have the potential to mediate anti-cancer effects, act synergistically with currently used chemotherapeutics and/or radiotherapy regimens and reduce their side effects. Recently, scientists became conscious that TE&RM strategies may not only be utilized to advance contemporary tissue reconstruction techniques but also to develop personalized diagnostic tools and clinically relevant disease models for cancer patients. Eventually, prospective randomized clinical trials combined with comparative outcome analyses are a conditio sine qua non to shape the benefits of personalized regenerative therapies for the standardized management of patients with musculoskeletal tumours.

Aguiar PN, Tadokoro H, da Silva GF, et al.
Definitive chemoradiotherapy for squamous head and neck cancer: cisplatin versus carboplatin? A meta-analysis.
Future Oncol. 2016; 12(23):2755-2764 [PubMed] Related Publications
AIM: Concomitant chemoradiotherapy (with cisplatin or carboplatin) is an option of definitive treatment for squamous head and neck cancer. We aimed to perform a meta-analysis comparing those two platinum agents.
MATERIALS & METHODS: We carried out a systematic search on English literature between 1990 and 17 April 2015 according to the Cochrane review guidelines.
RESULTS: Five of 60 studies fulfilled inclusion criteria with 491 patients. There was no difference in response rate. Cisplatin tends to be more active systemically than carboplatin, without statistically significance; 5-year survival rate: 30 and 27%, respectively (p = 0.33).
CONCLUSION: Despite the trend to improved outcomes in using cisplatin, carboplatin is also active and can be a reasonable option to treat patients.

Chua FH, Low SY, Tham CK, et al.
Disseminated extracranial metastatic meningioma.
J Clin Neurosci. 2016; 33:214-216 [PubMed] Related Publications
Meningiomas are usually low-grade, solitary lesions that rarely metastasize. In this group of central nervous system tumours, the higher grade subtypes are notorious for resistance to conventional chemo-radiation therapies. Recent studies have shown efficacy in the use of bevacizumab in patients with recurrent and, or progressive anaplastic meningioma. The authors report a case of a young patient with recurrent anaplastic meningioma who despite being treated with bevacizumab, progressed with disease dissemination to multiple extracranial sites. Although the majority of meningiomas are amendable to treatment, the higher grade subtypes remain therapeutically challenging. The unexpected resistance to anti-angiogenic therapy in this patient adds another layer of complexity to an elusive subset of a supposedly benign disease. This patient report reflects the need for in-depth studies, molecular characterization and overall, better disease understanding in order to improve prognosis for affected patients.

Song Y, Lv X, Liu J, et al.
Experience of nursing support from the perspective of patients with cancer in mainland China.
Nurs Health Sci. 2016; 18(4):510-518 [PubMed] Related Publications
This study was conducted to understand patients' experiences of nursing support, to identify gaps between patients' expected needs and the nursing support they received, and to explore reasons for such disparity. A qualitative study with a phenomenological approach was used. A purposive sample of 22 patients with different types of cancer was recruited and interviewed using semistructured guidelines. The data were analyzed using phenomenological analytic methods. Several needs regarding nursing support were expressed, including informational, psychological, clinical, care coordination and communication needs, and there were some unmet or partially-met needs. Reasons for the disparities covered both patient- and nurse-related factors, including patients' lack of awareness regarding how to acquire professional assistance and reluctance to express their needs, and nurses' lack of active communication with patients, inability to provide specific support, and limited resources for coordination. The expectations of nursing support did not always correspond with the actual delivery of nursing care. A tailored intervention is warranted to meet patients' expectations, which might contribute to quality-of-care improvements.

Lim G, Pineda LA
Applicability of Oncoplastic Breast Conserving Surgery in Asian Breast Cancer Patients.
Asian Pac J Cancer Prev. 2016; 17(7):3325-8 [PubMed] Related Publications
BACKGROUND: There are limited studies on oncoplastic breast conserving surgery in Asian women. We aimed to determine the applicability and safety of oncoplastic surgery, highlighting the specific circumstances when it will be most useful and compare our preferred technique with the worldwide practice of oncoplastic approaches.
MATERIALS AND METHODS: Breast cancer patients who underwent oncoplastic breast conserving surgery at a single institution from 1st May 201431st March 2015 were included. Data on patient demographics, tumor characteristics and the type of oncoplastic surgery performed were collected.
RESULTS: Nineteen breast cancer patients were identified. 42.1% of patients had grade I ptosis. The indications for surgery included a large tumor to breast size ratio (52.6%), multifocal/multicentric lesions (36.8%) and asymmetric breasts (10.6%), averting a mastectomy in 89.4%. Round block was the commonest technique in 63% of patients, in contrast to the inverted T pattern most frequently used in renowned institutions in the West. Mean and median tumor size and weight of specimen were 29.4/25mm (11 75mm) and 77g/64g (10 246g) respectively. Reexcision rate was 10.5%. Complete mastectomy was performed for one patient. One patient developed wound dehiscence which was treated conservatively. Cosmetic outcome was rated as excellent/good by 94.7% of patients. The patients remained clinically well after a median 16 months follow up.
CONCLUSIONS: Oncoplastic breast conserving surgery is useful in a specific subgroup of Asian patients with a relatively small breast volume and minimal ptosis. Round block was the commonest technique in our series, in contrast to the worldwide utility of oncoplastic techniques. It is oncologically safe and has good cosmetic outcomes.

Yeang SH, Chan A, Tan CW, et al.
Incidence and Management of Toxicity Associated with LAsparaginase in the Treatment of ALL and NK/TCell Lymphoma: an Observational Study.
Asian Pac J Cancer Prev. 2016; 17(7):3155-60 [PubMed] Related Publications
BACKGROUND: Lasparaginase (ASNase) is commonly used in the treatment of acute lymphoblastic leukemia (ALL) and natural killer (NK)/Tcell lymphoma. This study was designed to describe the incidence of toxicity associated with ASNase in Asian adults. Secondary objectives were to investigate the management and impact of toxicity on subsequent ASNase use, and to compare the actual management against current recommendations.
MATERIALS AND METHODS: In this retrospective, multicenter, observational study, Asian patients ≥ 18 years old who received ≥ 1 dose of the native E. coli ASNase from 2008 to 2013 were included. Patients were excluded if they did not receive ASNase. Endpoints of this study were development of specific toxicities, whether ASNase was discontinued or rechallenged, and developmentg of recurrent toxicity. All data analyses were performed using SPSS version 20.0.
RESULTS: A total of 56 patients were analyzed. Mean (±SD) age was 36.2 (±15.2) years old, with 62.5% being males, 55.4% with ALL and 28.6% with NK/Tcell lymphoma. Hypersensitivity (12.5%) was associated with the highest incidence of toxicity (6 out of 7 patients had Grade 3 and 4 toxicity), followed by 10.7% for hepatic transaminitis, 3.6% for nonCNS thrombosis and 1.8% each for hyperbilirubinemia and pancreatitis. Hypersensitivity recurred in the 3 patients who were rechallenged with E. coli ASNase.
CONCLUSIONS: ASNase is associated with a wide range of toxicities, with hypersensitivity being the most commonly observed among Asian adult patients.

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