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  1. Lim LY, Miao H, Lim JS, Lee SC, Bhoo-Pathy N, Yip CH, et al.
    Cancer Med, 2017 Jan;6(1):173-185.
    PMID: 28000426 DOI: 10.1002/cam4.985
    We aim to identify clinicopathologic predictors for response to neoadjuvant chemotherapy and to evaluate the prognostic value of pathologic complete response (pCR) on survival in Asia. This study included 915 breast cancer patients who underwent neoadjuvant chemotherapy at five public hospitals in Singapore and Malaysia. pCR following neoadjuvant chemotherapy was defined as 1) no residual invasive tumor cells in the breast (ypT0/is) and 2) no residual invasive tumor cells in the breast and axillary lymph nodes (ypT0/is ypN0). Association between pCR and clinicopathologic characteristics and treatment were evaluated using chi-square test and multivariable logistic regression. Kaplan-Meier analysis and log-rank test, stratified by other prognostic factors, were conducted to compare overall survival between patients who achieved pCR and patients who did not. Overall, 4.4% of nonmetastatic patients received neoadjuvant chemotherapy. The median age of preoperatively treated patients was 50 years. pCR rates were 18.1% (pCR ypT0/is) and 14.4% (pCR ypT0/is ypN0), respectively. pCR rate was the highest among women who had higher grade, smaller size, estrogen receptor negative, human epidermal growth factor receptor 2-positive disease or receiving taxane-based neoadjuvant chemotherapy. Patients who achieved pCR had better overall survival than those who did not. In subgroup analysis, the survival advantage was only significant among women with estrogen receptor-negative tumors. Patients with poor prognostic profile are more likely to achieve pCR and particularly when receiving taxane-containing chemotherapy. pCR is a significant prognostic factor for overall survival especially in estrogen receptor-negative breast cancers.
    Matched MeSH terms: Prognosis
  2. Ch'ng ES
    Breast Cancer, 2024 May;31(3):496-506.
    PMID: 38546966 DOI: 10.1007/s12282-024-01564-8
    BACKGROUND: Primary breast salivary gland-type carcinoma has weak evidence to support its management due to its rare occurrence and limited data regarding its clinicopathological features and prognosis. Therefore, this study aimed to assess clinicopathological features and prognosis for this type of carcinoma diagnosed over the past decade and compared those to the common breast invasive carcinoma of no special type (NST).

    METHODS: This study used the Surveillance, Epidemiology, and End Results (SEER) database to extract data regarding primary breast salivary gland-type carcinoma. Using a propensity score-matching approach, the prognosis was compared with invasive carcinoma, NST.

    RESULTS: This study included 488 cases of salivary gland-type carcinoma and 375,660 cases of invasive carcinoma, NST, giving an occurrence ratio of 1 to 770. Adenoid cystic carcinoma (81%) formed the majority of salivary gland-type carcinoma, followed by secretory carcinoma (13%). For salivary gland-type carcinoma, acinic cell carcinoma histological type, tumor grade 3, HER2-overexpressed status, and higher AJCC stage groups were significant worse prognostic factors for breast cancer-specific survival in univariate analyses (p 

    Matched MeSH terms: Prognosis
  3. Wickersham JA, Zahari MM, Azar MM, Kamarulzaman A, Altice FL
    Drug Alcohol Depend, 2013 Sep 01;132(1-2):378-82.
    PMID: 23414931 DOI: 10.1016/j.drugalcdep.2013.01.005
    OBJECTIVE: To evaluate the impact of methadone dose on post-release retention in treatment among HIV-infected prisoners initiating methadone maintenance treatment (MMT) within prison.

    METHODS: Thirty HIV-infected prisoners meeting DSM-IV pre-incarceration criteria for opioid dependence were enrolled in a prison-based, pre-release MMT program in Klang Valley, Malaysia; 3 died before release from prison leaving 27 evaluable participants. Beginning 4 months before release, standardized methadone initiation and dose escalation procedures began with 5mg daily for the first week and 5mg/daily increases weekly until 80 mg/day or craving was satisfied. Participants were followed for 12 months post-release at a MMT clinic within 25 kilometers of the prison. Kaplan-Meier survival analysis was used to evaluate the impact of methadone dose on post-release retention in treatment.

    FINDINGS: Methadone dose ≥80 mg/day at the time of release was significantly associated with retention in treatment. After 12 months of release, only 21.4% of participants on <80 mg were retained at 12 months compared to 61.5% of those on ≥80 mg (Log Rank χ(2)=(1,26) 7.6, p<0.01).

