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It is unclear whether the different histologic subtypes of epithelial ovarian carcinoma have different risk factors. We investigated the relationships between selected epidemiologic variables (i.e., parity, family history of ovarian cancer, oral contraceptive use, a history of tubal ligation and noncontraceptive estrogen use) and the major histologic subtypes of epithelial ovarian cancer in a hospital-based case-control study of adult women at Roswell Park Cancer Institute in Buffalo, NY, USA. Multivariate unconditional logistic regression models were used for statistical analysis. We observed a pattern of increased risk associated with family history and a pattern of risk reduction associated with parity, noncontraceptive estrogen use and tubal ligation across all histologic subtype groups. However, we did not observe a consistent pattern of risk associated with oral contraceptive use. These results provide some additional support for the hypothesis that the effects of various ovarian cancer risk factors may differ according to the histologic subtype.

Abstract Due to the low survival rates from invasive ovarian cancer, new effective treatment modalities are urgently needed. Compelling evidence indicates that the immune response against ovarian cancer may play an important role in controlling this disease. We herein summarize multiple immune-based strategies that have been proposed and tested for potential therapeutic benefit against advanced stage ovarian cancer. We will examine the evidence for the premise that an effective therapeutic vaccine against ovarian cancer is useful not only for inducing remission of the disease but also for preventing disease relapse. We will also highlight the questions and challenges in the development of ovarian cancer vaccines, and critically discuss the limitations of some of the existing immunotherapeutic strategies. Finally, we will summarize our own experience on the use of patient-specific tumor-derived heat shock protein-peptide complex for the treatment of advanced ovarian cancer.

Abstract Background Uncontrolled proliferation and increased motility are hallmarks of neoplastic cells, therefore markers of proliferation and motility may be valuable in assessing tumor progression and prognosis. MCM2 is a member of the minichromosome maintenance (MCM) protein family. It plays critical roles in the initiation of DNA replication and in replication fork movement, and is intimately related to cell proliferation. Ki-67 is a proliferation antigen that is expressed during all but G0 phases of the cell cycle. Gelsolin is an actin-binding protein that regulates the integrity of the actin cytoskeletal structure and facilitates cell motility. In this study, we assessed the prognostic significance of MCM2 and Ki-67, two markers of proliferation, and gelsolin, a marker of motility, in non-small cell lung cancer (NSCLC). Methods 128 patients with pathologically confirmed, resectable NSCLC (stage I-IIIA) were included. Immunohistochemistry was utilized to measure the expressions of these markers in formalin-fixed, paraffin-embedded tumor tissues. Staining and scoring of MCM2, Ki-67 and gelsolin was independently performed. Analyses were performed to evaluate the prognostic significance of single expression of each marker, as well as the prognostic significance of composite expressions of MCM2 and gelsolin. Cox regression and Kaplan-Meier survival analysis were used for statistical analysis. Results Of the three markers, higher levels of gelsolin were significantly associated with an increased risk of death (adjusted RR = 1.89, 95% CI = 1.17–3.05, p = 0.01), and higher levels of MCM2 were associated with a non-significant increased risk of death (adjusted RR = 1.36, 95% CI = 0.84–2.20, p = 0.22). Combined, adjusted analyses revealed a significantly poor prognostic effect for higher expression of MCM2 and gelsolin compared to low expression of both biomarkers (RR = 2.32, 95% CI = 1.21–4.45, p = 0.01). Ki-67 did not display apparent prognostic effect in this study sample. Conclusion The results suggest that higher tumor proliferation and motility may be important in the prognosis of NSCLC, and composite application of biomarkers might be of greater value than single marker application in assessing tumor prognosis.

Abstract Background We consider how representations of geographic variation in prostate cancer incidence across Southern New England, USA may be affected by selection of study area and/or properties of the statistical analysis. Method A spatial scan statistic was used to monitor geographic variation among 35,167 incident prostate cancer cases diagnosed in Massachusetts, Connecticut and Rhode Island from 1994 to 1998, in relation to the 1990 populations of men 20+ years of age living in that region. Results from the combined-states analysis were compared to those from single-states. Impact of scanning procedures set to examine up to 50% or no more than10% of at-risk populations also was evaluated. Results With scanning set to 50%, 5 locations in the combined-states analysis were identified with markedly distinct incidence rates. Fewer than expected cases were estimated for nearly all Connecticut, Rhode Island and West Central Massachusetts, whereas census tracts on and around Cape Cod, and areas of Southwestern Connecticut and adjacent to greater Boston were estimated to have yielded more than expected incidence. Results of single-state analyses exhibited several discrepancies from the combined-states analysis. More conservative scanning found many more locations with varying incidence, but discrepancies between the combined- and single-state analysis were fewer. Conclusion It is important to acknowledge the conditional nature of spatial analyses and carefully consider whether a true cluster of events is identified or artifact stemming from selection of study area size and/or scanning properties.

Abstract Background Although a large number of epidemiological studies have examined the role of aspirin in the chemoprevention of colon cancer and other solid tumors, there is a limited body of research focusing on the association between aspirin and lung cancer risk. Methods We conducted a hospital-based case-control study to evaluate the role of regular aspirin use in lung cancer etiology. Study participants included 868 cases with primary, incident lung cancer and 935 hospital controls with non-neoplastic conditions who completed a comprehensive epidemiological questionnaire. Participants were classified as regular aspirin users if they had taken the drug at least once a week for at least one year. Results Results indicated that lung cancer risk was significantly lower for aspirin users compared to non-users (adjusted OR = 0.57; 95% CI 0.41–0.78). Although there was no clear evidence of a dose-response relationship, we observed risk reductions associated with greater frequency of use. Similarly, prolonged duration of use and increasing tablet years (tablets per day × years of use) was associated with reduced lung cancer risk. Risk reductions were observed in both sexes, but significant dose response relationships were only seen among male participants. When the analyses were restricted to former and current smokers, participants with the lowest cigarette exposure tended to benefit most from the potential chemopreventive effect of aspirin. After stratification by histology, regular aspirin use was significantly associated with reduced risk of small cell lung cancer and non-small cell lung cancer. Conclusions Overall, results from this hospital-based case-control study suggest that regular aspirin use may be associated with reduced risk of lung cancer.

