Insulin resistance, central obesity, and risk of colorectal adenomas

BACKGROUND:

Increasing evidence supports insulin resistance (IR) as the underpinning of the obesity‐colorectal neoplasia link. The homeostasis model assessment‐IR (HOMA‐IR) is a widely accepted index of evolving hyperinsulinemia and early IR. Studies of the relation between HOMA‐IR and colorectal adenomas are limited. Therefore, the authors sought to determine the associations of HOMA‐IR and central obesity (waist to hip ratio [WHR]) with risk of colorectal adenomas in a screening colonoscopy‐based study.

METHODS:

The authors collected lifestyle information and fasting blood samples from 1222 participants (320 incident adenoma cases and 902 without adenomas) before their screening colonoscopies. Unconditional logistic regression models were used to assess risk associations.

RESULTS:

In multivariate analysis of participants (n = 1093) reporting no antidiabetic medication use, those in the top quartile of WHR were twice as likely (odds ratio [OR], 2.18; 95% confidence interval [CI], 1.33‐3.57; P‐trend = .003) and those in the top quartile of HOMA‐IR were 63% more likely (OR, 1.63; 95% CI, 1.09‐2.44; P‐trend = .01) to have adenomas compared with those in the bottom quartiles. Stratified analysis revealed a statistically significant interaction between HOMA‐IR and sex (P‐interaction = .04), with the association largely limited to men; compared with those in the bottom tertile, men in the top tertile of HOMA‐IR were twice more likely to have adenomas (OR, 2.11; 95% CI, 1.18‐3.78; P‐trend = .01).

CONCLUSIONS:

The results support central obesity and insulin resistance, particularly in men, as important risk factors for the development of early colorectal neoplasia. Cancer 2012;. © 2011 American Cancer Society.     

Colonoscopy screening rates among patients of colonoscopy-trained African American primary care physicians

BACKGROUND:

When performed competently, colonoscopy screening can reduce colorectal cancer rates, especially in high‐risk groups such as African Americans. Training primary care physicians (PCPs) to perform colonoscopy may improve screening rates among underserved high‐risk populations.

METHODS:

The authors compared colonoscopy screening rates and computed adjusted odds ratios for colonoscopy‐eligible patients of trained African American PCPs (study group) versus untrained PCPs (comparison group), before and after initiating colonoscopy training. All colonoscopies were performed at a licensed ambulatory surgery center with specialist standby support. Retrospective chart review was conducted on 200 consecutive, established outpatients aged ≥50 years at each of 12 PCP offices (7 trained African American PCPs and 5 untrained PCPs, practicing in the same geographic region). There were a total of 1244 study group and 923 comparison group patients.

RESULTS:

Post‐training colonoscopy rates in both groups were higher than pretraining rates: 48.3% versus 9.3% in the study group, 29.6% versus 9.8% in the comparison group (both P < .001). African American patients in the study group showed a >5‐fold increase (8.9% pretraining vs 52.8% post‐training), with no change among whites (18.2% vs 25.0%). Corresponding pretraining and post‐training rates among comparison patients were 10.4%% and 38.7%, respectively, among African Americans (P < .001), and 13.3% versus 13.2%, respectively, among whites. After adjusting for demographics, duration since becoming the PCP's patient, and health insurance, the study group had a 66% higher likelihood of colonoscopy in the post‐training period (odds ratio, 1.66; 95% confidence interval, 1.30‐2.13), and African Americans had a 5‐fold increased likelihood of colonoscopy relative to whites.

CONCLUSIONS:

Colonoscopy‐trained PCPs may help reduce colorectal cancer disparities. Cancer 2011;. © 2011 American Cancer Society.     