    CONCLUSIONS: Higher doses of MMT at time of release are associated with greater retention on MMT after release to the community. Important attention should be given to monitoring and optimizing MMT doses to address cravings and side effects prior to community re-entry from prisons.

    Matched MeSH terms: Prognosis
  4. Haron NH, Mohamad Hanif EA, Abdul Manaf MR, Yaakub JA, Harun R, Mohamed R, et al.
    Asian Pac J Cancer Prev, 2019 Feb 26;20(2):509-517.
    PMID: 30803214
    Introduction: Microsatellite instability (MSI) is a hallmark of defective DNA mismatch repair (MMR) of genes especially MLH1 and MSH2. It is frequently involved in the carcinogenesis of various tumours including gastric cancer (GC). However, MSI in GCs have not been reported in Malaysia before. Objective: This study was conducted to determine the microsatellite instability (MSI) status in gastric cancer by microsatellite analysis, sequencing, its association with MLH1 and MSH2 protein expression and H.pylori infection by immunohistochemistry. Method: A total of 60 gastric cancer cases were retrieved. DNA was extracted from paired normal and tumour tissues while MLH1 and MSH2 protein expression as well as H. pylori status were determined by IHC staining. For microsatellite analysis, polymerase chain reaction (PCR) was performed for paired tissue samples using a panel of five microsatellite markers. MSI-positive results were subjected for DNA sequencing to assess mutations in the MLH1 and MSH2 genes. Results: Microsatellite analysis identified ten MSI positive cases (16.7%), out of which only six cases (10.3%) showed absence of MLH1 (n=3) or MSH2 (n=3) protein expression by IHC. The most frequent microsatellite marker in MSI positive cases was BAT26 (90%). Nine of ten MSI positive cases were intestinal type with one diffuse and all were located distally. H. pylori infection was detected in 13 of 60 cases (21.7%) including in three MSI positive cases. All these results however were not statistically significant. Our sequencing data displayed novel mutations. However these data were not statistically correlated with expression levels of MLH1 and MSH2 proteins by IHC. This may be due to small sample size to detect small or moderately sized effects. Conclusion: The frequency of MSI in this study was comparable with published results. Determination of affected MMR genes by more than two antibodies may increase the sensitivity of IHC to that of MSI analysis.
    Matched MeSH terms: Prognosis
  5. Chan HC, Adnan WA, Jaalam K, Abdullah MR, Abdullah J
    PMID: 16295557
    Mild head injury (MHI) is a common presentation to many hospitals in both rural and urban settings in Southeast Asia, but it is not well studied. We studied 330 patients that presented to Hospital Universiti Sains Malaysia Emergency Department with possible MHI, with the intentions to identify prognostic factors that may improve the diagnosis of MHI in the emergency setting as well as to determine which patients would need follow-up. Patients' one-year outcomes were classified as discharged well (DW) for patients without post-traumatic signs and symptoms and discharged with long term follow-up (DFU) for patients with such signs and symptoms. Four patients died and 82 were DFU. An abnormal skull X ray was associated with mode of accident and type of transportation, older age, presence of vomiting, confusion, bleeding from ear, nose or throat, abnormal pupil size on the right side associated with orbital trauma, unequal pupillary reflexes, absence of loss of consciousness (LOC), a lower Glasgow Coma Scale (GCS) score, multiple clinical presentations, and DFU. An abnormal CT scan was associated with older age, multiple clinical presentation, skull X-ray findings, and DFU. A similar analysis on outcomes revealed that mode of accident, older age, vomiting, confusion, headache, bleeding from ear, nose and throat, neurological deficits, absence of LOC, pupil size, multiple presentation, abnormal skull X ray, CT scan of the brain, and a GCS of 13 was associated with DFU. In conclusion, all patients involved in motor vehicle accidents (MVAs), especially motorcycles, aged over 30 years of age, with multiple clinical presentations, including a lower GCS, and with abnormal radiological findings should have a longer follow-up due to persistent post-traumatic symptomatology.
    Matched MeSH terms: Prognosis
  6. Mohktar MS, Redmond SJ, Antoniades NC, Rochford PD, Pretto JJ, Basilakis J, et al.
    Artif Intell Med, 2015 Jan;63(1):51-9.
    PMID: 25704112 DOI: 10.1016/j.artmed.2014.12.003
    BACKGROUND: The use of telehealth technologies to remotely monitor patients suffering chronic diseases may enable preemptive treatment of worsening health conditions before a significant deterioration in the subject's health status occurs, requiring hospital admission.
    OBJECTIVE: The objective of this study was to develop and validate a classification algorithm for the early identification of patients, with a background of chronic obstructive pulmonary disease (COPD), who appear to be at high risk of an imminent exacerbation event. The algorithm attempts to predict the patient's condition one day in advance, based on a comparison of their current physiological measurements against the distribution of their measurements over the previous month.
    METHOD: The proposed algorithm, which uses a classification and regression tree (CART), has been validated using telehealth measurement data recorded from patients with moderate/severe COPD living at home. The data were collected from February 2007 to January 2008, using a telehealth home monitoring unit.
    RESULTS: The CART algorithm can classify home telehealth measurement data into either a 'low risk' or 'high risk' category with 71.8% accuracy, 80.4% specificity and 61.1% sensitivity. The algorithm was able to detect a 'high risk' condition one day prior to patients actually being observed as having a worsening in their COPD condition, as defined by symptom and medication records.
    CONCLUSION: The CART analyses have shown that features extracted from three types of physiological measurements; forced expiratory volume in 1s (FEV1), arterial oxygen saturation (SPO2) and weight have the most predictive power in stratifying the patients condition. This CART algorithm for early detection could trigger the initiation of timely treatment, thereby potentially reducing exacerbation severity and recovery time and improving the patient's health. This study highlights the potential usefulness of automated analysis of home telehealth data in the early detection of exacerbation events among COPD patients.
    Matched MeSH terms: Prognosis
  7. Hartanto FK, Karen-Ng LP, Vincent-Chong VK, Ismail SM, Mustafa WM, Abraham MT, et al.
    Asian Pac J Cancer Prev, 2015;16(3):953-8.
    PMID: 25735388
    BACKGROUND: Expression of KRT13, FAIM2 and CYP2W1 appears to be influenced by risk habits, thus exploring the associations of these genes in oral squamous cell cancer (OSCC) with risk habits, clinico-pathological parameters and patient survival may be beneficial in identifying relevant biomarkers with different oncogenic pathways.

