Chiranjeev Dash - Academia.edu (original) (raw)

Papers by Chiranjeev Dash

American Journal of Preventive Medicine, 2015

Research suggests that community involvement is integral to solving public health problems, inclu... more Research suggests that community involvement is integral to solving public health problems, including involvement in clinical trials-a gold standard. Significant racial/ethnic disparities exist in the accrual of participants for clinical trials. Location and cultural aspects of clinical trials influence recruitment and accrual to clinical trials. It is increasingly necessary to be aware of defining characteristics, such as location and culture of the populations from which research participants are enrolled. Little research has examined the effect of location and cultural competency in adapting clinical trial research for minority and underserved communities on accrual for clinical trials. Utilizing embedded community academic sites, the authors applied cultural competency frameworks to adapt clinical trial research in order to increase minority participation in nontherapeutic cancer clinical trials. This strategy resulted in successful accrual of participants to new clinical research trials, specifically targeting participation from minority and underserved communities in metropolitan Washington, DC. From 2012 to 2014, a total of 559 participants enrolled across six nontherapeutic clinical trials, representing a 62% increase in the enrollment of blacks in clinical research. Embedding cancer prevention programs and research in the community was shown to be yet another important strategy in the arsenal of approaches that can potentially enhance clinical research enrollment and capacity. The analyses showed that the capacity to acquire cultural knowledge about patients-their physical locales, cultural values, and environments in which they live-is essential to recruiting culturally and ethnically diverse population samples.

BMC Complementary and Alternative Medicine

Chemoprevention crossover trials of tea can be more efficient than parallel designs but the attri... more Chemoprevention crossover trials of tea can be more efficient than parallel designs but the attrition and compliance rates with such trials are unknown. Attrition (dropouts) and compliance with treatment were assessed in a 25-week randomized, placebo controlled, crossover, feasibility clinical trial of four tea treatments to investigate the effect of tea on oral cancer biomarkers. Each treatment lasted 4 weeks with 2 weeks of washout in between. Participants were 32 smokers and 33 non-smokers without any evidence of premalignant oral lesions. The interventions consisted of packets of green tea, black tea, caffeinated water, or placebo. Participants were assigned to each treatment for four weeks, and were instructed to drink five packets per day while on the treatment. Dropout from the trial and compliance (consumption of ≥85% of the prescribed treatment packets) are the main outcome measures reported. There was a high rate of dropout (51%) from the study, and the rates were signific...

Cancer Epidemiology Biomarkers & Prevention, 2014

Contemporary Clinical Trials, 2015

Metabolic syndrome and obesity are known risk factors for breast cancers. Exercise interventions ... more Metabolic syndrome and obesity are known risk factors for breast cancers. Exercise interventions can potentially modify circulating biomarkers of breast cancer risk but evidence in African-Americans and women with metabolic syndrome is lacking. The Focused Intervention on Exercise to Reduce CancEr (FIERCE) trial is a prospective, 6-month, 3-arm, randomized controlled trial to examine the effect of exercise on obesity, metabolic syndrome components, and breast cancer biomarkers among African-American women at high risk of breast cancer. Two hundred-forty inactive women with metabolic syndrome and absolute risk of breast cancer ≥1.40 will be randomized to one of the three trial arms: 1) a supervised, facility-based exercise arm; 2) a home-based exercise arm; and 3) a control group that maintains physical activity levels through the course of the trial. Assessments will be conducted at baseline, 3months, and 6months. The primary outcome variables are anthropometric indicators of obesity, metabolic syndrome components, and inflammatory, insulin-pathway, and hormonal biomarkers of breast cancer risk. The FIERCE trial will provide evidence on whether a short-term exercise intervention might be effective in reducing breast cancer risk among African-American women with comorbidities and high breast cancer risk - a group traditionally under-represented in non-therapeutic breast cancer trials. NCT02103140.

Journal of Clinical Gastroenterology, 2015

Hepatocellular carcinoma (HCC) surveillance in patients with cirrhosis is aimed at early detectio... more Hepatocellular carcinoma (HCC) surveillance in patients with cirrhosis is aimed at early detection so that effective therapeutic options may be offered. We undertook this study to assess the patterns of surveillance that had been offered to HCC patients evaluated at our center, and the effect of these strategies on outcome. Consecutive patients, age 18 years and older, diagnosed with HCC between December 2007 and December 2012 were identified. Surveillance was defined as α-fetoprotein measurement and/or imaging examination in the 12 months before HCC diagnosis. Logistic regression and survival analysis models were utilized to investigate the association of surveillance with patient characteristics and survival. A total of 305 patients with HCC and a background of cirrhosis were analyzed. HCC was detected by surveillance in 131 patients (43%). Of those who underwent surveillance, 92% were diagnosed with early-stage cancer (stages I and II) compared with 62% of those who did not undergo surveillance (P<0.001). The rate of surgical therapy (hepatic resection and liver transplantation) was almost doubled in the surveillance group (61% vs. 33%, P<0.05). At median follow-up of 27.3 months, overall survival was high at 55% and surveillance was significantly associated with longer survival (P=0.006). At our center, surveillance efficacy for HCC detection was notably higher than earlier reported. Patients who underwent surveillance were more likely to have their tumors detected at an early stage, to qualify for surgical therapy, and to have improved survival.

