Overwhelming Support Among Urban Irish COPD Patients for Lung Cancer Screening by Low-Dose CT Scan

Purpose

The National Lung Screening Trial (NLST) has renewed interest in low-dose computed tomography (LDCT) screening for lung cancer. Smokers may be less receptive toward LDCT screening, however, compared with never smokers. The views of patients with COPD, a particularly high-risk group, toward LDCT screening for lung cancer are currently unknown. We therefore evaluated attitudes of patients with COPD toward LDCT screening for lung cancer.

Methods

Interviews with Irish patients with COPD who satisfied NLST eligibility criteria were conducted in clinical settings using a questionnaire based on that of a comparable study of U.S. current/former smokers of unspecified disease status.

Results

A total of 142 subjects had a mean age of 65.09?±?6.07?years (46.4?% were male, mean pack years 54.5?±?33.3, mean FEV1 59.16?±?23?%); 97.8?% had an identifiable usual source of healthcare. Compared with data from a U.S. cohort of current/former smokers, a higher proportion of Irish COPD smokers: believed that they were at risk for lung cancer (63.6 vs. 15.7?%); believed that early detection improved chances of survival (90 vs. 51.2?%); were willing to consider LDCT screening (97.9 vs. 78.6?%); were willing to pay for a LDCT scan (68.6 vs. 36.2?%); and were willing to accept treatment recommendations arising (95.7 vs. 56.2?%; p?<?0.0001 for all comparisons).

Conclusions

Urban Irish smokers with COPD who would be eligible for LDCT screening are almost universally in favor of being screened and treated for screening-detected lung cancers. This readily accessible high-risk population should be actively targeted in future screening programs.     

Impact of Mammography Screening Interval on Breast Cancer Diagnosis by Menopausal Status and BMI

BACKGROUND

Controversy remains regarding the frequency of screening mammography. Women with different risks for developing breast cancer because of body mass index (BMI) may benefit from tailored recommendations.

OBJECTIVE

To determine the impact of mammography screening interval for women who are normal weight (BMI < 25), overweight (BMI 25–29.9), or obese (BMI ≥ 30), stratified by menopausal status.

DESIGN

Two cohorts selected from the Breast Cancer Surveillance Consortium. Patient and mammography data were linked to pathology databases and tumor registries.

PARTICIPANTS

The cohort included 4,432 women aged 40–74 with breast cancer; the false-positive analysis included a cohort of 553,343 women aged 40–74 without breast cancer.

MAIN MEASURES

Stage, tumor size and lymph node status by BMI and screening interval (biennial vs. annual). Cumulative probability of false-positive recall or biopsy by BMI and screening interval. Analyses were stratified by menopausal status.

KEY RESULTS

Premenopausal obese women undergoing biennial screening had a non-significantly increased odds of a tumor size > 20 mm relative to annual screeners (odds ratio [OR]?=?2.07; 95 % confidence interval [CI] 0.997 to 4.30). Across all BMI categories from normal to obese, postmenopausal women with breast cancer did not present with higher stage, larger tumor size or node positive tumors if they received biennial rather than annual screening. False-positive recall and biopsy recommendations were more common among annually screened women.

CONCLUSION

The only negative outcome identified for biennial vs. annual screening was a larger tumor size (> 20 mm) among obese premenopausal women. Since annual mammography does not improve stage at diagnosis compared to biennial screening and false-positive recall/biopsy rates are higher with annual screening, women and their primary care providers should weigh the harms and benefits when deciding on annual versus biennial screening.     

Trends in colorectal incidence by anatomic subsite from 1985 to 2005: a population-based study

Background

Conflicting results on the shift of right–left ratio in colon cancer incidence have been reported. We examine incidence trends by subsite in a population-based study.

Materials and methods

Colorectal cancer cases diagnosed in the 1985–2005 period were identified through the Tuscany Cancer Registry. Colon subsite was defined as proximal and distal; gender, age at diagnosis, histology, and stage were analyzed. Average annual incidence and age-specific rates according to subsite were calculated.