Background: Worse survival persists for African-Americans (AA) with breast cancer compared to other race/ethnic groups despite recent improvements for all. Unstudied in outcomes disparities to date is soluble LAG-3 (sLAG-3), cleaved from the LAG-3 immune checkpoint receptor which is a proposed target for deactivation in emerging immunotherapies due to its prominent immunosuppressive function in the tumoral microenvironment. A prior study has found that lower sLAG-3 baseline level was associated with poor outcomes., Methods: In a cross-sectional study of 95 patients with primary breast cancer (n = 58 Caucasian, n = 37 AA), we measured sLAG-3 (ELISA pg/ml) in pre-treatment blood samples using the non-parametric Mann-Whitney u-Test for independent samples, and, calculated Pearson r correlation coefficients of sLAG-3 with circulating cytokines by race., Results: Mean sLAG-3 level was lower in AA compared to Caucasian patients (1377.6 vs 3690.3, P = .002), and in patients with triple-negative breast cancer (TNBC) compared to those with non-TNBC malignancies (P = .02). When patients with TNBC tumors were excluded from analyses, the difference in sLAG-3 level between AA (n = 21) and Caucasian patients (n = 40) substantially remained (1937.4 vs 4182.4, P = .06). Among Caucasian patients, sLAG-3 was correlated with IL-6, IL-8 and IL-10 (r = .69, P < .001; r = .70, P < .001; and, r = .46, P = .01; respectively). For AA patients, sLAG-3 was correlated only with IL-6 (r = .37, P = .03)., Conclusions: We present the first report that African-American breast cancer patients might have comparatively low pre-treatment sLAG-3 levels, independent of TNBC status, along with reduced co-expression with circulating cytokines. The mechanistic and prognostic role of cleaved LAG-3, particularly in disparate outcomes, remains to be elucidated., (© 2024. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Preclinical evidence indicates the potential anti-tumor capabilities of cannabinoids in prostate cancer (PC). We undertook a cross-sectional study using National Survey on Drug Use and Health data from 2002 to 2020, involving 2503 participants in the USA. The independent variable was marijuana use status (current, former, never), while the dependent variable was self-reported PC (yes, no). Eleven other demographic variables were assessed as covariates. PC prevalence was lower among current marijuana users (46/145, 31.7%) and former users (323/1021, 31.6%) compared to non-users (534/1337, 39.9%, p < 0.001). PC prevalence was lower among users versus non-users in the elderly (≥65) (36.4% vs. 42.4%, p = 0.016) and non-Hispanic white subgroups (28.9% vs. 38.3%, p < 0.001). There were no significant PC prevalence differences between users and non-users in the younger population (50-64) or other race/ethnicity. In the multivariable analyses, former marijuana use was associated with lower PC compared to never using (odd ratio = 0.74, 95% CI 0.62-0.90, p = 0.001). Current use was also suggestive of reduced prevalence but was not statistically significant (odd ratio = 0.77, 95% CI 0.52-1.14, p = 0.198), possibly due to low sample size. Our findings from a large national survey provide additional data to link marijuana use with lower PC prevalence.

Objective: A more detailed understanding of unmet organizational support needs and workplace-based best practices for supporting cancer survivors is needed., Methods: Ninety-four working breast cancer survivors responded to an open-ended survey question regarding the desired types of organizational support that were and were not received during early survivorship. We performed content-analysis of qualitative data., Results: Major themes included instrumental support, emotional support, and time-based support. The need for flexible arrangements and reduced workloads was mostly met. Unmet needs included navigation/coordination, understanding/empathy, and time off for treatment and recovery., Conclusions: Organizational support can help cancer survivors manage their health and work roles, diminishing work-health conflict and turnover intent. Study findings can be used to design targeted interventions to fulfill cancer survivors' unmet organizational support needs, which may also apply to workers with other chronic health conditions., Competing Interests: Conflicts of interest: None declared., (Copyright © 2023 American College of Occupational and Environmental Medicine.)

Background and Objectives: The literature supporting Mohs micrographic surgery and staged excision in treating primary cutaneous melanoma is growing but has not been critically reviewed for bias., Methods: Articles concerning Mohs micrographic surgery and staged excision for melanoma were assessed using modified "Risk of Bias in Non-randomized Studies of Interventions" (ROBINS-I) criteria, which measures bias in 7 categories., Results: Forty-seven of 48 (97.9%) studies reviewed had serious or critical bias. None were randomized controlled trials. The most frequent cause of critical bias was poorly defined outcomes. The least frequent form of bias observed was change in intervention., Limitations: The modified ROBINS-I criteria cannot account for all study limitations. Modification of the criteria leads to some degree of subjectivity., Conclusion: The current body of literature suffers from limitations due to serious or critical bias in 1 or more ROBINS-I criteria. Local recurrence rate definitions are often poorly defined or not defined at all. Longer follow-up times, clear tumor classifications, and prospective, randomized study designs are necessary to improve the quality of future research., Competing Interests: Conflicts of interest None disclosed., (Copyright © 2021 American Academy of Dermatology, Inc. Published by Elsevier Inc. All rights reserved.)

Aim: This meta-research study aimed to investigate the level of compliance with the Sex and Gender Equity in Research (SAGER) Guidelines for the inclusion, analysis, and reporting of sex/gender, in periodontitis-related randomized controlled trials (RCTs)., Materials and Methods: Following the inclusion of RCTs related to the treatment of periodontitis published between 2018 and 2019, we applied the SAGER checklist to assess the adherence to sex/gender reporting guidelines. We used non-parametric descriptive statistics and correlation models to test the association of the dependent outcome with other variables., Results: One hundred and one articles were included in the analysis. The female enrolment ranged between 30% and 94%. Twenty-six studies enrolled less than 50% of female participants. The overall SAGER score (OSS) of item fulfilment ranged between 0 and 7 items with an average of 1.9 items signifying poor guideline adherence to the SAGER guidelines. These findings were not associated with the corresponding author gender (p = .623), publication year (p = .947), and funding source (p = .133). However, a significant but negative correlation with journal impact factor (r = -0.253, p = .026) was observed., Conclusions: Sex and gender were frequently disregarded in clinical trial reporting. This oversight might limit the understanding of sex/gender differences in periodontitis-related clinical trials., (© 2022 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

Introduction: The impact of demand ischemia on clinical outcomes in patients with delirium remains largely unexplored. This study aims to evaluate the effects of demand ischemia in older patients with delirium on in-hospital mortality and length of stay (LOS) using the largest US inpatient care database, National Inpatient Sample (NIS)., Methods: We obtained data from the year 2010 to 2014 National Inpatient Sample (NIS). We used the International Classification of Diseases-Ninth Edition-Clinical Modification (ICD-9-CM) diagnosis codes to identify all the records with a primary or secondary diagnosis of delirium with or without demand ischemia and other clinical characteristics. We then compared in-hospital mortality and length of stay (LOS) in patients with and without demand ischemia., Results: We analyzed 232,137 records. Patients with demand ischemia had higher overall in-hospital mortality than those without demand ischemia (28 vs. 12%, p < 0.001). After adjusting for clinical comorbidities and complications, demand ischemia was no longer associated with increased in-hospital mortality (OR: 1.14; 95% CI: 0.96-1.35; p = 0.141). However, further analysis with the exclusion of critically ill patients with non-cardiogenic shock or mechanical ventilation showed a significant association of demand ischemia with increased in-hospital mortality (adjusted OR: 1.39; 95% CI: 1.13-1.71; p = 0.002). Among non-critically ill survivors, patients with demand ischemia had a longer median LOS [4, (3-7) days] than those without demand ischemia [4, (2-6) days] ( p < 0.001). However, the difference was not statistically significant after adjustment for covariates., Conclusion/relevance: Demand ischemia did not affect mortality in critically sick patients. In non-critically ill patients, however, demand ischemia was significantly associated with increased in-hospital mortality, likely due to the severity of the underlying acute illness. Measures aimed at mitigating risk factors that contribute to delirium and/or demand ischemia need to be explored., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Kumar, Patil, Godoy, Kuo, Swede, Kuchel and Chen.)

