Background. The inconsistent finding was between hepatitis B virus (HBV) infections and cholangiocarcinoma (CCA). This meta-analysis is to explore this relationship in Asia. Methods. A literature search was performed using PubMed, Web of Science, and Cochrane Library to October 30, 2015. Pooled incidence rate and OR with 95% CI were calculated using STATA 11.0. Results. Thirty-nine studies were included. The pooled incidence rate of CCA patients with HBV infection was 31% (95% CI 22%-39%). The pooled OR showed increased risk of CCA incidence with HBV infection (OR = 2.72, 95% CI 1.90-3.88), especially in ICC (OR = 3.184, 95% CI 2.356-4.302), while it showed no risk in ECC (OR = 1.407, 95% CI 0.925-2.141). Also, the pooled OR showed increased risk of ICC and ECC incidence (OR = 6.857, 95% CI 4.421-10.633 and OR = 1.740, 95% CI 1.260-2.404) in patients with HBsAg+/HBcAb+. The pooled OR showed increased risk of ICC incidence (OR = 1.410, 95% CI 1.095-1.816) in patients with HBsAg-/HBcAb+. Conclusion. It is suggested that HBV infection is associated with an increased risk of CCA in Asia. Two HBV infection models (HBsAg+/HBcAb+ and HBsAg-/HBcAb+) increase the risk of CCA, and patients with HBsAg-/HBcAb+ also had a risk of ICC. This trial is registered with PROSPERO CRD42015029264.

BACKGROUND: Liver cancer exhibits geographic and ethnic differences in its prevalence and biology, which implies that it is impractical to develop universal guidelines for all patients. Thus, a meta-analysis was conducted to identify the accuracy of apparent diffusion coefficients (ADCs) for discriminating malignant from benign liver lesions in Asians.
METHODS: Eligible studies published in PubMed, Ovid, and Embase/Medline were updated onto October 2014. STATA 12.0 and Meta-Disc 1.4 were used to perform this meta-analysis.
RESULTS: Eight studies comprising 661 benign liver lesions and 598 malignant liver lesions fulfilled all the inclusion criteria. The pooled sensitivity, specificity, positive likelihood ratio, negative likelihood ratio, and diagnostic odds ratio were 0.88 (95% confidence interval [CI] 0.75-0.95), 0.93 (95% CI 0.86-0.97), 12.42 (95% CI 6.09-25.31), 0.13 (95% CI 0.06-0.29), and 95.58 (95% CI 35.29-258.89), respectively. Overall, the area under the summary receiver-operating characteristic curve was 0.96 (95% CI 0.94-0.98). Heterogeneity was found to originate potentially from the type of benign lesion. A subgroup analysis showed that differentiating between hemangiomas, cysts, and malignant liver lesions produced a significantly higher diagnostic accuracy than that of solid liver lesions.
CONCLUSION: Our meta-analysis indicated that ADC could be promising for characterizing liver lesions among Asians, indicating that the ADC value is a promising diagnostic criterion candidate. Meanwhile, the use of dual b values could be sufficient for liver lesion characterization. However, large-scale, high-quality trials should be conducted to identify specific standards, including cut-off values for further development of diffusion-weighted imaging as a routine clinical application among Asian populations.

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.

BACKGROUND: The cancer mortality-to-incidence ratio (MIR) has been established as an important measure of health disparities in local and global circumstances. Past work has corroborated a linkage between the colorectal cancer MIR and the World Health Organization (WHO) Health System ranking. The literature further documents many Asian countries having incomplete cancer registries and a lack of comprehensive colorectal cancer screening guidelines.
MATERIALS AND METHODS: The colorectal cancer MIR values for 23 Asian countries were calculated from data obtained from the 2012 GLOBOCAN database. The 2000 World Health Organization (WHO) Health System rankings were used as a proxy for health system infrastructure and responsiveness. A regression equation was calculated with the MIR as the dependent variable and the WHO Health System ranking as the independent variable. Predicted MIR values were next calculated based on the regression results. Actual MIR values that exceeded 0.20 from the predicted MIR were removed as 'divergent'points. The regression equation was then re-plotted. Goodness-of-fit for both regressions was assessed by the R-squared test.
RESULTS: Asian countries have a relatively wide colorectal cancer MIR range, from a minimum of 0.24 to a maximum of 0.86. For the full dataset, the adjusted R-squared value for this regression was 0.53. The equation was then used to calculate a predicted MIR, whereby two data points were identified as 'divergent' and removed. The adjusted R-squared for the edited dataset increased to 0.66.
CONCLUSIONS: Asian countries have a marked range in their colorectal cancer MIR values and there is a strong correlationwith the WHO Health System ranking. These results corroborate the contribution of the MIR as a potentially robust tool in monitoring changes in colorectal cancer care for Asian nations.