Prevalence of neoplasia at colonoscopy among testicular cancer survivors treated with platinum-based chemotherapy

Testicular cancer survivors (TCS) treated with platinum-based chemotherapy have an increased risk of colorectal cancer (CRC). We determined the yield of colonoscopy in TCS to assess its potential in reducing CRC incidence and mortality. We conducted a colonoscopy screening study among TCS in four Dutch hospitals to assess the yield of colorectal neoplasia. Neoplasia was defined as adenomas, serrated polyps (SPs), advanced adenomas (AAs: ≥10 mm diameter, high-grade dysplasia or ≥25% villous component), advanced serrated polyps (ASPs: ≥10 mm diameter or dysplasia) or CRC. Advanced neoplasia (AN) was defined as AA, ASP or CRC. Colonoscopy yield was compared to average-risk American males who underwent screening colonoscopy (n = 24,193) using a propensity score matched analysis, adjusted for age, smoking status, alcohol consumption and body mass index. A total of 137 TCS underwent colonoscopy. Median age was 50 years among TCS (IQR 43–57) vs 55 years (IQR 51–62) among American controls. A total of 126 TCS were matched to 602 controls. The prevalence of AN was higher in TCS than in controls (8.7% vs 1.7%; P = .0002). Nonadvanced adenomas and SPs were detected in 45.2% of TCS vs 5.5% of controls (P < .0001). No lesions were detected in 46.0% of TCS vs 92.9% of controls (P < .0001). TCS treated with platinum-based chemotherapy have a higher prevalence of neoplasia and AN than matched controls. These results support our hypothesis that platinum-based chemotherapy increases the risk of colorectal neoplasia in TCS. Cost-effectiveness studies are warranted to ascertain the threshold of AN prevalence that justifies the recommendation of colonoscopy for TCS.     

Evaluation of sleep disorders in cancer patients based on Pittsburgh Sleep Quality Index

Insomnia, poor sleep quality and short sleep durations are the most common problems seen in cancer patients. More studies are needed about sleep disorders in cancer patients. In our study, we aimed to investigate the prevalence of sleep disorders and the impact of these problems on the quality of life in cancer patients. Pittsburgh Sleep Quality Index (PSQI) was given to a total of 314 patients. The psychometric evaluation of the Turkish version of PSQI in cancer patients revealed that 127 (40.4%) patients had global PSQI scores >5, indicating poor sleep quality. There was no statistically significant relationship between PSQI scores and sexuality, marital status, cancer stage and chemotherapy type (P > 0.05); while the patients with bone and visceral metastasis had much lower PSQI scores (P = 0.006). Patients with Eastern Cooperative Oncology Group performance scores of 3 or more had also significantly lower PSQI scores (P = 0.02). In conclusion, PSQI questionnaire may be used to evaluate the sleep disorders in cancer patients. Consistent use of multi‐item measures such as PSQI with established reliability and validity would improve our understanding of difficulties experienced by cancer patients with chronic insomnia.     

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.     

Relation between normal rectal methylation,smoking status,and the presence or absence of colorectal adenomas

BACKGROUND:

Colorectal cancer (CRC) is 1 of the leading causes of death in the Western world. CRC develops from premalignant lesions, chiefly colorectal adenomas. Currently, the most accurate and recommended screening method for finding colorectal adenomas is colonoscopy performed on all individuals aged >50 years. However, the costs and risks associated with this procedure are relatively high. The objectives of the current study were to correlate epigenetic alterations that occur in normal rectal mucosa, smoking status, and age with the presence or absence of concomitant colorectal adenomas and to assess the potential clinical value of methylation in normal rectal biopsies as a screening assay for the presence of polyps and, hence, the need for a full colonoscopy.

METHODS:

One hundred thirteen normal rectal mucosal biopsies from 113 patients were studied. DNA was extracted, modified with sodium bisulfite, and subjected to real‐time quantitative, methylation‐specific polymerase chain reaction analysis for the following genes: adenomatous polyposis coli (APC); cadherin 1, type 1, E‐cadherin (epithelial) (CDH1); estrogen receptor 1 (ESR1); cytokine high in normal 1 (HIN1); hyperplastic polyposis protein 1 (HPP1); O‐6 methylguanine‐DNA methyltransferase (MGMT); neural epidermal growth factor‐like 1 (NELL1); splicing factor 3B, 14‐kDa subunit (p14); cyclin‐dependent kinase (CDK) inhibitor 2B (inhibits CDK4) (p15); retinoic acid receptor beta (RARβ); somatostatin (SST); tachykinin, precursor 1 (TAC1); and tissue inhibitor of metalloproteinase (TIMP) metallopeptidase inhibitor 3 (TIMP3). Data were then analyzed using several proprietary software programs.

