non-Asian Patients Research Articles

Clinical Presentation and Survival of Asian and Non-Asian Patients with HCV-Related Hepatocellular Carcinoma

Hepatitis C virus (HCV) is an important cause of hepatocellular carcinoma (HCC) in Asians; however, it is often overlooked due to the high prevalence of hepatitis B virus in Asians. This study examines HCV-related HCC in Asians. We conducted a retrospective cohort study of 792 consecutive Asian (n = 220) and non-Asian (n = 572) patients with HCV-related HCC identified at Stanford University Medical Center using International Classification of Diseases-9 diagnosis between July 1996 and June 2012. Asian patients were much older [66 (38-88) vs. 56 (31-87) years, P < 0.0001] and more likely to be female (33 vs. 19 %, P < 0.0001). A larger proportion of Asians were diagnosed with HCC within 2 years of HCV diagnosis (35 vs. 20 %, P = 0.001). Asian patients were more likely to undergo palliative therapy (46 vs. 28 %) and less likely to be listed for liver transplantation (20 vs. 48 %, P < 0.001), despite similar rates of meeting Milan criteria (52 vs. 58 %, P = 0.16). Overall, there was a trend for higher median survival rates in Asians (30 vs. 21 months, P = 0.091). Asians had higher long-term survival with palliative therapy only (5-year survival: 28 vs. 10 %, P < 0.0001); however, survival was similar among patients listed for liver transplantation. There were distinct differences in clinical presentations of Asian and non-Asian patients with HCV-related HCC. Asians with HCV-related HCC are less likely to undergo liver transplantation and more likely to have delayed HCV diagnosis. Improved strategies in HCV screening in Asians are needed, as it may lead to earlier diagnosis and treatment of HCV infection and possible prevention of HCC development.

Clinicopathologic Analysis of ROS1-Rearranged Non–Small-Cell Lung Cancer and Proposal of a Diagnostic Algorithm

We sought to evaluate the clinical and pathological characteristics of patients with non-small-cell lung cancer (NSCLC) that harbored a ROS1 rearrangement. Four hundred fifty-one Korean patients with resected NSCLC (the resected group) were examined for ROS1 rearrangements using a tissue microarray and ROS1 fluorescence in situ hybridization and analyzed for clinical and pathological features. Sixty-four patients with advanced pulmonary adenocarcinoma with no known oncogenic aberrations (the advanced group) were also screened for ROS1 rearrangements. Of the 451 consecutive patients from the resected group, ROS1 rearrangements were detected in eight cases (1.8%). In the advanced group, an additional eight patients (12.5%) were identified as harboring ROS1 rearrangements. ROS1 rearrangement was detected exclusively in adenocarcinomas and occurred more frequently in women than in men. With the exception of one patient with an EGFR deletion mutation in exon 19, ROS1-positive adenocarcinomas in all patients revealed no alterations in ALK, EGFR, KRAS, or MET genes. Most ROS1-rearranged tumors showed solid and papillary patterns. ROS1 rearrangements were detected in 1.8% of patients with resected NSCLC and were detected exclusively in adenocarcinomas, which is similar to the frequency detected in non-Asian patients. We suggest that ROS1 screening in adenocarcinoma patients with no known oncogenic aberrations is an effective strategy to find ROS1 rearrangements in NSCLC.

Prognostic role of D-dimer in patients with lung cancer: a meta-analysis

D-dimer detection in patients suffering from a variety of different types of cancer has become a hot point as an emerging and promising biomarker. In this study, therefore, we evaluated the prognostic role of D-dimer in lung cancer. Initial literature was identified using the PubMed, EMBASE, and CNKI. The primary data was hazard ratio (HR) with 95% confidence interval (CI) of survival outcomes in candidate articles, including overall survival (OS) and disease-free survival (DFS). Finally, 11 eligible studies were included in this meta-analysis, which were published between 1996 and 2013. The estimated pooled HR and 95% CI for OS of all studies was 2.06 (95% CI 1.64-2.58, p < 0.00001) and the HR and 95% CI for DFS in one study was 3.38 (95% CI 1.17-9.75, p = 0.002). The HRs and 95% CIs for OS in Asian and non-Asian patients were 2.48 (95% CI 1.60-3.84, p < 0.0001) and 1.89 (95% CI 1.44-2.47, p < 0.00001), respectively. When we further analyzed the data by various detecting methods, the pooled HR and 95% CI for OS were 3.22 (95% CI 1.99-5.21, p < 0.00001) for ELISA, 1.52 (95% CI 1.25-1.86, p < 0.0001) for Latex assay, and 1.79 (95% CI 1.19-2.69, p = 0.005) for immunoturbidimetry assay. We also did subgroup analysis according to the ratio of histological type and clinical stage. All the above analysis had positive results. This meta-analysis showed that D-dimer had a fine predictive role in lung cancer patients, especially in Asian group. Also, it demonstrated that D-dimer had a stronger predictive value by using the method ELISA.