BACKGROUND: Testicular cancer is one of the most common cancers among young men between ages 20-34 in countries with high or very high levels of the Human Development Index (HDI). This study investigated the incidence and mortality of prostate cancer and the relationship with the HDI and its dimensions in Asia in 2012.
MATERIALS AND METHODS: The study was conducted based on data from the world data of cancer and the World Bank (including the HDI and its components). Standardized incidence and mortality rates of testicular cancer were calculated for Asian countries. Correlations between incidence and/ormortality rates, and the HDI and its components were assessed with the use of the correlation test, using SPSS software.
RESULTS: There was a total of 14902 incidences and 5832 death were recorded in Asian countries in 2012. Among the Asian countries, the five countries with the highest standardized incidence rates of testicular cancer were Israel, Georgia, Turkey, Lebanon and Kazakhstan and the five countries with the highest standardized mortality rates were Turkey, Georgia, Jordan, Cambodia and the Syrian Arab Republic. A positive correlation of 0.382 was observed between the standardized incidence rates of testicular cancer and the HDI (p=0.009). Also a negative correlation of 0.298 between the standardized mortality rate of testicular cancer and the Human Development Index was noted although this relation was statistically non-significant (p=0.052).
CONCLUSIONS: There is a positive correlation between HDI and the standardized incidence rate of testicular cancer and negative correlation with standardized mortality rate.

Sonidegib is a selective inhibitor of Smoothened receptor, which is a key regulator of the Hedgehog signaling pathway. The purpose of this study was to determine the maximum tolerated dose based on dose-limiting toxicity (DLT) and the recommended dose (RD) of sonidegib in Asian patients with advanced solid tumors. This was an open-label, single-arm, multicenter, two-group, parallel, dose-escalation, phase I study undertaken in Asian patients; group 1 included patients from Japan and group 2 included patients from Hong Kong and Taiwan. Dose escalation was guided by a Bayesian logistic regression model dependent on DLTs in cycle 1 and other safety findings. A total of 45 adult Asian patients with confirmed advanced solid tumors were enrolled. Group 1 included 21 patients (12 treated with 400 mg q.d. [once daily] and 9 treated with 600 mg q.d.) and group 2 included 24 patients (12 treated with 400 mg q.d., 8 treated with 600 mg q.d., and 4 treated with 800 mg q.d.). Elevation in creatine kinase was the DLT in both groups. The most common adverse events suspected to be related to sonidegib in both patient groups were increase in creatine kinase levels, myalgia, fatigue, and abnormal hepatic function. The RD of 400 mg q.d. was defined in both groups. Difference in tolerability was noted between the East Asian patients and Western population. The RD in East Asian patients (400 mg q.d.) was lower than in patients from Europe and the USA (800 mg q.d. and 250 mg twice daily). (Registered with Clinicaltrials.gov: NCT01208831.).

BACKGROUND: Some risk classifications to determine prognosis of patients with non-muscle invasive bladder cancer (NMIBC) have disadvantages in the clinical setting. We investigated whether the EORTC (European Organization for Research and Treatment of Cancer) risk stratification is useful to predict recurrence and progression in Japanese patients with NMIBC. In addition, we developed and validated a novel, and simple risk classification of recurrence.
METHODS: The analysis was based on 1085 patients with NMIBC at six hospitals. Excluding recurrent cases, we included 856 patients with initial NMIBC for the analysis. The Kaplan-Meier method with the log-rank test were used to calculate recurrence-free survival (RFS) rate and progression-free survival (PFS) rate according to the EORTC risk classifications. We developed a novel risk classification system for recurrence in NMIBC patients using the independent recurrence prognostic factors based on Cox proportional hazards regression analysis. External validation was done on an external data set of 641 patients from Kyorin University Hospital.
FINDINGS: There were no significant differences in RFS and PFS rates between the groups according to EORTC risk classification. We constructed a novel risk model predicting recurrence that classified patients into three groups using four independent prognostic factors to predict tumour recurrence based on Cox proportional hazards regression analysis. According to the novel recurrence risk classification, there was a significant difference in 5-year RFS rate between the low (68.4%), intermediate (45.8%) and high (33.7%) risk groups (P<0.001).
INTERPRETATION: As the EORTC risk group stratification may not be applicable to Asian patients with NMIBC, our novel classification model can be a simple and useful prognostic tool to stratify recurrence risk in patients with NMIBC.
FUNDING: None.

We aimed to validate the liver fibrosis index FIB-4 as a model for risk stratification of hepatocellular carcinoma development in predominantly non-Asian patients with chronic hepatitis B infection seen at a tertiary referral center in Germany.We retrospectively analyzed 373 adult patients with chronic hepatitis B infection. Patient demographics, hepatitis B markers, antiviral treatment, laboratory parameters, results from liver imaging and histology were recorded. Patients were divided into 2 groups according to their FIB-4 levels and their hazard ratios for developing hepatocellular carcinoma were analyzed adjusted for age, sex, body mass index, alcohol consumption, and antiviral medication.Median follow-up was 8.7 years (range 1-21.3 years), 93% of patients were of non-Asian origin, and 64% were male. Compared with patients with a low FIB-4 (<1.25) patients with FIB-4 ≥1.25 showed a hazard ratio for incidence of hepatocellular carcinoma of 3.03 (95% confidence interval (CI): 1.24-7.41) and an adjusted hazard ratio of 1.75 (95% CI: 0.64-4.74). Notably, 68% of patients with liver cirrhosis and 68% of those who developed HCC during observation had a low FIB-4 (<1.25).We could not confirm that a FIB-4 value ≥1.25 is a reliable clinical indicator for incidence of hepatocellular carcinoma in predominantly non-Asian patients with chronic hepatitis B. Further studies in geographically and ethnically diverse populations are needed to prove its utility as a predictive tool.