    MATERIALS AND METHODS: cDNAs from 41 OSCC samples with and without risk habits were included in this study. Quantitative real-time PCR was used to analyze KRT13, FAIM2 and CYP2W1 in OSCC. The housekeeping gene (GAPDH) was used as an endogenous control.

    RESULTS: Of the 41 OSCC samples, KRT13 was down-regulated in 40 samples (97.6%), while FAIM2 and CYP2W1 were down-regulated in 61.0% and 48.8%, respectively. Overall, there were no associations between KRT13, FAIM2 and CYP2W1 expression with risk habits, selected socio-demographic and clinico-pathological parameters and patient survival.

    CONCLUSIONS: Although this study was unable to show significance, there were some tendencies in the associations of KRT13, FAIM2 and CYP2W1 expression in OSCC with selected clinic-pathological parameters and survival.

    Matched MeSH terms: Prognosis
  8. Latiff LA, Rahman SA, Wee WY, Dashti S, Andi Asri AA, Unit NH, et al.
    Asian Pac J Cancer Prev, 2015;16(2):559-64.
    PMID: 25684487
    BACKGROUND: The participation of women in cervical cancer screening in Malaysia is low. Self-sampling might be able to overcome this problem.The aim of this study was to assess the reliability of self-sampling for cervical smear in our country.

    MATERIALS AND METHODS: This cross-sectional study was conducted on 258 community dwelling women from urban and rural settings who participated in health campaigns. In order to reduce the sampling bias, half of the study population performed the self-sampling prior to the physician sampling while the other half performed the self-sampling after the physician sampling, randomly. Acquired samples were assessed for cytological changes as well as HPV DNA detection.

    RESULTS: The mean age of the subjects was 40.4±11.3 years. The prevalence of abnormal cervical changes was 2.7%. High risk and low risk HPV genotypes were found in 4.0% and 2.7% of the subjects, respectively. A substantial agreement was observed between self-sampling and the physician obtained sampling in cytological diagnosis (k=0.62, 95%CI=0.50, 0.74), micro-organism detection (k=0.77, 95%CI=0.66, 0.88) and detection of hormonal status (k=0.75, 95%CI=0.65, 0.85) as well as detection of high risk (k=0.77, 95%CI=0.4, 0.98) and low risk (K=0.77, 95%CI=0.50, 0.92) HPV. Menopausal state was found to be related with 8.39 times more adequate cell specimens for cytology but 0.13 times less adequate cell specimens for virological assessment.

