Long‐term risk of colorectal cancer after negative colonoscopy in a Danish gFOBT screening cohort

Faecal occult blood test (FOBT) screening for colorectal cancer (CRC) is implemented in several countries. Approximately half of all screen positive persons have negative colonoscopy, but consensus is lacking on how these persons should be followed up. Health authorities in Denmark and The Netherlands recommend suspending screening for 8–10 years, while patients in UK are invited to screening after 2 years. In this cohort‐study, we followed 166,277 individuals invited to FOBT‐screening in 2005–2006 and a reference group comprising the remaining 1,240,348 Danes of the same age. We linked Danish population and health service registers to obtain information about colonoscopy outcome and incident CRC. We estimated CRC risk by colonoscopy outcome (adenoma, other colorectal pathology or negative colonoscopy) for the reference group, the screening group, and subgroups. Persons with positive screening FOBT followed by negative colonoscopy had the same long‐term CRC risk as persons with adenoma detected due to a positive screening FOBT (aHR 1.33, 95% CI: 0.65–2.71). We found no difference in the long‐term CRC risk between persons with negative colonoscopy after a positive FOBT screening test and the unscreened reference population (aHR 1.05, 95% CI: 0.62–1.78). Since FOBT screen positive persons in our study remained at average risk of CRC despite of a negative index colonoscopy, we question the safety of suspending FOBT screening for this group. It needs to be monitored whether recent efforts to improve colonoscopy quality have been successful in ensuring low CRC risk after negative colonoscopy also in FOBT positive persons.     

Predictors of metachronous colorectal neoplasms in sporadic adenoma patients

Our objective was to assess the overall risk of subsequent colorectal neoplasms (cancer or adenoma) in relation with the various characteristics of the index lesion in a cohort of patients who underwent endoscopic polypectomies of colorectal adenomas. A total of 1086 patients with adenomas of the large bowel were reported between 1979 and 1999 at the National Cancer Institute of Milan during a screening program for colorectal carcinoma. Data on patients who had colonoscopic examinations and treatments were collected prospectively. The relation between colorectal cancer (CRC) and adenoma features was assessed by computing the hazard ratio (HR) values and corresponding confidence intervals (95% CI) according to Cox proportional hazard models. Of the 1086 eligible patients (487 females, 579 males), 736 had single adenomas (67.7%) and 350 had multiple adenomas (32.3%). Histologic examination revealed 772 cases of tubular adenoma (73%), 205 cases of tubulovillous adenoma and 80 cases of villous adenoma (7.5%). Severe dysplasia was found in 3.3% of the cases. During the 11393 person-years of follow-up, with an average time of surveillance of 10.5 years, colorectal carcinomas developed in 10 patients (0.8%) and a new adenoma in 323 patients (29%). Multivariate analysis showed that male gender (HR 1.6; 95% CI 1.3-2.0), multiple polyps (HR 1.6; 95% CI 1.3-2.0), polyps larger than 2 cm (HR 1.5; 95% CI 1.1-2.1), tubulovillous and villous histology (HR 1.3; 95% CI 1.0-1.6 and HR 1.8; 95% CI 1.2-2.6, respectively) at index polypectomy were statistically significant risk factors for developing metachronous adenomatous polyps. The standardized incidence rates (SIR) for CRC was 0.52 (95% CI 0.25-0.95). The SIR was increased in subjects with severe dysplasia (2.8; 95% CI 0.34-1.02). Some features of large bowel adenomas are strongly correlated with an increased risk of metachronous adenomas and colorectal cancer. However, the endoscopic polypectomy is able to reduce by 50% the incidence of CRC in patients with large bowel adenomas.     

