Etiology of hepatocellular carcinoma in West Africa, a case-control study.

Hepatocellular carcinoma (HCC) is a leading cause of cancer in West Africa where HBV infection is endemic. However, limited information is available on other risk factors such as alcohol use, HCV and HIV infection. A case-control study was conducted in referral hospitals of Abidjan (Cote d'Ivoire), Bamako (Mali) and Lome (Togo). Cases were matched with controls on age, gender and participating site. The diagnosis of HCC relied on the combination of one or more space-occupying lesions suggestive of an HCC on a standardized abdominal ultrasound and an α-fetoprotein level ≥400 ng/ml. HIV, HBV and HCV serology were performed. Hazardous alcohol use was assessed using the AUDIT questionnaire. A conditional logistic regression model was used to measure odds ratio (OR) with their 95% confidence intervals (CI). A total of 160 cases and 320 controls were included. Cases were predominantly men (80.0%) with a median age of 47 years (IQR 38-57). Hazardous alcohol use (OR = 4.5 [CI 1.1-18.5]), HBV infection (OR = 62.5 [CI 20.5-190.7]) and HCV infection OR = 35.9 [CI 10.0-130.3]) were independently associated with HCC. Combining the effect of HBV infection and alcohol, HBV-infected hazardous drinkers had an OR = 149.8 (CI 13.5-1 667.0), HBV mono-infected had an OR = 57.4 (CI 18.8-175.3) (ref: HBV-negative). Aside the independent association of alcohol use and HBV and HCV infection with HCC, a synergic effect between alcohol use and HBV infection was identified. Timely screening and care of HBV infection and hazardous drinking might prevent a significant number of HCC in West Africa.

Cancer and HIV infection in referral hospitals from four West African countries.

The consequences of the HIV epidemic on cancer epidemiology are sparsely documented in Africa. We aimed to estimate the association between HIV infection and selected types of cancers among patients hospitalized for cancer in four West African countries. A case-referent study was conducted in referral hospitals of Benin, Côte d'Ivoire, Nigeria and Togo. Each participating clinical ward included all adult patients seeking care with a confirmed diagnosis of cancer. All patients were systematically screened for HIV infection. HIV prevalence of AIDS-defining and some non-AIDS defining cancers (Hodgkin lymphoma, leukemia, liver, lung, skin, pharynx, larynx, oral cavity and anogenital cancers) were compared to a referent group of cancers reported in the literature as not associated with HIV. Odds ratios adjusted on age, gender and lifetime number of sexual partners (aOR) and their 95% confidence intervals (CI) were estimated. Among the 1644 cancer patients enrolled, 184 (11.2%) were identified as HIV-infected. The HIV prevalence in the referent group (n=792) was 4.4% [CI 3.0-5.8]. HIV infection was associated with Kaposi sarcoma (aOR 34.6 [CI: 17.3-69.0]), non-Hodgkin lymphoma (aOR 3.6 [CI 1.9-6.8]), cervical cancer (aOR 4.3 [CI 2.2-8.3]), anogenital cancer (aOR 17.7 [CI 6.9-45.2]) and squamous cell skin carcinoma (aOR 5.2 [CI 2.0-14.4]). A strong association is now reported between HIV infection and Human Papillomavirus (HPV)-related cancers including cervical cancer and anogenital cancer. As these cancers are amenable to prevention strategies, screening of HPV-related cancers among HIV-infected persons is of paramount importance in this African context.

Cosmetics as endocrine disruptors: are they a health risk?

Exposure to chemicals from different sources in everyday life is widespread; one such source is the wide range of products listed under the title "cosmetics", including the different types of popular and widely-advertised sunscreens. Women are encouraged through advertising to buy into the myth of everlasting youth, and one of the most alarming consequences is in utero exposure to chemicals. The main route of exposure is the skin, but the main endpoint of exposure is endocrine disruption. This is due to many substances in cosmetics and sunscreens that have endocrine active properties which affect reproductive health but which also have other endpoints, such as cancer. Reducing the exposure to endocrine disruptors is framed not only in the context of the reduction of health risks, but is also significant against the background and rise of ethical consumerism, and the responsibility of the cosmetics industry in this respect. Although some plants show endocrine-disrupting activity, the use of well-selected natural products might reduce the use of synthetic chemicals. Instruments dealing with this problem include life-cycle analysis, eco-design, and green labels; in combination with the committed use of environmental management systems, they contribute to "corporate social responsibility".