    CONCLUSIONS: This study revealed that self-sampling has a good agreement with physician sampling in detecting HPV genotypes. Self-sampling can serve as a tool in HPV screening while it may be useful in detecting cytological abnormalities in Malaysia.

    Matched MeSH terms: Prognosis
  9. Yatabe Y, Kerr KM, Utomo A, Rajadurai P, Tran VK, Du X, et al.
    J Thorac Oncol, 2015 Mar;10(3):438-45.
    PMID: 25376513 DOI: 10.1097/JTO.0000000000000422
    The efficacy of epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors in EGFR mutation-positive non-small-cell lung cancer (NSCLC) patients necessitates accurate, timely testing. Although EGFR mutation testing has been adopted by many laboratories in Asia, data are lacking on the proportion of NSCLC patients tested in each country, and the most commonly used testing methods.
    Matched MeSH terms: Prognosis
  10. Sakthiswary R, Shaharir SS, Mohd Said MS, Asrul AW, Shahril NS
    Int J Rheum Dis, 2014 Nov;17(8):872-7.
    PMID: 25292482 DOI: 10.1111/1756-185X.12443
    AIM: The main objective of this study is to elucidate the role of immunoglobulin A (IgA) rheumatoid factor (RF) in predicting the clinical response to tumour necrosis factor α inhibitors (TNFi) among patients with rheumatoid arthritis (RA).
    METHOD: We recruited all patients with RA who were ever on TNFi for a minimum duration of 3 months at our centre. Based on the European League Against Rheumatism response criteria, subjects were further divided into responders and non-responders. Age-matched RA patients who were on conventional disease-modifying anti-rheumatic drugs and in remission were enrolled as controls. Subjects were tested for quantitative values of IgA, IgM, IgG RF and anti-citrulinated cyclic peptides (CCP). Further, all subjects were assessed for the disease activity score that includes 28 joints (DAS28) and Stanford Health Assessment Questionnaire (HAQ) 8-item Disability Index (HAQ-DI).
    RESULTS: A total of 31 subjects with RA who had received TNFi and 15 controls were enrolled in this study. There was a trend for the non-responders (n = 10) to have higher levels of all isotypes of RF and anti-CCP. However, only the IgA RF and anti-CCP levels were significantly higher in the non-responder group compared to the responders and controls (P = 0.001, P = 0.034, respectively). On multivariate analysis, only the IgA RF remained significant (OR 0.989; 95% CI 0.980-0.999; P = 0.026).
    CONCLUSION: IgA RF is potentially a novel predictor of response to TNFi in RA patients. Testing for pretreatment IgA RF levels could be a reasonable consideration before commencement of TNFi.
    Study site: Pusat Perubatan Universiti Kebangsaan Malaysia (PPUKM), Kuala Lumpur, Malaysia
    Matched MeSH terms: Prognosis
  11. Lim CC, Teo BW, Ong PG, Cheung CY, Lim SC, Chow KY, et al.
    Eur J Prev Cardiol, 2015 Aug;22(8):1018-26.
    PMID: 24857889 DOI: 10.1177/2047487314536873
    BACKGROUND: Few studies have examined the impact of chronic kidney disease (CKD) on adverse cardiovascular outcomes and deaths in Asian populations. We evaluated the associations of CKD with cardiovascular disease (CVD) and all-cause mortality in a multi-ethnic Asian population.
    DESIGN: Prospective cohort study of 7098 individuals who participated in two independent population-based studies involving Malay adults (n = 3148) and a multi-ethnic cohort of Chinese, Malay and Indian adults (n = 3950).
    METHODS: CKD was assessed from CKD-EPI estimated glomerular filtration rate (eGFR) and urine albumin-to-creatinine ratio (UACR). Incident CVD (myocardial infarction, stroke and CVD mortality) and all-cause mortality were identified by linkage with national disease/death registries.