Adenoma characteristics associated with post-polypectomy proximal colon cancer incidence: a retrospective cohort study

Background Colorectal cancer (CRC) screening is less effective at reducing cancer incidence in the proximal colon compared to the distal colorectum. We aimed to identify adenoma characteristics associated with proximal colon cancer (PCC).Methods Endoscopy and pathology data for patients with ≥1 adenoma detected at baseline colonoscopy were obtained from 17 UK hospitals between 2001 and 2010. Multivariable Cox regression models were used to estimate adjusted hazard ratios (aHRs) and 95% confidence intervals (CIs) for PCC, and, for comparison, distal CRC incidence, by adenoma characteristics.Results Among 18,431 patients, 152 and 105 developed PCC and distal CRC, respectively, over a median follow-up of 9.8 years. Baseline adenoma characteristics positively associated with PCC incidence included number (≥3 vs. < 3: aHR 2.10, 95% CI: 1.42–3.09), histology (tubulovillous/villous vs. tubular: aHR 1.61, 95% CI: 1.10–2.35) and location (any proximal vs. distal only: aHR 1.70, 95% CI: 1.20–2.42), for which there was borderline evidence of heterogeneity by subsite (p = 0.055). Adenoma dysplasia (high vs. low grade) was associated with distal CRC (aHR 2.42, 95% CI: 1.44–4.04), but not PCC (p-heterogeneity = 0.023).Conclusions Baseline adenoma number, histology and proximal location were independently associated with PCC and may be important to identify patients at higher risk for post-polypectomy PCC.Subject terms: Epidemiology, Cancer epidemiology, Cancer screening, Colorectal cancer, Cancer prevention     

Cervical cancer risk in women living with HIV across four continents: A multicohort study

We compared invasive cervical cancer (ICC) incidence rates in Europe, South Africa, Latin and North America among women living with HIV who initiated antiretroviral therapy (ART) between 1996 and 2014. We analyzed cohort data from the International Epidemiology Databases to Evaluate AIDS (IeDEA) and the Collaboration of Observational HIV Epidemiological Research in Europe (COHERE) in EuroCoord. We used flexible parametric survival models to determine regional ICC rates and risk factors for incident ICC. We included 64,231 women from 45 countries. During 320,141 person-years (pys), 356 incident ICC cases were diagnosed (Europe 164, South Africa 156, North America 19 and Latin America 17). Raw ICC incidence rates per 100,000 pys were 447 in South Africa (95% confidence interval [CI]: 382–523), 136 in Latin America (95% CI: 85–219), 76 in North America (95% CI: 48–119) and 66 in Europe (95% CI: 57–77). Compared to European women ICC rates at 5 years after ART initiation were more than double in Latin America (adjusted hazard ratio [aHR]: 2.43, 95% CI: 1.27–4.68) and 11 times higher in South Africa (aHR: 10.66, 95% CI: 6.73–16.88), but similar in North America (aHR: 0.79, 95% CI: 0.37–1.71). Overall, ICC rates increased with age (>50 years vs. 16–30 years, aHR: 1.57, 95% CI: 1.03–2.40) and lower CD4 cell counts at ART initiation (per 100 cell/μl decrease, aHR: 1.25, 95% CI: 1.15–1.36). Improving access to early ART initiation and effective cervical cancer screening in women living with HIV should be key parts of global efforts to reduce cancer-related health inequities.     

Changes in colorectal cancer screening use after introduction of alternative screening offer in Germany: Prospective cohort study

In October 2002, screening colonoscopy was added to the German colorectal cancer (CRC) screening program as an alternative to fecal occult blood test (FOBT). We aimed to evaluate the change in CRC screening use after introduction of the dual screening offer and to assess determinants of screening use. Data were drawn from a population-based cohort study initiated during 2000–2002 in Germany (n = 5,845, age range at recruitment: 50–75 years). We conducted both cross-sectional and longitudinal analyses to obtain uptake rates of CRC screening based on four waves of data. Age-group specific proportions of participants having had FOBT within 2 years remained essentially unchanged at 61–67% between 2000 and 2002 (1st wave) and 2005–2007 (3rd wave). The proportions of participants having undergone screening colonoscopy within 10 years increased from 23–29% to 46–57%, leading to a substantial overall increase in being up-to-date with CRC screening from 66–68% to 77–80%. In 2008–2010 (4th wave), FOBT use declined and colonoscopy use continued to increase. Obesity was significantly associated with lower prevalence of being up-to-date with FOBT (odds ratio [OR] at 8-year follow-up 0.68; 95% confidence interval [CI], 0.58–0.80) and screening colonoscopy (OR, 0.73; 95% CI, 0.62–0.86). Also, smokers were less likely to have ever used FOBT (OR, 0.54; 95% CI, 0.40–0.75) or colonoscopy (OR, 0.75; 95% CI, 0.63–0.90) compared to nonsmokers. After the introduction of dual screening offer, the overall adherence to CRC screening steeply increased, mainly due to an increase in screening colonoscopy uptake. Screening tests kept being underused by obese people and smokers who are at elevated CRC risk.     

