Say Beng Tan

Microvascular invasion is a better predictor of tumor recurrence and overall survival following surgical resection for hepatocellular carcinoma compared to the Milan criteria.

Objective:To compare microvascular invasion (McVI) with parameters defined by the Milan criteria in predicting tumor recurrence and overall survival (OS) in patients with surgical resection (SR) for hepatocellular carcinoma (HCC). Summary Background Data:Although the Milan criteria is discriminatory for selecting patients with good outcomes in liver transplantation and SR for HCC, it neither adequately predict tumor recurrence nor explain differences in survival for patients with good liver function. McVI is a strong indicator of intrahepatic metastasis in HCC, but its relative significance for predicting clinical outcomes compared to the Milan criteria is unclear. Methods:Patients undergoing SR with curative intent from January 2000 to March 2009 at the Singapore General Hospital were followed up for long-term outcomes till January 1, 2010. They were stratified first by the Milan criteria and then by the presence of McVI and compared relative to OS. Results:Altogether, 454 of the 515 patients received curative SR. There were stratified into 4 groups (Milan+, McVI−), (Milan+, McVI+), (Milan−, McVI−), and (Milan−, McVI+). All pair-wise comparisons between groups relative to OS were significant except (Milan+, McVI−) (OS, 90%, 73%, and 60% at 1, 3, and 5 years) with (Milan−, McVI−) (OS, 86%, 71%, and 61% at 1, 3, 5 years) and (Milan+, McVI+) with (Milan−, McVI+). Multivariate Cox regression analysis showed that McVI was predictive of OS, after which Milan status did not add additional discriminative information. Conclusions:McVI is a better predictor of tumor recurrence and OS than the Milan criteria after SR for HCC. Assessment of McVI should aid in patient selection for adjuvant treatments to improve outcomes after SR.

Systematic review of outcomes of liver resection for early hepatocellular carcinoma within the Milan criteria

Long‐term overall survival after liver resection in patients with hepatocellular carcinoma (HCC) within the Milan criteria has been reported to improve in recent years. This study systematically reviewed the outcomes of surgical resection for HCC in patients with good liver function and meeting the Milan criteria for early HCC, published in the past 10 years.

Meteorological factors and El Niño Southern Oscillation are independently associated with dengue infections

Our objective was to determine the association between temperature, humidity, rainfall and dengue activity in Singapore, after taking into account lag periods as well as long-term climate variability such as the El Niño Southern Oscillation Index (SOI). We used a Poisson model which allowed for autocorrelation and overdispersion in the data. We found weekly mean temperature and mean relative humidity as well as SOI to be significantly and independently associated with dengue notifications. There was an interaction effect by periods of dengue outbreaks, but periods where El Niño was present did not moderate the relationship between humidity and temperature with dengue notifications. Our results help to understand the temporal trends of dengue in Singapore, and further reinforce the findings that meteorological factors are important in the epidemiology of dengue.

Ocular component growth curves among Singaporean children with different refractive error status.

PURPOSE To describe and compare ocular component growth curves among different refractive error groups in Singaporean children. METHODS Data collected yearly in 1775 Asian children aged 6 to 10 years with at least three visits were analyzed. Cycloplegic refractive error and biometry variables were measured by autorefractor and A-scan ultrasound machine. Growth curves were compared between five groups: persistent hyperopia of spherical equivalent (SE) > +1.00 D, emmetropizing hyperopia of SE > +1.00 D on the first visit and between -0.50 D and +1.00 D subsequently, persistent emmetropia of SE between -0.50 D and +1.00 D, incident myopia of SE <or= -0.50 D at subsequent visits, and persistent myopia of SE <or= -0.50 D. RESULTS The axial length and vitreous chamber elongated faster in the children younger than 10 years, but elongation slowed with age. Growth patterns of axial length and vitreous chamber in the children with newly developed or persistent myopia (P < 0.01) showed faster elongation than in the emmetropic children. The anterior chamber deepened until approximately 9 or 10 years of age but became shallower as the myopic and emmetropic children grew older. Conversely, the lens thinned at younger ages and thickened at older ages for all except the persistently hyperopic children. CONCLUSIONS In young Asian children, the axial length and vitreous chamber depth increased, but the elongation slowed with age. There was a U-shaped growth curve for lens thickness and an inverted U-shaped curve for anterior chamber depth. The findings of early lens thinning followed by thickening suggest a two-phase growth of the lens.

Visual impairment and its impact on health-related quality of life in adolescents.

PURPOSE To determine the impact of visual impairment on health-related quality of life (QoL) measures in adolescents. DESIGN School-based, cross-sectional study. METHODS Adolescents aged 11 to 18 years from the Singapore Cohort Study of the Risk Factors for Myopia were analyzed. QoL scores were determined using parallel child-self and parent proxy-report of PedsQL 4.0 Generic Core Scales. Refractive error was measured using the table-mounted autorefractor (model RK5 Canon Inc, Ltd, Tochigiken, Japan) and habitual distance logarithm of the minimal angle of resolution (logMAR) visual acuity charts were used. RESULTS Data on 1,249 adolescents and 948 parents were analyzed. The prevalence of better eye presenting visual impairment > 0.3 logMAR was 5.7%. The mean (standard deviation) total, physical, and psychosocial health scores of all adolescents were 83.6 (11.8), 89.9 (11.8), and 80.3 (13.7). Healthy adolescents with visual impairment reported statistically but not clinically lower total (-3.8; 95% confidence interval [CI], -7.1 to -0.5; P = .03), psychosocial (-4.2; 95% CI, -8.1 to -0.3; P = .03), and school functioning scores (-5.5, 95% CI, -10.2 to -0.9; P = .02) than those with normal vision. However, no significant difference was observed in the parent proxy-reported scores between the two groups. Differences in total scores between high (1.9; 95% CI, -0.6 to 4.4) and low-myopes (0.2; 95% CI, -1.3 to 1.6) compared with nonmyopes were not significant. Comparable scores were also reported by hyperopes, astigmatism, and their counterparts, as well as their parents. Concordance between child and parent proxy-report was < 0.07. CONCLUSION Healthy adolescents with visual impairment experienced statistically though not clinically impaired health related QoL, but refractive errors did not appear to have an impact on QoL.