Background: Immune-related adverse events (irAEs) are a major toxicity of immune checkpoint inhibitors. Studies have reported that pre-existing autoimmunity increases the risk of irAEs, but it remains unknown which clinical factors are linked to auto-immune disorders in cancer patients. This study aimed to evaluate if the prevalence of autoimmune diseases varied by specific cancer history and advanced age., Methods: Our cross-sectional medical record review consisted of 291,333 patients (age, ≥18 years) treated between 2000 and 2018. Patients were classified into four study groups (melanoma only, non-cutaneous solid cancer only, melanoma and non-cutaneous cancer, and no cancer history). Dependent variable was the presence of ≥1 autoimmune disorders based on 98 conditions using 317 ICD codes., Results: Non-cutaneous cancer, in the absence or presence of melanoma, was associated with a higher prevalence of autoimmunity (16.5, 95% CI 16.1-16.9; 20.0, 95% CI 18.3-21.7, respectively) compared to the rates in patients with melanoma only and those without cancer history (9.3, 95% CI 8.6-10.0; 6.2, 95% CI 6.1-6.3, respectively). Among patients with metastases at initial presentation, those in the melanoma and non-cutaneous cancer group had a prevalence of 24.0% (95% CI 20.1-27.9) compared to 19.1% (95% CI 17.2-21.0) in those without metastases. Multiple logistic regression demonstrated that patients > 75 years exhibited the highest odds of autoimmunity relative to other age groups, with age 18-34 as the referent (OR, 1.78, 95% CI 1.67-1.89)., Conclusions: Among patients with melanoma, the greatest prevalence of autoimmunity occurred with advanced age and a history of non-cutaneous cancer., (© 2021. The Author(s).)

Purpose: A substantial portion of breast cancer survivors are active in the workforce, yet factors that allow survivors to balance work with cancer management and to return to work are poorly understood. We examined breast cancer survivors' most valued/desired types of support in early survivorship., Methods: Seventy-six employed breast cancer survivors answered an open-ended survey question assessing the most valued/desired support to receive from healthcare providers during early survivorship to manage work and health. Cutrona's (Journal of Social and Clinical Psychology 9:3-14, 1990) optimal matching theory and House's (1981) conceptualization of social support types informed our analyses. Data were content-analyzed to identify themes related to support, whether needed support was received or not, and the types of healthcare providers who provided support., Results: We identified six themes related to types of support. Informational support was valued and mostly received by survivors, but they expected more guidance related to work. Emotional support was valued but lacking, attributed mainly to providers' lack of personal connection and mental health support. Instrumental (practical) support was valued but received by a small number of participants. Quality of life support to promote well-being and functionality was valued and often received. Other themes included non-specific support and non-support., Conclusions: This study expands our understanding of how breast cancer survivors perceive work-related support from healthcare professionals. Findings will inform targeted interventions designed to improve the support provided by healthcare professionals., Implications for Cancer Survivors: Breast cancer survivors managing work and health challenges may benefit by having their unmet support needs fulfilled., (© 2021. The Author(s), under exclusive licence to Springer Science+Business Media, LLC part of Springer Nature.)

Objective: We sought to determine if leisure-time physical activity (LTPA) modified the adverse relationship between high job demands and nonrestorative sleep (NRS)., Methods: We conducted a multivariate logistic regression analysis among workers from the cross-sectional National Healthy Worksite Project (n = 4683) using self-report Likert-Scale data on psychological and physical demands of jobs, LTPA and general health in relation to NRS., Results: Not engaging in LTPA was associated with NRS for workers with jobs at the lowest or highest levels of the physical demand scale (OR 1.64, 95% CI: 0.96-2.81, OR 2.06, 95% CI: 0.95-4.45; respectively) in comparison to those who met LTPA recommendations. When assessing psychological demands, poor general health was associated with NRS at all levels of the scale independent of LTPA., Conclusions: LTPA may reduce NRS for workers with jobs at either extreme of physical demands., Competing Interests: The authors report no conflict of interest., (Copyright © 2021 American College of Occupational and Environmental Medicine.)

Background: Colorectal cancer (CRC) is the third most common cancer worldwide and the second leading cause of cancer-related deaths. Given the significant prevalence of CRC, regular preventative screening is required. CRCs in different locations of the colon have variable molecular pathogenesis, gross appearance, and general disease outcomes. While the overall incidence of CRC has been decreasing, the decrease in proximally located CRC significantly lags behind the other forms of CRC. The objective of this study was to establish independent risk factors for proximal CRC for better identification of populations at risk for closer CRC monitoring and observation., Methods: A time-trend analysis was conducted using data from the National Cancer Institute's Surveillance, Epidemiology, and End Results (SEER) database from 1973-2007, comparing patient characteristics (age, sex, race/ethnicity, year of diagnosis, age of diagnosis, tumor grade, tumor stage, and urban-rural setting) between CRCs originating in different locations., Results: Analysis demonstrated that black race, female sex, age over 60, and being diagnosed in the 21st century (rather than 20th) were associated with an increased risk of proximal CRC compared to CRCs originating in other locations., Conclusions: Our study showed that black race, female sex, and age over 60 independently increased the likelihood of proximal CRC diagnosis. Furthermore, CRC trends identify an increasing proportion of all CRCs being of proximal origin. It is imperative that patients undergo regularly scheduled complete colonoscopies by trained endoscopists, especially if they belong to the high-risk groups previously identified., Competing Interests: Conflict of Interest: None, (Copyright: © Hellenic Society of Gastroenterology.)

Objective: Poor reporting in randomized clinical trial (RCT) abstracts reduces quality and misinforms readers. Spin, a biased presentation of findings, could frequently mislead clinicians to accept a clinical intervention despite non-significant primary outcome. Therefore, good reporting practices and absence of spin enhances research quality. We aim to assess the reporting quality and spin in abstracts of RCTs evaluating the effect of periodontal therapy on cardiovascular (CVD) outcomes., Methods: PubMed, Scopus, the Cochrane Central Register of Controlled Trials (CENTRAL), and 17 trial registration platforms were searched. Cohort, non-randomized, non-English studies, and pediatric studies were excluded. RCT abstracts were reviewed by 2 authors using the CONSORT for abstracts and spin checklists for data extraction. Cohen's Kappa statistic was used to assess inter-rater agreement. Data on the selected RCT publication metrics were collected. Descriptive analysis was performed with non-parametric methods. Correlation analysis between quality, spin and bibliometric parameters was conducted., Results: 24 RCTs were selected for CONSORT analysis and 14 fulfilled the criteria for spin analysis. Several important RCT elements per CONSORT were neglected in the abstract including description of the study population (100%), explicitly stated primary outcome (87%), methods of randomization and blinding (100%), trial registration (87%). No RCT examined true outcomes (CVD events). A significant fraction of the abstracts appeared with at least one form of spin in the results and conclusions (86%) and claimed some treatment benefit in spite of non-significant primary outcome (64%). High-quality reporting had a significant positive correlation with reporting of trial registration (p = 0.04) and funding (p = 0.009). Spinning showed marginal negative correlation with reporting quality (p = 0.059)., Conclusion: Poor adherence to the CONSORT guidelines and high levels of data spin were found in abstracts of RCTs exploring the effects of periodontal therapy on CVD outcomes. Our findings indicate that journal editors and reviewers should consider strict adherence to proper reporting guidelines to improve reporting quality and reduce waste., Competing Interests: No authors have competing interest.