Current status of screening for colorectal cancer

BackgroundColorectal cancer (CRC) is a leading cause of cancer morbidity and mortality. A well-defined precursor lesion (adenoma) and a long preclinical course make CRC a candidate for screening. This paper reviews the current evidence for the most important tests that are widely used or under development for population-based screening.Material and methodsIn this narrative review, we scrutinized all papers we have been aware of, and carried out searches in PubMed and Cochrane library for relevant literature.ResultsTwo screening methods have been shown to reduce CRC mortality in randomised trials: repetitive faecal occult blood testing (FOBT) reduces CRC mortality by 16%; once-only flexible sigmoidoscopy (FS) by 28%. FS screening also reduces CRC incidence (by 18%), FOBT does not. Colonoscopy screening has a potentially larger effect on CRC incidence and mortality, but randomised trials are lacking. New screening methods are on the horizon but need to be tested in large clinical trials before implementation in population screening.ConclusionsFS screening reduces CRC incidence and CRC mortality by removal of adenomas; FOBT reduces CRC mortality by early detection of cancer. Several other tests are available, but none has been evaluated in randomised trials. Screening strategies differ considerably across countries.     

Cervical cancer risk and impact of Pap‐based screening in HIV‐positive women on antiretroviral therapy in Johannesburg,South Africa

Data on invasive cervical cancer (ICC) incidence in HIV‐positive women and the effect of cervical cancer screening in sub‐Saharan Africa are scarce. We estimated i) ICC incidence rates in women (≥18 years) who initiated antiretroviral therapy (ART) at the Themba Lethu Clinic (TLC) in Johannesburg, South Africa, between 2004 and 2011 and ii) the effect of a Pap‐based screening program. We included 10,640 women; median age at ART initiation: 35 years [interquartile range (IQR) 30–42], median CD4 count at ART initiation: 113 cells/µL (IQR 46–184). During 27,257 person‐years (pys), 138 women were diagnosed with ICC; overall incidence rate: 506/100,000 pys [95% confidence interval (CI) 428–598]. The ICC incidence rate was highest (615/100,000 pys) in women who initiated ART before cervical cancer screening became available in 04/2005 and was lowest (260/100,000 pys) in women who initiated ART from 01/2009 onward when the cervical cancer screening program and access to treatment of cervical lesions was expanded [adjusted hazard ratio (aHR) 0.42, 95% CI 0.20–0.87]. Advanced HIV/AIDS stage (4 versus 1, aHR 1.95, 95% CI 1.17–3.24) and middle age at ART initiation (36–45 versus 18–25 years, aHR 2.51, 95% CI 1.07–5.88) were risk factors for ICC. The ICC incidence rate substantially decreased with the implementation of a Pap‐based screening program and improved access to treatment of cervical lesions. However, the risk of developing ICC after ART initiation remained high. To inform and improve ICC prevention and care for HIV‐positive women in sub‐Saharan Africa, implementation and monitoring of cervical cancer screening programs are essential.     

