Projected Cancer Incidence Rates and Burden of Incident Cancer Cases in HIV-Infected Adults in the United States Through 2030.

Background: Persons living with HIV (PLWH) have an elevated risk for certain types of cancer. With modern antiretroviral therapy, PLWH are aging and cancer rates are changing. Objective: To project cancer incidence rates and burden (number of new cancer diagnoses) among adult PLWH in the United States through 2030. Design: Descriptive. Setting: HIV/AIDS Cancer Match Study to project cancer rates and HIV Optimization and Prevention Economics model to project HIV prevalence. Participants: HIV-infected adults. Measurements: Projected cancer rates and burden among HIV-infected adults in the United States by age during 2006 to 2030 for AIDS-defining cancer (ADC)-that is, Kaposi sarcoma, non-Hodgkin lymphoma, and cervical cancer-and certain types of non-AIDS-defining cancer (NADC). All other cancer types were combined. Results: The proportion of adult PLWH in the United States aged 65 years or older is projected to increase from 8.5% in 2010 to 21.4% in 2030. Age-specific rates are projected to decrease through 2030 across age groups for Kaposi sarcoma, non-Hodgkin lymphoma, cervical cancer, lung cancer, Hodgkin lymphoma, and other cancer types combined, and among those aged 65 years or older for colon cancer. Prostate cancer rates are projected to increase. The estimated total cancer burden in PLWH will decrease from 8150 cases in 2010 (2730 of ADC and 5420 of NADC) to 6690 cases in 2030 (720 of ADC and 5980 of NADC). In 2030, prostate cancer (n = 1590) and lung cancer (n = 1030) are projected to be the most common cancer types. Limitation: Projections assume that current trends in cancer incidence rates, HIV transmission, and survival will continue. Conclusion: The cancer burden among PLWH is projected to shift, with prostate and lung cancer expected to emerge as the most common types by 2030. Cancer will remain an important comorbid condition, and expanded access to HIV therapies and cancer prevention, screening, and treatment is needed. Primary Funding Source: National Cancer Institute.

High-Quality Diets Associate With Reduced Risk of Colorectal Cancer: Analyses of Diet Quality Indexes in the Multiethnic Cohort.

BACKGROUND & AIMS: Healthy eating patterns assessed by diet quality indexes (DQIs) have been related to lower risk of colorectal cancer-mostly among whites. We investigated the associations between 4 DQI scores (the Healthy Eating Index 2010 [HEI-2010], the Alternative Healthy Eating Index 2010 [AHEI-2010], the alternate Mediterranean diet score [aMED], and the Dietary Approaches to Stop Hypertension score) and colorectal cancer risk in the Multiethnic Cohort. METHODS: We analyzed data from 190,949 African American, Native Hawaiian, Japanese American, Latino, and white individuals, 45 to 75 years old, who entered the Multiethnic Cohort study from 1993 through 1996. During an average 16 years of follow-up, 4770 invasive colorectal cancer cases were identified. RESULTS: Scores from all 4 DQIs associated inversely with colorectal cancer risk; higher scores associated with decreasing colorectal cancer risk (all P's for trend ≤ .003). Associations were not significant for AHEI-2010 and aMED scores in women after adjustment for covariates: for the highest vs lowest quintiles, the hazard ratio for the HEI-2010 score in men was 0.69 (95% confidence interval [CI], 0.59-0.80) and in women was 0.82 (95% CI, 0.70-0.96); for the AHEI-2010 score the hazard ratio in men was 0.75 (95% CI, 0.65-0.85) and in women was 0.90 (95% CI, 0.78-1.04); for the aMED score the hazard ratio in men was 0.84 (95% CI, 0.73-0.97) and in women was 0.96 (95% CI, 0.82-1.13); for the Dietary Approaches to Stop Hypertension score the hazard ratio in men was 0.75 (95% CI, 0.66-0.86) and in women was 0.86 (95% CI, 0.75-1.00). Associations were limited to the left colon and rectum for all indexes. The inverse associations were less strong in African American individuals than in the other 4 racial/ethnic groups. CONCLUSIONS: Based on an analysis of data from the Multiethnic Cohort Study, high-quality diets are associated with a lower risk of colorectal cancer in most racial/ethnic subgroups.

