Association of proinflammatory cytokines and chemotherapy-associated cognitive impairment in breast cancer patients: a multi-centered, prospective, cohort study.

BACKGROUND: Existing evidence suggests that proinflammatory cytokines play an intermediary role in postchemotherapy cognitive impairment. This is one of the largest multicentered, cohort studies conducted in Singapore to evaluate the prevalence and proinflammatory biomarkers associated with cognitive impairment in breast cancer patients. PATIENTS AND METHODS: Chemotherapy-receiving breast cancer patients (stages I-III) were recruited. Proinflammatory plasma cytokines concentrations [interleukin (IL)-1ß, IL-2, IL-4, IL-6, IL-8, IL-10, granulocyte-macrophage colony-stimulating factor, interferon-γ and tumor necrosis factor-α] were evaluated at 3 time points (before chemotherapy, 6 and 12 weeks after chemotherapy initiation). The FACT-Cog (version 3) was utilized to evaluate patients' self-perceived cognitive disturbances and a computerized neuropsychological assessment (Headminder) was administered to evaluate patients' memory, attention, response speed and processing speed. Changes of cognition throughout chemotherapy treatment were compared against the baseline. Linear mixed-effects models were applied to test the relationships of clinical variables and cytokine concentrations on self-perceived cognitive disturbances and each objective cognitive domain. RESULTS: Ninety-nine patients were included (age 50.5 ± 8.4 years; 81.8% Chinese; mean duration of education = 10.8 ± 3.3 years). Higher plasma IL-1ß was associated with poorer response speed performance (estimate: -0.78; 95% confidence interval (CI) -1.34 to -0.03; P = 0.023), and a higher concentration of IL-4 was associated with better response speed performance (P = 0.022). Higher concentrations of IL-1ß and IL-6 were associated with more severe self-perceived cognitive disturbances (P = 0.018 and 0.001, respectively). Patients with higher concentrations of IL-4 also reported less severe cognitive disturbances (P = 0.022). CONCLUSIONS: While elevated concentrations of IL-6 and IL-1ß were observed in patients with poorer response speed performance and perceived cognitive disturbances, IL-4 may be protective against chemotherapy-associated cognitive impairment. This study is important because cytokines would potentially be mechanistic mediators of chemotherapy-associated cognitive changes.

Association of common genetic variants with breast cancer risk and clinicopathological characteristics in a Chinese population.

Genome-wide association studies (GWAS) have identified various genetic susceptibility loci for breast cancer based mainly on European-ancestry populations. Differing linkage disequilibrium patterns exist between European and Asian populations, and thus GWAS-identified single nucleotide polymorphisms (SNPs) in one population may not be of significance in another population. In order to explore the role of breast cancer susceptibility variants in a Chinese population of Southern Chinese descent, we analyzed 22 SNPs for 1,191 breast cancer cases and 1,534 female controls. Associations between the SNPs and clinicopathological features were also investigated. In addition, we evaluated the combined effects of associated SNPs by constructing risk models. Eight SNPs were associated with an elevated breast cancer risk. Rs2046210/6q25.1 increased breast cancer risk via an additive model [per-allele odds ratio (OR) = 1.43, 95 % confidence interval (CI) = 1.26-1.62], and was associated with estrogen receptor (ER)-positive (per-allele OR = 1.39, 95 % CI = 1.20-1.61) and ER-negative (per-allele OR = 1.55, 95 % CI = 1.28-1.89) disease. Rs2046210 was also associated with stage 1, stage 2, and stage 3 disease, with per-allele ORs of 1.38 (1.14-1.68), 1.48 (1.25-1.74), and 1.58 (1.28-1.94), respectively. Four SNPs mapped to 10q26.13/FGFR2 were associated with increased breast cancer risk via an additive model with per-allelic risks (95 % CI) of 1.26 (1.12-1.43) at rs1219648, 1.22 (1.07-1.38) at rs2981582, 1.21 (1.07-1.36) at rs2981579, and 1.18 (1.04-1.35) at rs11200014. Variants of rs7696175/TLR1, TLR6, rs13281615/8q24, and rs16886165/MAP3K1 were also associated with increased breast cancer risk, with per-allele ORs (95 % CI) of 1.16 (1.00-1.34), 1.15 (1.02-1.29), and 1.15 (1.01-1.29), respectively. Five SNPs associated with breast cancer risk predominantly among ER-positive tumors (rs2981582/FGFR2, rs4415084/MRPS30, rs1219648/FGFR2, rs2981579/FGFR2, and rs11200014/FGFR2). Among our Chinese population, the risk of developing breast cancer increased by 90 % for those with a combination of 6 or more risk alleles, compared to patients with ≤3 risk alleles.

Towards identification of important plant areas (IPA) for Peninsular Malaysia. Methodology and future directions.

Malaysia is a megadiverse country and listed as one of the world's biodiversity hotspots. Land use changes and deforestation have led to the threat of, and extinction of plant species. In order to mitigate loss in population numbers, and to prevent species extinction events, Important Plant Areas (IPA) for Malaysia shall be identified. The identification of IPA is important to ensure that key natural areas are adequately protected and managed to preserve the species and its habitats. Currently, there are 1771 IPA identified globally and only seven tropical countries are actively involved excluding Malaysia. Inventory and biodiversity research are actively conducted in Malaysia, however, the initiative to identify IPA is still in its infancy. The first attempt for IPA identification was in the state of Terengganu by using herbarium database through scoring technique. In this paper, we discussed methods and criteria used in IPA identification globally. We also deliberated current IPA development in Terengganu and challenges such as collections biases and the need for a robust scoring technique to reduce judgement uncertainty. We suggested GIS based multi-criteria decision making, analytical hierarchy process and species distribution for Malaysian IPA. These strategies were considered to be effective tools in providing decision support for spatial planning aimed at plant conservation in Malaysia.