RESULTS:

By using several sets of genes, clinical characteristics, and multivariate analyses, the authors developed a prediction model for the presence of concomitant colorectal adenomas at the time of rectal biopsy. They also observed strong correlations between smoking status and rectal methylation pattern and between smoking status and the presence or risk of concomitant adenomas.

CONCLUSIONS:

A prediction model was developed for the presence of colorectal adenomas based on gene methylation patterns in the normal rectum. The results indicated that these genes may be involved in early stages of adenoma formation. The observed epigenetic alterations in these markers may be caused in part by the effects of smoking and/or age. Normal rectal methylation may be useful as a biomarker for narrowing the population in need of screening colonoscopy. Cancer 2010. © 2010 American Cancer Society.     

Occult tumor burden contributes to racial disparities in stage-specific colorectal cancer outcomes

BACKGROUND:

There are differences in outcomes in blacks compared with whites with lymph node–negative (pN0) colorectal cancer. Recurrence in pN0 patients suggests the presence of occult metastases undetected by conventional approaches. This study explores the association of racial differences in outcomes with occult tumor burden in regional lymph nodes.

METHODS:

Lymph nodes (range, 2‐159) from 282 prospectively enrolled pN0 colorectal cancer patients followed for a median of 24 months (range, 2‐63 months) were subjected to molecular analysis. Occult tumor burden was estimated by quantifying the expression of GUCY2C, a biomarker for metastatic colorectal cancer cells. Risk categories defined using occult tumor burden was the primary outcome measure. Association of prognostic variables and risk were defined by multivariate polytomous logistic regression.

RESULTS:

Occult tumor burden stratified this cohort of 259 whites and 23 blacks into categories with low (60%; recurrence rate [RR] = 2.3%; 95% confidence interval [CI], 0.1%‐4.5%), intermediate (31%; RR = 33.3%; 95% CI, 23.7%‐44.1%), and high (9%; RR = 68.0%; 95% CI, 46.5%‐85.1%; P < .001) risk. Blacks compared with whites exhibited 4‐fold greater occult metastases in individual lymph nodes (P < .001). Multivariate analysis revealed that race (P = .02), T stage (P = .02), and number of lymph nodes collected (P = .003) were independent prognostic markers of risk category. Blacks compared with whites were more likely to harbor levels of occult tumor burden, associated with the highest recurrence risk (adjusted odds ratio = 5.08; 95% CI, 1.69‐21.39; P = .007).

CONCLUSIONS:

Racial disparities in stage‐specific outcomes in colorectal cancer are associated with differences in occult tumor burden in regional lymph nodes. Cancer 2012. © 2011 American Cancer Society.     

Trastuzumab uptake and its relation to efficacy in an animal model of HER2-positive breast cancer brain metastasis

Purpose

To examine whether baseline sleep duration or changes in sleep duration are associated with breast cancer prognosis among early-stage breast cancer survivors in the multi-center Women’s Healthy Eating and Living Study.

Methods

Data were collected from 1995 to 2010. Analysis included 3047 women. Sleep duration was self-reported at baseline and follow-up intervals. Cox proportional hazard models were used to investigate whether baseline sleep duration was associated with breast cancer recurrence, breast cancer-specific mortality, and all-cause mortality. Time-varying models investigated whether changes in sleep duration were associated with breast cancer prognosis.

Results

Compared to women who slept 7–8 h/night at baseline, sleeping ≥9 h/night was associated with a 48% increased risk of breast cancer recurrence (Hazard ratio [HR] 1.48, 95% Confidence interval [CI] 1.01, 2.00), a 52% increased risk of breast cancer-specific mortality (HR 1.52, 95% CI 1.09, 2.13), and a 43% greater risk of all-cause mortality (HR 1.43, 95% CI 1.07, 1.92). Time-varying models showed analogous increased risk in those who inconsistently slept ≥9 h/night (all P < 0.05), but not in those who consistently slept ≥9 h/night.

Conclusions

Consistent long or short sleep, which may reflect inter-individual variability in the need for sleep, does not appear to influence prognosis among early-stage breast cancer survivors.

     

Establishing the link between hepatitis B virus infection and colorectal adenoma

Background

Chronic hepatitis B (CHB) infection has been associated with malignancy, most notably hepatocellular carcinoma. Previous research has shown that hepatitis C is associated with increased colorectal adenomas and neoplasia. Currently, there are no studies on the association of CHB and colorectal adenomas. We aimed to identify a possible link between CHB and colorectal adenoma.