Results

A total of 21,160 colorectal cancer cases were extracted; in 18,311 cases, the subsite was identified: 6,916 rectal, 5,239 proximal, and 6,156 distal. A larger proportion of distal colon cancers presented as early stage when compared with proximal. Incidence of rectal and distal colon cancer remained stable, while proximal colon cancer incidence increased.

Conclusions

Proximal colon cancer incidence rate increased through the period. Temporal variations in the incidence rate by subsite could suggest different carcinogenic pathways of right- and left-sided colon cancer.     

Comparative Effectiveness of Audit-Feedback Versus Additional Physician Communication Training to Improve Cancer Screening for Patients with Limited Health Literacy

BACKGROUND

We designed a continuing medical education (CME) program to teach primary care physicians (PCP) how to engage in cancer risk communication and shared decision making with patients who have limited health literacy (HL).

OBJECTIVE

We evaluated whether training PCPs, in addition to audit-feedback, improves their communication behaviors and increases cancer screening among patients with limited HL to a greater extent than only providing clinical performance feedback.

DESIGN

Four-year cluster randomized controlled trial.

PARTICIPANTS

Eighteen PCPs and 168 patients with limited HL who were overdue for colorectal/breast/cervical cancer screening.

INTERVENTIONS

Communication intervention PCPs received skills training that included standardized patient (SP) feedback on counseling behaviors. All PCPs underwent chart audits of patients’ screening status semiannually up to 24 months and received two annual performance feedback reports.

MAIN MEASURES

PCPs experienced three unannounced SP encounters during which SPs rated PCP communication behaviors. We examined between-group differences in changes in SP ratings and patient knowledge of cancer screening guidelines over 12 months; and changes in patient cancer screening rates over 24 months.

KEY RESULTS

There were no group differences in SP ratings of physician communication at baseline. At follow-up, communication intervention PCPs were rated higher in general communication about cancer risks and shared decision making related to colorectal cancer screening compared to PCPs who only received performance feedback. Screening rates increased among patients of PCPs in both groups; however, there were no between-group differences in screening rates except for mammography. The communication intervention did not improve patient cancer screening knowledge.

CONCLUSION

Compared to audit and feedback alone, including PCP communication training increases PCP patient-centered counseling behaviors, but not cancer screening among patients with limited HL. Larger studies must be conducted to determine whether lack of changes in cancer screening were due to clinic/patient sample size versus ineffectiveness of communication training to change outcomes.     

Identification of a high molecular weight kininogen fragment as a marker for early gastric cancer by serum proteome analysis

Background

Serum biomarkers currently available for gastric cancers are not sufficiently sensitive and specific.

Methods

We used matrix-assisted laser desorption/ionization time-of-flight mass spectrometry (MS) to generate comparative peptide profiles of serum samples obtained from gastric cancer patients (n?=?81) and age- and sex-matched healthy controls (n?=?66).

Results

Because of initial screening and further validation, we found that the intensities of a 2209 m/z MS peak were increased in the preoperative sera obtained from gastric cancer patients, and we identified this peak, a 2209?Da peptide, as a high molecular weight (HMW) kininogen fragment. Receiver operating characteristic analyses showed that the area under the curve (AUC) for the 2209?Da peptide (AUC?=?0.715) was greater than those for conventional tumor markers (carcinoembryonic antigen AUC?=?0.593, carbohydrate antigen 19-9 AUC?=?0.527) used for the detection of stage I gastric cancers. Inverse correlations were observed between the levels of intact HMW kininogen and the 2209?Da peptide, suggesting that the upregulation of some protease activities is responsible for the overproduction of a kininogen fragment in gastric cancer patients.

Conclusions

Serum levels of the 2209?Da peptide identified in this study have a greater diagnostic ability than those of conventional tumor markers used for the early detection of gastric cancer.     