Challenges in the detection, prevention, and treatment of HIV-associated malignancies in low- and middle-income countries in Africa.

Cancers associated with immunosuppression and infections have long been recognized as a major complication of HIV/AIDS. More recently, persons living with HIV are increasingly diagnosed with a wider spectrum of HIV-associated malignancies (HIVAM) as they live longer on combination antiretroviral therapy. This has spurred research to characterize the epidemiology and determine the optimal management of HIVAM with a focus on low-and middle-income countries (LMICs). Given background coinfections, environmental exposures, host genetic profiles, antiretroviral therapy usage, and varying capacities for early diagnosis and treatment, one can expect the biology of cancers in HIV-infected persons in LMICs to have a significant impact on chronic HIV care, as is now the case in high-income countries. Thus, new strategies must be developed to effectively prevent, diagnose, and treat HIVAM in LMICs; provide physical/clinical infrastructures; train the cancer and HIV workforce; and expand research capacity-particularly given the challenges posed by the limitations on available transportation and financial resources and the population's general rural concentration. Opportunities exist to extend resources supported by the President's Emergency Plan for AIDS Relief and the Global Fund to Fight AIDS, Tuberculosis, and Malaria to improve the health-care infrastructure and train the personnel required to prevent and manage cancers in persons living with HIV. These HIV chronic care infrastructures could also serve cancer patients regardless of their HIV status, facilitating long-term care and treatment for persons who do not live near cancer centers, so that they receive the same degree of care as those receiving chronic HIV care today.

Cervical cancer prevention in reproductive health services: knowledge, attitudes and practices of midwives in Côte d'Ivoire, West Africa.

BACKGROUND: Cervical cancer is the most common cancer among women and the leading cause of cancer deaths in women in Côte d'Ivoire. Low resource countries can now prevent this cancer by using HPV vaccine and effective and affordable screening tests. However the implementation of these prevention strategies needs well-trained human resources. Part of the solution could come from midwives by integrating cervical cancer prevention into reproductive health services. The aim of this survey was to assess knowledge, attitudes and practices of midwives towards cervical cancer prevention in Abidjan, Côte d'Ivoire, and to find out factors associated with appropriate knowledge. METHODS: A cross-sectional survey was conducted among midwives in the urban district of Abidjan, using a self-administered questionnaire. Knowledge was assessed by two scores. Factors associated with appropriate knowledge were determined using a logistic regression analysis. Attitudes and practices were described and compare using the Chi2 test. RESULTS: A total of 592 midwives were enrolled, including 24.5% of final-year students. 55.7% of midwives had appropriate knowledge on cervical cancer, and 42.4% of them had appropriate knowledge on cervical cancer prevention strategies. Conferences, courses taken at school of midwifery and special training sessions on cervical cancer (OR = 4.9, 95% CI [1.9 to 12.6], p <0.01) were associated with good knowledge on the management of this disease. Among these midwives, 18.4% had already benefited from a screening test for themselves, 37.7% had already advised screening to patients and 8.4% were able to perform a visual inspection. 50.3% of midwives knew HPV vaccine as a preventive method; among them 70.8% usually recommended it to young girls. CONCLUSION: Despite sufficient knowledge about cervical cancer prevention, attitudes and practices of midwives should be improved by organizing capacity building activities. This would ensure the success of integration of cervical cancer prevention into reproductive health services in countries like Côte d'Ivoire.

Risk factors for cervical intraepithelial neoplasia in HIV-infected women on antiretroviral treatment in Côte d'Ivoire, West Africa.

BACKGROUND: Facing the dual burden of invasive cervical cancer and HIV in sub-Saharan Africa, the identification of preventable determinants of Cervical Intraepithelial Neoplasia (CIN) in HIV-infected women is of paramount importance. METHODS: A cervical cancer screening based on visual inspection methods was proposed to HIV-infected women in care in Abidjan, Côte d'Ivoire. Positively screened women were referred for a colposcopy to a gynaecologist who performed directed biopsies. RESULTS: Of the 2,998 HIV-infected women enrolled, 132 (4.4%) CIN of any grade (CIN+) were identified. Women had been followed-up for a median duration of three years [IQR: 1-5] and 76% were on antiretroviral treatment (ART). Their median most recent CD4 count was 452 [IQR: 301-621] cells/mm3. In multivariate analysis, CIN+ was associated with a most recent CD4 count >350 cells/mm3 (OR: 0.3; 95% CI: 0.2-0.6) or ≥200-350 cells/mm3 (OR 0.6; 95% CI 0.4-1.0) (Ref: <200 cells/mm3 CD4) (p<10-4). CONCLUSIONS: The presence of CIN+ is less common among HIV-infected women with limited or no immune deficiency. Despite the potential impact of immunological recovery on the reduction of premalignant cervical lesions through the use of ART, cervical cancer prevention, including screening and vaccination remains a priority in West Africa while ART is rolled-out.