Journal of Transplantation, 2014

The efficacy of liver transplantation (LT) for hepatocellular (HCC) is limited by tumor recurrenc... more The efficacy of liver transplantation (LT) for hepatocellular (HCC) is limited by tumor recurrence rates of 10-15%. We undertook this pilot study to examine the use of sorafenib as adjuvant therapy in high-risk LT recipients. Methods. We prospectively enrolled patients transplanted for HCC into a treatment protocol utilizing sorafenib if their explant examination showed evidence of viable tumor exceeding Milan criteria. We utilized as historical controls patients transplanted previously, whose explant tumor characteristics exceeded Milan criteria, but who were not "preemptively" treated with sorafenib. Wilcoxon two-sample test and Fisher's exact test were used to compare survival and recurrence rates between the two groups. Results. Seven patients were treated with sorafenib and compared to 12 historical "controls. " Two of 7 treated patients suffered from HCC recurrence. Of the comparison group, 9 experienced HCC recurrence and all succumbed to disease. Dose reduction improved tolerance of drug. The overall rate of HCC recurrence was decreased in the adjuvant therapy group compared to historical controls (29% versus 75%, = 0.07). Disease free 1-year survival for the treated versus untreated group was 100% versus 66%, respectively. Conclusion. Adjuvant use of sorafenib is safe and decreases risk of HCC recurrence in high-risk LT recipients.

American Journal of Epidemiology, 2015

Although oxidative stress is implicated in colorectal carcinogenesis, human studies on associatio... more Although oxidative stress is implicated in colorectal carcinogenesis, human studies on associations of individual prooxidants and antioxidants with colorectal cancer (CRC) have been inconclusive. We incorporated individual environmental factors known to affect oxidative stress into 4 oxidative balance scores (OBS) and investigated their associations with CRC in the Cancer Prevention Study II Nutrition Cohort. During 1999-2009, a total of 1,109 incident CRC cases were identified among 80,063 participants in the Nutrition Cohort who had completed detailed questionnaires. Four OBS with different weighting methods (equal weights, literature review-based, a posteriori data-based, and weights based on Bayesian analysis) were created by combining 16 dietary and nondietary lifestyle factors. Higher values for all 4 OBS, representing more antioxidant exposures than prooxidant exposures, were associated with 41%-53% lower risks of CRC; for example, the relative risk for the highest OBS quartile versus the lowest in the Bayesian analysis was 0.50 (95% confidence interval: 0.41, 0.61). The associations were more modest when OBS was restricted to either dietary or nondietary components. These results, obtained using comprehensive summary measures of oxidative balance-especially considering the similarity of the findings derived using the different weighting methods-support the hypothesis that a predominance of antioxidant lifestyle exposures (both dietary and nondietary) over prooxidant lifestyle exposures reduces risk of CRC.

Frontiers in Oncology, 2012

Background: Fatigue is a common side effect of conventional prostate cancer radiation therapy. Th... more Background: Fatigue is a common side effect of conventional prostate cancer radiation therapy. The increased delivery precision necessitated by the high dose per fraction of stereotactic body radiation therapy (SBRT) offers the potential of reduce target volumes and hence the exposure of normal tissues to high radiation doses. Herein, we examine the level of fatigue associated with SBRT treatment. Methods: Forty patients with localized prostate cancer treated with hypofractionated SBRT, and a minimum of 12 months followup were included in this analysis. Self-reported fatigue and other quality of life measures were assessed at baseline and at 1, 3, 6, 9, and 12 months post-SBRT. Results: Mean levels of fatigue were elevated at 1 month post-SBRT compared to baseline values (P = 0.02). Fatigue at the 3-month follow-up and later were higher but not statistically significantly different compared to baseline. African-American patients reported higher fatigue post-SBRT than Caucasian patients. Fatigue was correlated with hormonal symptoms as measured by the Expanded Prostate Cancer Index Composite (EPIC) quality of life questionnaire, but not with urinary, bowel, or sexual symptoms. Age, co-morbidities, smoking, prostate specific antigen (PSA) levels, testosterone levels, tumor stage, and treatment variables were not associated with fatigue. Conclusion: This is the first study to investigate fatigue as a side effect of SBRT. In contrast to standard radiation therapy, results suggest SBRTrelated fatigue is short-term rather than a long-term side effect of SBRT. These results also suggest post-SBRT fatigue to be a more frequent complication in African-Americans than Caucasians.

Supportive Care in Cancer, 2014

Purpose With advancements in detection and treatment, the number of breast cancer survivors is gr... more Purpose With advancements in detection and treatment, the number of breast cancer survivors is growing. To reduce mortality among survivors, tailored health-promotion programs are needed to combat comorbidities. However, the demand for such programs exceed that which is available for a vastly diverse population of survivors. The goal of the present study was to describe the prevalence of comorbidities in a group of breast cancer survivors and to examine associations between biological proximal factors of and the more distal individuallevel factors on the number and types of comorbidities. Methods In addition to medical chart reviews, breast cancer survivors (N=369) from hospitals in two urban locations completed self-report measures. Bivariate analyses examined the relationship between distal and proximal predictors and the outcomes: number of comorbidities and comorbidity types.