Multicenter Phase II Study of Sequential Radioembolization-Sorafenib Therapy for Inoperable Hepatocellular Carcinoma

Background The safety and tolerability of sequential radioembolization-sorafenib therapy is unknown. An open-label, single arm, investigator-initiated Phase II study (NCT0071279) was conducted at four Asia-Pacific centers to evaluate the safety and efficacy of sequential radioembolization-sorafenib in patients with hepatocellular carcinoma (HCC) not amenable to curative therapies. Methods Sorafenib (400 mg twice-daily) was initiated 14 days post-radioembolization with yttrium-90 (90Y) resin microspheres given as a single procedure. The primary endpoints were safety and tolerability and best overall response rate (ORR) using RECIST v1.0.Secondary endpoints included: disease control rate (complete [CR] plus partial responses [PR] and stable disease [SD]) and overall survival (OS). Results Twenty-nine patients with Barcelona Clinic Liver Cancer (BCLC) stage B (38%) or C (62%) HCC received a median of 3.0 GBq (interquartile range, 1.0) 90Y-microspheres followed by sorafenib (median dose/day, 600.0 mg; median duration, 4.1 months). Twenty eight patients experienced ≥1 toxicity; 15 (52%) grade ≥3. Best ORR was 25%, including 2 (7%) CR and 5 (18%) PR, and 15 (54%) SD. Disease control was 100% and 65% in BCLC stage B and C, respectively. Two patients (7%) had sufficient response to enable radical therapy. Median survivals for BCLC stage B and C were 20.3 and 8.6 months, respectively. Conclusions This study shows the potential efficacy and manageable toxicity of sequential radioembolization-sorafenib. Trial Registration ClinicalTrials.gov NCT00712790.

Cost‐effectiveness analysis of liver resection versus transplantation for early hepatocellular carcinoma within the Milan criteria

Both liver resection (LR) and cadaveric liver transplantation (CLT) are potentially curative treatments for patients with hepatocellular carcinoma (HCC) within the Milan criteria and with adequate liver function. Adopting either as a first‐line therapy carries major cost and resource implications. The objective of this study was to estimate the relative cost‐effectiveness of LR against CLT for patients with HCC within the Milan criteria using a decision analytic model. A Markov cohort model was developed to simulate a cohort of patients aged 55 years with HCC within the Milan criteria and Child‐Pugh A/B cirrhosis, undergoing LR or CLT, and followed up over their remaining life expectancy. Analysis was performed in different geographical cost settings: the USA, Switzerland and Singapore. Transition probabilities were obtained from systematic literature reviews, supplemented by databases from Singapore and the Organ Procurement and Transplantation Network (USA). Utility and cost data were obtained from open sources. LR produced 3.9 quality‐adjusted life years (QALYs) while CLT had an additional 1.4 QALYs. The incremental cost‐effectiveness ratio (ICER) of CLT versus LR ranged from

A Randomized Phase II Trial of Single-Agent Gemcitabine, Vinorelbine, or Docetaxel in Patients with Advanced Non-small Cell Lung Cancer Who Have Poor Performance Status and/or Are Elderly

111,821/QALY in Singapore to

Elicitation of prior distributions for a phase III randomized controlled trial of adjuvant therapy with surgery for hepatocellular carcinoma.

156,300/QALY in Switzerland, and was above thresholds for cost‐effectiveness in all three countries. Sensitivity analysis revealed that CLT‐related 5‐year cumulative survival, one‐time cost of CLT, and post‐LR 5‐year cumulative recurrence rates were the most sensitive parameters in all cost scenarios. ICERs were reduced below threshold when CLT‐related 5‐year cumulative survival exceeded 84.9% and 87.6% in Singapore and the USA, respectively. For Switzerland, the ICER remained above the cost‐effectiveness threshold regardless of the variations. Conclusion: In patients with HCC within the Milan criteria and Child‐Pugh A/B cirrhosis, LR is more cost‐effective than CLT across three different costing scenarios: the USA, Switzerland, Singapore. (Hepatology 2015;61:227–237)

Confirmation of double-peaked time distribution of mortality among Asian breast cancer patients in a population-based study

Background: Patients with poor performance status and/or are elderly are frequently considered a compromised group at high risk of chemotherapy-related morbidities and less likely to benefit from treatment. We aimed to evaluate tolerability and efficacy of three single-agent regimens in these patients. Patients and Methods: Patients with advanced non-small cell lung cancer who had performance status 2/3 and/or were aged 70 and older were randomly assigned to receive gemcitabine, vinorelbine, or docetaxel. Objective response, toxicities, and quality of life were evaluated. Results: One hundred thirty-five patients were registered, of whom one was ineligible. Of the 134 patients, 43 received gemcitabine, 45 vinorelbine, and 46 docetaxel. The response rate was 16%, 20%, 22% for gemcitabine, vinorelbine, and docetaxel, respectively. The main grade 3/4 toxicities were fatigue (18%) and neutropenia (16%). There was improvement in global health scores, cough, and dyspnea for all treatment groups. The improvement in dyspnea was most marked in patients with performance status 3. Conclusion: There was no significant advantage of any of the treatment arms over the rest. There was benefit seen with improvement of quality of life in patients who were able to receive more cycles of chemotherapy.