Accuracy of Ovarian and Colon Cancer Risk Assessments by U.S. Physicians

BACKGROUND

Studies have shown a mismatch between published cancer screening and genetic counseling referral recommendations and physician-reported screening and referral practices. Inaccurate cancer risk assessment is one potential cause of this mismatch.

OBJECTIVE

To assess U.S. physicians’ ability to accurately determine a woman’s colon and ovarian cancer risk level.

DESIGN, PARTICIPANTS

Cross-sectional survey of U.S. family physicians, general internists, and obstetrician-gynecologists. A twelve-page questionnaire with a vignette of a woman’s annual examination included a question about the patient’s level of colon and ovarian cancer risk. The final study sample included 1,555 physicians weighted to represent practicing U.S. physicians nationally.

MAIN MEASURE

Accuracy of physicians’ ovarian and colon cancer risk assessments.

KEY RESULTS

Overall, most physicians accurately assessed women’s risk of ovarian (57.0 %, CI 54.3, 59.6) and colon cancer (62.0 %, CI 59.4, 64.6). However, 27.1 % (CI 23.0, 31.6) of physicians overestimated the ovarian cancer risk among women at the same risk as the general population, and 65.1 % (CI 60.2, 69.7) underestimated ovarian cancer risk among women at much higher risk than the general population. Physicians overestimated colon more than ovarian cancer risk (38.0 %, CI 35.4, 40.6 vs. 27.1 %, CI 23.0, 31.6) for women at the same risk as the general population.

CONCLUSIONS

Physicians’ misestimation of patient ovarian and colon cancer risk may put average risk patients in jeopardy of unnecessary screening and higher risk patients in jeopardy of missed opportunities for prevention or early detection of cancers.     

Risk of Colorectal Adenomas in Women with Prior Breast Cancer

Background and Aims

Longer life expectancy in patients with prior breast cancer may increase their risk of developing other primary cancers, including colorectal cancer (CRC). Whether the risk of developing CRC in this patient population is higher in comparison to those with no prior cancer remains unclear. The purpose of this study was to compare the prevalence of colorectal adenomas and any CRC in breast cancer survivors with those who have no history of prior cancer and assess any difference with use of antiestrogen therapy.

Methods

We compared the prevalence of colorectal cancer and adenomas in breast cancer survivors with that of a group of matched controls. Eligible survivors were ??85?years of age; had initially been diagnosed with stage 0, I, II, or III breast cancer; had completed all cancer treatments with the exception of adjuvant antiestrogen therapy; and had no evidence of recurrence on follow-up. We used the screening colonoscopy database at our institution to identify age-, sex-, and race-matched controls with no history of cancer.

Results

We identified 302 study-eligible breast cancer survivors and 302 matched controls. No colorectal cancers were found in either group. Forty-one breast cancer survivors and 30 controls had tubular adenomas; four survivors and three controls had villous adenoma; and eight survivors and ten controls had advanced adenoma. Multivariate regression analysis revealed that adjuvant antiestrogen therapy was not significantly associated with an increased risk of advanced adenoma.

Conclusions

The prevalence of colorectal adenomas in breast cancer survivors and controls was similar. Breast cancer survivors, including those receiving adjuvant antiestrogen therapies may follow the colorectal screening guidelines used for average-risk population.     

Barriers to screening colonoscopy in an urban population: a study to help focus further efforts to attain full compliance

Background

Awareness of colorectal cancer and decision for colorectal cancer screening is influenced by multiple factors including ethnicity, level of education, and adherence to regular medical follow up.

Objective

Our survey aimed at assessing barriers to colorectal cancer screening among urban population.

Design

This study is a survey of the general population.

Setting

This study was made at a local community in the downtown area of a metropolitan city.

Patients/subjects

The study population for this survey included 2000 non-institutionalized residents from local community of Brooklyn downtown area of City of Brooklyn, NY, USA. All participants were 50 years or older.

Intervention

No intervention was done.

Main outcome measurement

The survey questionnaire collected information about demographic, socioeconomic level, awareness of various cancers and their screening methods, and awareness of screening colonoscopy.