Polychlorinated biphenyls (PCBs) in Africa: a review of environmental levels.

Several studies have shown an increase in PCB sources in Africa due to leakage and wrongly disposed transformers, continuing import of e-waste from countries of the North, shipwreck, and biomass burning. Techniques used in the recycling of waste such as melting and open burning to recover precious metals make PCBs contained in waste and other semivolatile organic substances prone to volatilization, which has resulted in an increase of PCB levels in air, blood, breast milk, and fish in several regions of Africa. Consequences for workers performing these activities without adequate measures of protection could result in adverse human health effects. Recent biodegradation studies in Africa have revealed the existence of exotic bacterial strains exhibiting unique and unusual PCB metabolic capability in terms of array of congeners that can serve as carbon source and diversity of congeners attacked, marking considerable progress in the development of effective bioremediation strategies for PCB-contaminated matrices such as sediments and soils in tropical regions. Action must be taken to find and deal with the major African sources of these pollutants. The precise sources of the PCB plume should be pinned down and used to complete the pollutant inventories of African countries. These nations must then be helped to safely dispose of the potentially dangerous chemicals.

Evaluation of the impact of a breast cancer awareness program in rural Ghana: a cross-sectional survey.

Community awareness is crucial to early detection of breast cancer in low- and middle-income countries. In Ghana 60% of the cases are detected at late stages. Breast Care International (BCI) is a Ghanaian non-governmental organization dedicated to raising breast cancer awareness. A cross-sectional survey was designed to assess the impact of BCI program on knowledge, attitudes and practices (KAP) toward breast cancer among women from rural communities of Ghana. A total of 232 women were interviewed in June 2011 in the Ashanti region; of these 131 participants were from a community that received the BCI program in August 2010 (intervention group) and 101 from another community that received the program post-survey (referent group). Data analysis was performed using Epi-Info version 3.5.3. Knowledge about breast cancer among participants who received the program was better than among those who did not. Only 53.5% of participants from the referent group knew that breast cancer usually appears as painless breast lump when compared to 82.3% from the intervention group. Participants who attended the program were significantly more likely to obtain higher knowledge scores (odds ratio (OR) = 2.10, 95% confidence interval (CI) = 1.14-3.86) and to state practicing breast self-examination (OR = 12.29, 95% CI = 5.31-28.48). The BCI program improved KAP toward breast cancer. Further research is warranted to provide stronger evidence that the program improves breast cancer early detection.

Is mammographic density differentially associated with breast cancer according to receptor status? A meta-analysis.

Mammographic density (MD) is a strong marker of breast cancer risk, but it is debated whether the association holds, and is of a similar magnitude, for different subtypes of breast cancer defined by receptor status or gene expression profiles. A literature search conducted in June 2012 was used to identify all studies that had investigated the association of MD with subtype-specific breast cancer, independent of age. 7 cohort/case-control and 12 case-only studies were included, comprising a total of >24,000 breast cancer cases. Random effects meta-analysis models were used to combine relative risks (RR) of MD with subtype-specific breast cancer for case-control studies, and in case-only studies to combine relative risk ratios (RRR) of receptor positive versus negative breast tumors. In case-control/cohort studies, relative to women in the lowest density category, women in the highest density category had 3.1-fold (95 % confidence interval [CI] 2.2, 4.2) and 3.2-fold (1.7, 5.9) increased risk of estrogen receptor positive (ER+) and ER- breast cancer, respectively. In case-only analyses, RRRs of breast tumors being ER+ versus ER- were 1.13 (95 % CI 0.89, 1.42) for medium versus minimal MD. MD remained associated with screen-detected ER+ tumors, despite the expectation of this association to be attenuated due to masking bias and overdiagnoses of ER+ tumors. In eight contributing studies, the association of MD did not differ by HER2 status. This combined evidence strengthens the importance of MD as a strong marker of overall and of subtype-specific risk, and confirms its value in overall breast cancer risk assessment and monitoring for both research and clinical purposes.