Smoking and survival of colorectal cancer patients: Population‐based study from Germany

Current evidence on the association between smoking and colorectal cancer (CRC) prognosis after diagnosis is heterogeneous and few have investigated dose‐response effects or outcomes other than overall survival. Therefore, the association of smoking status and intensity with several prognostic outcomes was evaluated in a large population‐based cohort of CRC patients; 3,130 patients with incident CRC, diagnosed between 2003 and 2010, were interviewed on sociodemographic factors, smoking behavior, medication and comorbidities. Tumor characteristics were collected from medical records. Vital status, recurrence and cause of death were documented for a median follow‐up time of 4.9 years. Using Cox proportional hazards regression, associations between smoking characteristics and overall, CRC‐specific, non‐CRC related, recurrence‐free and disease‐free survival were evaluated. Among stage I–III patients, being a smoker at diagnosis and smoking ≥15 cigarettes/day were associated with lower recurrence‐free (adjusted hazard ratios (aHR): 1.29; 95% confidence interval (CI): 0.93–1.79 and aHR: 1.31; 95%‐CI: 0.92–1.87) and disease‐free survival (aHR: 1.26; 95%‐CI: 0.95–1.67 and aHR: 1.29; 95%‐CI: 0.94–1.77). Smoking was associated with decreased survival in stage I–III smokers with pack years ≥20 (Overall survival: aHR: 1.40; 95%‐CI: 1.01–1.95), in colon cancer cases (Overall survival: aHR: 1.51; 95%‐CI: 1.05–2.17) and men (Recurrence‐free survival: aHR: 1.51; 95%‐CI: 1.09–2.10; disease‐free survival: aHR: 1.49; 95%‐CI: 1.12–1.97), whereas no associations were seen among women, stage IV or rectal cancer patients. The observed patterns support the existence of adverse effects of smoking on CRC prognosis among nonmetastatic CRC patients. The potential to enhance prognosis of CRC patients by promotion of smoking cessation, embedded in tertiary prevention programs warrants careful evaluation in future investigations.     

The risk of colorectal cancer is associated with the frequency of meat consumption in a population-based cohort in Korea

Objective: To date, there have been few prospective cohort studies that have investigated the association between meat consumption and the risk of colorectal cancer (CRC) in Asian countries. A large, population-based cohort study was conducted to assess the effect of the frequency of meat consumption on the risk of CRC in Korean adults. Methods: The participants were Korean government employees, school faculty members, and their unemployed dependents, aged 30–80 years, who underwent health examinations between 1996 and 1997. In 2003, information on CRC incidence was obtained during the 6–7 year follow-up period. The final data analysis included 2,248,129 study subjects. The hazard ratio (HR) and 95% confidence interval (CI) of the HR were estimated using the Cox proportional hazards regression model. Results: During the follow-up period, CRC occurred in 4,501 men and 1,943 women (64.19 and 36.34 for age-standardized incidence rates per 100,000 person-years, respectively). In the total population, the estimated HRs and 95% CI for meat consumption of 2–3 times per week and more than 4 times per week compared with consumption of less than once per week were 1.06 (1.01–1.12) and 1.23 (1.13–1.35), respectively. In men only and women only groups, the HRs (95% CI) for consumption of more than 4 times per week compared with consumption of less than once per week were 1.13 (1.02–1.26) and 1.42 (1.21–1.66), respectively. Conclusion: The present findings suggest that frequency of meat consumption is positively associated with the risk of CRC.     

Accuracy of Self-Checked Fecal Occult Blood Testing for Colorectal Cancer in Thai Patients

Purpose: Colorectal cancer (CRC) screening with fecal occult blood testing (FOBT) has been associatedwith a reduction in CRC incidence and CRC-related mortality. However, a conventional FOBT requires stoolcollection and handling, which may be inconvenient for participants. The EZ-DetectTM (Siam PharmaceuticalThailand) is a FDA-approved chromogen-substrate based FOBT which is basically a self-checked FOBT (nostool handling required). This study aimed to evaluate the accuracy of EZ-Detect for CRC detection. Methods:This prospective study was conducted in the Faculty of Medicine, Siriraj Hospital, Bangkok, Thailand betweenNovember 2013 and May 2014. Some 96 patients with histologically-proven CRC and 101 patients with normalcolonoscopic findings were invited to perform self-checked FOBT according to the manufacturer’s instructions.Results were compared with endoscopic and pathologic findings. Sensitivity, specificity, positive predictive value(PPV), and negative predictive value (NPV) for CRC detection were calculated. Results: The present studyrevealed the sensitivity, specificity, PPV and NPV of this self-checked FOBT for CRC detection to be 41% (95%CI: 31-51), 97% (95% CI: 92-99), 93% (95% CI: 81-98) and 63% (95% CI: 55-70), respectively. The overallaccuracy of the self-checked FOBT for identifying CRC was 70%. The sensitivity for CRC detection based on7th AJCC staging was 29% for stage I, 32% for stage II and 50% for stage III/IV (P=0.19). The sensitivity was33% for proximal colon and 42% for distal colon and rectal cancer (P=0.76). Notably, none of nine infiltrativelesions gave a positive FOBT. Conclusions: The self-checked FOBT had an acceptable accuracy of CRC detectionexcept for infiltrative tumors. This home-administrated or ‘DIY’ do-it-yourself FOBT could be considered asone non-invasive and convenient tool for CRC screening.     