    RESULTS: Over a median follow-up of 4.3 years, 4.6% developed CVD and 6.1% died. Risks of both CVD and all-cause mortality increased with decreasing eGFR and increasing albuminuria (all p-trend <0.05). Adjusted hazard ratios (HR (95% confidence interval)) of CVD and all-cause mortality were: 1.54 (1.05-2.27) and 2.21 (1.67-2.92) comparing eGFR <45 vs ≥60; 2.81 (1.49-5.29) and 2.34 (1.28-4.28) comparing UACR ≥300 vs <30. The association between eGFR <60 and all-cause mortality was stronger among those with diabetes (p-interaction = 0.02). PAR of incident CVD was greater among those with UACR ≥300 (12.9%) and that of all-cause mortality greater among those with eGFR <45 (16.5%).
    CONCLUSIONS: In multi-ethnic Asian adults, lower eGFR and higher albuminuria were independently associated with incident CVD and all-cause mortality. These findings extend previously reported similar associations in Western populations to Asians and emphasize the need for early detection of CKD and intervention to prevent adverse outcomes.
    Matched MeSH terms: Prognosis
  12. Abu Hassan H, Abd Aziz N, Hassan Y, Hassan F
    PMID: 24868154 DOI: 10.2147/COPD.S56637
    BACKGROUND: Lack of awareness among ex-smokers on the benefits of sustaining smoking cessation may be the main cause of their smoking relapse. This study explored health-related quality of life (HRQoL) and hospital admission amongst chronic obstructive pulmonary disease (COPD) patients according to the duration of smoking cessation.
    MATERIALS AND METHODS: This study recruited COPD patients from a chest clinic who agreed to participate in a medication therapy-adherence program from January to June 2013. They were interviewed during their visits to obtain information regarding their smoking history and HRQoL. They were divided into three groups according to smoking status (sustained quitters, quit ≥5 years; quitters, quit <5 years; and smokers, smoking at least one cigarette/day). The effects of the duration of cessation on HRQoL and hospital admission were analyzed using a multinomial logistic model.
    RESULTS: A total of 117 participants with moderate COPD met the inclusion criteria, who were comprised of 41 sustained quitters, 40 quitters, and 36 smokers. Several features were similar across the groups. Most of them were married elderly men (aged >64 years) with low-to-middle level of education, who smoked more than 33 cigarettes per day and had high levels of adherence to the medication regimen. The results showed that sustained quitters were less likely to have respiratory symptoms (cough, phlegm and dyspnea) than smokers (odds ratio 0.02, confidence interval 0-0.12; P<0.001). The hospital admission rate per year was increased in quitters compared to smokers (odds ratio 4.5, confidence interval 1.91-10.59; P<0.005).
    CONCLUSION: A longer duration of quitting smoking will increase the benefits to COPD patients, even if they experience increased episodic respiratory symptoms in the early period of the cessation. Thus, the findings of this study show the benefits of early smoking cessation.
    KEYWORDS: HRQoL; chronic obstructive pulmonary disease (COPD); hospital admission and hospital stay
    Study site: Chest Clinic, Hospital Melaka, Malaysia
    Matched MeSH terms: Prognosis
  13. Hamzi Abdul Raub S, Isa NM, Zailani HA, Omar B, Abdullah MF, Mohd Amin WA, et al.
    Asian Pac J Cancer Prev, 2014;15(2):651-6.
    PMID: 24568473
    BACKGROUND: Cervical cancer is the third commonest type of cancer among women in Malaysia. Our aim was to determine the distribution of human papilloma virus (HPV) genotypes in cervical cancer in our multi-ethnic population.