The spectrum of cancers in West Africa: associations with human immunodeficiency virus.

BACKGROUND: Cancer is a growing co-morbidity among HIV-infected patients worldwide. With the scale-up of antiretroviral therapy (ART) in developing countries, cancer will contribute more and more to the HIV/AIDS disease burden. Our objective was to estimate the association between HIV infection and selected types of cancers among patients hospitalized for diagnosis or treatment of cancer in West Africa. METHODS: A case-referent study was conducted in referral hospitals in Côte d'Ivoire and Benin. Each participating clinical ward enrolled all adult patients seeking care for a confirmed diagnosis of cancer and clinicians systematically proposed an HIV test. HIV prevalence was compared between AIDS-defining cancers and a subset of selected non-AIDS defining cancers to a referent group of non-AIDS defining cancers not reported in the literature to be positively or inversely associated with HIV. An unconditional logistic model was used to estimate odds ratios (OR) and their 95% confidence intervals (CI) of the risk of being HIV-infected for selected cancers sites compared to a referent group of other cancers. RESULTS: The HIV overall prevalence was 12.3% (CI 10.3-14.4) among the 1,017 cancer cases included. A total of 442 patients constituted the referent group with an HIV prevalence of 4.7% (CI 2.8-6.7). In multivariate analysis, Kaposi sarcoma (OR 62.2 [CI 22.1-175.5]), non-Hodgkin lymphoma (4.0 [CI 2.0-8.0]), cervical cancer (OR 7.9 [CI 3.8-16.7]), anogenital cancer (OR 11.6 [CI 2.9-46.3]) and liver cancer (OR 2.7 [CI 1.1-7.7]) were all associated with HIV infection. CONCLUSIONS: In a time of expanding access to ART, AIDS-defining cancers remain highly associated with HIV infection. This is to our knowledge, the first study reporting a significant association between HIV infection and liver cancer in sub-Saharan Africa.

Gastric cancer and Helicobacter pylori infection in the eastern Libya: a descriptive epidemiological study.

BACKGROUND AND STUDY AIMS: The aim of this study was to determine the pattern of histologically-proven gastric cancer in Eastern Libya and explore its association with Helicobacter pylori infection. PATIENTS AND METHODS: The registries of the Departments of Histopathology, Faculty of Medicine, Benghazi University and Oncology, Al-Jomhoria Hospital, Benghazi, were reviewed for cases with primary gastrointestinal cancer from January 2000 to December 2002 (sole Histopathology and Oncology Departments in Eastern Libya). Slides of hematoxylin and eosin stain of gastric cancer patients were re-stained to detect H. pylori. The American Joint Committee on Cancer Tumor, Node, Metastasis staging was used for clinical and pathologic staging. Gastric cancer biopsy materials were classified into intestinal or diffuse type according to Lauren criteria. RESULTS: One hundred and fourteen cases of gastric cancer were diagnosed. Tumor stages were: 2 (14%), 3 (21%), 4 (57%) and unknown (8%). Most common site of involvement was the antrum (48%). Diffuse adenocarcinoma occurred in 56 patients (49.1%), intestinal adenocarcinoma in 46 (40.4%) and malignant gastric lymphoma in 12 (10.5%). The overall frequency of H. pylori infection was 63.2% (72/114), more frequent in intestinal adenocarcinoma (71.7%) and malignant lymphoma (66.6%) than diffuse adenocarcinoma (55.3%). The frequency of gastric cancer increased throughout the three years of study. CONCLUSION: The majority of the patients were diagnosed in locally advanced or metastatic stage. Clearly more efforts need to be given to early detection. We showed a stronger association of H. pylori infection with intestinal type gastric adenocarcinoma and malignant lymphoma than diffuse adenocarcinoma suggesting that H. pylori infection is the most probable causal factor of gastric cancer in this part of Libya.

Cervical cancer screening by visual inspection in Côte d'Ivoire, operational and clinical aspects according to HIV status.