Nasopharyngeal Carcinoma (NPC) in British Columbia (BC): A Population-Based Comparison of Asian and Non-Asian Patients

The incidence of NPC in Asian countries is 5-9 times higher than in North America. It is recognized that the WHO histological subtype of NPC varies with ethnicity and may impact survival. Our study compares the outcomes of Asian and Non-Asian pts with NPC in BC, a unique Canadian province with a 20% Asian population.

Letter by Kawada Regarding Article, “Dabigatran Versus Warfarin: Effects on Ischemic and Hemorrhagic Strokes and Bleeding in Asians and Non-Asians With Atrial Fibrillation”

Hori et al1 conducted a randomized study of long-term anticoagulation therapy for Asian and non-Asian patients with atrial fibrillation by using 2 doses of dabigatran etexilate (DE) versus warfarin on several types of stroke and bleeding rates. They handled 2782 Asian patients and 15 331 non-Asian patients, and Cox regression model was applied for risk assessment.1 Hemorrhagic stroke was significantly reduced by using DE 110 mg and DE 150 mg versus warfarin in Asian patients, presenting hazard ratios (95% confidence interval) of 0.15 (0.03–0.66) and 0.22 (0.06–0.77), respectively. In non-Asian patients, hazard ratios (95% confidence interval) of DE 110 mg and DE 150 mg versus warfarin …

Hypoxia-inducible Factor 1 Alpha (HIF-1α) as a Prognostic Indicator in Patients with Gastric Tumors: A Meta-analysis

Though researched for years, the prognostic role of hypoxia-inducible factor 1 alpha (HIF-1α) in gastric cancer is still controversial. We thus undertook a systematic review to assess the relationship. A systematically literature search of Pubmed, Embase, Web of Science, China Biological Medicine Disc and Cochrane Library was undertaken in February 2013, and the reference lists of articles were retrieved. 12 trials (1,555 participants) were included to assess the association between HIF-1α expression and survival. Summary hazard ratios (HRs) were calculated. HIF-1α expression was significantly correlated with poor overall survival of gastric cancer patients (HR=1.34, 95%CI: 1.13-1.58; P=0.0009), but not with poor disease free survival of gastric cancer patients (HR=1.67, 95%CI: 0.99-2.82; P=0.06). HIF-1α was associated with poor OS, but not DFS, especially for Asian patients. But studies evaluating relationships of HIF- 1α with OS and DFS in non-Asian gastric cancer patients appear needed.

The “smoker's paradox” in Asian versus non-Asian patients with percutaneous coronary intervention longer than 6 months follow-up: A collaborative meta-analysis with the ET-CHD registry