BACKGROUND: The aim of this study was to evaluate the incidence and mortality of stomach cancer, and its relationship with the Human Development Index (HDI) and its components in Asia in 2012.
MATERIALS AND METHODS: This ecological study was conducted based on GLOBOCAN project of WHO for Asian countries. We assessed the correlations between standardized incidence rates (SIR) and standardized mortality rates (SMR) of stomach cancer with HDI and its components using SPSS18.
RESULTS: A total of 696,231 cases (68.7% in males and 31.3% in females, ratio of 2.19:1) and 524,465 deaths (67.1% in men and 33.0% in women, ratio 2.03:1) were included in 2012. Five countries with the highest SIR of stomach cancer were Republic Korea, Mongolia, Japan, China and Tajikistan. Five countries with the highest SMR of stomach cancer were Mongolia, Tajikistan, Kyrgyzstan, Kazakhstan and China. Correlation between HDI and SIR was 0.241 (p = 0.106), in men 0.236 (p = 0.114) and in women -0.250 (p = 0.094). Also between HDI and SMR -0.250 (p = 0.871) in men -0.018 (p = 0.903) and in women -0.014 (p = 0.927).
CONCLUSIONS: No significant correlation was observed between the SIR of stomach cancer, and the HDI and its dimensions, such as life expectancy at birth, mean years of schooling, and income level of the population.

BACKGROUND: Genetic aetiology of pheochromocytoma (PCC) and paraganglioma (PGL) is increasingly being studied; however, Asian Indian data on this aspect are scarce.
OBJECTIVE: To study the prevalence of germline mutations and genotype-phenotype correlation in Asian Indian PCC/PGL patients.
DESIGN: In this study, 150 index patients (M:F, 73:77) with PCC/PGL were evaluated. Phenotypic data were collected. Germline mutations in five susceptibility genes (RET, VHL, SDHB, SDHD and SDHC) were tested by sequencing and NF1 was diagnosed according to phenotype.
RESULT: Of the total population, 49 (32.7%) PCC/PGL patients had germline mutations (VHL: 23 (15.3%), RET: 13 (8.7%), SDHB: 9 (6%), SDHD: 2 (1.3%) and NF1: 2 (1.3%)). Amongst the 30 patients with familial and/or syndromic presentation, all had germline mutations (VHL: 14 (46.7%), RET: 13 (43.3%), SDHB: 1 (3.3%) and NF1: 2 (6.7%)). Out of 120 patients with apparently sporadic presentation, 19 (15.8%) had a germline mutation (VHL: 9 (7.5%), SDHB: 8 (6.7%) and SDHD: 2 (1.7%)). Mutation carriers were younger (29.9 ± 14.5 years vs 36.8 ± 14.9; P = 0.01) and had a higher prevalence of bilateral PCC (26.5% vs 2.9%, P < 0.001) and multifocal tumours (12.2% vs 0.96%, P = 0.06). Based on syndromic features, metastasis, location and number of tumours, around 96% mutations in our cohort could be detected by appropriately selected single gene testing.
CONCLUSION: Asian Indians with PCC/PGL differ from Western cohorts in having preponderance of VHL mutations in multifocal tumours and apparently sporadic unilateral PCC. Syndromic presentation, metastasis, location and number of PCC/PGL can be effectively used for guiding genetic prioritisation.

BACKGROUND: Breast cancer is the second most common cancer in women in Cambodia, a low income country in SouthEast Asia. The Sihanouk Hospital Centre of Hope (SHCH) is a charity hospital set up by an international nongovernmental organisation, HOPE Worldwide. In 2008, SHCH partnered with AmeriCares, a global health organisation to set up and deliver a breast cancer programme to provide education, diagnosis and treatment for women with breast cancer. The objective of this study is to characterise the presentation, diagnosis, treatment and outcomes of women treated under this program.
MATERIALS AND METHODS: A total of 215 women newly diagnosed with breast cancer from 1 March 2008 until 31 March 2011 were studied. Age at diagnosis, tumour size, histological type, tumour grade, ER, lymph node involvement, treatment modalities (surgery, radiotherapy, chemotherapy, hormone therapy) were recorded. Data on mortality at 3 years were obtained whenever possible.
RESULTS: The median age was 47 years old. Some 77.8% were diagnosed with stage 3 and 4 lesions, and 78.5% underwent mastectomy, of which 28.4% the intent was palliative. Of those whose ER status were known, only 48.3% were ER positive. Only 6 patients could afford chemotherapy while only 1 patient had radiotherapy. Hormone therapy was provided free for those who were ER positive. The overall survival rate at 3 years was 39.1%.
CONCLUSIONS: Breast cancer presents at a late stage, and because treatment is suboptimal, survival is poor in Cambodia. A more aggressive approach to early detection and treatment needs to be developed to improve outcome from this potentially curable disease.