BACKGROUND: Cervical cancer screening is not yet standard of care of women attending HIV care clinics in Africa and presents operational challenges that need to be addressed. METHODS: A cervical cancer screening program based on visual inspection methods was conducted in clinics providing antiretroviral treatment (ART) in Abidjan, Côte d'Ivoire. An itinerant team of midwives was in charge of proposing cervical cancer screening to all HIV-positive women enrolled in ART clinics as well as to HIV-negative women who were attending the Abidjan national blood donor clinic. Positively screened women were systematically referred to a colposcopic examination. A phone-based tracking procedure was implemented to reach positively screened women who did not attend the medical consultation. The association between HIV status and cervical cancer screening outcomes was estimated using a multivariate logistic model. RESULTS: The frequency of positive visual inspection was 9.0% (95% CI 8.0-10.0) in the 2,998 HIV-positive women and 3.9% (95% CI 2.7-5.1) in the 1,047 HIV-negative ones (p < 10-4). In multivariate analysis, HIV infection was associated with a higher risk of positive visual inspection [OR = 2.28 (95% CI 1.61-3.23)] as well as more extensive lesions involving the endocervical canal [OR = 2.42 (95% CI 1.15-5.08)]. The use of a phone-based tracking procedure enabled a significant reduction of women not attending medical consultation after initial positive screening from 36.5% to 19.8% (p < 10-4). CONCLUSION: The higher frequency of positive visual inspection among HIV-positive women supports the need to extend cervical cancer screening program to all HIV clinics in West Africa. Women loss to follow-up after being positively screened is a major concern in cervical screening programs but yet, partly amenable to a phone tracking procedure.

HIV and cancer in Africa: mutual collaboration between HIV and cancer programs may provide timely research and public health data.

The eruption of Kaposi sarcoma (KS) and aggressive non-Hodgkin lymphoma (NHL) in young homosexual men in 1981 in the West heralded the onset of the human immunodeficiency virus (HIV) infection epidemic, which remains one of the biggest challenges to global public health and science ever. Because KS and NHL were increased >10,000 and 50-600 times, respectively, with HIV, they were designated AIDS defining cancers (ADC). Cervical cancer (CC), increased 5-10 times was also designated as an ADC. A few other cancers are elevated with HIV, including Hodgkin lymphoma (10 times), anal cancer (15-30 times), and lung cancer (4 times) are designated as non-AIDS defining cancers (NADCs). Since 1996 when combination antiretroviral therapy (cART) became widely available in the West, dramatic decreases in HIV mortality have been observed and substantial decrease in the incidence of ADCs. Coincidentally, the burden of NADCs has increased as people with HIV age with chronic HIV infection. The impact of HIV infection on cancer in sub-Saharan Africa, where two thirds of the epidemic is concentrated, remains poorly understood. The few studies conducted indicate that risks for ADCs are also increased, but quantitatively less so than in the West. The risks for many cancers with established viral associations, including liver and nasopharynx, which are found in Africa, do not appear to be increased. These data are limited because of competing mortality, and cancer is under diagnosed, pathological confirmation is rare, and cancer registration not widely practiced. The expansion of access to life-extending cART in sub-Saharan Africa, through programs such as the Global Fund for AIDS, Malaria, and Tuberculosis and the US President's Emergency Program for AIDS Relief (PEPFAR), is leading to dramatic lengthening of life of HIV patients, which will likely influence the spectrum and burden of cancer in patients with HIV. In this paper, we review current literature and explore merits for integrating cancer research in established HIV programs to obtain timely data about the incidence and burden of cancer in HIV-infected persons in Africa.

Factors influencing general practitioners in the referral of elderly cancer patients.

BACKGROUND: A number of studies have identified advanced age as a barrier to accessing specialised oncological care. Many factors can influence the care provided for elderly patients after a diagnosis of cancer has been established or is suspected. Only one European study has analysed the decision processes leading general practitioners (GPs) to refer elderly patients with cancer to oncologists. The objectives of the current study are to describe the factors that influence these decisions and to identify the particular factors and GP characteristics that are associated with systematic referral of these patients in South-West France. METHODS: This is a cross-sectional study on a representative sample of GPs in Aquitaine, South-West France. Questionnaire items were selected using a Delphi consensus approach and sent by post. Two logistic regression models were constructed to investigate GPs' decisions to refer these patients. RESULTS: The response rate obtained was 30%. Half of the general practitioners reported "always" referring their elderly cancer patients to oncologists. More than 75% reported being influenced by patient-related elements (patient and/or family wishes, comorbid factors, unsuitability of invasive investigations, physical and mental autonomy), by cancer-related elements (severity of symptoms, expected side-effects) and an organisational element (whether the general practitioner was used to collaborating with oncologists). Logistic regression analysis showed that cancer site and organisational difficulties in patient management were significantly associated with the decision to refer elderly patients with early-stage cancer. For advanced stages, oncology training, patient age, organisational difficulties in patient management and stage of cancer were significantly associated with the decision to refer elderly patients. CONCLUSIONS: Cancer-linked factors and organisational difficulties have been highlighted as influencing the decisions of GPs in the referral of elderly patients to a cancer team. These results highlight the need to implement continuous medical education specific for the management of elderly patients, to better apprehend the nature of these difficulties and to suggest solutions suited to local settings.