We tested the hypothesis that successful weight loss post-bariatric surgery would be associated with healthier chemosensory function, food likes, and dietary behaviors than either unsuccessful weight loss or pre-surgery morbid obesity. In a case-control design, pre-surgical women with morbid obesity ( n = 49) were compared with those 1-year post-surgery (24 Roux-en-Y Bypass, 24 Sleeve Gastrectomy) and defined by excess or percent weight loss as successful/unsuccessful. For self-reported smell/taste perception, more post-surgery than pre-surgery reported improved/distorted perception, especially if weight loss successful. Measured taste function (perceived quinine and NaCl intensity) was lower among weight loss unsuccessful versus pre-surgery patients, yet a genetic variation in taste probe (propylthiouracil bitterness) matched expected frequencies without significant pre/post-surgery difference. Regarding survey-reported liking, higher diet quality was seen in the weight loss successful (independent of surgery type) versus pre-surgical patients, with differences driven by lower sweet and refined carbohydrate liking. The post versus pre-surgical patients had greater restraint but less hunger and disinhibition. Patients reporting both higher diet quality and lower hunger showed greater % weight loss, independent of surgery type. Thus, successful weight loss 1-year post-bariatric surgery was associated with improved or distorted chemosensation and patterns of liking associated with healthier diets, especially if coupled with less hunger., Competing Interests: The authors declare no conflict of interest. The funders had no role in the design of the study; in the collection, analyses, or interpretation of data; in the writing of the manuscript, or in the decision to publish the results.

African-American (AA) cancer patients have long-experienced worse outcomes compared to non-Hispanic whites (NHW). No studies to date have evaluated the prognostic impact of sickle cell trait (SCT) and other inherited haemoglobinopathies, of which several are disproportionately high in the AA population. In a cohort analysis of treated patients diagnosed with breast or prostate cancer in the linked SEER-Medicare database, the relative risk (RR) for ≥1 serious adverse events (AEs), defined as hospitalisations or emergency department visits, was estimated for 371 AA patients with a haemoglobinopathy (AA+) compared to patients without haemoglobinopathies (17,303 AA-; 144,863 NHW-). AA+ patients had significantly increased risk for ≥1 AEs compared to AA- (RR = 1.19; 95% CI 1.11-1.27) and NHW- (RR = 1.23; 95% CI 1.15-1.31) patients. The magnitude of effect was similar by cancer type, and in analyses of AA+ with SCT only. Our findings suggest a novel hypothesis for disparities in cancer outcomes.

Objectives: We examined the association between three inflammatory markers (Interleukin (IL)-6, C-reactive protein (CRP), tumor necrosis factor (TNF)-α) and incident lung cancer using baseline, updated, and averaged inflammatory measures in older adults., Methods: We fitted multivariable Cox models to assess whether circulating levels of inflammation markers were associated with incident lung cancers in the Health Aging, Body and Composition (HealthABC) prospective cohort of 3075 older adults aged 70-79 years at baseline. IL-6 and CRP were measured biennially, whereas TNF-α was measured at baseline., Results: Baseline levels of IL-6 were significantly associated with incident lung cancer risk in a model that adjusted for age, gender, race, and site (Model 1) (Hazard Ratio T3 vs. T1 : 3.34, 95% Confidence Interval: 1.91, 5.85) and in a model adjusted for health factors linked to chronic inflammation (Model 2) (HR T3 vs. T1 : 2.57, 95% CI: 1.41, 4.65). The associations observed in time-updated IL-6 (HR T3 vs. T1 : 2.47, 95% CI: 1.43, 4.28), cumulatively averaged IL-6 (HR T3 vs. T1 : 2.47, 95% CI: 1.43, 4.35), and baseline CRP levels (HR T3 vs. T1 : 1.85, 95% CI: 1.11, 3.08) with incident lung cancer in Model 1 were not statistically significant in Model 2., Conclusions: Baseline CRP and IL-6 levels were associated with increased risk of lung cancer in Model 1 and both models, respectively. Chronic IL-6 inflammation, as quantified by repeated measures was associated with incident lung cancer in Model 1, but not Model 2. Further research is needed to understand the role of CRP and IL-6 in lung carcinogenesis., (Copyright © 2018 Elsevier Inc. All rights reserved.)

Purpose: Excess dietary fat consumption is strongly associated with the risk of colorectal cancer, but less is known about its role in the earliest stages of carcinogenesis, particularly within the proximal colon. In the following case-control study, we evaluated the relationship between the intake of dietary fats and the frequency of early proximal neoplasia [aberrant crypt foci (ACF) or polyps], detectable by high-definition colonoscopy with contrast dye-spray., Methods: Average-risk screening individuals underwent a high-definition colonoscopy procedure as part of larger ongoing clinical study of precancerous lesions in the proximal colon. Dietary fat intake was assessed using the Block Brief Food Frequency Questionnaire, which estimates average dietary intake based on 70 food items. The diets of individuals with no endoscopically identifiable lesions (n = 36) were compared to those with either ACF or polyps detected in the proximal colon., Results: In multivariate analysis, high dietary intake of total polyunsaturated fatty acids (PUFAs) and intake of omega-6 and omega-3 fatty acids were positively associated with neoplastic lesions in the proximal colon. When comparing ACF and polyp groups separately, a positive association was observed for both proximal polyps (OR 2.28; CI 1.16-7.09) and ACF (OR 2.86; CI 1.16-7.09) for total PUFA intake. Furthermore, the prevalence of proximal ACF was increased with higher intake of omega-6 (OR 3.54; CI 1.32-9.47) and omega-3 fatty acids (OR 2.29; CI 1.02-5.13), although there was no discernible difference in the omega-6/omega-3 ratio., Conclusions: These results suggest that dietary PUFAs may be positively associated with risk of early neoplasia in the proximal colon. This study provides further evidence that dietary PUFA composition may play an important role in altering the microenvironment within the human colon.

Objective: Variation in taste perception and exposure to risk factors of taste alterations have been independently linked with elevated adiposity. Using a laboratory database, taste-adiposity associations were modeled and examined for whether taste functioning mediates the association between taste-related risk factors and adiposity., Methods: Healthy women (n = 407, 35.5 ± 16.9 y) self-reported histories of risk factors of altered taste functioning (tonsillectomy, multiple ear infections, head trauma) and were assessed for taste functioning (tongue-tip and whole-mouth intensities of quinine and salt) and density of taste papillae. Twenty-four percent had elevated waist circumferences; thirty-nine percent had overweight or obesity. Using structural equation modeling, direct and indirect associations between taste-related risk factors, taste functioning, and adiposity were tested., Results: In models with good fit, elevated central adiposity was explained directly by history of risk factors (tonsillectomy, multiple ear infections) and directly by lower taste functioning (lower tongue-tip taste function, lower papillae density). Risk factors of taste alterations were significantly associated with lower taste functioning, with taste mediating the association between head trauma and reduced adiposity., Conclusions: This large laboratory-based study supports associations between taste-related risk factors, taste functioning, and adiposity. These findings need to be confirmed with other population-based studies, including the National Health and Nutrition Examination Survey 2013-2014 taste data., (© 2017 The Obesity Society.)