Urologic Oncology: Seminars and Original Investigations, 2014

Background: Bladder cancer is the most prevalent form of cancer in men among Egyptians, for whom ... more Background: Bladder cancer is the most prevalent form of cancer in men among Egyptians, for whom tobacco smoke exposure and Schistosoma haematobium (SH) infection are the major risk factors. We hypothesized that functional polymorphisms in NAD(P)H:quinone oxidoreductase 1 (NQO1) and superoxide dismutase 2 (SOD2), modulators of the effects of reactive oxidative species, can influence an individual's susceptibility to these carcinogenic exposures and hence the risk of bladder cancer.

The Breast, 2011

Background: Recent epidemiologic and laboratory studies have suggested that non-steroidal antiinf... more Background: Recent epidemiologic and laboratory studies have suggested that non-steroidal antiinflammatory drugs (NSAIDs) may reduce the risk of breast cancer through inhibition of cyclooxygenase-2 (COX-2). Methods: We conducted a caseecontrol study to measure the association between selective cox-2 inhibitors, particularly celecoxib, rofecoxib, valdecoxib and non-specific NSAID subgroups, and breast cancer risk. Between 2003 and 2006, a total of 18,368 incident breast cancer cases were identified in the Ingenix/Lab Rx insurance database, which contains clinical encounter and drug prescription data. Four controls per case were randomly selected, matched on age and time in database. Odds ratios (OR) and 95% confidence intervals (CI) were estimated using conditional logistic regression. Results: Breast cancer risk was inversely associated with both non-specific NSAID and selective COX-2 inhibitor use. Greater than 12 months' duration of use of Celecoxib at a standard dose (200 mg/day) was associated with a 16% decrease in breast cancer risk (OR ¼ 0.84, 95% CI ¼ 0.73, 0.97). We observed the greatest risk reduction in association with >2 years of rofecoxib exposure (OR ¼ 0.54, 95% CI ¼ 0.37, 0.80). Acetaminophen, a compound with less biological plausibility for chemoprevention, showed no significant association with the risk of developing breast cancer. Conclusion: Consistent with animal models and laboratory investigations, higher doses of selective COX-2 inhibitors were more protective against breast cancer than non-specific NSAIDs. With exposure to rofecoxib, a selective COX-2 inhibitor, breast cancer risk reduction was appreciable (46%), suggesting a possible role for selective COX-2 inhibitors in breast cancer prophylaxis.

Mutation Research/Reviews in Mutation Research, 2006

UK PubMed Central (UKPMC) is an archive of life sciences journal literature.

Journal of Community Genetics, 2014

Although research involving biospecimens is essential in advancing cancer research, minorities, e... more Although research involving biospecimens is essential in advancing cancer research, minorities, especially African-Americans, are underrepresented in such research. We conducted a mixed-method (qualitative focus groups among African-Americans and quantitative cross-sectional surveys) study on factors associated with biospecimen knowledge and donation intent in the medically underserved urban communities in Southeast and Southwest Washington, DC. Focus groups were conducted among 41 African-Americans and survey data was available from 302 community residents of different races/ethnicities using convenience sampling. We used logistic regression to model the association between biospecimen knowledge and donation intent with selected sociodemographic variables using survey data. Only 47 % of the participants had knowledge of the different types of biospecimens. In multivariate logistic regression models, male gender, African-American race, and low education levels were significantly associated with lower knowledge about biospecimens. Compared to Whites (79 %), fewer African-Americans (39 %) and Hispanics (57 %) had knowledge of biospecimens but the difference was significant for African-Americans only. Positive intent to donate biospecimens for research was observed among 36 % of the survey respondents. After multivariate adjustment, only biospecimen knowledge was associated with donation intent (odds ratio = 1.91, 95 % confidence interval 1.12, 3.27). Contrary to popular opinion, "mistrust of the medical community" was not the most commonly reported barrier for biospecimen donation among African-Americans. "Not knowing how biospecimens will be used" and "lack of knowledge of biospecimens" were the most common barriers. Our study highlights the importance of education on biospecimens among community residents to increase minority participation in biospecimen research.

Clinical Gastroenterology and Hepatology, 2007

Up to 25% of hepatocellular carcinomas (HCCs) seen in U.S. centers are of unknown etiology. Anima... more Up to 25% of hepatocellular carcinomas (HCCs) seen in U.S. centers are of unknown etiology. Animal studies suggest that hypothyroidism can directly cause liver cell damage and might be a risk factor for HCC. We conducted a case-control study to evaluate the relationship between hypothyroidism and HCC. Cases (n = 54) were HCC patients seen at Mayo Clinic Rochester in whom no underlying etiology for chronic liver disease could be determined. Two groups of controls were selected, HCC patients with HCV (n = 57) and HCC patients with alcoholic liver disease (n = 49). Hypothyroidism was defined as thyroid-stimulating hormone level >5.0, history of hypothyroidism before HCC diagnosis, or a history of being on thyroid replacement at the time of HCC diagnosis. We used multivariate logistic regression to model the relationship between hypothyroidism and HCC etiology. Of the 160 patients, 18 (11%) had a history of hypothyroidism. Twelve (22%) of those with no known etiology for HCC, 2 (4%) of those with HCV, and 4 (8%) of those with alcoholic liver disease had hypothyroidism. Patients with HCC of unknown etiology were significantly more likely to have a history of hypothyroidism as compared with HCC patients with HCV (adjusted odds ratio, 12.7; 95% confidence interval, 1.4-117.1) and as compared with all controls (adjusted odds ratio, 6.8; 95% confidence interval, 1.1-42.1). Hypothyroidism is more prevalent in HCC patients with an unknown etiology. It should be further investigated as a potential risk factor in liver carcinogenesis.