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.

BACKGROUND: The incidence of lung adenocarcinoma (LUAD) is increasing worldwide with different prognosis even in early-stage patients. We aimed to identify a prognostic panel with multiple DNA methylation biomarkers to predict survival in early-stage LUAD patients of different racial groups.
METHODS: The methylation array, pyrosequencing methylation assay, Cox regression and Kaplan-Meier analyses were conducted to build the risk score equations of selected probes in a training cohort of 69 Asian LUAD patients. The risk score model was verified in another cohort of 299 Caucasian LUAD patients in The Cancer Genome Atlas (TCGA) database.
RESULTS: We performed a Cox regression analysis, in which the regression coefficients were obtained for eight probes corresponding to eight genes (AGTRL1, ALDH1A3, BDKRB1, CTSE, EFNA2, NFAM1, SEMA4A and TMEM129). The risk score was derived from sum of each methylated probes multiplied by its corresponding coefficient. Patients with the risk score greater than the median value showed poorer overall survival compared with other patients (p = 0.007). Such a risk score significantly predicted patients showing poor survival in TCGA cohort (p = 0.036). A multivariate analysis was further performed to demonstrate that the eight-probe panel association with poor outcome in early-stage LUAD patients remained significant even after adjusting for different clinical variables including staging parameters (hazard ratio, 2.03; p = 0.039).
CONCLUSIONS: We established a proof-of-concept prognostic panel consisting of eight-probe signature to predict survival of early-stage LUAD patients of Asian and Caucasian populations.

AIM: There is an increased prevalence of anxiety and depression in Asian patients diagnosed with cancers; these are known to interfere with treatment, treatment adherence and mortality. This study sought to investigate the prevalence and predictors of subsyndromal anxiety and depression in first-year Asian cancer patients.
METHODS: A total of 206 patients newly diagnosed with cancer in Singapore completed the Hospital Anxiety and Depression Scale (HADS) at T1 (baseline; on average 2 months post-diagnosis), T2 (3 months post-baseline) and T3 (6 months post-baseline). Subsyndromal anxiety and depression were identified using locally validated cut-offs (HADS-A ≥5 and HADS-D ≥7). Adjusted odds ratios were calculated using baseline predictors.
RESULTS: Across the three time points, 68-69% of participants were identified as having subsyndromal anxiety and close to 27-38% participants were identified as having subsyndromal depression. Multivariate logistic regressions revealed a lack of predictors for T1 subsyndromal anxiety and depression. Participants with late/metastatic stages of cancer were almost four times as likely to suffer from subsyndromal anxiety at T2. Single participants had a 75% lowered odds, but those living in three to four room public housing were close to four times as likely to suffer from subsyndromal depression at T2. Older patients and those who had undergone surgery were found to significantly suffer from subsyndromal depression at T3.
CONCLUSION: The significant levels of depression and anxiety coupled with the lack of consistent predictors across the first year following cancer diagnosis further underscore the importance of careful assessment and clinician-vigilance in recognizing and identifying Asian patients who may express these emotional sequelae following the cancer diagnosis. A better understanding of patients' pathophysiological and psychological responses and individual strengths and coping skills are thus essential.

Several retrospective analyses on patients who underwent gastric cancer (GC) surgery revealed different survival outcomes between Eastern (Korean, Japanese) and Western (USA, Europe) countries due to potential ethnical and biological differences. This study investigates treatment outcomes between specialized institution for GC in Korea and Germany.The prospectively documented databases of the Gastric Cancer Center of the National Cancer Center, Korea (NCCK) and the Department of Surgery of the Technische Universitaet Muenchen (TUM), Germany were screened for patients who underwent primary surgical resection for GC between 2002 and 2008. Baseline characteristics were compared using χ testing, and 2 cohorts were matched using a propensity score matching (PSM) method. Patients' survival was estimated using Kaplan-Meier method, and multivariable Cox proportional hazard model was used for comparison.Three thousand seven hundred ninety-five patients were included in the final analysis, 3542 from Korea and 253 from Germany. Baseline characteristics revealed statistically significant differences for age, tumor location, pT stage, grading, lymphatic vessel infiltration (LVI), comorbidities, number of dissected lymph nodes (LN), postoperative complications, lymph-node ratio stage, and application of adjuvant chemotherapy. After PSM, 171 patients in TUM were matched to NCCK patients, and baseline characteristics for both cohorts were well balanced. Patients in Korea had significantly longer survival than those in Germany both before and after PSM. When the analysis was performed for each UICC stage separately, same trend was found over all UICC stages before PSM. However, significant difference in survival was observed only for UICC I after PSM.This analysis demonstrates different survival outcomes after surgical treatment of GC on different continents in specialized centers after balancing of baseline characteristics by PSM.