Cigarettesmokingis recognizedasanimportantriskfactorfor car-diovascular disease for decades [1]. Among patients with acute coro-nary events, current smoker has been observed to be paradoxicallyassociated with a survival benefit. This is called as the “smoker's para-dox” [2,3]. On average, symptomatic smokers were found with youngeragesandlowerratesofcomorbiditythannon-smokersatentryinprevi-ous studies [4]. Therefore, thephenomenon may be mostly reasoned bythe discrepancies in baseline characteristics. In addition, some reportsuncovered that the “smoker's paradox” was only present in short-termbutitwasalmostabsentwithfollow-uplongerthan6 months[5].Nota-bly, most of these studies were carried out in the fibrinolysis era. Hencetherewerefewerreportswithregardtotheissuespeci ficallyforpatientsundergoing percutaneous coronary intervention (PCI). Furthermore, arecent large-sized report from the combined Korean Acute MyocardialInfarction Registry (KAMIR) and the Korean Myocardial Infarction(KorMI) registry revealed that current smokers were associated with a48% decrease in the risk of total death in reference to non-smokers at1 year after primary PCI for acute MI [6]. This study implied that anethnic differencemightbe presentin the “smoker's paradox”.Thereforewe conducted a meta-analysis to compare the impact of smoking statusat baseline on the subsequent coronary events between Asian andnon-Asian patients with PCI and follow-up longer than 6 months.Detailedsearchstrategiesweredesignedtoidentifystudiesevaluatingtheeffectofbaselinesmokingstatusonthemortalityandcardiaceventsfollowing PCI for at least 6 months. One author (Lin GM) pre-screenedthe search results from MEDLINE and Cochrane Central Register ofControlled Trials (CENTRAL) from 1970 to 2013 and removed citationsthat were not relevant. Two reviewers (Lin GM and Li YH) indepen-dently reviewed the remaining citations and performed data extrac-tion. Disagreements were resolved through consensus. Study qualitywas assessed using the New Castle–Ottawa quality scale (NOS) for ob-servational studies [7]. Studies were required to separately report theadjusted risk ratios of total or cardiac deaths/events in patients by thesmokingstatusatentry.Theprimaryoutcomewastotalorcardiacmor-tality and the secondary outcomes were target vessel revascularization(TVR) and recurrent MI. Finally, there were ten articles (four for Asiansand six for non-Asians) extracted to synthesize their results and thestudy characteristics were displayed in Table 1 [6,8–16].Ofnote,thefollow-upperiodsinmostoftheseselectedPCIregistrieswere reported between 6 months and 1 year(three for Asians and fivefor non-Asians) and longer than 3 years (one for Asians and one fornon-Asians). Additionally, we analyzed the adjusted hazard ratios(HRs) of all-cause death at 1 year and 3 years, respectively betweensmokers and non-smokers with PCI in the Eastern Taiwan integratedhealth care delivery system of Coronary Heart Disease (ET-CHD) regis-try in Table 2 [17–19].The baseline profiles of patients undergoing PCI werepresented aspercentages or as mean ± SD. Chi-square tests were used to testbaseline differences across the study groups for categorical variables.Since most continuous variables in this study did not follow a normaldistribution, Wilcoxon rank sum test, a nonparametric method with-out the requirement of normal assumption, was used to determinethe difference between smokers and non-smokers. Cox proportionalhazard regression models were used to determine the adjusted HRsfor total death associated with the baseline smoking status. All con-founders listed in Table 2 were entered into the model except totalcholesterol, triglycerides, and glucose levels which were removedfrom thefinal model due to their high association with the other co-variates. All statistical analyses were performed with SAS version 9.2(SAS Institute, Cary, NC). A P b 0.05 was considered statisticallysignificant.

Functional Diversity of the Glutathione Peroxidase Gene Family Among Human Populations: Implications for Genetic Predisposition to Disease and Drug Response

To analyze the human genetic variation of glutathione peroxidases (GPX), estimating the functional differences among human populations and suggesting interethnic differences in predisposition to disease and drug response. Using 1000 Genomes Project data, we analyzed 723 GPX variants in 1092 individuals belonging to 14 populations. Combining functional prediction analyses of coding and noncoding variants, we developed a method to estimate haplotype functionality. GPX rare variants have a higher functional impact than common variants. The frequency among Asian patients of haplotypes associated with normal functionality is significantly higher for GPX1 and lower for GPX3 than for non-Asian patients; no adaptation signals in GPX1 and GPX3 were found in Asian patients. GPX1 and GPX3 differences may be associated with alterations in antioxidant capacity and redox regulation, which suggests diverse susceptibility to complex disease and diverse response to relevant drugs in Asians compared with individuals with other ethnic origins.

Dabigatran Versus Warfarin

Intracranial hemorrhage rates are higher in Asians than non-Asians, especially in patients receiving warfarin. This randomized evaluation of long-term anticoagulation therapy subgroup analysis assessed dabigatran etexilate (DE) and warfarin effects on stroke and bleeding rates in patients from Asian and non-Asian countries. There were 2782 patients (15%) from 10 Asian countries and 15 331 patients from 34 non-Asian countries. A Cox regression model, with terms for treatment, region, and their interaction was used. Rates of stroke or systemic embolism in Asians were 3.06% per year on warfarin, 2.50% per year on DE 110 mg BID (DE 110), and 1.39% per year on DE 150 mg BID (DE 150); in non-Asians, the rates were 1.48%, 1.37%, and 1.06% per year with no significant treatment-by-region interactions. Hemorrhagic stroke on warfarin occurred more often in Asians than non-Asians (hazard ratio [HR], 2.4; 95% confidence interval [CI], 1.3-4.7; P=0.007), with significant reductions for DE compared with warfarin in both Asian (DE 110 versus warfarin HR, 0.15; 95% CI, 0.03-0.66 and DE 150 versus warfarin HR, 0.22; 95% CI, 0.06-0.77) and non-Asian (DE 110 versus warfarin HR, 0.37; 95% CI, 0.19-0.72 and DE 150 versus warfarin HR, 0.28; 95% CI, 0.13-0.58) patients. Major bleeding rates in Asians were significantly lower on DE (both doses) than warfarin (warfarin 3.82% per year, DE 110 2.22% per year, and DE 150 2.17% per year). Hemorrhagic stroke rates were higher on warfarin in Asians versus non-Asians, despite similar blood pressure, younger age, and lower international normalized ratio values. Hemorrhagic strokes were significantly reduced by DE in both Asians and non-Asians. DE benefits were consistent across Asian and non-Asian subgroups. http://www.clinicaltrials.gov. Unique identifier: NCT00262600.