Predictors of colorectal cancer screening from patients enrolled in a managed care health plan

BACKGROUND: Despite the growing recognition of the importance of colorectal cancer (CRC) screening in reducing cancer mortality, national screening rates are low, indicating a critical need to understand the barriers and remedies for underutilization of CRC screening tests. METHODS: Using results from independent cross-sectional telephone surveys with patients aged>or=50 years performed before (2000; n=498) and after (2003; n=482) a quality improvement intervention for CRC screening within a large managed care health plan, the trends and predictors of CRC screening with fecal occult blood test (FOBT) and/or endoscopy (flexible sigmoidoscopy/colonoscopy) were examined from a patient perspective. RESULTS: In 2000, patient reported screening rates within guidelines were 38% for any test, 23% for endoscopy, and 22% for FOBT. In 2003, screening rates increased to 50% for any test, 39% for endoscopy, and 24% for FOBT. Having discussed CRC with a doctor significantly increased the odds of being screened (FOBT: odds ratio [OR], 2.09 [95% confidence interval (95% CI), 1.47-2.96]; endoscopy: OR, 2.33 [95% CI, 1.67-3.26]; and any test: OR, 2.86 [95% CI, 2.06-3.96]), and reporting barriers to CRC in general decreased the odds of being screened (FOBT: OR, 0.76 [95% CI, 0.60-0.95]; endoscopy: OR, 0.74 [95% CI, 0.60-0.92]; and any test: OR, 0.66 [95% CI, 0.54-0.80]). CONCLUSIONS: Although screening rates increased over the 3-year period, evidence was found of ongoing underutilization of CRC screening. The 2 strongest determinants of obtaining CRC screening were provider influence and patient barriers related to CRC screening in general, pointing to the need for multilevel interventions that target both the provider and patient.     

Development of new non‐invasive tests for colorectal cancer screening: The relevance of information on adenoma detection

Researchers are actively pursuing the development of a new non‐invasive test (NIT) for colorectal cancer (CRC) screening as an alternative to fecal occult blood tests (FOBTs). The majority of pilot studies focus on the detection of invasive CRC rather than precursor lesions (i.e., adenomas). We aimed to explore the relevance of adenoma detection for the viability of an NIT for CRC screening by considering a hypothetical test that does not detect adenomas beyond chance. We used the Simulation Model of Colorectal Cancer (SimCRC) to estimate the effectiveness of CRC screening and the lifetime costs (payers' perspective) for a cohort of US 50‐years‐old persons to whom CRC screening is offered from age 50–75. We compared annual screening with guaiac and immunochemical FOBTs (with sensitivities up to 70 and 24% for CRC and adenomas, respectively) to annual screening with a hypothetical NIT (sensitivity of 90% for CRC, no detection of adenomas beyond chance, specificity and cost similar to FOBTs). Screening with the NIT was not more effective, but was 29–44% more costly than screening with FOBTs. The findings were robust to varying the screening interval, the NIT's sensitivity for CRC, adherence rates favoring the NIT, and the NIT's unit cost. A comparative modelling approach using a model that assumes a shorter adenoma dwell time (MISCAN‐COLON) confirmed the superiority of the immunochemical FOBT over an NIT with no ability to detect adenomas. Information on adenoma detection is crucial to determine whether a new NIT is a viable alternative to FOBTs for CRC screening. Current evidence thus lacks an important piece of information to identify marker candidates that hold real promise and deserve further (large‐scale) evaluation.     