INTRODUCTION: A paradigm shift appears to have occurred worldwide in surgery for primary hyperparathyroidism with the advent of sensitive preoperative imaging techniques. Preoperative imaging for parathyroid adenoma localisation was not found to be useful in a study conducted in Singapore in the 1990s. This study aimed to explore what the change has been in preoperative localisation tools compared to the previous study and if the ability of these tools to correctly localise pathologic parathyroid glands has improved.
MATERIALS AND METHODS: A retrospective review of patients who had surgery for primary hyperparathyroidism at our institution during the period 2005 to 2014 was carried out. Individuals with positive, as opposed to those with negative preoperative imaging, were compared with regard to whether they underwent limited focal or bilateral neck exploration. Length of hospital stay (LOHS) was also compared between patients who underwent limited versus bilateral exploration.
RESULTS: Fifty-eight patients who had preoperative imaging and surgery were evaluated. True positive rates of sestamibi, ultrasound and 4-dimensional (4D) computed tomography (CT) scans were 63.8%, 72.4% and 90%, respectively. Eighty percent of patients who had positive localisation had limited exploration. LOHS was 2.8 days (1.6, 4.8) and 4.3 days (2.1, 9.0) for limited and bilateral exploration respectively, P = 0.011.
CONCLUSION: Our study highlights the marked change in the surgical landscape for primary hyperparathyroidism in the last 2 decades in Singapore. Improved preoperative localisation has resulted in a swing from predominantly bilateral, to limited exploration in almost all cases of primary hyperparathyroidism due to solitary adenoma. LOHS was significantly shorter in patients who had limited as compared to those who had bilateral exploration.

AIM: Current estimates of the human epidermal growth factor receptor 2 (HER2)-positivity rate in breast cancer are largely based on studies from the United States, Europe and Australia, and might not reflect the rate among breast cancer patients in Asia. The primary aim of this study was to conduct a clinical audit of laboratories across eight countries in Asia to determine the incidence of HER2-positive breast cancer in this region.
METHODS: Pathology laboratories submitted data on breast cancers consecutively tested for HER2 over a two-year period. The proportion of HER2-positive, -equivocal and -negative tumors was determined for each country and overall. HER2-positivity rate by age and histological grade was also determined.
RESULTS: HER2 results from 30 179 breast cancers were submitted by 96 laboratories. The overall HER2-positivity rate was 23.5%; the rate between countries ranged from 19.7% to 44.2%, and from 4.4% to 51.6% between laboratories. An equivocal HER2 result was recorded in 18.2% of cases. Discrepancies between laboratories suggest that testing expertise contributes to variations seen in HER2 status across laboratories, as well as the generally higher rate of HER2-positivity that was recorded.
CONCLUSION: In this study, the incidence of HER2-positive breast cancer diagnosed in Asian women was higher than published studies on women from Western countries. In addition, the study found that women in Asian countries presented with breast cancer at an earlier age, with a higher histological grade. This study serves to highlight the challenges with HER2 testing and data collection in a large multicenter Asian cohort.

Numerous studies regarding the association between the CYP1A1 MspI polymorphism and oral cancer risk in Asian populations have shown controversial results. To get a more precise estimation of this relationship, we conducted a comprehensive meta-analysis. PubMed, the Cochrane Library, Elsevier Science Direct, Web of Knowledge, the Chinese National Knowledge Infrastructure, VIP, and Wan Fang Med Online were searched. Pooled odds ratios (ORs) with 95% confidence intervals (95%CIs) were calculated using fixed-effects or random-effects models. Heterogeneity among studies was assessed using the Cochran Q test and I(2) statistics. Twelve articles including 1925 oral cancer patients and 2335 controls were ultimately included in the meta-analysis. Overall, the meta-analysis showed that the CYP1A1 MspI polymorphism was associated with oral cancer risk in Asians (m1/m1 vs m2/m2: OR = 0.46, 95%CI = 0.30-070, POR = 0.000; m1/m1 vs m1/m2+m2/m2: OR = 0.70, 95%CI = 0.51-0.98, POR = 0.037; m1/m1+m1/m2 vs m2/m2: OR = 0.48, 95%CI = 0.35-0.65, POR = 0.000). Subgroup analyses showed that the control source (hospital-based or population-based), the genotyping method [polymerase chain reaction (PCR) or PCR-restriction fragment length polymorphism], the country in which the study was conducted, and Hardy-Weinberg equilibrium (Yes or No) were positively related to the association. Sensitivity analysis suggested that the overall results showed no significant change in three genetic models when any one study was removed, and publication bias was undetected by the Egger test. The CYP1A1 MspI polymorphism may be associated with oral cancer risk in Asian populations.