Hepatocellular Carcinoma in Chronic Hepatitis C in the Absence of Advanced Fibrosis or Cirrhosis

The objective of our study was to describe the cross-sectional imaging appearance of hepatocellular carcinoma (HCC) in patients with chronic hepatitis C virus (HCV) infection in the absence of advanced fibrosis and cirrhosis. This study is a retrospective review of our surgical database to identify patients with chronic HCV infection and HCC who underwent hepatectomy and who had undergone preoperative CT or MRI. Only patients with a Metavir fibrosis score of F0, F1, or F2 on pathology were included. Patients with hepatitis B virus coinfection or other causes of chronic liver disease and patients with histopathologic evidence of advanced fibrosis or cirrhosis (Metavir scores F3 and F4) were excluded. Contrast-enhanced CT or MRI examinations performed within 2 months before surgery were reviewed for the number, size, and location of tumors; tumor enhancement characteristics; and presence of macrovascular invasion. Two hundred forty-five resections of HCC in patients with HCV were performed in our institution from 1987 to 2012. Of this group, 26 patients (10.6%) had a Metavir fibrosis score of F0, F1, or F2; of those patients, 19 (18 men and one woman; 18 non-Asian patients and one Asian patient; mean age, 64 years) had imaging studies available for review. Twenty-one HCCs (mean size, 4.5 cm; range, 0.9-14.8 cm) were evaluated at imaging. Typical wash-in and washout characteristics were seen in 16 of 19 viable lesions (84.2%). The remaining two HCCs were completely necrotic after transarterial chemoembolization. Eighteen patients had a solitary tumor. Most tumors (15/21, 71.4%) developed in the right hepatic lobe. HCC can develop in patients with chronic HCV without advanced fibrosis or cirrhosis, most frequently in older non-Asian men, and usually appears as a large solitary tumor with a typical wash-in-washout enhancement pattern.

Su1930 Differences in Patient Characteristics, Tumor Presentations, and Treatment Outcomes in Asian Versus Non-Asian Patients With Hepatitis β Virus-Associated Hepatocellular Carcinoma (HBV/HCC)

Su1930 Differences in Patient Characteristics, Tumor Presentations, and Treatment Outcomes in Asian Versus Non-Asian Patients With Hepatitis β Virus-Associated Hepatocellular Carcinoma (HBV/HCC)

613 Hepatitis C Virus (HCV) Diagnosis and Clinical Outcomes of Patients With HCV-Related Hepatocellular Carcinoma (HCC): A Comparative Study of Asians Versus Non-Asians

BACKGROUND AND AIMS: In addition to hepatitis B virus, HCV is also an important cause of HCC in Asians; however, it is often overlooked. This study aims to examine baseline characteristics, timing of HCV diagnosis and long-term survival of HCV-related HCC in Asians compared to non-Asian patients. METHODS: We conducted a retrospective cohort study of 798 consecutive Asian (n=220) and non-Asian (n=572) patients with HCV-related HCC who were identified via computer query using ICD-9 diagnosis at a U.S. university medical center between 7/1996 and 6/2012. Individual records were reviewed. RESULTS: Asians were much older (66 [38-88] vs. 56 [31-87] years, P ,0.0001) and more likely to be female (33% vs. 19%, P,0.0001). A significantly larger proportion of Asians were also diagnosed with HCC within only 2 years of HCV diagnosis compared to non-Asians (35% vs. 20%, p=0.001). Non-Asians were more likely to have decompensated liver disease and had higher median Child-Turcotte-Pugh score (6 [5-11] vs. 7 [5-13], P ,0.0001). Asian patients were more likely to undergo liver-directed palliative therapy (46% vs. 28%) and much less likely to be listed for liver transplantation(20% vs. 48%) (P ,0.001), despite similar rates of meeting Milan criteria for liver transplantation (52 vs.58%, P=0.16). Overall, there was a trend for higher median survival rates in Asians compared to non-Asians (30 vs. 21 months, P=0.091). Among those who were listed for liver transplantation, there was no statistically significant difference in survival between Asians and non-Asians in the first 2 years (72% vs. 68%) but there was divergence with Asians having higher survival afterwards (61% vs. 51%) (Figure 1). However, among those undergoing liver-directed palliative therapy, Asians had significantly higher long-term survival compared to non-Asians (5-year survival: 28% vs. 10%, P,0.0001) (Figure 2). On multivariate Cox proportional hazards model also inclusive of age, sex, BCLC staging, Child-Pugh score, meeting Milan criteria, liver transplantation listing, non-Asian ethnicity was an independent predictor for lower overall survival (HR=0.70 [0.52-0.86]). CONCLUSIONS: Despite being older and having a lower rate of liver transplantation listing, Asian HCV/HCC patients had higher median survival compared to non-Asian patients, particularly among those undergoing palliative therapy. Non-Asians were more likely to have decompensated liver disease and non-Asian ethnicity was an independent predictor for poorer long-term survival. Compared to non-Asians, Asians with HCV-related HCCwere also muchmore likely to have delayed HCV diagnosis. Improved strategies in HCV screening in Asians are needed as it may lead to earlier diagnosis and treatment of HCV infection and possible prevention of HCC development in this ethnic population with a disproportionate HCC disease burden.