Methods

A retrospective chart review was performed on 588 consecutive patients undergoing screening or diagnostic colonoscopy that were previously screened or diagnosed with hepatitis B. Comparisons between categorical variables were analyzed with Chi Square test and t-test for continuous variables. Unconditional logistic regression was used to generate age-, gender-and race-adjusted odds ratios and their 95% confidence intervals (CI) comparing medication users with non-users. Statistical analyses were performed with SAS 9.3 software.

Results

A total of 487 patients were analyzed in the control group vs. 71 in the hepatitis B group. The adenoma detection rate was 23.9% in hepatitis B vs. 15.9% in the non-hepatitis B group for all cause colonoscopy; however this did not reach statistical significance. There was a significantly higher number of adenomas present in the distal colon compared to control (OR =2.16; 95% CI, 1.06-4.43; P=0.04). There were no significant findings between hepatitis B infection with size, multiplicity or presence of proximal adenomas. There was a significant difference noted in regards to smoking history, BMI and age between two groups.

Conclusions

Although the adenoma detection rate was higher in hepatitis B population vs. the non-hepatitis B group this did not reach statistical significance. However, we did find an association between CHB infection and the presence of distal colorectal adenomas. Larger prospective studies are needed to strengthen our findings along with future studies examining hepatitis B virus (HBV) and mechanisms inducing colorectal carcinogenesis.     

Increased risk of colorectal polyps in patients with non-alcoholic fatty liver disease undergoing liver transplant evaluation

Background

Screening colonoscopy is a standard part of the liver transplant (LT) evaluation process. We aimed to evaluate the yield of screening colonoscopy and determine whether non-alcoholic fatty liver disease (NAFLD) was associated with an increased risk of colorectal neoplasia.

Methods

We retrospectively assessed all patients who completed LT evaluation at our center between 1/2008-12/2012. Patients <50 years old and those without records of screening colonoscopy, or with greater than average colon cancer risk were excluded.

Results

A total of 1,102 patients were evaluated, 591 met inclusion criteria and were analyzed. The mean age was 60 years, 67% were male, 12% had NAFLD and 88% had other forms of chronic liver disease. Overall, 42% of patients had a polyp found on colonoscopy: 23% with adenomas, 14% with hyperplastic polyps and with 1% inflammatory polyps. In the final multivariable model controlling for age, NAFLD [odds ratio (OR) 2.41, P=0.001] and a history of significant alcohol use (OR 1.69, P=0.004) were predictive of finding a polyp on colonoscopy. In addition, NAFLD (OR 1.95, P=0.02), significant alcohol use (OR 1.70, P=0.01) and CTP class C (OR 0.57, P=0.02) were associated with adenoma, controlling for age.

Conclusions

Screening colonoscopy in patients awaiting LT yields a high rate of polyp (43%) and adenoma (22%) detection, perhaps preventing the accelerated progression to carcinoma that can occur in immunosuppressed post-LT patients. Patients with NAFLD may be at a ~2 fold higher risk of adenomas and should be carefully evaluated prior to LT.     

A randomized phase 2 trial comparing 3‐hour versus 96‐hour infusion schedules of paclitaxel for the treatment of metastatic breast cancer

BACKGROUND:

This study was performed to compare efficacy and toxicity profiles of paclitaxel using 3‐hour versus 96‐hour infusion schedules.

METHODS:

Patients with metastatic breast cancer (MBC) were randomly assigned to receive paclitaxel starting at a dose of 250 mg/m² intravenously (iv) over 3 hours every 21 days or paclitaxel starting at a dose of 140 mg/m² iv over 96 hours every 21 days. Stratification variables included number of prior chemotherapy regimens and previous response to anthracyclines. Response was assessed every 2 cycles using bidimensional measurements. Patients were allowed to cross over at disease progression or therapy intolerance.