Alcohol use and non-adherence to antiretroviral therapy in HIV-infected patients in West Africa.

AIM: To investigate the association between alcohol use and adherence to highly active antiretroviral treatment (HAART) among human immunodeficiency virus (HIV)-infected patients in sub-Saharan Africa. DESIGN AND SETTING: Cross-sectional survey conducted in eight adult HIV treatment centres from Benin, Côte d'Ivoire and Mali. Participants and measurements During a 4-week period, health workers administered the Alcohol Use Disorders Identification Test to HAART-treated patients and assessed treatment adherence using the AIDS Clinical Trials Group follow-up questionnaire. FINDINGS: A total of 2920 patients were enrolled with a median age of 38 years [interquartile range (IQR) 32-45 years] and a median duration on HAART of 3 years (IQR 1-4 years). Overall, 91.8% of patients were identified as adherent to HAART. Non-adherence was associated with current drinking [odds ratio (OR) 1.4; 95% confidence interval (CI) 1.1-2.0], hazardous drinking (OR 4.7; 95% CI 2.6-8.6) and was associated inversely with a history of counselling on adherence (OR 0.7; 95% CI 0.5-0.9). CONCLUSIONS: Alcohol consumption and hazardous drinking is associated with non-adherence to HAART among HIV-infected patients from West Africa. Adult HIV care programmes should integrate programmes to reduce hazardous and harmful drinking.

Carbon dioxide is largely responsible for the acute inflammatory effects of tobacco smoke.

Tobacco smoking is responsible for a vast array of diseases, particularly chronic bronchitis and lung cancer. It is still unclear which constituent(s) of the smoke is responsible for its toxicity. The authors decided to focus on carbon dioxide, since its level of concentration in mainstream cigarette smoke is about 200 times higher than in the atmosphere. The authors previously demonstrated that inhalation of carbon dioxide concentrations above 5% has a deleterious effect on lungs. In this study, the authors assessed the inflammatory potential of carbon dioxide contained in cigarette smoke. Mice were exposed to cigarette smoke containing a high or reduced CO(2) level by filtration through a potassium hydroxyde solution. The inflammatory response was evaluated by histological analysis, protein phosphatase 2 A (PP2A) and nuclear factor (NF)-kappaB activation, and proinflammatory cytokine secretion measurements. The data show that the toxicity of cigarette smoke may be largely due to its high level of CO(2). Pulmonary injuries consequent to tobacco smoke inhalation observed by histology were greatly diminished when CO(2) was removed. Cigarette smoke exposure causes an inflammatory response characterized by PP2A and NF-kappaB activation followed by proinflammatory cytokine secretion. This inflammatory response was reduced when the cigarette smoke was filtered through a potassium hydroxide column, and reestablished when CO(2) was injected downstream from the filtration column.Given that there is an extensive literature linking a chronic inflammatory response to the major smoking-related diseases, these data suggest that carbon dioxide may play a key role in the causation of these diseases by tobacco smoking.

Subsite-specific differences of estrogen receptor beta expression in the normal colonic epithelium: implications for carcinogenesis and colorectal cancer epidemiology.

OBJECTIVE: This study aimed at investigating whether a differential estrogen receptor beta (ER-beta) expression between the colonic subsites could correspond to a modification in proliferation, apoptosis, and adhesion of the normal colonocytes. METHODS: ER-beta, Ki-67, Bcl-2, and E-cadherin expressions were investigated immunohistochemically, in normal epithelium biopsies from the ascending and the descending colon of 53 individuals, who underwent colonoscopy for the investigation of anemia and in whom no local pathology was identified. RESULTS: ER-beta immunoreactivity has been shown to be stronger at the superficial epithelium than the crypts' base, the difference being important only for the ascending colon. In addition, ER-beta expression was higher in the superficial epithelium of the ascending colon than that of the descending colon. The variations of ER-beta expression did not correspond to the alterations in Ki-67, Bcl-2, and E-cadherin expression. CONCLUSION: A subsite-specific variation of ER-beta expression has been shown in the normal colonic epithelium. This modulation of ER-beta might account for some well established specificities of colorectal cancer epidemiology like the right-sided predominance of the neoplasm in women and its gradual shift to more proximal sites over time.