Results

Colonoscopy was identified as the best screening test by 31 % of the subjects. Pain and discomfort was the major reason for not having a colonoscopy. The fear of a complication declined significantly after the first colonoscopy but fear of pain and discomfort increased. Difficulty with bowel preparation before a colonoscopy was a significant problem; it discouraged significant number of participants from having another colonoscopy.

Limitation

This study is limited by its small sample size.

Conclusion

Physician/family and peer influence seems important but influencing only a minority of subjects. Fear of complications should be allayed using accurate statistical information. Pain should be significantly diminished and/or eliminated during colonoscopy. Future research should focus to minimize complexity and discomfort associated with bowel preparation.     

Two-year Trends in Cancer Screening Among Low Socioeconomic Status Women in an HMO-based High-deductible Health Plan

BACKGROUND

Cancer screening is often fully covered under high-deductible health plans (HDHP), but low socioeconomic status (SES) women still might forego testing.

OBJECTIVE

To determine the impact of switching to a HDHP on breast and cervical cancer screening among women of low SES.

DESIGN

Pre-post with comparison group.

PARTICIPANTS

Four thousand one hundred and eighty-eight health plan members enrolled for one year before and up to two years after an employer-mandated switch from a traditional HMO to an HMO-based HDHP, compared with 9418 propensity score matched controls who remained in HMOs by employer choice. Both groups had low outpatient copayments. High-deductible members had full coverage of mammography and Pap smears, but $500 to $2000 individual deductibles for most other services. HMO members had full coverage of cancer screening and low copayments for other services without any deductible. We stratified analyses by SES.

INTERVENTION

Transition to a HDHP.

MAIN MEASURES

Annual breast and cervical cancer screening rates; rates of annual preventive outpatient visits.

KEY RESULTS

In follow-up years 1 and 2, low SES HDHP members experienced no statistically detectable changes in rates of breast cancer screening (ratio of change, 1.14, 95?% CI, [0.93,1.40] and 1.05, [0.80,1.37], respectively) or preventive visits (difference-in-differences, +1.9?%, [?11.9?%,+17.7?%] and +10.1?%, [?9.4?%,+33.7?%], respectively) relative to HMO counterparts. Similarly, among low SES HDHP members eligible for cervical cancer screening, no significant changes occurred in either screening rates (1.01, [0.86,1.20] and 1.08, [0.86,1.35]) or preventive visits (+0.2?%, [?11.4?%,+13.3?%] and ?1.4?%, [?18.1,+18.6]). Patterns were statistically similar for high SES members.

CONCLUSION

During two follow-up years, transition to an HMO-based HDHP with coverage of primary care visits and cancer screening did not lead to differentially lower rates of breast and cervical cancer screening or preventive visits for low SES women. Generalizability is limited to commercially insured women transitioning to HDHPs with low cost-sharing for cancer screening and primary care visits, a common design.     

Diabetes mellitus negatively impacts survival of patients with colon cancer, particularly in stage II disease

Purpose

This retrospective study aimed to determine the effects of diabetes on overall survival (OS) and cancer-specific survival (CSS) in patients with newly diagnosed colon cancers, with particular focus on the impact of diabetes on survival at each stage of colon cancer.

Methods

From January 1999 to January 2008, 2762 consecutive patients diagnosed with colon cancer in Taipei Veterans General Hospital were enrolled. The general characteristics as well as presence of diabetes prior to colon cancer diagnosis were identified. Cox proportional hazard analyses were used for prognostic factors determination; and survival was analyzed using the Kaplan?CMeier method with log-rank test.

Results

A total of 469 patients (17%) had diabetes at diagnosis of colon cancer. Patients with diabetes had baseline characteristics comparable to those without diabetes with the exception that the patients with diabetes were older (>65?years). Diabetes significantly and negatively impacted OS and CSS in multivariate analyses. After adjusting for possible confounding factors, the prognostic impact of diabetes on OS and CSS was particularly significant in patients with stage II colon cancer.