RESULTS:

A total of 214 patients received therapy (107 patients per arm). Response rates were similar: 23.4% in the 3‐hour arm and 29.9% in the 96‐hour arm (P = .28). The median duration of response (8.9 months vs 5.7 months; P = .75) and progression‐free survival (5.0 months vs 3.8 months; P = .17) slightly favored the 96‐hour arm. Overall survival was slightly longer in the 3‐hour arm (14.2 months vs 12.7 months; P = .57). One patient who crossed over to the 96‐hour arm (N = 18) developed a partial response; no response was noted with crossover to the 3‐hour arm (N = 10). Myalgia/arthralgia and neuropathy were more frequent in the 3‐hour arm, whereas mucositis, neutropenic fever/infection, and diarrhea were more common in the 96‐hour arm.

CONCLUSIONS:

Paclitaxel given by 3‐hour or 96‐hour infusion was active in MBC. The 96‐hour paclitaxel regimen did not significantly improve response or time to disease progression, was more cumbersome to administer, and was associated with greater myelosuppression (but less neuropathy and myalgia) compared with the 3‐hour schedule. Cancer 2010. © 2010 American Cancer Society.     

Improved outcome of patients with low- and intermediate-risk cytogenetics acute myeloid leukemia (AML) in first relapse with gemtuzumab and cytarabine versus cytarabine: results of a retrospective comparative study

BACKGROUND:

Acute myeloid leukemia (AML) in first relapse is associated with a poor outcome even when treated with intermediate‐ to high‐dose cytarabine (IHDAraC). Gemtuzumab ozogamycin (GO) used as a single agent has clinical activity in relapsed and refractory AML. Various combination regimens of GO have been developed, but few data are available regarding their efficacy compared with IHDAraC‐based regimens.

METHODS:

The authors performed a retrospective analysis of response and survival in 90 AML patients in first relapse treated with either IHDAraC (n = 56) or IHDAraC + GO (n = 34). Patient characteristics of the two groups were comparable.

RESULTS:

Median follow‐up was 37 months. Compared with IHDAraC, IHDAraC + GO induction was associated with a better response rate (68% vs 45%, P = .04), a better overall survival (median, 35 months vs 6 months, P = .001), and a better event‐free survival (24 months vs 6 months, P = .002). This effect was limited to patients with low‐risk and intermediate‐risk cytogenetics. In multivariate analysis, age, cytogenetic risk, first complete remission duration, and the use of IHDAraC + GO were independently associated with better results.

CONCLUSIONS:

This study showed that the addition of GO to IHDAraC is associated with a better efficacy for patients in first relapse of AML with low‐ or intermediate‐risk cytogenetics. Prospective controlled studies of GO in this population are warranted. Patients with high‐risk cytogenetics should be offered investigational new drugs. Cancer 2011. © 2010 American Cancer Society.     

A prospective study of erythrocyte polyunsaturated fatty acids and risk of colorectal serrated polyps and conventional adenomas

The influence of polyunsaturated fatty acids (PUFAs) on risk of colorectal cancer precursors remains largely unknown. We examined the associations of erythrocyte PUFAs, including n?3 and n?6 PUFAs, with risk of colorectal conventional adenomas and serrated polyps in 4517 participants from three US prospective cohorts who had provided a blood sample and undergone at least one endoscopic examination. We calculated the multivariable odds ratios (ORs) per 1 SD increment in individual PUFAs and the ratio of n?6/n?3 PUFAs. We considered P < .005 statistically significant to account for multiple testing. During a median of 20 years of follow‐up, we documented 493 conventional adenomas and 316 serrated polyps. After adjusting for various CRC risk factors, no associations for PUFAs achieved the stringent statistical significance for either conventional adenomas or serrated polyps (ORs per 1 SD ranged from 0.90 to 1.14). Some associations achieved nominal significance (P < .05), including the association of dihomogammalinolenic acid (DGLA) (20:3, n?6) with lower risk of conventional adenomas (OR = 0.91; 95% confidence interval [CI] = 0.83‐1.00), total n?6 PUFAs with higher risk of proximal serrated polyps (OR = 1.32; 95% CI = 1.01‐1.74) and eicosadienoic acid (20:2, n?6) and DGLA with lower risk of advanced adenomas (OR = 0.83; 95% CI = 0.71‐0.97 and OR = 0.84; 95% CI = 0.72‐0.98, respectively). Our findings indicate that erythrocyte PUFAs in a typical American diet are unlikely to have a substantial influence on risk of colorectal cancer precursors. The subgroup associations require further confirmation.     