The challenge of AIDS-related malignancies in sub-Saharan Africa.

BACKGROUND: With the lengthening of life expectancy among HIV-positive subjects related to the use of highly active antiretroviral treatments, an increased risk of cancer has been described in industrialized countries. The question is to determine what occurs now and will happen in the future in the low income countries and particularly in sub-Saharan Africa where more than two-thirds of all HIV-positive people live in the world. The objective of our paper is to review the link between HIV and cancer in sub-Saharan Africa, putting it in perspective with what is already known in Western countries. METHODS AND FINDINGS: Studies for this review were identified from several bibliographical databases including Pubmed, Scopus, Cochrane, Pascal, Web of Science and using keywords "HIV, neoplasia, epidemiology and Africa" and related MesH terms. A clear association was found between HIV infection and AIDS-classifying cancers. In case-referent studies, odds ratios (OR) were ranging from 21.9 (95% Confidence Interval (CI) 12.5-38.6) to 47.1 (31.9-69.8) for Kaposi sarcoma and from 5.0 (2.7-9.5) to 12.6 (2.2-54.4) for non Hodgkin lymphoma. The association was less strong for invasive cervical cancer with ORs ranging from 1.1 (0.7-1.2) to 1.6 (1.1-2.3), whereas ORs for squamous intraepithelial lesions were higher, from 4.4 (2.3-8.4) to 17.0 (2.2-134.1). For non AIDS-classifying cancers, squamous cell conjunctival carcinoma of the eye was associated with HIV in many case-referent studies with ORs from 2.6 (1.4-4.9) to 13.0 (4.5-39.4). A record-linkage study conducted in Uganda showed an association between Hodgkin lymphoma and HIV infection with a standardized incidence ratio of 5.7 (1.2-17) although OR in case-referent studies ranged from 1.4 (0.7-2.8) to 1.6 (1.0-2.7). Other cancer sites found positively associated with HIV include lung, liver, anus, penis, vulva, kidney, thyroid and uterus and a decreased risk of female breast cancer. These results so far based on a relatively small number of studies warrant further epidemiological investigations, taking into account other known risk factors for these tumors. CONCLUSION: Studies conducted in sub-Saharan Africa show that HIV infection is not only strongly associated with AIDS-classifying cancers but also provided some evidence of association for other neoplasia. African countries need now to implement well designed population-based studies in order to better describe the spectrum of AIDS-associated malignancies and the most effective strategies for their prevention, screening and treatment.

Separate and combined analysis of successive dependent outcomes after breast-conservation surgery: recurrence, metastases, second cancer and death.

BACKGROUND: In the setting of recurrent events, research studies commonly count only the first occurrence of an outcome in a subject. However this approach does not correctly reflect the natural history of the disease. The objective is to jointly identify prognostic factors associated with locoregional recurrences (LRR), contralateral breast cancer, distant metastases (DM), other primary cancer than breast and breast cancer death and to evaluate the correlation between these events. METHODS: Patients (n = 919) with a primary invasive breast cancer and treated in a cancer center in South-Western France with breast-conserving surgery from 1990 to 1994 and followed up to January 2006 were included. Several types of non-independent events could be observed for the same patient: a LRR, a contralateral breast cancer, DM, other primary cancer than breast and breast cancer death. Data were analyzed separately and together using a random-effects survival model. RESULTS: LRR represent the most frequent type of first failure (14.6%). The risk of any event is higher for young women (less than 40 years old) and in the first 10 years of follow-up after the surgery. In the combined analysis histological tumor size, grade, number of positive nodes, progesterone receptor status and treatment combination are prognostic factors of any event. The results show a significant dependence between these events with a successively increasing risk of a new event after the first and second event. The risk of developing a new failure is greatly increased (RR = 4.25; 95%CI: 2.51-7.21) after developing a LRR, but also after developing DM (RR = 3.94; 95%CI: 2.23-6.96) as compared to patients who did not develop a first event. CONCLUSION: We illustrated that the random effects survival model is a more satisfactory method to evaluate the natural history of a disease with multiple type of events.