Association of screening status,polygenic risk score and environmental risk factors with colorectal cancer incidence and mortality risks

Whether screening can attenuate the influence of genetic risk and environmental risk factors for colorectal cancer (CRC) mortality risk remains unknown. Our study is to investigate the association of the screening history, genetic risk and environmental risk factors with CRC incidence and mortality risks using UK Biobank data. Screening history was associated with lower CRC incidence (hazard ratio [HR]: 0.63, 95% confidence interval [CI]: 0.58-0.69) and mortality risk (HR: 0.56, 95% CI: 0.49-0.63). Compared to the HRs of participants with a low genetic risk, low environmental risk and no screening history, the HRs of participants with a high genetic risk, high environmental risk and no screening history were 3.42 (95% CI: 2.76-4.24) for CRC incidence and 3.36 (95% CI: 2.48-4.56) for CRC mortality. In contrast, the HRs of participants with a high genetic risk and no screening history, but a low environmental risk, were 1.92 (95% CI: 1.55-2.36) for CRC incidence and 1.88 (95% CI: 1.39-2.53) for CRC mortality. Furthermore, the HRs of participants with a high genetic risk and a low environmental risk, but a screening history were 1.62 (95% CI: 1.15-2.28) for CRC incidence and 1.77 (95% CI: 1.08-2.89) for CRC mortality. Participants benefited more substantially from screenings for CRC mortality than for CRC incidence risk. A higher environmental risk was associated with higher risk of CRC incidence and mortality within each category of genetic risk. These findings emphasize the importance of CRC screening and identifying environmental factors to reduce CRC incidence and mortality risks.     

Factors of Never Screened with Faecal Occult Blood Test in Public Primary Care Facilities

Background: Colorectal cancer (CRC) is still a major public health threat. In the effort to reduce CRC incidence and mortality, faecal occult blood test (FOBT) is currently the screening tools used for early detection of CRC. However, the uptake of FOBT screening is less than promising. This study aims to identify the prevalence and predictors of Never Screened with FOBT (NS-FOBT). Methods: A cross sectional study was conducted in five health clinics under Kota Kinabalu district, Sabah, Malaysia Borneo involving 162 attendees with age of 50 years old and above. A validated self-administered questionnaire was used to collect the data. Multiple logistic regression analysis was used to determine the predictors of NS-FOBT. Results: The prevalence of NS-FOBT was 85.8% (n=139). Important predictors of NS-FOBT were age (aOR: 0.922; 95% CI: 0.855, 0.995; p=0.035), Bumiputera ethnicity (vs Non Bumiputera; aOR: 4.285; 95% CI: 1.384, 13.263; p=0.012), knowledge score (aOR: 0.921; 95% CI: 0.856, 0.99; p=0.027), and attitude score (aOR: 0.801; 95% CI: 0.702, 0.913; p=0.001). Conclusion: There is high prevalence of NS-FOBT. Age, ethnicity, knowledge, and attitude were important predictors of NS-FOBT. Strategies are needed to improve FOBT screening rate among the public. Socio-culturally tailored health promotion strategies as well as strengthening the communication, collaboration, and education to enhance the role of family physician is vital in improving the CRC prevention and care.     

Physical activity and other lifestyle factors in relation to the prevalence of colorectal adenoma: a colonoscopy-based study in asymptomatic Koreans

Purpose

To evaluate physical activity and other lifestyle risk factors in relation to the prevalence of colorectal adenomas in asymptomatic Koreans.

Methods

A total of 1,526 asymptomatic subjects who underwent a colonoscopy were enrolled. Lifestyle factors such as physical activity and smoking data were obtained using a questionnaire. The subjects were grouped into three exposure levels by tertiles of metabolic equivalent hours per week. We evaluated the risk factors in subjects with adenomas by risk stratification (low-risk adenoma group vs. high-risk adenoma group) and by anatomic location (proximal colon, distal colon, rectum, and multiple locations). The high-risk adenoma group was defined as subjects with advanced adenomas or multiple (≥3) adenomas.