Factors influencing patient decision-making between simple mastectomy and surgical alternatives.

Background: Despite similar survival rates, breast-conserving therapy (BCT) remains a distant second choice after simple mastectomy for patients with early-stage breast cancer in Singapore. Uptake of reconstruction after mastectomy is also low (18 per cent). The aim of this study was to explore the factors influencing a patient's choice for mastectomy when eligible for BCT, and why patients decline reconstruction after mastectomy. Methods: Patients from the National Cancer Centre Singapore, who were eligible for BCT but chose mastectomy without reconstruction, between December 2014 and December 2015 were included. An interviewer-administered questionnaire focusing on patients' reasons for choosing mastectomy over BCT and not opting for immediate breast reconstruction after mastectomy was used. Tumour characteristics were retrieved from medical records. Spearman's rank correlation coefficient, Mann-Whitney U and Kruskal-Wallis tests were used to analyse the correlation between the patient's self-rated influential factors and variables. Statistical significance was taken as P < 0·050. Results: Ninety-one patients were included (90·1 per cent response rate). The main reasons for choosing mastectomy over BCT were: fear of cancer recurrence (considered very important in 74 per cent), the perception that health outweighs breast retention (49 per cent) and the possibility of second surgery for margins (40 per cent). Key factors for rejecting immediate reconstruction after mastectomy were: patient-perceived 'old age' (very important in 53 per cent), concern about two sites of surgery (42 per cent) and financial cost (29 per cent). Given a second chance, 19·8 per cent of patients would undergo BCT instead of mastectomy. Conclusion: This study has identified the considerations that women in Singapore have when deciding on breast cancer surgery. Some perceptions need to be addressed for women to make a fully informed decision, especially as one-fifth regret their initial choice.

Single institution's initial experience with sentinel lymph node biopsy in breast cancer patients.

BACKGROUND: The sentinel lymph node is the first draining node from a cancer-bearing area and is therefore the first to manifest metastasis. In breast cancer it has been shown to predict the axillary status. Axillary dissection provides information determining prognosis and need for adjuvant therapy but carries a certain morbidity. Our aim was to determine the feasibility of detecting the sentinel node in a teaching hospital and whether the sentinel node accurately predicts the axillary status. METHODS: All patients with stage I and II breast cancer and non-palpable axillary nodes were eligible, including those with previous excision biopsy. We excluded pregnant women, those with previous axillary surgery and women with advanced breast cancer with enlarged axillary nodes. The sentinel node was detected with technetium-99m-labelled tin colloid and vital blue dye and removed, and axillary clearance was performed. RESULTS: A total of 312 patients were examined from August 1996 to December 1998. The mean age was 53 years (range 28-83) and mean tumour size 2.6 cm (range 0.2-9.0). The detection rate of the sentinel node was 86%. The sentinel lymph node predicted the axillary status with a sensitivity of 83% and specificity of 100%. The false-negative rate was 16.7%. CONCLUSIONS: Detection of the sentinel lymph node is feasible and it can accurately predict the nodal status of the axilla. However, the high false-negative rate precludes as yet the use of sentinel lymph node biopsy in replacing axillary clearance as the standard of care for breast cancer.

A comparison of trucut biopsy with fine needle aspiration cytology in the diagnosis of breast cancer.

INTRODUCTION: Carcinoma of the breast is common in Singapore and many patients may present with just a suspicious breast lump. AIM: To determine the accuracy of fine needle aspiration cytology (FNAC) and trucut biopsy in the diagnosis of suspicious breast lumps in an outpatient setting. METHODS: A total of 39 women, from May 1995 to November 1995, who had a suspicious breast lump were subjected to concurrent FNAC and trucut biopsy. RESULTS: The accuracy of FNAC is 90% whereas trucut biopsy is 67%, the difference being statistically significant with a p < 0.02. CONCLUSION: FNAC is recommended for the diagnosis of suspicious breast lumps.

Extended resection of locally advanced (T4) stomach cancer.

INTRODUCTION: The surgical management of locally advanced (T4) stomach cancer remains controversial and many still question the benefits of an extended resection. The aims of this study were to examine the morbidity and mortality associated with extended resection and also to determine the survival benefit. MATERIALS AND METHODS: A retrospective review of all stomach cancer operations performed from 1989 to 1998 was carried out and the relevant case histories retrieved and analysed. RESULTS: Out of the 980 stomach cancer operations performed, 784 (80%) had tumour resection and 20 (2.5%) also had extended resection of adjacent involved organs. These 20 patients had a 10% postoperative morbidity and the operative mortality was 15%. The survival ranged from 2 to 35 months (median 17 months). CONCLUSIONS: Extended resection of T4 stomach cancer is feasible and carries an acceptable operative morbidity and mortality. However, there is poor survival benefit and it should only be performed in a selected group of patients.

Spectrum of roller-blading injuries.

We studied 32 patients who presented to the Accident and Emergency Department of Toa Payoh Hospital with injuries sustained while roller-blading (in-line roller skating). This sporting activity carries risk of injuries, often fractures, due to 3 principal mechanisms of injury. The first and main mechanism of injury is that of a forward fall with the arms outstretched as a protective gesture. This is associated with fractures of the distal radius in the majority of cases, although other injuries to the upper limb can occur. The second important mechanism is that of a backward fall with resulting injury to the back of the head. Lastly, the patient may fall sideways, often together with a twisting force to the lower limbs, resulting in ankle sprains and meniscus injuries to the knee. The vast majority of patients are young teenagers who are beginners and had not been properly clad in protective gear. Roller-blading therefore carries a very real risk of sporting injury.