Cancer Prevention Research, 2009

To further clarify and/or develop calcium and vitamin D as chemopreventive agents against colorec... more To further clarify and/or develop calcium and vitamin D as chemopreventive agents against colorectal cancer in humans, understand the mechanisms by which these agents reduce risk for the disease, and develop "treatable" biomarkers of risk for colorectal cancer, we conducted a pilot, randomized, double-blind, placebo-controlled, 2 x 2 factorial clinical trial to test the effects of calcium and vitamin D3, alone and in combination on markers of apoptosis, in the normal colorectal mucosa. Ninety-two men and women with at least one pathology-confirmed colorectal adenoma were treated with 2.0 g/d calcium or 800 IU/d vitamin D3, alone or in combination, versus placebo over 6 months. Overall expression and colorectal crypt distributions of Bcl-2 (an apoptosis inhibitor) and Bax (an apoptosis promoter) in biopsies of normal-appearing rectal mucosa were detected by automated immunohistochemistry and quantified by image analysis. After 6 months of treatment, Bax expression along the full lengths of crypts increased 56% (P = 0.02) in the vitamin D group and 33% in both the calcium (P = 0.31) and calcium plus vitamin D (P = 0.36) groups relative to the placebo group. The vitamin D treatment effect was more pronounced in the upper 40%, or differentiation zone, of crypts (80%; P = 0.01). There were no statistically significant treatment effects on Bcl-2 expression. Overall, these preliminary results suggest that calcium and vitamin D, individually or together, may enhance apoptosis in the normal human colorectal epithelium, and the strongest treatment effects may be vitamin D related and in the upper sections of the colorectal crypts.

Cancer Epidemiology Biomarkers & Prevention, 2009

To characterize the expression of the mismatch repair gene MutL-homolog 1 (MLH1) in normal colore... more To characterize the expression of the mismatch repair gene MutL-homolog 1 (MLH1) in normal colorectal crypts in humans, and assess parameters of its expression as a potential biomarker of risk for colorectal neoplasms, we conducted a pilot, colonoscopy-based case-control study (51 cases, 154 controls) of incident, sporadic colorectal adenoma. Biopsies of normal-appearing rectal, sigmoid, and ascending colon mucosa were procured, immunohistochemically processed for MLH1 protein, and analyzed using custom quantitative image analysis procedures. MLH1 expression in the ascending colon was, on average, 49% proportionally lower in cases than controls (P = 0.03), but there was little evidence for case-control differences in the rectum and sigmoid colon. In cases and controls, average MLH1 expression in the ascending colon tended to be lower with increased age [by 56% (P = 0.02) and 25% (P = 0.16), respectively, for those > or =55 years], and with a history of colorectal cancer in a first-degree relative (by 22% [P = 0.56] and 34% [P = 0.16], respectively). Among cases, but not controls, average MLH1 expression tended to be higher with current alcohol consumption, regular aspirin use, and higher total intakes of calcium, vitamin D, and folate. There was little indication of similar differences in the rectum. These preliminary data suggest that lower MLH1 expression in the normal colonic mucosa, at least in the ascending colon, may be associated with increased risk of incident, sporadic colorectal adenoma, as well as with modifiable risk factors for colorectal neoplasms, thus supporting further investigation of MLH1 expression as a potential "treatable" biomarker of risk for colorectal neoplasms.

Cancer Causes & Control, 2008

Despite compelling basic science evidence, the search for causal associations linking specific pr... more Despite compelling basic science evidence, the search for causal associations linking specific pro- and anti-oxidants to presumably oxidative stress-related neoplasms, such as colorectal adenoma, has produced inconsistent results. We developed an oxidative balance score (OBS) to characterize the pro-oxidant and anti-oxidant exposures of 2,305 participants in a case-control study of colorectal adenoma that used both endoscopy-confirmed and community controls. Twelve lifestyle medical and dietary factors with known pro- or anti-oxidant properties were considered. Each high anti-oxidant exposure and low pro-oxidant exposure was awarded one or two points depending on the level of exposure, and the points for each OBS component were summed. We observed a significant inverse association between OBS (continuous variable) and colorectal adenoma in the analyses with either community, or endoscopy controls (each p-trend < 0.01). When the OBS was treated as an ordinal variable and a score of <or=3 points was used as the referent category, in the analyses with the endoscopy controls the adjusted odds ratios for scores of 4-6, 7-9, 10-12, 13-15, and 16+, were 0.42, 0.32, 0.22, 0.20, and 0.19, respectively, with all 95% confidence intervals excluding 1.0. The corresponding analysis for community controls showed a similar trend. Our findings are in line with the basic science evidence supporting the role of oxidative stress in colorectal neoplasia.