616 C-FOS Mediated Regulation of the Apical Sodium Dependent Bile Acid Transporter (ASBT) Plays a Critical Role in the Ileal Response to FGF-19

BACKGROUND AND AIMS: In addition to hepatitis B virus, HCV is also an important cause of HCC in Asians; however, it is often overlooked. This study aims to examine baseline characteristics, timing of HCV diagnosis and long-term survival of HCV-related HCC in Asians compared to non-Asian patients. METHODS: We conducted a retrospective cohort study of 798 consecutive Asian (n=220) and non-Asian (n=572) patients with HCV-related HCC who were identified via computer query using ICD-9 diagnosis at a U.S. university medical center between 7/1996 and 6/2012. Individual records were reviewed. RESULTS: Asians were much older (66 [38-88] vs. 56 [31-87] years, P ,0.0001) and more likely to be female (33% vs. 19%, P,0.0001). A significantly larger proportion of Asians were also diagnosed with HCC within only 2 years of HCV diagnosis compared to non-Asians (35% vs. 20%, p=0.001). Non-Asians were more likely to have decompensated liver disease and had higher median Child-Turcotte-Pugh score (6 [5-11] vs. 7 [5-13], P ,0.0001). Asian patients were more likely to undergo liver-directed palliative therapy (46% vs. 28%) and much less likely to be listed for liver transplantation(20% vs. 48%) (P ,0.001), despite similar rates of meeting Milan criteria for liver transplantation (52 vs.58%, P=0.16). Overall, there was a trend for higher median survival rates in Asians compared to non-Asians (30 vs. 21 months, P=0.091). Among those who were listed for liver transplantation, there was no statistically significant difference in survival between Asians and non-Asians in the first 2 years (72% vs. 68%) but there was divergence with Asians having higher survival afterwards (61% vs. 51%) (Figure 1). However, among those undergoing liver-directed palliative therapy, Asians had significantly higher long-term survival compared to non-Asians (5-year survival: 28% vs. 10%, P,0.0001) (Figure 2). On multivariate Cox proportional hazards model also inclusive of age, sex, BCLC staging, Child-Pugh score, meeting Milan criteria, liver transplantation listing, non-Asian ethnicity was an independent predictor for lower overall survival (HR=0.70 [0.52-0.86]). CONCLUSIONS: Despite being older and having a lower rate of liver transplantation listing, Asian HCV/HCC patients had higher median survival compared to non-Asian patients, particularly among those undergoing palliative therapy. Non-Asians were more likely to have decompensated liver disease and non-Asian ethnicity was an independent predictor for poorer long-term survival. Compared to non-Asians, Asians with HCV-related HCCwere also muchmore likely to have delayed HCV diagnosis. Improved strategies in HCV screening in Asians are needed as it may lead to earlier diagnosis and treatment of HCV infection and possible prevention of HCC development in this ethnic population with a disproportionate HCC disease burden.