Background: Several technologies have been developed to aid dermatologists in the detection of melanoma in vivo including dermoscopy, multispectral digital skin lesion analysis (MDSLA), and reflectance confocal microscopy (RCM). To our knowledge, there have been no studies directly comparing MDSLA and RCM., Objective: We conducted a repeated measures analysis comparing the sensitivity and specificity of MDSLA and RCM in the detection of melanoma (n = 55 lesions from 36 patients)., Methods: Study patients (n = 36) with atypical-appearing pigmented lesions (n = 55) underwent imaging by both RCM and MDSLA. Lesions were biopsied and analyzed by histopathology., Results: RCM exhibited superior test metrics (P = .001, McNemar test) compared with MDSLA. Respectively, sensitivity measures were 85.7% and 71.4%, and specificity rates were 66.7% and 25.0%., Limitations: The sample size was relatively small and was collected from only one dermatologist's patient base; there was some degree of dermatopathologist interobserver variability; and only one confocalist performed the RCM image evaluations., Conclusion: RCM is a useful adjunct during clinical assessment of in vivo lesions suspicious for melanoma or those requiring re-excision because of high level of dysplasia or having features consistent with an atypical melanocytic nevus with severe cytologic atypia., (Copyright © 2016 American Academy of Dermatology, Inc. Published by Elsevier Inc. All rights reserved.)

Mortality from metastatic cutaneous melanoma is substantially heterogeneous as reflected in three distant metastatic (M1) subtypes with metastasis to skin, subcutaneous tissue, or distant lymph nodes (M1a), conferring nearly half the risk of death compared with distant visceral metastasis (M1c). It remains unknown whether older patients experience the survival benefit from the M1a subtype given a higher overall mortality risk. Surveillance, Epidemiology, and End Result data were retrieved from 1878 metastatic melanoma patients, from 2005 to 2009, with follow-up through 2011. Hazard ratios (HRs) for 2-year overall survival were estimated for M1 subtypes among older (≥65) and younger (<65) patients. Proportional subdistribution hazard ratios (SHRs) were calculated for melanoma-specific and competing risk mortality. For both older and younger patients, worse overall survival was observed for the M1c compared to the M1a subtype [HR: 2.65, 95% confidence interval (CI): 2.02-3.49; and, SHR: 3.36, 95% CI: 2.56-4.41; respectively]. For competing mortality, older compared to younger patients had increased risk in the M1a and M1b subtypes (SHR: 6.07, 95% CI: 1.94-19.0, and SHR: 2.34, 95% CI: 1.08-5.05, respectively). Conversely, when examining melanoma-specific mortality, older patients had decreased risk in M1a and M1b subtypes (SHR: 0.28, 95% CI: 0.14-0.53, and SHR: 0.60, 95% CI: 0.38-0.94, respectively) compared to those under 65 years. The persistent prognostic advantage of M1a among older patients should be considered when calculating the risk-benefit ratio for treatment. Prior reports of a protective effect of older age on melanoma-specific mortality, when based on traditional competing risks analyses, might be explained as an artifact of increased competing mortality risk.

Purpose: A comparatively high prevalence of comorbidities among African-American/Blacks (AA/B) has been implicated in disparate survival in breast cancer. There is a scarcity of data, however, if this effect persists when accounting for the adverse triple-negative breast cancer (TNBC) subtype which occurs at threefold the rate in AA/B compared to white breast cancer patients., Methods: We reviewed charts of 214 white and 202 AA/B breast cancer patients in the NCI-SEER Connecticut Tumor Registry who were diagnosed in 2000-2007. We employed the Charlson Co-Morbidity Index (CCI), a weighted 17-item tool to predict risk of death in cancer populations. Cox survival analyses estimated hazard ratios (HRs) for all-cause mortality in relation to TNBC and CCI adjusting for clinicopathological factors., Results: Among patients with SEER local stage, TNBC increased the risk of death (HR 2.18, 95 % CI 1.14-4.16), which was attenuated when the CCI score was added to the model (Adj. HR 1.50, 95 % CI 0.74-3.01). Conversely, the adverse impact of the CCI score persisted when controlling for TNBC (Adj. HR 1.49, 95 % CI 1.29-1.71; per one point increase). Similar patterns were observed in SEER regional stage, but estimated HRs were lower. AA/B patients with a CCI score of ≥3 had a significantly higher risk of death compared to AA/B patients without comorbidities (Adj. HR 5.65, 95 % CI 2.90-11.02). A lower and nonsignificant effect was observed for whites with a CCI of ≥3 (Adj. HR 1.90, 95 % CI 0.68-5.29)., Conclusions: comorbidities at diagnosis increase risk of death independent of TNBC, and AA/B patients may be disproportionately at risk.

Evidence of the association between chronic inflammation and the risk of colorectal cancer (CRC) and other obesity-related cancers (OBRC) remains inconsistent, possibly due to a paucity of studies examining repeated measures of inflammation. In the Health ABC prospective study of 2,490 adults aged 70-79 years at baseline, we assessed whether circulating levels of three markers of systemic inflammation, IL-6, CRP and TNF-α, were associated with the risk of CRC and OBRC, a cluster including cancers of pancreas, prostate, breast and endometrium. Inflammatory markers were measured in stored fasting blood samples. While only baseline measures of TNF-α were available, IL-6 and CRP were additionally measured at Years 2, 4, 6 and 8. Multivariable Cox models were fit to determine whether tertiles and log-transformed baseline, updated and averaged measures of CRP and IL-6 and baseline measures of TNF-α were associated with the risk of incident cancer(s). During a median follow-up of 11.9 years, we observed 55 and 172 cases of CRC and OBRC, respectively. The hazard of CRC in the highest tertile of updated CRP was more than double that in the lowest tertile (HR = 2.29; 95% CI: 1.08-4.86). No significant associations were seen between colorectal cancer and IL-6 or TNF-α. Additionally, no significant associations were found between obesity-related cancers and the three inflammatory markers overall, but we observed a suggestion of effect modification by BMI and NSAID use. In summary, in this population, higher CRP levels were associated with increased risk of CRC, but not of OBRC. The findings provide new evidence that chronically elevated levels of CRP, as reflected by repeated measures of this marker, may play a role in colorectal carcinogenesis in older adults., (© 2015 UICC.)

Purpose: Based on suggestive findings from a recent study of high-risk Japanese patients, we sought to determine whether the risk of colorectal polyps associated with smoking may be modified by daily use of aspirin in an analysis of a large US screening population., Methods: This is a cross-sectional study of 2,918 consecutive colonoscopy patients at a university hospital over a 30-month period. Data were abstracted from electronic medical records. Multivariate models of polyp counts were used to examine the competing risks of smoking and aspirin use. Models were further stratified by polyp location (proximal vs. distal) and pathologic subtype (dysplastic vs. serrated)., Results: Incidental rate of polyps was higher among active smokers [incidence rate ratio (IRR) 1.72; 95 % confidence interval (CI) 1.46-2.02] and lower among daily aspirin users (IRR 0.73; 95 % CI 0.61-0.86) compared to those who used neither. Smoking interacts significantly with aspirin use resulting in loss of aspirin protection (IRR 1.69; 95 % CI 1.28-2.24). Stratified analyses demonstrate that aspirin specifically reduces the risk of traditional dysplastic adenomas (IRR 0.72; 95 % CI 0.61-0.86) not serrated/hyperplastic polyps (IRR 0.92; 95 % CI 0.72-1.17) and that the modification of aspirin protection by smoking is primarily observed within the distal colorectum (p < 0.03)., Conclusions: We report for the first time, in a typical risk US clinical population, a lack of protective association of aspirin for polyps among active smokers. Future prospective studies are recommended to confirm this mitigating effect in order to improve the precision of the growing evidence base about the chemopreventive benefit of aspirin in colorectal cancer.