    MATERIALS AND METHODS: This was a multicentre study with a total of 280 cases of cervical cancer from 4 referral centres in Malaysia, studied using real-time polymerase chain reaction (qPCR) detection of 12 high risk-HPV genotypes.

    RESULTS: Overall HPV was detected in 92.5% of cases, in 95.9% of squamous cell carcinomas and 84.3%of adenocarcinomas. The five most prevalent high-risk HPV genotypes were HPV 16 (68.2%), 18 (40%), 58 (10.7%), 33 (10.4%) and 52 (10.4%). Multiple HPV infections were more prevalent (55.7%) than single HPV infections (36.8%). The percentage of HPV positive cases in Chinese, Malays and Indians were 95.5%, 91.9% and 80.0%, respectively. HPV 16 and 18 genotypes were the commonest in all ethnic groups. We found that the percentage of HPV 16 infection was significantly higher in Chinese (75.9%) compared to Malays (63.7%) and Indians (52.0%) (p<0.05), while HPV 18 was significantly higher in Malays (52.6%) compared to Chinese (25.0%) and Indians (28%) (p<0.05). Meanwhile, HPV 33 (17.9%) and 52 (15.2%) were also more commonly detected in the Chinese (p<0.05).

    CONCLUSIONS: This study showed that the distribution of HPV genotype in Malaysia is similar to other Asian countries. Importantly, we found that different ethnic groups in Malaysia have different HPV genotype infection rates, which is a point to consider during the implementation of HPV vaccination.

    Matched MeSH terms: Prognosis
  14. Yap NY, Ng KL, Ong TA, Pailoor J, Gobe GC, Ooi CC, et al.
    Asian Pac J Cancer Prev, 2013;14(12):7497-500.
    PMID: 24460324
    BACKGROUND: This study concerns clinical characteristics and survival of renal cell carcinoma (RCC) patients in University Malaya Medical Centre (UMMC), as well as the prognostic significance of presenting symptoms.

    MATERIALS AND METHODS: The clinical characteristics, presenting symptoms and survival of RCC patients (n=151) treated at UMMC from 2003-2012 were analysed. Symptoms evaluated were macrohaematuria, flank pain, palpable abdominal mass, fever, lethargy, loss of weight, anaemia, elevated ALP, hypoalbuminemia and thrombocytosis. Univariate and multivariate Cox regression analyses were performed to determine the prognostic significance of these presenting symptoms. Kaplan Meier and log rank tests were employed for survival analysis.

    RESULTS: The 2002 TNM staging was a prognostic factor (p<0.001) but Fuhrman grading was not significantly correlated with survival (p=0.088). At presentation, 76.8% of the patients were symptomatic. Generally, symptomatic tumours had a worse survival prognosis compared to asymptomatic cases (p=0.009; HR 4.74). All symptoms significantly affect disease specific survival except frank haematuria and loin pain on univariate Cox regression analysis. On multivariate analysis adjusted for stage, only clinically palpable abdominal mass remained statistically significant (p=0.027). The mean tumour size of palpable abdominal masses, 9.5±4.3cm, was larger than non palpable masses, 5.3±2.7cm (p<0.001).

    CONCLUSIONS: This is the first report which includes survival information of RCC patients from Malaysia. Here the TNM stage and a palpable abdominal mass were independent predictors for survival. Further investigations using a multicentre cohort to analyse mortality and survival rates may aid in improving management of these patients.

    Matched MeSH terms: Prognosis
  15. Elias MH, Baba AA, Azlan H, Rosline H, Sim GA, Padmini M, et al.
    Leuk. Res., 2014 Apr;38(4):454-9.
    PMID: 24456693 DOI: 10.1016/j.leukres.2013.12.025
    Discovery of imatinib mesylate (IM) as the targeted BCR-ABL protein tyrosine kinase inhibitor (TKI) has resulted in its use as the frontline therapy for chronic myeloid leukemia (CML) across the world. Although high response rates are observed in CML patients who receive IM treatment, a significant number of patients develop resistance to IM. Resistance to IM in patients has been associated with a heterogeneous array of mechanisms of which point mutations within the ABL tyrosine kinase domain (TKD) are the frequently documented. The types and frequencies of mutations reported in different population studies have shown wide variability. We screened 125 Malaysian CML patients on IM therapy who showed either TKI refractory or resistance to IM to investigate the frequency and pattern of BCR-ABL kinase domain mutations among Malaysian CML patients undergoing IM therapy and to determine the clinical significance. Mutational screening using denaturing high performance liquid chromatography (dHPLC) followed by DNA sequencing was performed on 125 IM resistant Malaysian CML patients. Mutations were detected in 28 patients (22.4%). Fifteen different types of mutations (T315I, E255K, G250E, M351T, F359C, G251E, Y253H, V289F, E355G, N368S, L387M, H369R, A397P, E355A, D276G), including 2 novel mutations were identified, with T315I as the predominant type of mutation. The data generated from clinical and molecular parameters studied were correlated with the survival of CML patients. Patients with Y253H, M351T and E355G TKD mutations showed poorer prognosis compared to those without mutation. Interestingly, when the prognostic impact of the observed mutations was compared inter-individually, E355G and Y253H mutations were associated with more adverse prognosis and shorter survival (P=0.025 and 0.005 respectively) than T315I mutation. Results suggest that apart from those mutations occurring in the three crucial regions (catalytic domain, P-loop and activation-loop), other rare mutations also may have high impact in the development of resistance and adverse prognosis. Presence of mutations in different regions of BCR-ABL TKD leads to different levels of resistance and early detection of emerging mutant clones may help in decision making for alternative treatment. Serial monitoring of BCR-ABL1 transcripts in CML patients allows appropriate selection of CML patients for BCR-ABL1 KD mutation analysis associated with acquired TKI resistance. Identification of these KD mutations is essential in order to direct alternative treatments in such CML patients.
    Matched MeSH terms: Prognosis
  16. Lee WC, Yusof MM, Lau FN, Phua VC
    Asian Pac J Cancer Prev, 2013;14(6):3941-4.
    PMID: 23886211
    BACKGROUND: The use of preoperative chemoirradiation is the commonest treatment strategy employed in Malaysia for locally advanced rectal cancer. We need to determine the local control and survival rates for comparison with established rates in the literature.