614 The Oncogenic Role of Praja1 on Disrupting TGF-β Signaling in Hepatocellular Cancer

BACKGROUND AND AIMS: In addition to hepatitis B virus, HCV is also an important cause of HCC in Asians; however, it is often overlooked. This study aims to examine baseline characteristics, timing of HCV diagnosis and long-term survival of HCV-related HCC in Asians compared to non-Asian patients. METHODS: We conducted a retrospective cohort study of 798 consecutive Asian (n=220) and non-Asian (n=572) patients with HCV-related HCC who were identified via computer query using ICD-9 diagnosis at a U.S. university medical center between 7/1996 and 6/2012. Individual records were reviewed. RESULTS: Asians were much older (66 [38-88] vs. 56 [31-87] years, P ,0.0001) and more likely to be female (33% vs. 19%, P,0.0001). A significantly larger proportion of Asians were also diagnosed with HCC within only 2 years of HCV diagnosis compared to non-Asians (35% vs. 20%, p=0.001). Non-Asians were more likely to have decompensated liver disease and had higher median Child-Turcotte-Pugh score (6 [5-11] vs. 7 [5-13], P ,0.0001). Asian patients were more likely to undergo liver-directed palliative therapy (46% vs. 28%) and much less likely to be listed for liver transplantation(20% vs. 48%) (P ,0.001), despite similar rates of meeting Milan criteria for liver transplantation (52 vs.58%, P=0.16). Overall, there was a trend for higher median survival rates in Asians compared to non-Asians (30 vs. 21 months, P=0.091). Among those who were listed for liver transplantation, there was no statistically significant difference in survival between Asians and non-Asians in the first 2 years (72% vs. 68%) but there was divergence with Asians having higher survival afterwards (61% vs. 51%) (Figure 1). However, among those undergoing liver-directed palliative therapy, Asians had significantly higher long-term survival compared to non-Asians (5-year survival: 28% vs. 10%, P,0.0001) (Figure 2). On multivariate Cox proportional hazards model also inclusive of age, sex, BCLC staging, Child-Pugh score, meeting Milan criteria, liver transplantation listing, non-Asian ethnicity was an independent predictor for lower overall survival (HR=0.70 [0.52-0.86]). CONCLUSIONS: Despite being older and having a lower rate of liver transplantation listing, Asian HCV/HCC patients had higher median survival compared to non-Asian patients, particularly among those undergoing palliative therapy. Non-Asians were more likely to have decompensated liver disease and non-Asian ethnicity was an independent predictor for poorer long-term survival. Compared to non-Asians, Asians with HCV-related HCCwere also muchmore likely to have delayed HCV diagnosis. Improved strategies in HCV screening in Asians are needed as it may lead to earlier diagnosis and treatment of HCV infection and possible prevention of HCC development in this ethnic population with a disproportionate HCC disease burden.

Mo2026 Epidemiology and Clinical Outcomes of Asians With Hepatocellular Carcinoma (HCC) Compared to Non-Asian Patients

Background : Endoscopic ultrasonography (EUS) is considered to be the best modality to predict the neoplastic polyps of the gallbladder. However, EUS has several limitations following as 1) the considerable experience of investigators, 2) presence of the interobserver variations and 3) unavailability of EUS in some centers. Multidetector computed tomography (MDCT) provides fine section image of gallbladder and allows to reduce the interobserver variations. We evaluated the accuracy of MDCT combined with high resolution ultrasonography (HRUS) for gallbladder polyps smaller than 2cm compared with EUS. Methods : From Dec 2005 to June 2010, 109 patients who underwent cholecystectomy due to gallbladder polyps were enrolled. Subjects were divided in two groups (reference group : 63 patients who were performed MDCT and HRUS vs. validation group : 46 patients who underwent MDCT, HRUS, and EUS). New scoring system was developed from reference group, and applied to validation group, while previously reported EUS scoring system was applied to the same validation group. Results : In reference group, size (p,0.001), number (p=0.015), shape (p=0.001), and CT/US size ratio of polyps (p=0.008) were significant variables in univariate analysis. Area under the ROC curve draw by new scoring system was 0.859 and cut-off value was set to 3. In validation group, new scoring system showed comparable accuracy (65.2%) with previously reported EUS scoring system(73.9%, p=0.434). Conclusion : MDCT combined with HRUS provide comparatively high accuracy in small gallbladder polyps in distinguishing between neoplastic and non-neoplastic polyps as preoperative diagnostic modality.

Abstract 2339: Prevalence of MET expression, activating mutations of KRAS and IDH1/2, and ROS1 fusions in cholangiocarcinoma patient tumor samples.