AIM: PROCLAIM, a phase III trial of patients with nonsquamous non-small cell lung cancer comparing concurrent pemetrexed-cisplatin and thoracic radiation therapy followed by consolidation pemetrexed, did not meet its primary endpoint of superior overall survival versus etoposide-cisplatin and thoracic radiation therapy followed by a consolidation platinum doublet of choice. The results from an East Asian subgroup analysis are presented here.
METHODS: A subgroup analysis was performed for all patients randomized from China (n = 61), Taiwan (n = 25), and Korea (n = 11).
RESULTS: Baseline characteristics were balanced between treatment arms for East Asian patients. In the 97 randomized East Asian patients, median overall survival was 26.8 months for the pemetrexed-cisplatin arm and 36.3 months for the etoposide-cisplatin arm (hazard ratio: 1.23; 95% confidence interval: 0.70-2.14; P = 0.469). Median progression-free survival was 10.0 months for the pemetrexed-cisplatin arm and 7.6 months for the etoposide-cisplatin arm (hazard ratio: 0.97; 95% confidence interval: 0.61-1.54; P = 0.890). The objective response rate was 47.7% in the pemetrexed-cisplatin arm and 34.0% in the etoposide-cisplatin arm (P = 0.167). In the 90 treated East Asian patients, the overall incidence of drug-related grade 3-4 treatment-emergent adverse events was significantly lower in the pemetrexed-cisplatin arm versus the etoposide-cisplatin arm (61.4% vs 91.3%; P = 0.001).
CONCLUSION: For East Asian patients, pemetrexed-cisplatin combined with thoracic radiation therapy, followed by consolidation pemetrexed, did not improve overall survival but did have a good safety profile with a trend for improved progression-free survival and objective response rate compared to standard chemoradiotherapy for stage III unresectable nonsquamous non-small cell lung cancer.

OBJECTIVES: We report a case of hemophagocytosis-related (Asian variant) intravascular large B-cell lymphoma (IVLBCL) in a patient of Western origin initially diagnosed by splenectomy with diffuse large B-cell lymphoma (DLBCL) with a micronodular pattern. The clonal relationship between these two DLBCL subtypes is also investigated.
METHODS: Hemophagocytosis-related (Asian variant) IVLBCL was identified at autopsy in a 62-year-old Hispanic woman, in North America, following an antemortem diagnosis of massive splenic involvement by DLBCL with a micronodular pattern, a feature not expected of IVLBCL.
RESULTS: These two apparently distinct lymphoma types demonstrated similar immunophenotypic profiles and IgH gene rearrangements of identical size suggesting a clonal relationship. The 2008 WHO classification system describes IVLBCL in the spleen as having a sinusoidal pattern.
CONCLUSIONS: Our observations provide the first molecular genetic support for a seemingly underrecognized micronodular pattern of IVLBCL in the spleen and further support the proposal of a "mixed variant" of IVLBCL with concomitant "intravascular" and "solid" phases of disease.

BACKGROUND: The purpose of this study was to present our experience with robot-assisted radical prostatectomy (RARP) for localized prostate cancer in renal transplant recipients (RTRs) and to determine the feasibility and efficacy of RARP in these patients.
METHODS: We retrospectively reviewed the medical records of 236 patients who underwent RARP for localized prostate cancer at our institution between August 2011 and July 2015 and identified 3 patients who were RTRs. We reviewed the available clinical data of the 3 patients.
RESULTS: All patients underwent RARP successfully without any major complications. The mean operation time was 162 minutes (range, 127-195 minutes). The mean estimated blood loss was 52 mL (range, 30-75 mL); therefore, the patients did not need any perioperative blood transfusion. In all cases, graft function, as determined according to the serum creatinine level, was stable during and after the operation. Pathological examination showed negative surgical margins with organ-confined disease in all patients.
CONCLUSIONS: We reported 3 RTRs with localized prostate cancer who were treated with RARP. RARP might be a feasible and effective minimally invasive technique for the treatment of localized prostate cancer in carefully selected RTRs.

Bladder cancer is the 8th most common cancer with 74,000 new cases in the United States in 2015. Non-muscle invasive bladder cancer (NMIBC) accounts for 75% of all bladder cancer cases. Transurethral resection and intravesical treatments remain the main treatment modality. Up to 31-78% of cases recur, hence the need for intensive treatment and surveillance protocols which makes bladder cancer one of the most expensive cancers to manage. The purpose of this review is to compare contemporary guidelines from Europe, (European Association of Urology), the United States (National Comprehensive Cancer Network), the United Kingdom (National Institute for Health and Care Excellence), Japan (Japanese Urological Association) and the International Consultation on Bladder Cancer (ICUD). We compare and contrast the different guidelines and the evidence on which their recommendations are based.

BACKGROUND: Liver cancer (LC) is the sixth world most common cancer and the second leading cause of cancer death. Due to the importance and necessity of awareness about the incidence and mortality of diseases to perform prevention programs, this study focused on data for LC and its relationship with the human development index (HDI) and its components in Asia in 2012.
MATERIALS AND METHODS: This ecological study was based on GLOBOCAN data for Asian countries. We assessed correlations between standardized incidence rates (SIR) and standardized mortality rates (SMR) of LC with HDI and its components using of SPSS18.
RESULTS: A total of 582,420 incident cases and 557,097 deaths were recorded in Asian countries in 2012. The five with the highest SIR were Mongolia, Lao PDR, Vietnam, Republic of Korea and Thailand and those with the highest SMR were Mongolia, Lao PDR, Vietnam, Cambodia and Thailand. A negative relation was observed between HDI and LC for SIR of 0.049 (P=0.748) and for SMR of 0.07 (P=0.645), with life expectancy at birth a positive relation for SIR of 0.061 (P=0.687) and a negative relation for SMR of 0.079 (P=0.603), with the average years of education a negative relation fo SIR of 0.476 (p=0.952) and for SMR of 0.032 (P=0.832), and with the country income level per person a negative relation for SMI of 0.11 (p=0.465) and for SMR of 0.113 (P=0.455).
CONCLUSIONS: The incidence of LC is more in less developed and developing countries but statistically significant correlations were not found between standardized incidence and mortality rates of LC, and HDI and its dimensions.