    MATERIALS AND METHODS: This retrospective study analyzed all newly diagnosed patients with rectal adenocarcinoma who underwent long course preoperative radiotherapy (RT) at the Department of Radiotherapy and Oncology, Kuala Lumpur Hospital (HKL) between 1st January 2004 and 31st December 2010. The aim of the study was to determine the radiological response post radiotherapy, pathological response including circumferential resection margin (CRM) status, 3 years local control, 3 years overall survival (OS) and 3 years disease free survival (DFS). Statistical analysis was performed using the SPSS software. Kaplan-Meier and log rank analysis were used to determine survival outcomes.

    RESULTS: A total of 507 patients with rectal cancer underwent RT at HKL. Sixty seven who underwent long course preoperative RT were eligible for this study. The median age at diagnosis was 60 years old with a range of 26-78 years. The median tumour location was 6 cm from the anal verge. Most patients had suspicion of mesorectum involvement (95.5%) while 28.4% of patients had enlarged pelvic nodes on staging CT scan. All patients underwent preoperative chemo-irradiation except for five who had preoperative RT alone. Only 38 patients underwent definitive surgery (56.7%). Five patients were deemed to be inoperable radiologically and 3 patients were found to have unresectable disease intraoperatively. The remaining 21 patients defaulted surgery (31.3%). The median time from completion of RT to surgery was 8 weeks (range 5.6 to 29.4 weeks). Fifteen patients (39.5%) had surgery more than 8 weeks after completion of RT. Complete pathological response was noted in 4 patients (10.5%). The pathological CRM positive rate after RT was 18.4%. With a median follow-up of 38.8 months, the 3 year local control rate was 67%. The 3 years rate for CRM positive (<2 mm), CRM clear (>2 mm) and pCR groups were 0%, 88.1% and 100% respectively (p-value of 0.007). The 3 year OS and DFS were 57.3% and 44.8% respectively.