Abstract Cholangiocarcinoma (CCA) originates from biliary tract epithelium and can be classified anatomically into intrahepatic or extrahepatic CCA. Although a relatively rare disease in the United States and Europe, the incidence of intrahepatic CCA is on the rise with unknown causes. CCA incidence is higher in Asia and the etiology is associated with infections such as liver fluke and hepatitis B/C. Prognosis at diagnosis is poor with median survival time of &amp;lt; 1 year, and only 10-20% of patients are eligible for tumor resection at diagnosis. This study examined the prevalence of MET over-expression, activating single point mutations of KRAS and IDH1/2, and ROS1 gene fusions in ∼100 intrahepatic and extrahepatic CCA FFPE tumor tissues obtained from non-Asian (n=40) and Asian (n=60) patients. Immunohistochemistry performed with an anti-MET-specific antibody (A2) demonstrated that MET is expressed in the majority of all intrahepatic CCA samples analyzed, with ∼50% of samples reported with membranocytoplasmic scores of 2+ (moderate intensity) or 3+ (strong intensity) on a 0-3+ scale. Interestingly, most non-malignant bile ducts and much vascular endothelia also stained lightly positive for MET. To determine mutation frequencies of KRAS and IDH1/2, competitive allele-specific Taqman® PCR (castPCR) was performed on DNA extracted from FFPE CCA tissue (limit of mutation detection 0.1%). Fourteen KRAS activating mutations (G12S, G12R, G12A, G13C, G13S, G13R, G12D, G13D, G12V, G12C, Q61R, Q61L, Q61H (c.183A&amp;gt;C and c.183A&amp;gt;T for Q61H), 5 IDH1 mutations (R132G, R132S, R132H, R132C, R132L), and 5 IDH2 mutations (R172G, R172M, R172K, R172W, R172S) were analyzed. Overall, 25% of analyzed samples were positive for KRAS mutation, and G12D was the predominant mutation (∼60%). One-third of Asian samples were positive for KRAS mutation, whereas less than one-fifth of non-Asian samples contained KRAS mutations. For IDH1, the frequency of mutation was less than 10% overall, and the majority of patients with IDH1 mutations were non-Asian. The R132C mutation was the predominant IDH1 mutation, and all tissues that were positive for IDH1 mutations were of intrahepatic origin. Interestingly, 2 out of the 7 samples positive for IDH1 mutations (R132C) were also positive for G12D KRAS mutation. There is no trend of MET expression correlating with either KRAS or IDH1 mutations. IDH2 analyses by castPCR and FISH studies examining ROS1 gene fusion are ongoing. Based on these data, inhibitors of receptor tyrosine kinases and their signaling pathways such as MET and ROS1 may merit clinical evaluation in CCA patients. LY2801653, a MET inhibitor which also has inhibitory activity against ROS1 and MKNK1/2 is currently in phase 1 clinical testing in patients with advanced cancer (trial I3O-MC-JSBA, NCT01285037). Citation Format: Megan N. Thobe, S. Betty Yan, Kelly M. Credille, Aejaz Nasir, Jessica A. Roseberry Baker, Mary Lajiness, Nathan A. Brooks, Darryl W. Ballard, Donna M. Farley, Victoria L. Peek, Suzane L. Um, G. Jason Jin, Raymond Gilmour, Christoph Reinhard, Jeremy R. Graff, Andrew E. Schade, Aaron M. Gruver, Bruce Colligan, Larry Douglass, Julia Carter, Richard A. Walgren. Prevalence of MET expression, activating mutations of KRAS and IDH1/2, and ROS1 fusions in cholangiocarcinoma patient tumor samples. [abstract]. In: Proceedings of the 104th Annual Meeting of the American Association for Cancer Research; 2013 Apr 6-10; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2013;73(8 Suppl):Abstract nr 2339. doi:10.1158/1538-7445.AM2013-2339

Prognostic value of TTF-1 expression in patients with non-small cell lung cancer: a meta-analysis

Background: Observational studies on the prognostic role of thyroid transcription factor 1 (TTF-1) in non-small cell lung cancer (NSCLC) are controversial. Methods: To clarify the impact of TTF-1 in NSCLC survival, we performed this meta-analysis that included eligible studies. The combined hazard ratios and their corresponding 95% confidence intervals were calculated in terms of overall survival. Results: A total of 17 studies with 2,235 patients were evaluable for this meta-analysis. The studies were categorized by histology, disease stage and patient race. Our results suggested that TTF-1 overexpression had a favorable impact on survival of patients with NSCLC, the HR (95% CI) was 0.49 (0.42 to 0.55) overall, 0.46 (0.38-0.54) in Asian patients, 0.52 (0.42-0.63) in non-Asian patients, 0.45 (0.38-0.52) in adenocarcinoma, 0.63 (0.39-0.86) in stage I NSCLC, 0.43 (0.33-0.53) in stage IIIb-IV NSCLC. The data collected were not sufficient to determine the prognostic value of VEGF in patients with squamous cell lung carcinomas. But there was a high heterogeneity between the studies. Conclusions: TTF-1 overexpression indicates a favorable prognosis for patients with NSCLC, this effect appears also significant when the analysis is restricted in lung AC patients, stage I and stage IIIb-IV NSCLC.

Efficacy of everolimus with exemestane versus exemestane alone in Asian patients with HER2-negative, hormone-receptor-positive breast cancer in BOLERO-2.