Results

A total of 456 participants had colorectal adenomas, and 861 had no polyps. In multivariate analyses, higher levels of physical activity were associated with a significantly decreased risk of colorectal adenomas (OR = 0.56, 95 % CI 0.40–0.79). This inverse association was stronger for the risk of high-risk adenomas (OR = 0.39, 95 % CI 0.21–0.73) than for low-risk adenomas (OR = 0.62, 95 % CI 0.43–0.89). The negative relation of physical activity was significant for distal colon adenomas (OR = 0.54, 95 % CI 0.30–0.95) and the adenomas with multiple locations (OR = 0.39, 95 % CI 0.21–0.72).

Conclusions

Increased physical activity is associated with a reduced prevalence of colorectal adenomas. The inverse association between physical activity and adenoma was stronger for the risk of advanced or multiple adenomas.     

Measuring interval cancers in population-based screening using different assays of fecal occult blood testing: the District of Florence experience

The fecal occult blood test (FOBT) has demonstrated its efficacy in reducing mortality from colorectal cancer (CRC). The guaiac-based FOBT has been criticized for its low sensitivity. In this study, two different assays for FOBT (guaiac or an immunochemical test based on reversed passive hemagglutination [RPHA]) were tested for comparison within a population-based screening program for colorectal cancer in the province of Florence (Italy). The proportional incidence method was used to calculate sensitivity for both FOBTs, according to rank of screening (first or repeat), age at entry (two groups of 50 to 59 and 60 to 70 years old) and lesion site (colon or rectum). When comparing FOBTs, the sensitivity multivariate Poisson regression was used to adjust for other variables. The sensitivity after the first 2 years was 50% (95% confidence interval [CI] 34% to 63%) for the guaiac test versus 82% (95% CI 67% to 92%) for RPHA. At multivariate analysis the risk of developing an interval cancer after a guaiac test is almost 3 times that after RPHA (rate ratio = 2.64; 95% CI 1.3 to 5.4). Our study confirms that RPHA is more sensitive than the guaiac test. The assumption that FOBT screening for CRC has to be based on a guaiac test should be reconsidered, and RPHA should be recommended as the standard FOBT for screening purposes.     

Predictive value of rectal bleeding for distal colonic neoplastic lesions in a screened population

The aim of this study was to determine the diagnostic value of rectal bleeding for distal colorectal cancer (CRC), or large (> or =10 mm) adenomas among an average-risk population. A cross-sectional survey was conducted among individuals aged 55-64 years, who attended sigmoidoscopy (FS) screening in the context of a multicentre randomised trial of FS screening for CRC. Sensitivity, specificity and positive predictive value (PPV) of rectal bleeding for large distal adenomas or CRC were calculated. Rectal bleeding was reported by 8.8% of 8507 patients examined (15% of those with large adenomas and 29% of those with CRC). The risk of CRC was increased when bleeding was associated with an altered bowel habit: odds ratio (OR)=10.42; 95% Confidence Interval (CI): 4.08-26.59; the corresponding OR for isolated bleeding was 5.29 (95% CI: 2.28-12.30). Rectal bleeding carries an increased risk of distal neoplastic lesions. However, most lesions are detected among asymptomatic subjects. This finding suggests that screening represents the optimal strategy to detect CRC or large adenomas in the distal colon in the targeted age range.     

Variation risks of SFRP2 hypermethylation between precancerous disease and colorectal cancer