American Journal of Preventive Medicine, 2015

Research suggests that community involvement is integral to solving public health problems, inclu... more Research suggests that community involvement is integral to solving public health problems, including involvement in clinical trials-a gold standard. Significant racial/ethnic disparities exist in the accrual of participants for clinical trials. Location and cultural aspects of clinical trials influence recruitment and accrual to clinical trials. It is increasingly necessary to be aware of defining characteristics, such as location and culture of the populations from which research participants are enrolled. Little research has examined the effect of location and cultural competency in adapting clinical trial research for minority and underserved communities on accrual for clinical trials. Utilizing embedded community academic sites, the authors applied cultural competency frameworks to adapt clinical trial research in order to increase minority participation in nontherapeutic cancer clinical trials. This strategy resulted in successful accrual of participants to new clinical research trials, specifically targeting participation from minority and underserved communities in metropolitan Washington, DC. From 2012 to 2014, a total of 559 participants enrolled across six nontherapeutic clinical trials, representing a 62% increase in the enrollment of blacks in clinical research. Embedding cancer prevention programs and research in the community was shown to be yet another important strategy in the arsenal of approaches that can potentially enhance clinical research enrollment and capacity. The analyses showed that the capacity to acquire cultural knowledge about patients-their physical locales, cultural values, and environments in which they live-is essential to recruiting culturally and ethnically diverse population samples.

BMC Complementary and Alternative Medicine

Chemoprevention crossover trials of tea can be more efficient than parallel designs but the attri... more Chemoprevention crossover trials of tea can be more efficient than parallel designs but the attrition and compliance rates with such trials are unknown. Attrition (dropouts) and compliance with treatment were assessed in a 25-week randomized, placebo controlled, crossover, feasibility clinical trial of four tea treatments to investigate the effect of tea on oral cancer biomarkers. Each treatment lasted 4 weeks with 2 weeks of washout in between. Participants were 32 smokers and 33 non-smokers without any evidence of premalignant oral lesions. The interventions consisted of packets of green tea, black tea, caffeinated water, or placebo. Participants were assigned to each treatment for four weeks, and were instructed to drink five packets per day while on the treatment. Dropout from the trial and compliance (consumption of ≥85% of the prescribed treatment packets) are the main outcome measures reported. There was a high rate of dropout (51%) from the study, and the rates were signific...

Cancer Epidemiology Biomarkers & Prevention, 2014

Contemporary Clinical Trials, 2015

Metabolic syndrome and obesity are known risk factors for breast cancers. Exercise interventions ... more Metabolic syndrome and obesity are known risk factors for breast cancers. Exercise interventions can potentially modify circulating biomarkers of breast cancer risk but evidence in African-Americans and women with metabolic syndrome is lacking. The Focused Intervention on Exercise to Reduce CancEr (FIERCE) trial is a prospective, 6-month, 3-arm, randomized controlled trial to examine the effect of exercise on obesity, metabolic syndrome components, and breast cancer biomarkers among African-American women at high risk of breast cancer. Two hundred-forty inactive women with metabolic syndrome and absolute risk of breast cancer ≥1.40 will be randomized to one of the three trial arms: 1) a supervised, facility-based exercise arm; 2) a home-based exercise arm; and 3) a control group that maintains physical activity levels through the course of the trial. Assessments will be conducted at baseline, 3months, and 6months. The primary outcome variables are anthropometric indicators of obesity, metabolic syndrome components, and inflammatory, insulin-pathway, and hormonal biomarkers of breast cancer risk. The FIERCE trial will provide evidence on whether a short-term exercise intervention might be effective in reducing breast cancer risk among African-American women with comorbidities and high breast cancer risk - a group traditionally under-represented in non-therapeutic breast cancer trials. NCT02103140.

Journal of Clinical Gastroenterology, 2015

Hepatocellular carcinoma (HCC) surveillance in patients with cirrhosis is aimed at early detectio... more Hepatocellular carcinoma (HCC) surveillance in patients with cirrhosis is aimed at early detection so that effective therapeutic options may be offered. We undertook this study to assess the patterns of surveillance that had been offered to HCC patients evaluated at our center, and the effect of these strategies on outcome. Consecutive patients, age 18 years and older, diagnosed with HCC between December 2007 and December 2012 were identified. Surveillance was defined as α-fetoprotein measurement and/or imaging examination in the 12 months before HCC diagnosis. Logistic regression and survival analysis models were utilized to investigate the association of surveillance with patient characteristics and survival. A total of 305 patients with HCC and a background of cirrhosis were analyzed. HCC was detected by surveillance in 131 patients (43%). Of those who underwent surveillance, 92% were diagnosed with early-stage cancer (stages I and II) compared with 62% of those who did not undergo surveillance (P<0.001). The rate of surgical therapy (hepatic resection and liver transplantation) was almost doubled in the surveillance group (61% vs. 33%, P<0.05). At median follow-up of 27.3 months, overall survival was high at 55% and surveillance was significantly associated with longer survival (P=0.006). At our center, surveillance efficacy for HCC detection was notably higher than earlier reported. Patients who underwent surveillance were more likely to have their tumors detected at an early stage, to qualify for surgical therapy, and to have improved survival.