Conclusions

Diabetes is a poor prognostic factor in patients with newly diagnosed colon cancer, and it may directly impact the tumor behavior of stage II disease. Further study is required to elucidate the underlying pathophysiologic mechanisms.     

Impact of Comorbidity on Colorectal Cancer Screening Cost-Effectiveness Study in Diabetic Populations

BACKGROUND

Although comorbidity has been shown to affect the benefits and risks of colorectal cancer (CRC) screening, it has not been accounted for in prior cost-effectiveness analyses of CRC screening.

OBJECTIVE

To evaluate the impact of diagnosis of diabetes mellitus, a highly prevalent comorbidity in U.S. adults aged 50 and older, on health and economic outcomes of CRC screening.

DESIGN

Cost-effectiveness analysis using an integrated modeling framework.

DATA SOURCES

Derived from basic and epidemiologic studies, clinical trials, cancer registries, and a colonoscopy database.

TARGET POPULATION

U.S. 50-year-old population.

TIME HORIZON

Lifetime.

PERSPECTIVE

Costs are based on Medicare reimbursement rates.

INTERVENTIONS

Colonoscopy screening at ten-year intervals, beginning at age 50, and discontinued after age 50, 60, 70, 80 or death.

OUTCOME MEASURES

Health outcomes and cost effectiveness.

RESULTS OF BASE-CASE ANALYSIS

Diabetes diagnosis significantly affects cost-effectiveness of CRC screening. For the same CRC screening strategy, a person without diabetes at age 50 gained on average 0.07?C0.13 life years more than a person diagnosed with diabetes at age 50 or younger. For a population of 1,000 patients diagnosed with diabetes at baseline, increasing stop age from 70?years to 80?years increased quality-adjusted life years (QALYs) gained by 0.3, with an incremental cost-effectiveness ratio of $206,671/QALY. The corresponding figures for 1,000 patients without diabetes are 2.3 QALYs and $46,957/QALY.

RESULTS OF SENSITIVITY ANALYSIS

Cost-effectiveness results are sensitive to cost of colonoscopy and adherence to colonoscopy screening.

LIMITATIONS

Results depend on accuracy of model assumptions.

CONCLUSION

Benefits of CRC screening differ substantially for patients with and without diabetes. Screening for CRC in patients diagnosed with diabetes at age 50 or younger is not cost-effective beyond age 70. Screening recommendations should be individualized based on the presence of comorbidities.     

Cervical Cancer Screening, Diagnosis and Treatment Interventions for Racial and Ethnic Minorities: A Systematic Review

OBJECTIVES

To systematically review the literature to determine which interventions improve the screening, diagnosis or treatment of cervical cancer for racial and/or ethnic minorities.

DATA SOURCES

Medline on OVID, Cochrane Register of Controlled Trials, CINAHL, PsycINFO and Cochrane Systematic Reviews.

STUDY ELIGIBILITY CRITERIA, PARTICIPANTS AND INTERVENTIONS

We searched the above databases for original articles published in English with at least one intervention designed to improve cervical cancer prevention, screening, diagnosis or treatment that linked participants to the healthcare system; that focused on US racial and/or ethnic minority populations; and that measured health outcomes. Articles were reviewed to determine the population, intervention(s), and outcomes. Articles published through August 2010 were included.

STUDY APPRAISAL AND SYNTHESIS METHODS

One author rated the methodological quality of each of the included articles. The strength of evidence was assessed using the criteria developed by the GRADE Working Group.45,46

RESULTS

Thirty-one studies were included. The strength of evidence is moderate that telephone support with navigation increases the rate of screening for cervical cancer in Spanish- and English-speaking populations; low that education delivered by lay health educators with navigation increases the rate of screening for cervical cancer for Latinas, Chinese Americans and Vietnamese Americans; low that a single visit for screening for cervical cancer and follow up of an abnormal result improves the diagnosis and treatment of premalignant disease of the cervix for Latinas; and low that telephone counseling increases the diagnosis and treatment of premalignant lesions of the cervix for African Americans.