Combining aneuploidy and dysplasia for colitis' cancer risk assessment outperforms current surveillance efficiency: a meta-analysis.

PURPOSE: Cancer risk assessment for ulcerative colitis patients by evaluating histological changes through colonoscopy surveillance is still challenging. Thus, additional parameters of high prognostic impact for the development of colitis-associated carcinoma are necessary. This meta-analysis was conducted to clarify the value of aneuploidy as predictor for individual cancer risk compared with current surveillance parameters. METHODS: A systematic web-based search identified studies published in English that addressed the relevance of the ploidy status for individual cancer risk during surveillance in comparison to neoplastic mucosal changes. The resulting data were included into a meta-analysis, and odds ratios (OR) were calculated for aneuploidy or dysplasia or aneuploidy plus dysplasia. RESULTS: Twelve studies addressing the relevance of aneuploidy compared to dyplasia were comprehensively evaluated and further used for meta-analysis. The meta-analysis revealed that aneuploidy (OR 5.31 [95 % CI 2.03, 13.93]) is an equally effective parameter for cancer risk assessment in ulcerative colitis patients as dysplasia (OR 4.93 [1.61, 15.11]). Strikingly, the combined assessment of dysplasia and aneuploidy is superior compared to applying each parameter alone (OR 8.99 [3.08, 26.26]). CONCLUSIONS: This meta-analysis reveals that aneuploidy is an equally effective parameter for individual cancer risk assessment in ulcerative colitis as the detection of dysplasia. More important, the combined assessment of dysplasia and aneuploidy outperforms the use of each parameter alone. We suggest image cytometry for ploidy assessment to become an additional feature of consensus criteria to individually assess cancer risk in UC.

Overweight and obesity on the island of Ireland: an estimation of costs.

OBJECTIVES: The increasing prevalence of overweight and obesity worldwide continues to compromise population health and creates a wider societal cost in terms of productivity loss and premature mortality. Despite extensive international literature on the cost of overweight and obesity, findings are inconsistent between Europe and the USA, and particularly within Europe. Studies vary on issues of focus, specific costs and methods. This study aims to estimate the healthcare and productivity costs of overweight and obesity for the island of Ireland in 2009, using both top-down and bottom-up approaches. METHODS: Costs were estimated across four categories: healthcare utilisation, drug costs, work absenteeism and premature mortality. Healthcare costs were estimated using Population Attributable Fractions (PAFs). PAFs were applied to national cost data for hospital care and drug prescribing. PAFs were also applied to social welfare and national mortality data to estimate productivity costs due to absenteeism and premature mortality. RESULTS: The healthcare costs of overweight and obesity in 2009 were estimated at €437 million for the Republic of Ireland (ROI) and €127.41 million for NI. Productivity loss due to overweight and obesity was up to €865 million for ROI and €362 million for NI. The main drivers of healthcare costs are cardiovascular disease, type II diabetes, colon cancer, stroke and gallbladder disease. In terms of absenteeism, low back pain is the main driver in both jurisdictions, and for productivity loss due to premature mortality the primary driver of cost is coronary heart disease. CONCLUSIONS: The costs are substantial, and urgent public health action is required in Ireland to address the problem of increasing prevalence of overweight and obesity, which if left unchecked will lead to unsustainable cost escalation within the health service and unacceptable societal costs.

Immunohistochemical assessment of a unique basal pattern of p53 expression in ulcerative-colitis-associated neoplasia using computer-assisted cytometry.