Breast cancer is the most common malignancy in women around the world. Information on the incidence and mortality of breast cancer is essential for planning health measures. This study aimed to investigate the incidence and mortality of breast cancer in the world using age-specific incidence and mortality rates for the year 2012 acquired from the global cancer project (GLOBOCAN 2012) as well as data about incidence and mortality of the cancer based on national reports. It was estimated that 1,671,149 new cases of breast cancer were identified and 521,907 cases of deaths due to breast cancer occurred in the world in 2012. According to GLOBOCAN, it is the most common cancer in women, accounting for 25.1% of all cancers. Breast cancer incidence in developed countries is higher, while relative mortality is greatest in less developed countries. Education of women is suggested in all countries for early detection and treatment. Plans for the control and prevention of this cancer must be a high priority for health policy makers; also, it is necessary to increase awareness of risk factors and early detection in less developed countries.

OBJECTIVES: First, to evaluate awareness of oral cancer amongst the young South-Asian community in London and identify any aspects of knowledge about oral cancer that are lacking; and, second, to determine whether demographic factors or health-related behaviours are associated with knowledge of oral cancer.
RESEARCH DESIGN: Cross-sectional questionnaire survey.
PARTICIPANTS: South Asians aged 18-44 years attending community centres or places of worship in London.
MAIN OUTCOME MEASURES: Oral cancer awareness; health-related behaviours.
RESULTS: Respondents (n = 201) were mainly male (61%), Indian (77%) and Hindu (35%). Over half (58%; n = 113) had one or more negative health-related behaviours and only 18% had attended a dentist in the previous two years. Chewing paan with betel nut (OR = 4.08, 95% CI = 1.58-10.59, p < 0.01), and time since last visit to a dentist (OR = 4.90, 95% CI = 2.13-11.28, p < 0.01) were independently associated with respondents level of knowledge of mouth cancer; the former positively and the latter negatively.
CONCLUSIONS: The results suggest that young adults in the South Asian Community are exposed to a number of risk factors for oral cancer yet have poor knowledge of the implications of these health-related behaviours, and ways in which oral cancer can be detected earlier. The survey highlighted specific issues for action.

Pancreatic cancer (PC) is known to be frequently associated with venous thromboembolism (VTE). Although treatment and prophylaxis strategies for VTE in PC patients were updated recently, these were mainly based on data from Western populations and were not verified in East Asian ethnic populations.We investigated the clinical characteristics of VTE in East Asian PC patients. We reviewed electronic medical records (EMR) of 1334 patients diagnosed with pancreatic adenocarcinoma from 2005 to 2010 at single tertiary hospital in Korea. All the patients with newly diagnosed VTE were classified by anatomical site and manifestation of symptoms. The primary outcomes of interest were 2-year cumulative incidence of VTE events. Cox proportional hazards models were used to analyze associations between risk factors and clinical outcomes.A total of 1115 patients were eligible for enrollment. The 2-year cumulative VTE incidence was 9.2%. Major risk factors associated with VTE event were advanced cancer stage, major surgery, and poor performance status. Risk factors associated with mortality after PC diagnosis included advanced cancer stage, poor performance score, leukocytosis, and lower albumin level. The overall VTE did not affected mortality. However in subgroup analysis, symptomatic VTE and deep vein thrombosis/pulmonary thromboembolism (DVT/PTE) showed worse prognosis than incidental or intra-abdominal VTE.The overall incidence of VTE events in Korean PC patients was lower than previous studies. Advanced cancer stage was the most important factor for VTE event and mortality. Unlike Western population group, VTE event did not affect overall prognosis after PC diagnosis. However, symptomatic VTE and DVT/PTE showed higher mortality after VTE event.