Objectives: We considered changes in the geographic distribution of early stage breast cancer among White and non-White women while secular trends in lifestyle and health care were under way., Methods: We aggregated tumor registry and census data by age, race, place of residence, and year of diagnosis to evaluate rate variation across Connecticut census tracts between 1985 and 2009. Global and local cluster detection tests were completed., Results: Age-adjusted incidence rates increased by 2.71% and 0.44% per year for White and non-White women, respectively. Significant global clustering was identified during surveillance of these populations, but the elements of clustering differed between groups. Among White women, fewer local clusters were detected after 1985 to 1989, whereas clustering increased over time among non-White women., Conclusions: Small-area variation of breast cancer incidence rates across time periods proved to be dynamic and race-specific. Incidence rates might have been affected by secular trends in lifestyle or health care. Single cross-sectional analyses might have confused our understanding of disease occurrence by not accounting for the social context in which patient preferences or provider capacity influence the numbers and locations of diagnosed cases. Serial analyses are recommended to identify "hot spots" where persistent geographic disparities in incidence occur.

Purpose: Given the relatively high prevalence of sickle cell trait and disease among African Americans and established racial disparities in cancer outcomes, we reviewed the literature regarding adverse events in cancer patients with these hematologic genotypes. Erythrocyte sickling can result from extreme hypoxia and other physiologic stressors, as might occur during cancer therapy. Further, tumoral hypoxia, a poor prognostic and predictive factor, could lead to a cycle of local sickling and increased hypoxia., Methods: A search of PubMed produced 150 publications, most of which were excluded because of incidental relevance. Eleven case reports of patients diagnosed from 1993 to 2013 were reviewed., Results: Two reports of patients with sickle cell trait describe an abundance of sickled erythrocytes within tumors, and a third report describes sickling-related events requiring multiday hospitalization. Eight reports of patients with sickle cell disease delineated multiorgan failure, vaso-occlusive crises, and rapid renal deterioration. Hypothesized triggers are delayed clearance of anticancer agents attributable to baseline kidney damage, activation of vasoadherent neutrophils from treatment to counter chemotherapy-induced neutropenia, hypoxia from general anesthesia, and intratumoral hypoxia., Conclusion: Clinical implications include pretreatment genotyping for prophylaxis, dose adjustment, and enhanced patient monitoring. With the current lack of high-quality evidence, however, the scope of poor outcomes remains unknown.

Several prospective studies suggest that C-reactive protein (CRP), a nonspecific serologic marker of inflammation, might be linked to risk of colorectal cancer (CRC), whereas others have reported null or protective effects. We analyzed data from 7,072 participants (50-85 years) in the U.S. National Health and Nutrition Examination Survey III (1988-1994), a nationally representative cohort (n = 33,994; 2 months-85 years) with vital status follow-up to 2000. Hazard ratios (HRs) for mortality associated with baseline clinically raised (≥1.00 mg/dL) and intermediate (≥0.22-0.99 mg/dL) CRP levels were estimated using Cox proportional hazards regression controlling for CRC risk factors. There were 59 deaths from CRC, 106 from other obesity-related cancers (other-ORCs) and 1,130 from cardiovascular disease (CVD). Participants with clinically raised CRP at baseline were found to have a statistically significant greater risk of CRC death (HRs = 2.36-2.47) in comparison to persons with undetected levels. HRs were lower for death from other-ORC and CVD (1.82, 95% CI 1.05-3.15; 1.53, 95% CI 1.29-1.81, respectively). Intermediate CRP level was associated with a nonsignificant 10-21% increased risk for CRC death. HR for CRC death was higher among persons with a normal BMI (2.16, 95% 0.96-4.87, p = 0.06) compared to those who were overweight (1.22, 95% CI 0.53-2.78) or obese (1.23, 95% CI, 0.37-4.08). A similar pattern was observed for waist circumference. This effect modification suggests that the impact of chronic inflammation may be independent of excess body fat. Future research is recommended to confirm emerging data that elevated serologic CRP might reflect underlying colonic inflammation., (© 2013 UICC.)

Objective: In comparison to non-Hispanic whites, a number of health-care disparities, including poor oral health, have been identified among Hispanics in general and Mexican Americans in particular. We hypothesized that Mexican Americans with chronic kidney disease (CKD) would have higher prevalence of chronic periodontitis compared with Mexican Americans with normal kidney function, and that the level of kidney function would be inversely related to the prevalence of periodontal disease., Methods: We examined this hypothesis using the National Health and Nutrition Examination Survey 1988-1994 (NHANES III) data set. We followed the American Academy of Periodontology/Center for Disease Control and Prevention case definition for periodontitis. Glomerular filtration rate was estimated using the CKD-Epidemiology equation for Hispanic populations. The classification to CKD stages was based on the National Kidney Foundation Kidney Disease Outcomes Quality Initiative., Results: Periodontitis prevalence increased across the kidney function groups showing a statistically significant dose-response association (P<0.001). Mexican Americans with reduced kidney function were twofold more likely to have periodontitis compared with Mexican Americans with normal kidney function after adjusting for potential confounders such as smoking, diabetes, and socioeconomic status. Multivariate adjusted odds ratio for periodontitis significantly increased with 1, 5, and 10 mL/minute estimated glomerular filtration rate reduction from the mean., Conclusion: This is the first report, to the best our knowledge, that showed an increase of periodontitis prevalence with decreased kidney function in this population., (© 2012 American Association of Public Health Dentistry.)

Objective: To estimate the risk for colorectal neoplasia detected on repeat colonoscopy in relation to aberrant crypt foci (ACF) frequency reported during the previous baseline examination., Methods: From July 2003 until December 2008, patients had a colonoscopy with an ACF study using a magnifying colonoscope. The distal 20 cm section of colon was sprayed with Methylene Blue to ascertain the ACF frequency, the independent variable. Patients were categorized into low and high ACF count using the median as the cut point. Data collected from consenting patients included age, gender, height, weight, ethnicity, smoking history, family history of colorectal cancer (CRC), and personal history of colorectal neoplasia. A follow-up colonoscopy was performed at an interval as dictated by clinical surveillance guidelines. The main outcome was surveillance detected advanced colorectal neoplasia (SDAN) detected on repeat colonoscopy. Logistic Regression was used to calculate risk of SDAN on repeat colonoscopy in relation to baseline ACF count., Results: 74 patients had a baseline ACF exam and a repeat surveillance colonoscopy. The median ACF was six and thus a high ACF count was >6 ACF and a low ACF count was ≤6 ACF. Patients diagnosed with SDAN were more likely to have had a high ACF number at baseline compared to patients without these lesions at follow-up (adjusted odds ratio = 12.27; 95% confidence interval: 2.00-75.25) controlling for age, sex, smoking, history of prior adenoma, family history of colon cancer, obesity, and time interval to surveillance exam. A sub analysis of our results demonstrated that this relationship was observed in 48 patients who were undergoing a surveillance colonoscopy for a previous adenoma and not those receiving surveillance for a family history of neoplasia., Conclusions: Increased number of ACF in the distal colorectum was independently associated with substantial risk for future advanced neoplasia. This relationship was observed in patients undergoing surveillance for previous adenomas. Thus, ACF may serve as potential biomarkers in patients with adenomas to help identify patients who may need additional surveillance.