LIMITATIONS

Studies that did not focus on racial and/or ethnic minority populations may have been excluded. In addition, this review excluded interventions that did not link racial and ethnic minorities to the health care system. While inclusion of these studies may have altered our findings, they were outside the scope of our review.

CONCLUSIONS AND IMPLICATIONS OF KEY FINDINGS

Patient navigation with telephone support or education may be effective at improving screening, diagnosis, and treatment among racial and ethnic minorities. Research is needed to determine the applicability of the findings beyond the populations studied.     

Non-attendance at diabetic eye screening and risk of sight-threatening diabetic retinopathy: a population-based cohort study

Aims/hypothesis

This study evaluated whether repeated non-attendance for diabetic eye screening is associated with the risk of sight-threatening diabetic retinopathy (STDR).

Methods

This was a cohort study of 6,556 residents with diabetes who were invited for screening between 2008 and 2011 in a population-based eye screening programme in inner London and who attended for their first-ever screen in 2008. The proportion of participants with STDR was evaluated in relation to the number of years in which screening was missed.

Results

The proportion of participants who did not attend screening decreased between 2009 and 2011 (annual reduction 1.6% [95% CI 0.9%, 2.3%]). The adjusted relative odds of STDR for 210 participants who did not attend two consecutive years of screening were 3.76 (95% CI 2.14, 6.61; p?<?0.001), compared with participants who were screened annually. In 605 participants with mild non-proliferative retinopathy at the first screen, the adjusted relative odds of developing proliferative or moderate to severe non-proliferative retinopathy were 5.72 (95% CI 7.43, 22.83; p?=?0.013) for 53 participants who missed two screens.

Conclusions/interpretation

Patients who do not attend diabetic eye screening are at increased risk of developing STDR. Tracing of non-attenders with evidence of established retinopathy should be an important fail-safe procedure.     

Significance of cancer-associated fibroblasts in the regulation of gene expression in the leading cells of invasive lung cancer

Purpose

Cancer-associated fibroblasts (CAFs) contribute to tumor progression through multiple pathways. However, the effect of CAFs on gene expression in lung cancer has been largely unknown. Here we systematically compared the gene expression changes in lung cancer cells induced by normal fibroblasts and CAFs.

Methods

Wound healing and cell proliferation assays were used to identify the property of CAFs used in this study. We used cDNA microarray analysis to compare gene expression in lung cancer cells cultured with either conditioned medium (CM) from lung CAFs or normal lung fibroblasts, the result of which was confirmed by RT-PCR and Western blot analysis. Immunohistochemistry on tissue sections from lung cancers was conducted to further confirm the results of cDNA microarray analysis.

Results

The expression of many genes was upregulated in cancer cells by CAF CM, particularly cell adhesion molecules, integrins, and anti-apoptotic protein Bcl-2. Expression of integrins appeared to be upstream from Bcl-2. We identified transforming growth factor-β as a candidate factor that induced the expression of those genes in cancer cells. Immunohistochemical studies of clinical lung cancer tissues revealed that integrins and Bcl-2 were more highly expressed in the leading cells (LCs) than in the following cells, at the invasive front of cancer nests, which are adjacent to or in proximity to the stroma. Furthermore, the expression of integrins and Bcl-2 in LCs had a tendency to correlate with the clinical stage of cancer progression, including lymph node metastasis.

Conclusions

Our results suggest that CAFs promote lung cancer progression partly through the direct regulation of gene expression in the LCs of invasive cancer nests.     

Effects of Massachusetts Health Reform on the Use of Clinical Preventive Services

BACKGROUND

Expansion of health insurance coverage, and hence clinical preventive services (CPS), provides an opportunity for improvements in the health of adults. The degree to which expansion of health insurance coverage affects the use of CPS is unknown.

OBJECTIVE

To assess whether Massachusetts health reform was associated with changes in healthcare access and use of CPS.