Clinical impact of anti-epidermal growth factor receptor monoclonal antibodies in first-line treatment of metastatic colorectal cancer: meta-analytical estimation and implications for therapeutic strategies

BACKGROUND:

Antiepidermal growth factor receptor (anti‐EGFR) monoclonal antibodies (MoAbs) are indicated for the treatment of metastatic colorectal cancer patients, but some scientific issues concerning their efficacy are currently unsolved.

METHODS:

A literature‐based meta‐analysis was conducted. Hazard ratios (HRs) were extracted from randomized trials for progression‐free survival (PFS) and overall survival (OS); the event‐based risk ratio was derived for response. Sensitivity analyses to look for interactions according to KRAS status and chemotherapy association regimens were performed.

RESULTS:

Eight trials (6609 patients) were identified. A significant interaction according to KRAS status was found for PFS (wild type vs mutant, P = .001) and response rate (wild type vs mutant, P < .0001). The addition of an anti‐EGFR MoAb to first‐line chemotherapy increased PFS in the KRAS wild‐type population (HR, 0.91; 95% confidence interval [CI], 0.84‐0.99; P = .03), and had a detrimental effect in the KRAS mutant population (HR, 1.13; 95% CI, 1.03‐1.25; P = .013). A significant increase in the probability of achieving a response was evident in KRAS wild‐type patients (relative risk, 1.17; 95% CI, 1.04‐1.33; P = .011). In this population, the interaction in response rate according to adopted chemotherapy favored irinotecan‐containing regimens (P = .01), and at meta‐regression analysis the relative increase in response rate was significantly related to PFS (P = .00001) and OS (P = .00193) benefit.

CONCLUSIONS:

The addition of an anti‐EGFR MoAb to first‐line chemotherapy produces a clear benefit in response rate. This advantage is restricted to KRAS wild‐type patients and translates into a small benefit in PFS. At present, irinotecan‐based backbone chemotherapy could be a preferable option. The correlation between activity and survival parameters corroborates the hypothesis that anti‐EGFR MoAbs might be more suitable for patients needing tumoral shrinkage. Cancer 2011;. © 2011 American Cancer Society.     

<Emphasis Type="Italic">Helicobacter pylori</Emphasis> infection is an independent risk factor for colonic adenomatous neoplasms

Purpose

Helicobacter pylori infection is considered to have a positive association with colorectal neoplasms. In this study, we evaluated the association between H. pylori infection and colorectal adenomas, based on the characteristics of these adenomas in Korea, where the prevalence of H. pylori infection is high and the incidence of colorectal cancer continues to increase.

Methods

The study cohort consisted of 4,466 subjects who underwent colonoscopy and esophagogastroduodenoscopy during screening (1,245 colorectal adenomas vs. 3,221 polyp-free controls). We compared the rate of H. pylori infection between patients with adenoma and polyp-free control cases, using multivariable logistic regression analysis.

Results

The overall rate of positive H. pylori infection was higher in adenoma cases than in polyp-free control cases (55.0 vs. 48.5%, p < 0.001). The odds ratio (OR) of positive H. pylori infection in patients with adenoma compared to polyp-free controls was 1.28 (95% CI 1.11–1.47). The positive association of H. pylori infection with colorectal adenomas was more prominent in advanced adenomas (OR 1.84, 95% CI 1.25–2.70) and multiple adenomas (OR 1.72, 95% CI 1.26–2.35). Based on the location of these adenomas, the OR was significant only in patients with colonic adenomas (OR 1.31, 95% CI 1.13–1.52) and not in those with rectal adenoma (OR 0.85, 95% CI 0.58–1.24).

Conclusion

Helicobacter pylori infection is an independent risk factor for colonic adenomas, especially in cases of advanced or multiple adenomas, but not for rectal adenomas.

     

Rates and predictors of colorectal cancer screening by race among motivated men participating in a Prostate Cancer Risk Assessment Program

BACKGROUND:

Screening by fecal occult blood test and lower endoscopy has lowered colorectal cancer (CRC) mortality, but compliance gaps persist. Of concern are possible disparities in uptake of CRC screening between white and African American men. The goal of this study was to assess for disparities in uptake of CRC screening among men participating in a high‐risk prostate cancer clinic. If present, such disparities could support hypotheses for further research examining racial differences in awareness and patient preferences in undergoing CRC screening.