DNA hypermethylation of secreted frizzled-related protein 2 (SFRP2) gene associated with the Wnt signaling pathway has been studied previously. However, the risk size and changing rules between colorectal cancer (CRC) and SFRP2 hypermethylation from precancerous disease to CRC remain unclear. The aim of work was therefore to investigate the risk size and changing rule based on detections on large numbers of tissue and feces samples. Association study and meta-analysis were performed to analyze the risk size of SFRP2 hypermethylation in tissue and fecal detections from 2,912 samples, including 1,436 patients with CRC, 866 patients with colon adenomas or polyps, and 610 samples with both normal controls. Based on normal controls as standard reference, the analysis showed that SFRP2 hypermethylation in CRC and adenoma tissues had a significantly higher risk with 92.81 (28.76–299.45) and 22.46 (4.13–122.04) odds ratio (OR) (95 % confidence interval (CI)) respectively, and that the risk sizes of SFRP2 hypermethylation in CRC and adenoma patients were 41.86 (18.91–92.67) and 11.76 (6.98–19.84) of OR (95 % CI) in fecal samples, and that the OR risk in both tissue and fecal samples increased significantly to 70.35 and 30.10 from precancerous disease (adenoma or polyp) to CRC. There were significant differences between tissue and fecal hypermethylation frequency. On the basis of the hypermethylation frequency of colorectal tissue, the coincidence rates of fecal hypermethylation in CRC and colorectal adenoma were 0.89 and 0.9, respectively. The risk size of SFRP2 hypermethylation from normal control to adenoma or polyp as well as from adenoma or polyp to CRC increased gradually in both tissue and feces. Therefore, SFRP2 hypermethylation is an important biomarker both in noninvasive diagnosis in feces detection and in colon tissue.     

Stroke as a late treatment effect of Hodgkin's Disease: a report from the Childhood Cancer Survivor Study.

PURPOSE: The objectives of this report are to examine the incidence of and risk factors for stroke among childhood Hodgkin's disease (HD) survivors. PATIENTS AND METHODS: The Childhood Cancer Survivor Study is a multi-institutional cohort study of more than 5-year cancer survivors diagnosed between 1970 and 1986 and a sibling comparison group. Incidence rates of stroke among HD survivors (n = 1,926) and siblings (n = 3,846) were calculated and compared. Cox proportional hazards models were used to estimate the hazard ratios, reported as relative risks (RR), of developing stroke between HD survivors and siblings. RESULTS: Nine siblings reported a stroke, for an incidence of 8.00 per 100,000 person-years (95% CI, 3.85 to 14.43 per 100,000 person-years). Twenty-four HD survivors reported a stroke. The incidence of late-occurring stroke among HD survivors was 83.6 per 100,000 person-years (95% CI, 54.5 to 121.7 per 100,000 person-years). The RR of stroke among HD survivors was 4.32 (95% CI, 2.01 to 9.29; P = .0002). All 24 survivors received mantle radiation exposure (median dose, 40 Gy). The incidence of late-occurring stroke among HD survivors treated with mantle radiation was 109.8 per 100,000 person-years (95% CI, 70.8 to 161.1 per 100,000 person-years). The RR of late-occurring stroke among HD survivors treated with mantle radiation was 5.62 (95% CI, 2.59 to 12.25; P < .0001). CONCLUSION: Survivors of childhood HD are at increased risk of stroke. Mantle radiation exposure is strongly associated with subsequent stroke. Potential mechanisms may include carotid artery disease or cardiac valvular disease.     

Incidence of interstitial pneumonitis among breast cancer patients: a 10-year Danish population-based cohort study

Chemotherapy and radiation therapy may increase risk for interstitial pneumonitis (IP) in breast cancer patients, but there are little current population-based data on IP incidence in these patients. We assessed population-based incidence rates (IRs) of IP among Danish breast cancer patients and compared these with IRs for the Danish general population. Through the Danish Cancer Registry, we identified all Danish breast cancer patients (n=35 823) diagnosed between 1994 and 2004. Treatment data were obtained from the Danish Breast Cancer Cooperation Group database, and data on IP, from the Danish National Registry of Patients. We computed IRs of IP among breast cancer patients and age-standardised incidence rate ratios (SIRs) comparing breast cancer patients with the general population. During follow-up, 28 breast cancer patients were registered with an IP diagnosis (IR=17.3 per 100,000 person-years (p-y) (95% confidence intervals (95% CI): 11.7-24.6)). When follow-up was restricted to 1 year after the first breast cancer diagnosis, eight patients with IP were identified (IR=23.4 per 100,000 p-y (95% CI: 11.0-44.1)). The SIR comparing breast cancer patients with the general population was 8.4 (95% CI: 5.7-11.9). Thus, although IP is a rare adverse event among breast cancer patients, its risk is substantially higher than that in the general population.