DESIGN

We used a difference-in-differences framework to examine change in healthcare access and use of CPS among working-aged adults pre-reform (2002–2005) and post-reform (2007–2010) in Massachusetts compared with change in other New England states (ONES).

SETTING

Population-based, cross-sectional Behavioral Risk Factor Surveillance System surveys.

PARTICIPANTS

A total of 208,831 survey participants aged 18 to 64 years.

INTERVENTION

Massachusetts health reform enacted in 2006.

MEASUREMENTS

Four healthcare access measures outcomes and five CPS.

KEY RESULTS

The proportions of adults who had health insurance coverage, a healthcare provider, no cost barrier to healthcare, an annual routine checkup, and a colorectal cancer screening increased significantly more in Massachusetts than those in the ONES. In Massachusetts, the prevalence of cervical cancer screening in pre-reform and post-reform periods was about the same; however, the ONES had a decrease of ?1.6 percentage points (95 % confidence interval [CI] ?2.5, ?0.7; p <0.001). As a result, the prevalence of cervical cancer screening in Massachusetts was increased relative to the ONES (1.7, 95 % CI 0.2, 3.2; p?=?0.02). Cholesterol screening, influenza immunization, and breast cancer screening did not improve more in Massachusetts than in the ONES.

LIMITATIONS

Data are self-reported.

CONCLUSIONS

Health reform may increase healthcare access and improve use of CPS. However, the effects of health reform on CPS use may vary by type of service and by state.     

Low Prevalence of Microsatellite Instability in Interval Gastric Cancers

Background and Aim

Esophagogastroduodenoscopy (EGD) is recommended at 2-year intervals in countries with a high prevalence of gastric cancer. The aim of this study was to determine whether interval gastric cancers that develop within 2 years of a previous complete screening are associated with microsatellite instability (MSI).

Methods

Newly diagnosed gastric cancer patients who had undergone gastrectomy were included. Of these 459 patients, 177 were classified as interval gastric cancer since they were diagnosed within 2 years of a previous EGD. Noninterval gastric cancer patients were subclassified into 65 patients who underwent previous EGD between the past 2 and 10 years and 217 patients without EGD during the last 10 years. Analysis for MSI was conducted using two mononucleotide and three dinucleotide markers.

Results

MSI was found more frequently in noninterval gastric cancers than in interval gastric cancers (p = 0.009). Interval gastric cancers were associated with a higher prevalence of early gastric cancer (p = 0.006), smaller size (p < 0.001), and lower TNM stages (p = 0.006). On logistic regression analysis, noninterval gastric cancers were related to MSI (p = 0.010) and larger size (≥4 cm) (p = 0.009). Subjects with interval gastric cancer showed better survival than those with noninterval gastric cancer (p = 0.006).

Conclusions

During a 2-year screening interval, noninterval gastric cancers tend to be larger, more advanced, and associated with MSI. Biannual EGD screening is effective for detecting small gastric cancers at an early stage, but is not useful in detecting gastric cancers with MSI.     

Early Identification of Small Airways Disease on Lung Cancer Screening CT: Comparison of Current Air Trapping Measures

Background

Lung cancer screening CT scans might provide valuable information about air trapping as an early indicator of smoking-related lung disease. We studied which of the currently suggested measures is most suitable for detecting functionally relevant air trapping on low-dose computed tomography (CT) in a population of subjects with early-stage disease.

Methods

This study was ethically approved and informed consent was obtained. Three quantitative CT air trapping measures were compared against a functional reference standard in 427 male lung cancer screening participants. This reference standard for air trapping was derived from the residual volume over total lung capacity ratio (RV/TLC) beyond the 95th percentile of predicted. The following CT air trapping measures were compared: expiratory to inspiratory relative volume change of voxels with attenuation values between ?860 and ?950 Hounsfield Units (RVC_{?860 to ?950}), expiratory to inspiratory ratio of mean lung density (E/I-ratio_MLD) and percentage of voxels below ?856?HU in expiration (EXP_?856). Receiver operating characteristic (ROC) analysis was performed and area under the ROC curve compared.