BACKGROUND: The basal pattern of p53 expression, defined as its immunoreactivity confined to the basal half of the glands, is associated with early neoplastic lesions in ulcerative colitis (UC). However, their clinical utility of this finding is limited by the use of "visual estimation" (approximate immunoreactivity on the basis of scanning the stained slide, without formal counting). This study was designed to analyze the basal pattern of p53 using computer-assisted cytometry and to identify the optimal cutoff value for discriminating between UC-associated early-stage neoplasia and regenerative atypia. METHODS: The specimens were obtained from eight UC patients undergoing colectomy and were classified according to the criteria by the Research Committee of Inflammatory Bowel Disease of the Ministry of Health and Welfare in Japan. Patients with classes UC-IIa (indefinite for dysplasia, probably regenerative), UC-IIb (indefinite for dysplasia, probably dysplastic), and UC-III (definitive dysplasia) were enrolled in the study. Based on the percentage of immunoreactive cells in the basal half of the crypt with visual estimation, basal positivity of p53 was classified into three categories: grade 1 (1 - 9%), grade 2 (10 - 19%), and grade 3 (≥ 20%). Next, crypts classified as grade 3 by visual estimation were analyzed by computer-assisted image analysis. RESULTS: Using visual estimation, grade-3 p53 basal positivity was observed in 46.0% of UC-IIa crypts (128 of 278), 61.9% of UC-IIb crypts (39 of 63), and 94.2% of UC-III crypts (81 of 86). Using image analysis, the median p53 basal positivities were 30.3% in UC-IIa, 52.3% in UC-IIb, and 65.4% in UC-III (P ≤ 0.002). A receiver operating characteristics curve was generated to determine the method's diagnostic utility in differentiating UC-IIa from UC-III. In this cohort, the sensitivity was 0.78; the specificity was 0.98; the negative predictive value was 87.4%; the positive predictive value was 95.5%, and the accuracy was 90.2% with a cutoff value for p53 basal positivity of 46.1%. CONCLUSIONS: Our findings indicate that assessing p53 basal positivity by image analysis with an optimal threshold represents an alternative to visual estimation for the accurate diagnosis of UC-associated early-stage neoplasia. VIRTUAL SLIDES: The virtual slide(s) for this article can be found here: http://www.diagnosticpathology.diagnomx.eu/vs/3588120501252608.

Primary sclerosing cholangitis and extraintestinal manifestations in patients with ulcerative colitis and ileal pouch-anal anastomosis.

OBJECTIVE: The aim of this study was to assess complications and functional outcomes in patients having ileal pouch-anal anastomosis for ulcerative colitis with or without primary sclerosing cholangitis or extraintestinal manifestations and to assess if primary sclerosing cholangitis is a risk factor for pouchitis. MATERIALS AND METHODS: From 1984 to 2007, 289 patients underwent proctocolectomy with ileal pouch-anal anastomosis for ulcerative colitis. Mean follow-up time was 12 years and data was recorded prospectively. Eleven patients had primary sclerosing cholangitis, six had pyoderma gangrenosum, and 12 had arthritis or ankylosing spondylitis. RESULTS: Early complications were similar for patients with or without extraintestinal manifestations. Functional outcomes were similar, but more incontinence among patients with sclerosing cholangitis was found. These patients had more frequent pouchitis, 5.25 vs. 2.72 average episodes of pouchitis (p = 0.048), and more chronic pouchitis, 4/11 vs. 17/260 (p < 0.001) compared to patients without adjunct disease. Neoplasm of the colon was more frequent in patients with primary sclerosing cholangitis, 4/11 vs. 4/260 in ulcerative colitis patients (p < 0.001). CONCLUSION: An association between primary sclerosing cholangitis and chronic/severe pouchitis was found, but not with other extraintestinal manifestations. Functional results were good and alike in patients with and without primary sclerosing cholangitis. Primary sclerosing cholangitis is a risk factor for chronic pouchitis and is associated with neoplasia.

Criteria for the evaluation of large cohort studies: an application to the nurses' health study.

Evaluating the success of major funding programs from the National Institutes of Health (NIH) remains a vexing challenge. We propose a set of criteria to evaluate epidemiological studies that fit within the discovery, development, and delivery paradigm introduced by the NIH. We apply these criteria to the Nurses' Health Study (NHS), a large epidemiological cohort study initiated in the 1970s to evaluate the associations between oral contraceptives and risk of breast cancer and between diet and other lifestyle factors and risk of cancer overall. Our evaluation suggests that the NHS has led to important changes in health practice, and it underscores the need to develop metrics that are suitable to the evaluation of large epidemiological cohort studies.

Assessment of ecological regression in the study of colon, breast, ovary, non-Hodgkin's lymphoma, or prostate cancer and residential UV.