Background: During the multiyear progression to colorectal cancer, numerous genomic alterations arise in events ranging from single base mutations to gains or losses of entire chromosomes. A single genetic change might not stand out as an independent predictor of outcome. The goal of this study was to determine if more comprehensive measurements of genomic instability provide clinically relevant prognostic information., Methods: Our study included 65 sporadic colorectal cancer patients diagnosed from 1987 to 1991 with last follow-up ascertained in 2006. We estimated an overall tally of alterations using the genome-wide sampling technique of inter-(simple sequence repeat [SSR]) polymerase chain reaction (PCR), and evaluated its relationship with all-cause survival. We also extended and sensitized the Bethesda criteria for microsatellite instability (MSI), by analyzing 348 microsatellite markers instead of the normal five. We expanded the MSI categories into four levels: MSI stable (MSS), very low-level MSI, moderately low-level MSI, and classical high-level MSI., Results: Tumors with genomic instability above the median value of 2.6% as measured by inter-SSR PCR, were associated with far greater risk of death compared to tumors with lower levels of genomic instability. Adverse outcome was most pronounced for patients presenting with stage 3 disease. A gradient of increased survival was observed across increasing MSI levels but did not reach statistical significance., Conclusion: Our findings suggest genomic instabilities quantified by inter-SSR PCR and increased precision in MSI values may be clinically useful tools for estimating prognosis in colorectal cancer.

Introduction: Emerging research suggests a substantially greater prevalence of the adverse triple-negative (TN) subtype (human epidermal growth factor receptor [HER]2(-), estrogen receptor [ER](-), and progesterone receptor [PR])(-)) among black patients with breast cancer. No reports however have been generated from a statewide cancer registry., Patients and Methods: The study consisted of all black patients (N = 643) and a random sample of white patients (n = 719) diagnosed with primary invasive breast cancer (2000-2003) listed in the National Cancer Institute-Surveillance Epidemiology and End Results (NCI-SEER) Connecticut Tumor Registry (CTR). HER2 status was obtained from pathology reports submitted to the registry. Remaining data were obtained from the registry database., Results: TN tumors were more prevalent in black compared with white patients (30.8% vs. 11.2%, respectively; P < .001.) There was a 2-fold greater frequency of ER(-) and PR(-) phenotypes among black patients, but HER2 status did not differ by race. Patients with lobular cancer were less likely to have TN breast cancer compared with patients with ductal tumors (odds ratio [OR] = 0.23; 95% confidence interval [CI], 0.10-0.58). Among patients with regional disease, black patients exhibited increased risk of death (relative risk [RR] = 2.71; 95% CI, 1.48-4.97) independent of TN status. No survival disparity was found among patients with local disease., Discussion: These registry-based data corroborate reports that TN breast cancer varies substantially by race and histologic subtype. A survival disparity among patients with advanced disease, but not local disease, casts some doubt on TN status as an explanation for differences., Conclusion: More research is warranted to understand why black patients with advanced breast cancer may be at increased risk for death whether or not their tumors express the TN phenotype., (Copyright © 2011 Elsevier Inc. All rights reserved.)

Background: Psychosocial factors may impact cancer risk but sex differences in this domain are understudied. Examining psychosocial factors, such as depression and social support, among colon cancer patients allows for a unique opportunity to study sex differences in the association between psychosocial factors and colon cancer risk in this population., Objective: The primary aim of this study was to evaluate sex differences in the association between key psychosocial factors and aberrant crypt foci (ACF), a putative biomarker of colon cancer risk. We hypothesized that higher levels of depression in women and lower levels of social support in men were associated with greater numbers of ACF among individuals at heightened risk for colon cancer., Methods: Participants were self-referred or referred by physicians for routine colonoscopy. Within 2 weeks before colonoscopy, participants completed standardized measures assessing psychosocial factors. At colonoscopy, individuals were examined for ACF frequency in the distal 20 cm of the colorectum. Regression β weights were used to examine the association between the psychosocial factors and ACF., Results: A total of 93 individuals (51% women, 49% men) consented to the study. Among women, higher levels of depressive symptoms were associated with greater numbers of ACF; among men, lower levels of social support were associated with greater numbers of ACF., Conclusions: These results suggest that although colon cancer affects men and women equally with regard to morbidity and mortality rates, there were important sex differences in how psychosocial variables were related to colon cancer risk. Psychosocial interventions aimed at targeting these types of factors are warranted but need to consider the role of sex., (Copyright © 2011 Elsevier HS Journals, Inc. All rights reserved.)

Background: MicroRNAs (miRNAs) are small non-coding RNAs (18-24 nucleotides) that have recently been shown to regulate gene expression during cancer progression. Dicer, a central enzyme in the multi-component miRNA biogenesis pathway, is involved in cutting precursor miRNAs to functionally mature forms. Emerging evidence shows that Dicer expression is deregulated in some human malignancies and it correlates with tumor progression, yet this role has not yet been investigated in skin cancers., Methods and Findings: Using an anti-human monoclonal antibody against Dicer and immunohistochemistry, we compared the expression of Dicer protein among 404 clinically annotated controls and skin tumors consisting of melanocytic nevi (n = 71), a variety of melanomas (n = 223), carcinomas (n = 73) and sarcomas (n = 12). Results showed a cell-specific up-regulated Dicer in 81% of cutaneous, 80% of acrolentiginous and 96% of metastatic melanoma specimens compared to carcinoma or sarcoma specimens (P<0.0001). The expression of Dicer was significantly higher in melanomas compared to benign melanocytic nevi (P<0.0001). In patients with cutaneous melanomas, Dicer up-regulation was found to be significantly associated with an increased tumor mitotic index (P = 0.04), Breslow's depth of invasion (P = 0.03), nodal metastasis (P = 0.04) and a higher American Joint Committee on Caner (AJCC) clinical stage (P = 0.009). Using western blot analysis, we confirmed the cell-specific up-regulation of Dicer protein in vitro. A pooled-analysis on mRNA profiling in cutaneous tumors showed up-regulation of Dicer at the RNA level in cutaneous melanoma, also showing deregulation of other enzymes that participate in the biogenesis and maturation of canonical miRNAs., Conclusions: Increased Dicer expression may be a clinically useful biomarker for patients with cutaneous melanoma. Understanding deregulation of Dicer and its influence on miRNA maturation is needed to predict the susceptibility of melanoma patients to miRNA-based therapy in the future.

Objectives: The American College of Gastroenterology has published guidelines recently that suggest that smokers with a history of >20 pack years may need screening for colorectal cancer (CRC) at an earlier age than non-smokers. Aberrant crypt foci (ACF) may represent important precursors for colorectal neoplasms and potential surrogate biomarkers. Clarifying the role of ACF in relation to known CRC risk factors such as smoking may have important implications for screening as well as our understanding of tobacco use and colorectal carcinogenesis. Our goal was to examine whether smoking at least 20 pack years was associated with an increased frequency of ACF., Methods: We gathered detailed smoking history, personal and family history of CRC, and other epidemiologic data (age, gender, height, weight, ethnicity, and medication use) from 125 patients undergoing routine screening or surveillance colonoscopy. We used a magnifying colonoscope (Olympus Close Focus Colonoscope XCF-Q160ALE, Olympus Corporation, Tokyo, Japan) and examined the distal 20 cm section of colon after staining with 0.5% methylene blue. ACF were counted and characterized histologically. Hyperplastic ACF were further characterized as either serrated or non-serrated., Results: Smoking at least 20 pack years was associated with an increased likelihood (adjusted odds ratio (OR)=3.45; 95% confidence interval (CI)=1.93-6.18) of having more than the median number of ACF (> or = 15) compared with non-smokers. Similarly, patients with a personal history of advanced neoplasia were more likely (adjusted OR=3.42; 95% CI=1.01-11.67) to have a greater than median number of ACF compared with patients without this diagnosis. Smokers were more likely than non-smokers to have serrated ACF (P=0.002)., Conclusions: Smoking at least 20 pack years seems to be associated with increased number of ACF in the rectum and distal sigmoid, especially those with serrated histology. Our data support ACG guidelines for earlier screening for CRC among smokers and add to our understanding of how colorectal carcinogenesis is related to tobacco use.