Results

Functionally relevant air trapping was present in 38 (8.9?%) participants. E/I-ratio_MLD showed the largest area under the curve (0.85, 95?% CI 0.813?C0.883), which was significantly larger than RVC_{?860 to ?950} (0.703, 0.657?C0.746; p?<?0.001) and EXP_?856 (0.798, 0.757?C0.835; p?=?0.002). At the optimum for sensitivity and specificity, E/I-ratio_MLD yielded an accuracy of 81.5?%.

Conclusions

The expiratory to inspiratory ratio of mean lung density (E/I-ratio_MLD) is most suitable for detecting air trapping on low-dose screening CT and performs significantly better than other suggested quantitative measures.     

Impact of a Family History of Colorectal Cancer on the Prevalence of Advanced Neoplasia at Colonoscopy in 4,967 Asymptomatic Patients

Background and Aims

A family history of colorectal cancer is considered an independent risk factor for advanced neoplasia at colonoscopy. The expected outcome for screening colonoscopy in patients with a family history is not well established in all populations.

Methods

We designed a large, prospective study of an unselected population in San Diego, California to assess the impact of a family history of colorectal cancer on the prevalence of advanced neoplasia on screening colonoscopy.

Results

We evaluated 6,905 consecutive patients referred for colonoscopy between January 2005 and December 2006. Of the 4,967 who met the inclusion criteria, the mean age was 58.8 and consisted of 58.6% women. Overall 930 (18.7%) had neoplasia and 249 (5%) had advanced neoplasia, eight (0.16%) of which were cancer. The 4,967 patients were divided into 643 with and 4,324 without a family history of colorectal cancer. Of the 643 patients with a family history, 38 (5.9%) had advanced neoplasia, one of which was cancer. Of the 4,324 patients without a family history, 211 (4.9%) had advanced neoplasia including seven cancers. The relative risk for finding advanced neoplasia in patients with a single affected first degree relative was 1.21 (95% CI, 0.87?C1.69; P?=?0.31).

Conclusions

A family history of one first-degree relative with colorectal cancer did not predict a significantly higher prevalence of advanced neoplasia at screening colonoscopy in this Southwestern cohort.     

Methylation profiling of serum DNA from hepatocellular carcinoma patients using an Infinium Human Methylation 450 BeadChip

Background

Alterations in DNA methylation frequently occur in hepatocellular cancer (HCC). The methylation status of circulating DNA might serve as a potential biomarker for cancers.

Methods

Six early stage HCC patients with chronic hepatitis B virus (HBV) infection and six age-matched healthy controls were selected for genome-scale DNA methylation screening of serum by Illumina Infinium Human Methylation 450 BeadChip. The chosen methylation sites were reassessed by bisulfite sequencing in four healthy controls and four early stage HCC patients with chronic HBV infection and were used for bead array screening. Another 27 healthy controls and 31 early stage HCC patients with chronic HBV infection were also chosen for further bisulfite sequencing validation.

Results

Whole-genome methylation was significantly lower in serum from HCC patients than in that from healthy controls. After bioinformatics analysis, methylation at DBX2 and Thy-1 membrane glycoprotein (THY1) was reassessed by bisulfite sequencing. The correlation coefficients of DBX2 and THY1 between the Illumina 450 BeadChip and bisulfite sequencing were respectively 0.9145 and 0.8232. Twenty-seven healthy controls and 31 early stage HCC patients with chronic HBV infection were chosen for further validation. The diagnostic sensitivity and specificity of DBX2 for differentiating healthy controls and early stage HCC were 88.89 and 87.10 % and of THY1 were 85.19 and 80.65 %.

Conclusions

The results demonstrated that the 450K BeadChip is a useful tool for whole-genome serum DNA methylation screening of HCC, and some HCC-related DNA methylation sites were screened.