Recent ecological studies have suggested a possible association between exposure to ultraviolet-B (UVB) radiation and reduction in the risk of various cancers; however, ecological studies are known to be subject to bias. The objective of this study was to demonstrate difficulties with the ecological approach. We conducted a multicountry ecological study using cancer incidence rates, residential UV levels, dietary intake, and different sociodemographic variables for 38 locations spanning 33 countries worldwide. The effect of residential UV exposure on cancer incidence was assessed using multiple linear regression models. The results of our multivariate analyses show no indication of an inverse association between residential UV levels and the risk of colon, non-Hodgkin's lymphoma (NHL), ovarian, prostate, or breast cancer in women. For colon cancer and NHL, a significant positive association was calculated. The rates of melanoma, which were used to examine the methods of this study, showed a strong and significant (P<0.01) association with solar radiation. Our results provide no evidence to support previous ecological results that UV exposure may reduce the risk of NHL, colon, breast, ovary, or prostate cancer. The study demonstrates the high sensitivity of ecological studies to adjustments for various confounders, and casts doubts on results of ecological analyses in this field.

Fatal colon cancer in a young egg donor: a physician mother's call for follow-up and research on the long-term risks of ovarian stimulation.

OBJECTIVE: To present a case report of fatal colon cancer in a young, previously healthy woman 4 years after repeated ovarian stimulation for egg donation, review previous publications on the risks of ovarian stimulation, and make recommendations for further egg donor follow-up, research, and actions by professional associations and regulatory agencies. DESIGN: Case report and review of the literature. SETTING: Case report and review of the literature. PATIENT(S): One patient and published cases. INTERVENTION(S): None. MAIN OUTCOME MEASURE(S): None. RESULT(S): There has been no systematic study of the long-term risk of cancer or other adverse outcomes in healthy egg donors. CONCLUSION(S): At present, potential egg donors cannot give truly informed consent because insufficient information exists about their long-term risks.

The management of small polyps found by virtual colonoscopy: results of a decision analysis.

BACKGROUND & AIMS: There is a firm consensus that larger (> or =10 mm) colonic polyps should be removed; however, the importance of removing smaller polyps (<10 mm) is more controversial. If computed tomographic colonography (CTC) is used for colorectal cancer screening, the majority of polypoid lesions identified will be less than 10 mm in size. Decision-analytic techniques were used to compare the outcomes of 2 management strategies for smaller (6-9 mm) polyps discovered by CTC. METHODS: Hypothetic average-risk patients who had undergone a CTC examination and found to have a small (6-9 mm) polyp were simulated to either: (1) undergo immediate colonoscopy for polypectomy (COLO), or (2) wait 3 years for a repeat CTC examination (WAIT). A Markov model was constructed to analyze outcomes including the number of deaths and cancers after a 3-year follow-up period or time horizon. Values for the model parameters were derived from the published literature and from Surveillance Epidemiology and End Results data, and an extensive sensitivity analysis was performed. RESULTS: The COLO strategy resulted in 14 total deaths per 100,000 patients compared with 79 total deaths in the WAIT strategy, for a difference of 65 deaths. The COLO strategy resulted in 39 cancers per 100,000 patients vs 773 in the WAIT strategy, for a difference of 734 cancers. Sensitivity analysis found that model findings were robust and only sensitive at extreme parameter values. CONCLUSIONS: Managing smaller polyps detected on a screening CTC with another CTC examination 3 years later likely will result in more deaths and cancers than immediate colonoscopy and polypectomy.

Assessment of JC polyoma virus in colon neoplasms.

PURPOSE: Research data have recently emphasized an intriguing association of JC polyoma virus with colon carcinogenesis. Tumorigenicity of JC virus is attributed to the T-antigen of its Mad-1 variant. Controversy arose when another research group did not confirm this association. The purpose of this study was to detect JC virus in a series of colon neoplasms from Greek patients. METHODS: A nested polymerase chain reaction assay was used to detect JC virus in 80 cancerous, 25 adenomatous specimens of large bowel, and 20 colonoscopic biopsy samples from normal patients without colorectal neoplasia. Quantitation of JC virus DNA was performed by real-time polymerase chain reaction. RESULTS: JC polyoma virus nucleotide sequence was detected in 61 percent of colon adenocarcinomas and in 60 percent of adenomas, at a viral load of 9 x 10(3) to 20 x 10(3) copies/microg DNA. Adjacent normal mucosa in 35 positive colon adenocarcinoma specimens, and normal mucosa from six patients of the control group, had low viral loads (50-450 copies/microg DNA). CONCLUSIONS: JC polyoma virus genome is present in colon neoplasms. JC virus detection in adenomas at comparable viral loads to malignant tumors suggests its implication at early steps of colonic carcinogenesis. Taking into consideration other published data, infection of colonic epithelium with JC virus might be a prime candidate for a role in chromosomal and genomic instability.