BackgroundThe addition of mTOR inhibitor everolimus (EVE) to exemestane (EXE) was evaluated in an international, phase 3 study (BOLERO-2) in patients with hormone-receptor-positive (HR+) breast cancer refractory to letrozole or anastrozole. The safety and efficacy of anticancer treatments may be influenced by ethnicity (Sekine et al. in Br J Cancer 99:1757–62, 2008). Safety and efficacy results from Asian versus non-Asian patients in BOLERO-2 are reported.MethodsPatients were randomized (2:1) to 10 mg/day EVE + EXE or placebo (PBO) + EXE. Primary endpoint was progression-free survival (PFS). Secondary endpoints included overall survival, response rate, clinical benefit rate, and safety.ResultsOf 143 Asian patients, 98 received EVE + EXE and 45 received PBO + EXE. Treatment with EVE + EXE significantly improved median PFS versus PBO + EXE among Asian patients by 38 % (HR = 0.62; 95 % CI, 0.41–0.94). Median PFS was also improved among non-Asian patients by 59 % (HR = 0.41; 95 % CI, 0.33–0.50). Median PFS duration among EVE-treated Asian patients was 8.48 versus 4.14 months for PBO + EXE, and 7.33 versus 2.83 months, respectively, in non-Asian patients. The most common grade 3/4 adverse events (stomatitis, anemia, elevated liver enzymes, hyperglycemia, and dyspnea) occurred at similar frequencies in Asian and non-Asian patients. Grade 1/2 interstitial lung disease occurred more frequently in Asian patients. Quality of life was similar between treatment arms in Asian patients.ConclusionAdding EVE to EXE provided substantial clinical benefit in both Asian and non-Asian patients with similar safety profiles. This combination represents an improvement in the management of postmenopausal women with HR+/HER2− advanced breast cancer progressing on nonsteroidal aromatase inhibitors, regardless of ethnicity.

Differences in the glucose-lowering efficacy of dipeptidyl peptidase-4 inhibitors between Asians and non-Asians: a systematic review and meta-analysis

The aim of this work was to compare the glucose-lowering efficacy of dipeptidyl peptidase-4 (DPP-4) inhibitors between Asian and non-Asian patients with type 2 diabetes. We searched MEDLINE, EMBASE, LILACS, CENTRAL, ClinicalTrials.gov and conference proceedings. Studies were eligible if they were randomised controlled trials with a treatment duration of at least 12weeks, compared a DPP-4 inhibitor with a placebo as either monotherapy or oral combination therapy, had information on ethnicity and HbA1c values and were published or described in English. A systematic review and meta-analysis with a meta-regression analysis was conducted. Among 809 potentially relevant studies, 55 trials were included. A meta-analysis revealed that DPP-4 inhibitors lowered HbA1c to a greater extent in studies with ≥50% Asian participants (weighted mean difference [WMD] -0.92%; 95% CI -1.03, -0.82) than in studies with <50% Asian participants (WMD -0.65%; 95% CI -0.69, -0.60). The between-group difference was -0.26% (95% CI -0.36, -0.17, p < 0.001). The baseline BMI significantly correlated with the HbA1c-lowering efficacy of DPP-4 inhibitors. The RR of achieving the goal of HbA1c <7.0% (53.0mmol/mol) was higher in studies with ≥50% Asian participants (3.4 [95% CI 2.6, 4.7] vs 1.9 [95% CI 1.8, 2.0]). The fasting plasma glucose-lowering efficacy was higher with monotherapy in the Asian-dominant studies, but the postprandial glucose-lowering efficacy and changes in body weight were comparable between the two groups. DPP-4 inhibitors exhibit a better glucose-lowering efficacy in Asians than in other ethnic groups; this requires further investigation to understand the underlying mechanism, particularly in relation to BMI.

Prognostic value of COX-2 expression in patients with non-small cell lung cancer: a systematic review and meta-analysis.

Cyclooxygenase-2 (COX-2) has been implicated in tumorigenesis and metastasis, and it presumably mediates the proliferation of endothelial cells and promotes vascular permeability. However, the prognostic value of COX-2 overexpression in patients with non-small cell lung cancer (NSCLC) remains controversial. A systematic review of eligible studies with meta-analysis was performed to quantitatively review the correlation of COX-2 overexpression with survival in patients with NSCLC. We conducted a final analysis of 1,892 patients from 16 studies. The studies were categorized by histology, disease stage, patient race and laboratory techniques used. Combined hazard ratios (HR) suggested that COX-2 overexpression was not associated with a significant impact on survival, the HR (95% CI) was 0.90 (95% CI: 0.76-1.04) overall, 0.99 (0.71-1.26) in Asian patients, 0.87 (0.71-1.03) in non-Asian patients, 0.63 (0.33-0.93) in adenocarcinoma, 1.42 (1.02-1.81) in stage I NSCLC, 0.83 (0.72-1.08) in NSCLC by IHC, 3.28 (1.48-5.13) in NSCLC by RT-PCR. COX-2 overexpression seems to have no significant impact on survival of NSCLC patients. However, the statistically significant was found in stage I NSCLC, suggesting that COX-2 expression could be useful at early stages to distinguish those with a worse prognosis.