Due to the low survival rates from invasive ovarian cancer, new effective treatment modalities are urgently needed. Compelling evidence indicates that the immune response against ovarian cancer may play an important role in controlling this disease. We herein summarize multiple immune-based strategies that have been proposed and tested for potential therapeutic benefit against advanced stage ovarian cancer. We will examine the evidence for the premise that an effective therapeutic vaccine against ovarian cancer is useful not only for inducing remission of the disease but also for preventing disease relapse. We will also highlight the questions and challenges in the development of ovarian cancer vaccines, and critically discuss the limitations of some of the existing immunotherapeutic strategies. Finally, we will summarize our own experience on the use of patient-specific tumor-derived heat shock protein-peptide complex for the treatment of advanced ovarian cancer.

Background: Women with invasive breast cancer should be tested for human epidermal growth factor receptor-2 (HER2) status at the time of diagnosis. To date, no population-based patterns of use studies have examined demographic and clinicopathologic factors associated with decisions by clinicians to test patients., Methods: We reviewed summary pathology reports submitted to the Connecticut Tumor Registry for all Black/African American (B/AA) women (n=644) and a 7% random sample (n=720) of White women diagnosed in 2000-2003 with primary invasive breast carcinoma. Receipt of a HER2 test (yes vs. no) was examined in relation to patient race, age, socioeconomic status, year of diagnosis, estrogen receptor (ER) status, tumor grade, lymph node status, size and stage at diagnosis., Results: A greater proportion of tumors from B/AA patients were tested compared to those of White women (69.5% vs. 61.9%, p<0.05). Tumors of patients under the age of 60 were 1.50-times more likely than older women to have been tested, and B/AA women were 1.40-times more likely than White patients to be tested. HER2 testing was more likely to be observed when information also was reported about ER status (OR=15.9, p<0.001), tumor grade (OR=2.28, p<0.05), tumor size (OR=2.16, p<0.05), and lymph node status (OR=2.06, p<0.05)., Conclusions: Variation in which breast cancer patients received HER2 testing appears to reflect expectations about a woman's prognosis. Discrepancies in receipt of testing deserve further study as current guidelines call for all tumors to be assessed in order to adequately characterize prognosis and determine eligibility for HER2-targeted therapy.

Background: Dysregulation of the insulin-like growth factor (IGF) system, a common consequence of adiposity-induced insulin resistance, may be a key underlying mechanism linking excess body weight with colon cancer. Evidence has been derived from studies of cancer and polyps. Supporting data about aberrant crypt foci (ACF), putative pre-polyp changes, have been generated only from animal studies to date., Methods: We randomly selected 26 patients with sex-specific elevated waist-hip-ratio (WHR) and 26 with normal values from a series of 150 patients seeking routine colonoscopy at the University of Connecticut Health Center. Cross-sectional analyses were performed of ACF number (<5, > or = 5) in relation to total IGF1, IGF-binding protein-3 (IGFBP3), insulin, body mass index (BMI), WHR and waist circumference (WC). Visualized ACF in the 20 cm of the distal colon were counted using advanced endoscopic imaging., Results: Patients with > or = 5 ACF had higher BMI, WHR, and WC compared with patients with >5 ACF (p = 0.04, p = 0.03, and p = 0.01, respectively). IGFBP3 was reduced (p = 0.02) and IGF1:IGFBP3 molar ratio was greater (p = 0.03) in patients with > or = 5 ACF. We did not observe significant associations between ACF number and insulin or total IGF1., Conclusions: Our study provides the first report in humans of a possible association of ACF prevalence and IGF1 bioavailability as characterized by IGF1:IGFBP3 molar ratio and IGFBP3 level. More research is needed to determine whether this relationship is varied by ACF features (e.g., size, dysplasia, molecular changes), synchronous cancer and polyps, and is modified by colon cancer risk factors.

TGFbeta is involved in the response to DNA damage and signaling the cell cycle checkpoint response, in large part achieved by modulating the activity of the ATM kinase. We have investigated if the presence of a common polymorphism in the TGFbeta receptor TGFBR1 might impact genomic instability in human colorectal cancer. In order to obtain statistically significant numbers of patients with the lesser polymorphism, 177 colorectal cancer patients were genotyped for either the major form of the TGFBR1 receptor gene, homozygous for an internal segment of 9 alanines (9A/9A), or the lesser form, heterozygous for the polymorphism containing 6 alanines (9A/6A). Intrachromosomal genomic instability in the tumors was then quantified by the robust inter-(simple sequence repeat) PCR method. Tumors from all 26 patients heterozygous with the (9A/6A) polymorphism in TGFBR1 exhibited significantly lower genomic instability than from a randomly selected set [the first identified] of 37 patients with the (9A/9A) polymorphism (p=0.0002, Mann-Whitney). The median age of onset for the (9A/6A) patients was 70 years, compared with a median age of onset of 63 years for the patients carrying the (9A/9A) form (p=0.031, Mann-Whitney). These results are consistent with the model wherein genomic instability facilitates tumor progression, with lesser instability associated with later disease presentation. Clinically, our findings may be developed into improved screening guidelines with respect to the age at which colonoscopy is initiated in carriers of the TGFBR1*6A allele.

Since first described in a rodent model in 1987, aberrant crypt foci (ACF) in the colon have been shown to exhibit many of the molecular features of the more advanced colonic neoplasms including cancer. Therefore, they may be early lesions with potential for progression, and be valuable biomarkers for reduction of risk of colorectal cancer (CRC). For this review, we searched PubMed, and reference lists of recent publications, for studies which reported on associations of features of ACF in humans, such as number or size, with subject characteristics, such as age or family history of CRC. Over 150 papers have reported on ACF in humans. However, the vast majority of these publications are concerned with molecular and morphological features of biopsied lesions, and not their epidemiology. None of the epidemiological studies were of optimum design, primarily due to their absence of a well-defined subject sampling frame or method. Given their 'first-generation' nature, consistent findings were of increased ACF number with age and with synchronous advanced colonic neoplasia. One study reported a higher mean number of ACF in subjects with a family history of CRC than in those without. The strongest evidence on the ability of ACF to predict a diagnosis of CRC will be from prospective studies with baseline ACF assessment in a large sample of disease-free persons (many thousands) who are followed carefully for many years. In the interim, because ACF are asymptomatic, well-designed cross-sectional studies are feasible and will yield valuable information on the relation of ACF to the known risk factors for CRC. This information can then be used to improve the design of prospective studies, and of clinical intervention trials that use ACF as an intermediate endpoint.