Cancer risk assessment: quality and impact of the family history interview.

BACKGROUND: Identification of individuals at high risk for colon and breast cancer requires an adequate family history assessment and can influence cancer screening and genetic testing decisions. Little data exist that evaluate the completeness of the family history interview in primary care. METHODS: Retrospective chart review of 995 new patient visits to 28 primary care physicians evaluating the completeness of the family cancer history for colon or breast cancer. Family history information was evaluated for inclusion of age at diagnosis, degree of kinship, and specification of disease of interest. RESULTS: Family history information on cancer diagnoses was collected on 679 (68%) of the patients. Specific information regarding the individual affected and the cancer diagnosis was present in 414 (61%) of the records. Affected first-degree relatives were more likely to have their age of cancer diagnosis recorded than second-degree relatives (39%, 95% confidence interval [CI]=34%-44% vs 16%, 95% CI=12%-20%). Age at diagnosis of cancer in first-degree relatives was documented in 51% of colon cancers, 38% of breast cancers, and 27% of ovarian cancers. Only 17% of individuals who meet criteria for early-onset breast cancer genetic testing were referred for genetic services. CONCLUSIONS: Adequate cancer risk assessment using family history information requires age at cancer diagnosis and specification of a cancer diagnosis. Age at diagnosis was frequently missing from family history assessments, which could have a potential impact on identification of high-risk individuals. When family history information does identify high-risk individuals, only the minority are referred for genetic services.

Constipation, anthranoid laxatives, melanosis coli, and colon cancer: a risk assessment using aberrant crypt foci.

The associations between colorectal cancer (CRC) and constipation, anthranoid laxative use, and melanosis coli are controversial. Aberrant crypt foci (ACF) are microscopic lesions of the colonic mucosa suspected of being preneoplastic, and their investigation has been advocated to evaluate the cause-effect relationship between putative risk factors and CRC. To this aim, we investigated the relationship between sigmoid cancer (SC) and constipation, anthranoid laxative use, and melanosis coli using ACF analysis as an additional tool of investigation. Fifty-five surgical patients with SC, 41 surgical patients with diverticular disease (DD), and 96 age- and sex-matched subjects without intestinal disease (controls) were interviewed on their history of constipation and anthranoid laxative use. Melanosis coli and ACF characteristics were investigated on sigmoid mucosa in patients with SC or DD. Constipation and anthranoid laxative use were similar between patients with SC (30.9% and 32.7%, respectively) and those with DD (39% and 26.8%) but higher than among controls (18.8% and 8.3%). Melanosis coli was found in 38.2% of patients with SC and in 39% of those with DD. Mean ACF frequency was higher in patients with SC (0.24/cm(2)) than in those with DD (0.10/cm(2); P < 0.0001), and it did not vary according to constipation, laxative use, or melanosis coli in either group. This study confirms the association of ACF frequency with colon cancer and does not support the hypothesis of a cause-effect relationship of CRC with constipation, anthranoid laxative, use or melanosis coli.

Lifestyle and colon cancer: an assessment of factors associated with risk.

Studies of the etiology of colon cancer indicate that it is strongly associated with diet and lifestyle factors. The authors use data from a population-based study conducted in northern California, Utah, and Minnesota in 1991-1995 to determine lifestyle patterns and their association with colon cancer. Data obtained from 1,993 cases and 2,410 controls were grouped by using factor analyses to describe various aspects of lifestyle patterns. The first five lifestyle patterns for both men and women loaded heavily on dietary variables and were labeled: "Western," "moderation," "calcium/low-fat dairy;" "meat and mutagens," and "nibblers, smoking, and coffee." Other important lifestyle patterns that emerged were labeled "body size," "medication and supplementation," "alcohol," and "physical activity." Among both men and women, the lifestyle characterized by high levels of physical activity was the most marked lifestyle associated with colon cancer (odds ratios = 0.42, 95% confidence interval: 0.32, 0.55 and odds ratio = 0.52, 95% confidence interval: 0.39, 0.69, for men and women, respectively) followed by medication and supplementation (odds ratio = 1.68, 95% confidence interval: 1.29, 2.18 and odds ratio = 1.63, 95% CI 1.23, 2.16, respectively). Other lifestyles that were associated with colon cancer were the Western lifestyle, the lifestyle characterized by large body size, and the one characterized by calcium and low-fat dairy. Different lifestyle patterns appear to have age- and tumor site-specific associations.