BACKGROUND: Migration to the UK has increased considerably, which is reflected in the diverse multicultural population which includes asylum seekers and economic migrants. Differences in ethnic and cultural values between the host and newcomer populations could impact on effective health care provision, especially in gender-biased conditions such as breast cancer. Breast cancer is rare in men and the diagnosis is often met with disbelief. This case report describes an unusual case of breast cancer in an Afghan man who is an asylum seeker of Asian ethnic origin.
CASE PRESENTATION: A focused ethnographic case study and in-depth interview was used to gain qualitative data and insight into the personal experiences of a male Afghan asylum seeker, age unknown (estimated to be in his 30s), with post-traumatic stress disorder who was electively admitted into hospital for the investigation of a suspicious lump in his left breast, which was subsequently found to be breast cancer. He was extremely reluctant to accept a breast cancer diagnosis and initially would not consent to any treatment, preferring to seek further opinion. During consultation with various members of the breast team he continually declined to accept the diagnosis and felt there was an error in the investigative protocol. Through the involvement of a Muslim nurse, fluent in Urdu and knowledgeable of the Afghan culture and religious background, we learned about his experiences and feelings; he opened up to her about his experiences in Afghanistan, detailing his experiences of trauma as a result of war, and disclosing that he had been diagnosed as having post-traumatic stress disorder by his physician. He saw breast cancer as a "woman's disease" which deeply affected his feelings of masculinity and left him feeling vulnerable.
CONCLUSIONS: While sensitivity is undoubtedly required when diagnosing gender-biased conditions such as breast cancer in men, our experience showed this is exacerbated in ethnic minority groups where language barriers often exist and awareness of cultural differences is required. Awareness of the possibility of post-traumatic stress disorder in migrant populations from conflict-torn areas is also recommended during consultation.

PURPOSE: This study describes variations in mammography and Pap test use across and within subgroups of Asian women in the USA.
METHODS: Using data from the National Health Interview Survey (2008, 2010, and 2013), we calculated weighted proportions for selected Asian subgroups (Asian Indian, Chinese, Filipino, Other Asian) of women reporting mammography and Pap test use.
RESULTS: The proportion of women aged 50-74 years who reported a mammogram within the past 2 years did not differ significantly across Asian subgroups. The proportion of women aged 21-65 years who received a Pap test within the past 3 years differed significantly across Asian subgroups, with lower proportions among Asian Indian, Chinese, and Other Asian women. Recent immigrants, those without a usual source of care, and women with public or no health insurance had lower proportions of breast and cervical cancer screening test use.
CONCLUSIONS: Patterns of mammography and Pap test use vary among subgroups of Asian women, by length of residency in the USA, insurance status, usual source of care, and type of cancer screening test. These findings highlight certain Asian subgroups continue to face significant barriers to cancer screening test use.

The Japan National Committee for the Union for International Cancer Control (UICC) and UICC - Asia Regional Office organized an international session as part of the 74th Annual Meeting of the Japanese Cancer Association on the topic "What are the implications of sharing the concept of Universal Health Coverage for cancer in Asia?" Universal Health Coverage (UHC) is included in the United Nations' Sustainable Development Goals and aims to ensure that all people can receive high-quality medical services, are protected from public health risks, and are prevented from falling into poverty due to medical costs or loss of income arising from illness. The session discussed the growing cost of cancer and the challenges that this poses to the establishment and deployment of UHC in the Asian region, where countries face budgetary and other systemic constraints in tackling and controlling cancer. It was noted how sharing concepts on UHC will assist mutual learning among Asian countries and help in the formation of guidelines that can be adapted to national and regional realities. Presentations included a status report on UHC for cancer control in Thailand, and a report from the WHO Kobe Centre concerning prospects for collaborative research on UHC. Also discussed were the current status of cancer burden and control in China and Korea and Japan's progress in systemizing cost-effectiveness evaluation. The final presentation highlighted the importance of gathering social and economic data across Asia in order to build a picture of commonalities and differences in the region.

AIM: To evaluate the safety and efficacy of the combination therapy of fluorouracil, leucovorin and irinotecan (FOLFIRI) and aflibercept in Asian patients with metastatic colorectal cancer (mCRC), who had progressed after oxaliplatin-based chemotherapy.
METHODS: This is a retrospective analysis of 19 mCRC patients who received FOLFIRI and aflibercept (4 mg/kg intravenously) every 2 weeks via a Named Patient Program (supported by Sanofi Aventis) in Singapore. Treatment was administered until disease progression or unacceptable toxicities. Kaplan-Meier method was used to estimate progression-free survival (PFS) and overall survival (OS). Efficacy and toxicities were summarized using descriptive statistics. Statistical analysis was performed using STATA 12.0 software.
RESULTS: The majority (84%) of the patients were of chinese ethnicity. The median age was 59 years, with 63.2% of the patients having an Eastern Cooperative Oncology Group status of 1. Four patients (21.1%) achieved partial response and 8 patients (42.1%) achieved stable disease. After a median follow-up of 9.6 months [95% confidence interval (CI), 2.2-13.1 months], the median OS was 11.6 months (95% CI, 6.1 to not-estimable), and median PFS was 4.1 months (95% CI, 2.2-5.9). Majority of the toxicities were grade 1-2, and include leucopenia (84.2%), anemia (73.7%), liver enzyme elevation (68.4%) and fatigue (68.4%). The most frequently reported grade 3 toxicities were neutropenia and neutropenic complications (both 15.8%). All adverse events resolved with supportive management.
CONCLUSION: The clinical benefit and safety profile of the combination of FOLFIRI/aflibercept in Asian patients with mCRC are consistent with that of Western population. FOLFIRI/aflibercept may be an appropriate therapeutic option in Asian patients with mCRC previously treated with an oxaliplatin-based regimen.