METHODS:

Baseline data on a racially diverse cohort of men aged 50 to 69 years at increased risk of prostate cancer collected via the Prostate Cancer Risk Assessment Program at Fox Chase Cancer Center were analyzed. Predictors of uptake of CRC screening were assessed using multivariate logistic regression.

RESULTS:

Compared with whites, African American men had statistically significantly lower uptake of fecal occult blood testing (African American 49.0% vs white 60.7%, P = .035), lower endoscopy (African American 44.1% vs white 58.5%, P = .011), and any CRC screening (African American 66.2% vs white 76.3%, P = .053). Predictors of uptake of lower endoscopy among African American men included older age (odds ratio [OR], 3.61; 95% confidence interval [CI], 1.87‐6.97), family history of CRC (OR, 3.47; 95% CI, 1.30‐9.25), and insurance status (OR, 1.90; 95% CI, 1.04‐3.46).

CONCLUSIONS:

Despite awareness of cancer risk and motivation to seek prostate cancer screening through a specialized prostate cancer risk assessment program, evidence supporting compliance gaps with CRC screening among men was found. Tailored messages to younger African American men with and without a family history of CRC are needed. Cancer 2011;. © 2011 American Cancer Society.     

Impact of lympho‐vascular space invasion on tumor characteristics and survival outcome of women with low‐grade serous ovarian carcinoma

Background and Objectives

To examine association of lympho‐vascular space invasion (LVSI) with clinico‐pathological factors and to evaluate survival of women with low‐grade serous ovarian carcinoma containing areas of LVSI.

Methods

This is a multicenter retrospective study examining consecutive cases of surgically treated stage I‐IV low‐grade serous ovarian carcinoma (n = 178). Archived histopathology slides for the ovarian tumors were reviewed, and LVSI was scored as present or absent. LVSI status was correlated to clinico‐pathological findings and survival outcome.

Results

LVSI was seen in 79 cases (44.4%, 95% confidence interval [CI] 37.1‐51.7). LVSI was associated with increased risk of omental metastasis (87.0% vs 64.9%, odds ratio [OR] 3.62, P = 0.001), high pelvic lymph node ratio (median 12.9% vs 0%, P = 0.012), and malignant ascites (49.3% vs 32.6%, OR 2.01, P = 0.035). On multivariable analysis, controlling for age, stage, and cytoreductive status, presence of LVSI in the ovarian tumor remained an independent predictor for decreased progression‐free survival (5‐year rates 21.0% vs 35.7%, adjusted‐hazard ratio 1.57, 95%CI 1.06‐2.34, P = 0.026). LVSI was significantly associated with increased risk of recurrence in lymph nodes (OR 2.62, 95%CI 1.08‐6.35, P = 0.047).

Conclusion

LVSI in the ovarian tumor is associated with adverse clinico‐pathological characteristics and decreased progression‐free survival in women with low‐grade serous ovarian carcinoma.

     

Assessing individual risk for high‐risk colorectal adenoma at first‐time screening colonoscopy

Assessing risk of colorectal adenoma at first‐time colonoscopy that are of higher likelihood of developing advanced neoplasia during surveillance could help tailor first‐line colorectal cancer screening. We developed prediction models for high‐risk colorectal adenoma (at least one adenoma ≥1 cm, or with advanced histology, or ≥3 adenomas) among 4,881 asymptomatic white men and 17,970 women who underwent colonoscopy as their first‐time screening for colorectal cancer in two prospective US studies using logistic regressions. C‐statistics and Hosmer–Lemeshow tests were used to evaluate discrimination and calibration. Ten‐fold cross‐validation was used for internal validation. A total of 330 (6.7%) men and 678 (3.8%) women were diagnosed with high‐risk adenoma at first‐time screening colonoscopy. The model for men included age, family history of colorectal cancer, BMI, smoking, sitting watching TV/VCR, regular aspirin/NSAID use, physical activity, and a joint term of multivitamin and alcohol. For women, the model included age, family history of colorectal cancer, BMI, smoking, alcohol, beef/pork/lamb as main dish, regular aspirin/NSAID, calcium, and oral contraceptive use. The C‐statistic of the model for men was 0.67 and 0.60 for women (0.64 and 0.57 in cross‐validation). Both models calibrated well. The predicted risk of high‐risk adenoma for men in the top decile was 15.4% vs. 1.8% for men in the bottom decile (Odds Ratio [OR] = 9.41), and 6.6% vs. 2.1% for women (OR = 3.48). In summary, we developed and internally validated an absolute risk assessment tool for high‐risk colorectal adenoma among the US population that may provide guidance for first‐time colorectal cancer screening.     