Cancer of the colon in an egg donor: policy repercussions for donor recruitment.

This paper describes the tragic case of a young woman who died of cancer of the colon after successfully donating eggs to her younger sister. Although there is no direct link between her operation and the subsequent development of bowel carcinoma, this case imparts a feeling of unease when seen in conjunction with other cases reported during the last few years. It is a reminder that little is known of the long-term consequences of some aspects of assisted conception. Women undergoing ovarian stimulation for themselves or a matched recipient have the right to be advised, in an agreed format, that there is some concern about unproven potential risks from the stimulatory drugs. The safety of egg donors must assume priority over all other considerations, including lack of donors or any moral position. The recent decision by the Human Fertilisation and Embryology Authority (HFEA) to withdraw any form of payment or recompense to egg donors does not seem to us to be based on a balance of scientific advances, patient needs and the ethics of gamete supply. They state that the intention to withdraw payments was implicit in the 1990 Human Fertilisation and Embryology (HFE) Act. However the Act was based on the Warnock report made 6 years earlier. Even in 1990 ovum donation was uncommon and fertility drugs had not yet caused any unease. The Act provided the HFEA with discretionary powers to issue directions so that the future policies would be consistent with any emerging new medical evidence. It is imperative that the HFEA provide convincing evidence on how the current policy of payment to donors harms society, donors or recipients, and how in the UK the new policy will improve medical practice in assisted conception. Successful pilot studies must precede the implementation of any new policy. Failure to do this could cause irreversible harm to the practice of assisted conception using donor gametes, which will ultimately be against the basic aims of the 1990 HFE Act.

Dietary fats and colon cancer: assessment of risk associated with specific fatty acids.

There are many biological mechanisms whereby dietary fat and specific dietary fatty acids may alter risk of colon cancer in addition to their contribution to total energy intake. To evaluate these potential associations, we used detailed dietary intake data collected in a population-based study of 1,993 incident colon cancer cases and 2,410 controls conducted in 3 areas of the United States. The most commonly consumed fatty acid in the study population was oleic acid. One-third of dietary fats consumed came from additions to other foods at the table or from the preparation of other foods. After adjusting for total energy intake, physical activity and body size, neither total dietary fat nor specific fatty acids was associated with risk of colon cancer. However, among older women, fats from food preparation were associated with increased risk of colon cancer (OR 1.84, 95% CI 1.20-2.80), while fats from foods themselves or from additions to other foods were not. While dietary fats were not associated with colon cancer risk in the total population, subgroups of the population appeared to be at slightly greater risk if they consumed a high-fat diet. Women who consumed a diet high in mono-unsaturated fatty acids (MFAs) and poly-unsaturated fatty acids (PFAs) and who had a family history of colorectal cancer were at greater risk of colon cancer than those with similar intakes but without a family history of colorectal cancer. Similar associations with family history were noted among men diagnosed at younger ages for MFA, linolenic acid and 20-carbon PFA.

Colonic cancer surveillance in ulcerative colitis is not essential for every patient.

It is generally recognised that there is an increased risk of colonic cancer in patients with long-standing extensive colitis, and regular annual or biennial colonoscopic surveillance protocols have been recommended in order to detect early cancer. There is, however, little evidence to suggest that these protocols are of value. There have been no properly conducted controlled trials in this area, and the studies that have been reported are flawed by selection bias, the inclusion of patients with "pseudo disease" and protocol violators. Many studies have not distinguished between "screening colonoscopy" and "colonoscopic surveillance". Some have not drawn attention to the failures in the surveillance, i.e. patients with Dukes' grade C or worse, and overall the conclusions drawn have been unrealistically optimistic. The diagnosis of low grade dysplasia which has been accorded importance is insensitive, non-specific and is subject to gross interobserver error. It is of little clinical value. Colonoscopic surveillance using currently available techniques is of only marginal benefit to patients included within the protocol. It is not cost-effective and cannot be made to be so.