    CONCLUSIONS: In conclusion, the approach of long course preoperative chemoirradiation for rectal cancer needs to be re-examined in our local setting. The high rate of local recurrence is worrying and is mainly due to patient defaulting post-preoperative chemoirradiation or delayed definitive surgery.
    Matched MeSH terms: Prognosis
  17. Ezat SW, Hod R, Mustafa J, Mohd Dali AZ, Sulaiman AS, Azman A
    Asian Pac J Cancer Prev, 2013;14(5):2991-9.
    PMID: 23803068
    BACKGROUND: Introduction of the HPV vaccine is a forefront primary prevention method in reducing the incidence of carcinogenic human papillomavirus (HPV) and cervical cancer. The Malaysia government has implemented the National HPV immunisation programme since 2010, supplying HPV vaccine free to targeted 13 year olds. This study aimed to explore the level of knowledge among mothers on cervical cancer, HPV, HPV vaccine and National HPV (NHPV) immunisation programme since its' implementation. It also assessed acceptance of mothers towards HPV vaccine being administered to their daughter, son or themselves.
    MATERIALS AND METHODS: A cross sectional study was conducted on 155 respondents using self-administered questionnaires; conducted in December 2012 at the Obstetrics and Gynaecology Clinic in a teaching hospital in Kuala Lumpur. Respondents were selected using a multistage sampling technique.
    RESULTS: A response rate of 100% was obtained. Overall, 51.0% of mothers had good knowledge, with 55% having good knowledge of cervical cancer, 54.2% for both HPV and the National HPV immunisation programme and 51.0% for the HPV vaccine. Regression analyses showed that ethnicity was associated with knowledge on cervical cancer (p=0.003) while education was associated with knowledge on HPV (p=0.049). Three factors are associated with knowledge of the National HPV immunisation programme; ethnicity (p=0.017), mothers' education (p=0.0005) and number of children (p=0.020). The acceptance of HPV vaccine to be administered among daughter was the highest at 87.1%, followed by for mothers themselves at 73.5%, and the least is for sons 62.6%.
    CONCLUSIONS: This study found that the overall level of knowledge was moderate. Adequate information on cervical cancer, HPV, HPV vaccination and the National HPV immunisation programme should be provided to mothers in order to increase acceptance of the HPV vaccine which can reduce the disease burden in the future.
    Study site: O&G clinic, Pusat Perubatan Universiti Kebangsaan Malaysia, Kuala Lumpur, Malaysia
    Matched MeSH terms: Prognosis
  18. Ibrahim A, Lee KY, Kanoo LL, Tan CH, Hamid MA, Hamedon NM, et al.
    Spine (Phila Pa 1976), 2013 Mar 1;38(5):419-24.
    PMID: 22914700 DOI: 10.1097/BRS.0b013e31826ef594
    Cross-sectional study.
    Matched MeSH terms: Prognosis
  19. Zanaruddin SN, Saleh A, Yang YH, Hamid S, Mustafa WM, Khairul Bariah AA, et al.
    Hum Pathol, 2013 Mar;44(3):417-26.
    PMID: 23026198 DOI: 10.1016/j.humpath.2012.06.007
    The presence of lymph node (LN) metastasis significantly affects the survival of patients with oral squamous cell carcinoma (OSCC). Successful detection and removal of positive LNs are crucial in the treatment of this disease. Current evaluation methods still have their limitations in detecting the presence of tumor cells in the LNs, where up to a third of clinically diagnosed metastasis-negative (N0) patients actually have metastasis-positive LNs in the neck. We developed a molecular signature in the primary tumor that could predict LN metastasis in OSCC. A total of 211 cores from 55 individuals were included in the study. Eleven proteins were evaluated using immunohistochemical analysis in a tissue microarray. Of the 11 biomarkers evaluated using receiver operating curve analysis, epidermal growth factor receptor (EGFR), v-erb-b2 erythroblastic leukemia viral oncogene homolog 2 (HER-2/neu), laminin, gamma 2 (LAMC2), and ras homolog family member C (RHOC) were found to be significantly associated with the presence of LN metastasis. Unsupervised hierarchical clustering-demonstrated expression patterns of these 4 proteins could be used to differentiate specimens that have positive LN metastasis from those that are negative for LN metastasis. Collectively, EGFR, HER-2/neu, LAMC2, and RHOC have a specificity of 87.5% and a sensitivity of 70%, with a prognostic accuracy of 83.4% for LN metastasis. We also demonstrated that the LN signature could independently predict disease-specific survival (P = .036). The 4-protein LN signature validated in an independent set of samples strongly suggests that it could reliably distinguish patients with LN metastasis from those who were metastasis-free and therefore could be a prognostic tool for the management of patients with OSCC.
    Matched MeSH terms: Prognosis
  20. Jaafar H, Abdullah S, Murtey MD, Idris FM
    Asian Pac J Cancer Prev, 2012;13(8):3857-62.
    PMID: 23098483
    A total of 96 cases of invasive breast ductal carcinoma were examined for immunohistochemical expression of Bax and Bcl-2 in the epithelial tumor cells and endothelial cells of the blood vessels. We also investigated the association between both proteins in the epithelium in relation to tumor characteristics such as tumor size, grade, lymph node involvement, microvessel density (MVD), hormonal receptors expression and c-erbB-2 overexpression. Bax expression showed a significant association between tumor and endothelial cells (p<0.001) while Bcl-2 expression in tumor cells was inversely associated with that in the endothelial cells (p<0.001). Expression of Bcl-2 in tumor cells was strongly associated with expression of estrogen and progesterone receptors (p=0.003 and p=0.004, respectively). In addition, intratumoral MVD was significantly higher than peritumoral MVD (p<0.001) but not associated with Bax or Bcl-2 expression and other tumor characteristics. We concluded that the number of endothelial cells undergoing apoptosis was in direct linkage with the number of apoptotic tumor cells. Anti-apoptotic activity of the surviving tumor cells appears to propagate cancer progression and this was influenced by the hormonal status of the cells. Tumor angiogenesis was especially promoted in the intratumoral region and angiogenesis was independent of anti-apoptotic activity.
    Matched MeSH terms: Prognosis
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