Intensity-modulated radiation therapy versus conventional radiation therapy for squamous cell carcinoma of the anal canal

BACKGROUND:

The purpose of this study was to compare outcomes in patients with anal canal squamous cell carcinoma (SCCA) who were treated with definitive chemoradiotherapy by either intensity‐modulated radiation therapy (IMRT) or conventional radiotherapy (CRT).

METHODS:

Forty‐six patients who received definitive chemoradiotherapy from January 1993 to August 2009 were included. Forty‐five patients received 5‐fluorouracil with mitomycin C (n = 39) or cisplatin (n = 6). Seventeen (37%) were treated with CRT and 29 (63%) with IMRT. The median dose was 54 Gy in both groups. Median follow‐up was 26 months (CRT) and 32 months (IMRT). T3‐T4 stage (P = .18) and lymph node‐positive disease (P = .6) were similar between groups.

RESULTS:

The CRT group required longer treatment duration (57 days vs 40 days, P < .0001), more treatment breaks (88% vs 34.5%, P = .001), and longer breaks (12 days vs 1.5 days, P < .0001) than patients treated with IMRT. Eleven (65%) patients in the CRT group experienced grade >2 nonhematologic toxicity compared with 6 (21%) patients in the IMRT group (P = .003). The 3‐year overall survival (OS), locoregional control (LRC), and progression‐free survival were 87.8%, 91.9%, and 84.2%, respectively, for the IMRT groups and 51.8%, 56.7%, and 56.7%, respectively, for the CRT group (all P < .01). On multivariate analysis, T stage, use of IMRT, and treatment duration were associated with OS, and T stage and use of IMRT were associated with LRC.

CONCLUSIONS:

The use of IMRT was associated with less toxicity, reduced need for treatment breaks, and excellent LRC and OS compared with CRT in patients with SCCA of the anal canal. Cancer 2011. © 2011 American Cancer Society.     

Ethnic disparities in the risk of colorectal adenomas associated with aspirin and statin use: a retrospective multiethnic study

Background

Although data on the inverse association between colorectal adenomas (CRA) and daily aspirin or statin therapy exists in white and black patients, scarce data exists on these associations in the Hispanic population. With a rapidly increasing Hispanic population in the United States, defining the association in Hispanics is crucial.

Methods

The study sample included 1,843 consecutive patients who underwent a colonoscopy (screening or diagnostic) from 2009 to 2011 at a community hospital in East Meadow, New York. Data was then extracted from patient charts regarding aspirin and/or statin use. Adjusted odds ratios (OR) and their 95% confidence intervals (CI) were calculated to assess the association between colonoscopy findings and aspirin, statin, or aspirin/statin use.

Results

In our total population including all races, aspirin user had an increased risk for having two or more adenomas (OR =1.73, 95% CI: 1.00, 2.99, P=0.05) and presence of an adenoma in the proximal colon (OR =1.66, 95% CI: 1.07, 2.58, P=0.02). In the total study population, those who used both statin and aspirin had an increased risk for having two or more adenomas (OR =2.56, 95% CI: 1.21, 5.39, P=0.01). In the Hispanic population, users of both medications had an increased risk for having two or more adenomas (OR =19.04, 95% CI: 1.30, 280.09, P=0.03), adenoma present in the distal colon (OR =5.75, 95% CI: 1.64, 20.21, P=0.01) and largest adenoma in distal colon (OR =5.75, 95% CI: 1.64, 20.21, P=0.01).

Conclusions

Aspirin use and aspirin/statin use was associated with abnormal colonoscopy findings, particularly in the Hispanic population. These findings may be due to environmental factors such as dietary, colonic flora, or genetic susceptibility. The findings warrant further investigational research, particularly in Hispanics.