Journal of Transplantation, 2014

The efficacy of liver transplantation (LT) for hepatocellular (HCC) is limited by tumor recurrenc... more The efficacy of liver transplantation (LT) for hepatocellular (HCC) is limited by tumor recurrence rates of 10-15%. We undertook this pilot study to examine the use of sorafenib as adjuvant therapy in high-risk LT recipients. Methods. We prospectively enrolled patients transplanted for HCC into a treatment protocol utilizing sorafenib if their explant examination showed evidence of viable tumor exceeding Milan criteria. We utilized as historical controls patients transplanted previously, whose explant tumor characteristics exceeded Milan criteria, but who were not "preemptively" treated with sorafenib. Wilcoxon two-sample test and Fisher's exact test were used to compare survival and recurrence rates between the two groups. Results. Seven patients were treated with sorafenib and compared to 12 historical "controls. " Two of 7 treated patients suffered from HCC recurrence. Of the comparison group, 9 experienced HCC recurrence and all succumbed to disease. Dose reduction improved tolerance of drug. The overall rate of HCC recurrence was decreased in the adjuvant therapy group compared to historical controls (29% versus 75%, = 0.07). Disease free 1-year survival for the treated versus untreated group was 100% versus 66%, respectively. Conclusion. Adjuvant use of sorafenib is safe and decreases risk of HCC recurrence in high-risk LT recipients.

American Journal of Epidemiology, 2015

Although oxidative stress is implicated in colorectal carcinogenesis, human studies on associatio... more Although oxidative stress is implicated in colorectal carcinogenesis, human studies on associations of individual prooxidants and antioxidants with colorectal cancer (CRC) have been inconclusive. We incorporated individual environmental factors known to affect oxidative stress into 4 oxidative balance scores (OBS) and investigated their associations with CRC in the Cancer Prevention Study II Nutrition Cohort. During 1999-2009, a total of 1,109 incident CRC cases were identified among 80,063 participants in the Nutrition Cohort who had completed detailed questionnaires. Four OBS with different weighting methods (equal weights, literature review-based, a posteriori data-based, and weights based on Bayesian analysis) were created by combining 16 dietary and nondietary lifestyle factors. Higher values for all 4 OBS, representing more antioxidant exposures than prooxidant exposures, were associated with 41%-53% lower risks of CRC; for example, the relative risk for the highest OBS quartile versus the lowest in the Bayesian analysis was 0.50 (95% confidence interval: 0.41, 0.61). The associations were more modest when OBS was restricted to either dietary or nondietary components. These results, obtained using comprehensive summary measures of oxidative balance-especially considering the similarity of the findings derived using the different weighting methods-support the hypothesis that a predominance of antioxidant lifestyle exposures (both dietary and nondietary) over prooxidant lifestyle exposures reduces risk of CRC.

Frontiers in Oncology, 2012

Background: Fatigue is a common side effect of conventional prostate cancer radiation therapy. Th... more Background: Fatigue is a common side effect of conventional prostate cancer radiation therapy. The increased delivery precision necessitated by the high dose per fraction of stereotactic body radiation therapy (SBRT) offers the potential of reduce target volumes and hence the exposure of normal tissues to high radiation doses. Herein, we examine the level of fatigue associated with SBRT treatment. Methods: Forty patients with localized prostate cancer treated with hypofractionated SBRT, and a minimum of 12 months followup were included in this analysis. Self-reported fatigue and other quality of life measures were assessed at baseline and at 1, 3, 6, 9, and 12 months post-SBRT. Results: Mean levels of fatigue were elevated at 1 month post-SBRT compared to baseline values (P = 0.02). Fatigue at the 3-month follow-up and later were higher but not statistically significantly different compared to baseline. African-American patients reported higher fatigue post-SBRT than Caucasian patients. Fatigue was correlated with hormonal symptoms as measured by the Expanded Prostate Cancer Index Composite (EPIC) quality of life questionnaire, but not with urinary, bowel, or sexual symptoms. Age, co-morbidities, smoking, prostate specific antigen (PSA) levels, testosterone levels, tumor stage, and treatment variables were not associated with fatigue. Conclusion: This is the first study to investigate fatigue as a side effect of SBRT. In contrast to standard radiation therapy, results suggest SBRTrelated fatigue is short-term rather than a long-term side effect of SBRT. These results also suggest post-SBRT fatigue to be a more frequent complication in African-Americans than Caucasians.

Supportive Care in Cancer, 2014

Purpose With advancements in detection and treatment, the number of breast cancer survivors is gr... more Purpose With advancements in detection and treatment, the number of breast cancer survivors is growing. To reduce mortality among survivors, tailored health-promotion programs are needed to combat comorbidities. However, the demand for such programs exceed that which is available for a vastly diverse population of survivors. The goal of the present study was to describe the prevalence of comorbidities in a group of breast cancer survivors and to examine associations between biological proximal factors of and the more distal individuallevel factors on the number and types of comorbidities. Methods In addition to medical chart reviews, breast cancer survivors (N=369) from hospitals in two urban locations completed self-report measures. Bivariate analyses examined the relationship between distal and proximal predictors and the outcomes: number of comorbidities and comorbidity types.

Urologic Oncology: Seminars and Original Investigations, 2014

Background: Bladder cancer is the most prevalent form of cancer in men among Egyptians, for whom ... more Background: Bladder cancer is the most prevalent form of cancer in men among Egyptians, for whom tobacco smoke exposure and Schistosoma haematobium (SH) infection are the major risk factors. We hypothesized that functional polymorphisms in NAD(P)H:quinone oxidoreductase 1 (NQO1) and superoxide dismutase 2 (SOD2), modulators of the effects of reactive oxidative species, can influence an individual's susceptibility to these carcinogenic exposures and hence the risk of bladder cancer.

The Breast, 2011

Background: Recent epidemiologic and laboratory studies have suggested that non-steroidal antiinf... more Background: Recent epidemiologic and laboratory studies have suggested that non-steroidal antiinflammatory drugs (NSAIDs) may reduce the risk of breast cancer through inhibition of cyclooxygenase-2 (COX-2). Methods: We conducted a caseecontrol study to measure the association between selective cox-2 inhibitors, particularly celecoxib, rofecoxib, valdecoxib and non-specific NSAID subgroups, and breast cancer risk. Between 2003 and 2006, a total of 18,368 incident breast cancer cases were identified in the Ingenix/Lab Rx insurance database, which contains clinical encounter and drug prescription data. Four controls per case were randomly selected, matched on age and time in database. Odds ratios (OR) and 95% confidence intervals (CI) were estimated using conditional logistic regression. Results: Breast cancer risk was inversely associated with both non-specific NSAID and selective COX-2 inhibitor use. Greater than 12 months' duration of use of Celecoxib at a standard dose (200 mg/day) was associated with a 16% decrease in breast cancer risk (OR ¼ 0.84, 95% CI ¼ 0.73, 0.97). We observed the greatest risk reduction in association with >2 years of rofecoxib exposure (OR ¼ 0.54, 95% CI ¼ 0.37, 0.80). Acetaminophen, a compound with less biological plausibility for chemoprevention, showed no significant association with the risk of developing breast cancer. Conclusion: Consistent with animal models and laboratory investigations, higher doses of selective COX-2 inhibitors were more protective against breast cancer than non-specific NSAIDs. With exposure to rofecoxib, a selective COX-2 inhibitor, breast cancer risk reduction was appreciable (46%), suggesting a possible role for selective COX-2 inhibitors in breast cancer prophylaxis.

Mutation Research/Reviews in Mutation Research, 2006

UK PubMed Central (UKPMC) is an archive of life sciences journal literature.

Journal of Community Genetics, 2014

Although research involving biospecimens is essential in advancing cancer research, minorities, e... more Although research involving biospecimens is essential in advancing cancer research, minorities, especially African-Americans, are underrepresented in such research. We conducted a mixed-method (qualitative focus groups among African-Americans and quantitative cross-sectional surveys) study on factors associated with biospecimen knowledge and donation intent in the medically underserved urban communities in Southeast and Southwest Washington, DC. Focus groups were conducted among 41 African-Americans and survey data was available from 302 community residents of different races/ethnicities using convenience sampling. We used logistic regression to model the association between biospecimen knowledge and donation intent with selected sociodemographic variables using survey data. Only 47 % of the participants had knowledge of the different types of biospecimens. In multivariate logistic regression models, male gender, African-American race, and low education levels were significantly associated with lower knowledge about biospecimens. Compared to Whites (79 %), fewer African-Americans (39 %) and Hispanics (57 %) had knowledge of biospecimens but the difference was significant for African-Americans only. Positive intent to donate biospecimens for research was observed among 36 % of the survey respondents. After multivariate adjustment, only biospecimen knowledge was associated with donation intent (odds ratio = 1.91, 95 % confidence interval 1.12, 3.27). Contrary to popular opinion, "mistrust of the medical community" was not the most commonly reported barrier for biospecimen donation among African-Americans. "Not knowing how biospecimens will be used" and "lack of knowledge of biospecimens" were the most common barriers. Our study highlights the importance of education on biospecimens among community residents to increase minority participation in biospecimen research.

Clinical Gastroenterology and Hepatology, 2007

Up to 25% of hepatocellular carcinomas (HCCs) seen in U.S. centers are of unknown etiology. Anima... more Up to 25% of hepatocellular carcinomas (HCCs) seen in U.S. centers are of unknown etiology. Animal studies suggest that hypothyroidism can directly cause liver cell damage and might be a risk factor for HCC. We conducted a case-control study to evaluate the relationship between hypothyroidism and HCC. Cases (n = 54) were HCC patients seen at Mayo Clinic Rochester in whom no underlying etiology for chronic liver disease could be determined. Two groups of controls were selected, HCC patients with HCV (n = 57) and HCC patients with alcoholic liver disease (n = 49). Hypothyroidism was defined as thyroid-stimulating hormone level >5.0, history of hypothyroidism before HCC diagnosis, or a history of being on thyroid replacement at the time of HCC diagnosis. We used multivariate logistic regression to model the relationship between hypothyroidism and HCC etiology. Of the 160 patients, 18 (11%) had a history of hypothyroidism. Twelve (22%) of those with no known etiology for HCC, 2 (4%) of those with HCV, and 4 (8%) of those with alcoholic liver disease had hypothyroidism. Patients with HCC of unknown etiology were significantly more likely to have a history of hypothyroidism as compared with HCC patients with HCV (adjusted odds ratio, 12.7; 95% confidence interval, 1.4-117.1) and as compared with all controls (adjusted odds ratio, 6.8; 95% confidence interval, 1.1-42.1). Hypothyroidism is more prevalent in HCC patients with an unknown etiology. It should be further investigated as a potential risk factor in liver carcinogenesis.

Cancer Prevention Research, 2009

To further clarify and/or develop calcium and vitamin D as chemopreventive agents against colorec... more To further clarify and/or develop calcium and vitamin D as chemopreventive agents against colorectal cancer in humans, understand the mechanisms by which these agents reduce risk for the disease, and develop "treatable" biomarkers of risk for colorectal cancer, we conducted a pilot, randomized, double-blind, placebo-controlled, 2 x 2 factorial clinical trial to test the effects of calcium and vitamin D3, alone and in combination on markers of apoptosis, in the normal colorectal mucosa. Ninety-two men and women with at least one pathology-confirmed colorectal adenoma were treated with 2.0 g/d calcium or 800 IU/d vitamin D3, alone or in combination, versus placebo over 6 months. Overall expression and colorectal crypt distributions of Bcl-2 (an apoptosis inhibitor) and Bax (an apoptosis promoter) in biopsies of normal-appearing rectal mucosa were detected by automated immunohistochemistry and quantified by image analysis. After 6 months of treatment, Bax expression along the full lengths of crypts increased 56% (P = 0.02) in the vitamin D group and 33% in both the calcium (P = 0.31) and calcium plus vitamin D (P = 0.36) groups relative to the placebo group. The vitamin D treatment effect was more pronounced in the upper 40%, or differentiation zone, of crypts (80%; P = 0.01). There were no statistically significant treatment effects on Bcl-2 expression. Overall, these preliminary results suggest that calcium and vitamin D, individually or together, may enhance apoptosis in the normal human colorectal epithelium, and the strongest treatment effects may be vitamin D related and in the upper sections of the colorectal crypts.

Cancer Epidemiology Biomarkers & Prevention, 2009

To characterize the expression of the mismatch repair gene MutL-homolog 1 (MLH1) in normal colore... more To characterize the expression of the mismatch repair gene MutL-homolog 1 (MLH1) in normal colorectal crypts in humans, and assess parameters of its expression as a potential biomarker of risk for colorectal neoplasms, we conducted a pilot, colonoscopy-based case-control study (51 cases, 154 controls) of incident, sporadic colorectal adenoma. Biopsies of normal-appearing rectal, sigmoid, and ascending colon mucosa were procured, immunohistochemically processed for MLH1 protein, and analyzed using custom quantitative image analysis procedures. MLH1 expression in the ascending colon was, on average, 49% proportionally lower in cases than controls (P = 0.03), but there was little evidence for case-control differences in the rectum and sigmoid colon. In cases and controls, average MLH1 expression in the ascending colon tended to be lower with increased age [by 56% (P = 0.02) and 25% (P = 0.16), respectively, for those > or =55 years], and with a history of colorectal cancer in a first-degree relative (by 22% [P = 0.56] and 34% [P = 0.16], respectively). Among cases, but not controls, average MLH1 expression tended to be higher with current alcohol consumption, regular aspirin use, and higher total intakes of calcium, vitamin D, and folate. There was little indication of similar differences in the rectum. These preliminary data suggest that lower MLH1 expression in the normal colonic mucosa, at least in the ascending colon, may be associated with increased risk of incident, sporadic colorectal adenoma, as well as with modifiable risk factors for colorectal neoplasms, thus supporting further investigation of MLH1 expression as a potential "treatable" biomarker of risk for colorectal neoplasms.

Cancer Causes & Control, 2008

Despite compelling basic science evidence, the search for causal associations linking specific pr... more Despite compelling basic science evidence, the search for causal associations linking specific pro- and anti-oxidants to presumably oxidative stress-related neoplasms, such as colorectal adenoma, has produced inconsistent results. We developed an oxidative balance score (OBS) to characterize the pro-oxidant and anti-oxidant exposures of 2,305 participants in a case-control study of colorectal adenoma that used both endoscopy-confirmed and community controls. Twelve lifestyle medical and dietary factors with known pro- or anti-oxidant properties were considered. Each high anti-oxidant exposure and low pro-oxidant exposure was awarded one or two points depending on the level of exposure, and the points for each OBS component were summed. We observed a significant inverse association between OBS (continuous variable) and colorectal adenoma in the analyses with either community, or endoscopy controls (each p-trend < 0.01). When the OBS was treated as an ordinal variable and a score of <or=3 points was used as the referent category, in the analyses with the endoscopy controls the adjusted odds ratios for scores of 4-6, 7-9, 10-12, 13-15, and 16+, were 0.42, 0.32, 0.22, 0.20, and 0.19, respectively, with all 95% confidence intervals excluding 1.0. The corresponding analysis for community controls showed a similar trend. Our findings are in line with the basic science evidence supporting the role of oxidative stress in colorectal neoplasia.