Multiple primary cancers in BRCA 1/2 carriers - A review of literature and our observations.

An increasing number of patients with diagnosed synchronous or metachronous neoplasms that arc gene as well as non-gene dependent which are associated with the development of new oncological treatment, and environmental factors, prompted the authors of this study to conduct an analysis in a narrow group of patients with multiple cancers and simultaneous BRCA1I mutations (confirmed by genetic analysis). BRCA1 mutation, as well as multiple cancers were found in seven patients treated between 2007 and 2013. The patients diagnosed with a second cancer shared a uniquely common trait - a 5382insC mutation. The study describes four patients that did not carry a BRCA 1/2 mutation, yet were diagnosed with multiple cancers. A brief review of literature was performed concerning multiple cancers in women.

Investing in prospective cohorts for etiologic study of occupational exposures.

Prospective cohorts have played a major role in understanding the contribution of diet, physical activity, medical conditions, and genes to the development of many diseases, but have not been widely used for occupational exposures. Studies in agriculture are an exception. We draw upon our experience using this design to study agricultural workers to identify conditions that might foster use of prospective cohorts to study other occupational settings. Prospective cohort studies are perceived by many as the strongest epidemiologic design. It allows updating of information on exposure and other factors, collection of biologic samples before disease diagnosis for biomarker studies, assessment of effect modification by genes, lifestyle, and other occupational exposures, and evaluation of a wide range of health outcomes. Increased use of prospective cohorts would be beneficial in identifying hazardous exposures in the workplace. Occupational epidemiologists should seek opportunities to initiate prospective cohorts to investigate high priority, occupational exposures.

Small cell carcinoma of the ovary of the hypercalcemic type (SCCOHT)--case report.

Small cell carcinoma of the ovary of the hypercalcemic type (SCCOHT) is a very rare malignant disease, seen mostly in young women, with a very poor prognosis. There is no standard treatment for patients with this disease and most literature is limited to short series or case reports. This report describes the case of a 34-year-old woman with aggressive course of SCCOHT and poor outcome. What proved difficult was the process of establishing the diagnosis due to non-specific first symptoms of disease and consequently the combined treatment of surgery and chemotherapy with concurrent side effects.

Late recurrence of ovarian cancer: a literature review and description of two cases.

Ovarian cancer is not the most frequent malignancy of female reproductive system, but it causes many deaths in women with this diagnosis. Mostly of the patients with ovarian cancer will have recurrence after first-line standard treatment containing surgery and chemotherapy. This article presents two cases with late recurrence in women with ovarian cancer; both were nine years after the first diagnosis and both were operated and received second-line chemotherapy. The authors reviewed medical literature with late recurrence of ovarian cancer.

Development of antiangiogenic therapies for ovarian cancer.

Angiogenesis is a dynamic process which leads to a development of cancer and metastases. The most recognized and dominant prognostic factor is vascular endothelial growth factor (VEGF) and its receptors. VEGF was identyfied in 1989. There are three receptors for VEGF: VEGFR1 (VEGF receptor 1) and VEGFR2 that play the role in angiogenesis and development of ascites, and VEGFR3 is critical for lymphangiogenesis. There is bevacizumab--a new drug, monoclonal antibody that can block connection VEGF to its receptors. The first notification of activity of bevacizumab in ovarian cancer was in 2005. The aim of the article is to show some clinical trials in ovarian cancer and their results. The bevacizumab was registered in November 2011 in first line with standard chemotherapy in ovarian cancer. There is a new weapon against this disease.

Factors affecting response of chemotherapy in women with ovarian cancer.

Chemotherapy plays an important role in the treatment of ovarian cancer. Patients' response to chemotherapy is determined by a variety of acknowledged factors, but one might expect that many of them are yet to be described. The aim of this paper was to present the most essential yet still to be generally assessed in clinical practice, factors, which include: E-cadhedrin, hypoxia inducible factor alpha, survivin, COX-2, clusterin, BRCA1 protein, TP53 protein, YY1 protein, multidrug resistance protein, and interleukin-8.

GSTM1 null and NAT2 slow acetylation genotypes, smoking intensity and bladder cancer risk: results from the New England bladder cancer study and NAT2 meta-analysis.

Associations between bladder cancer risk and NAT2 and GSTM1 polymorphisms have emerged as some of the most consistent findings in the genetic epidemiology of common metabolic polymorphisms and cancer, but their interaction with tobacco use, intensity and duration remain unclear. In a New England population-based case-control study of urothelial carcinoma, we collected mouthwash samples from 1088 of 1171 cases (92.9%) and 1282 of 1418 controls (91.2%) for genotype analysis of GSTM1, GSTT1 and NAT2 polymorphisms. Odds ratios and 95% confidence intervals of bladder cancer among New England Bladder Cancer Study subjects with one or two inactive GSTM1 alleles (i.e. the 'null' genotype) were 1.26 (0.85-1.88) and 1.54 (1.05-2.25), respectively (P-trend = 0.008), compared with those with two active copies. GSTT1 inactive alleles were not associated with risk. NAT2 slow acetylation status was not associated with risk among never (1.04; 0.71-1.51), former (0.95; 0.75-1.20) or current smokers (1.33; 0.91-1.95); however, a relationship emerged when smoking intensity was evaluated. Among slow acetylators who ever smoked at least 40 cigarettes/day, risk was elevated among ever (1.82; 1.14-2.91, P-interaction = 0.07) and current heavy smokers (3.16; 1.22-8.19, P-interaction = 0.03) compared with rapid acetylators in each category; but was not observed at lower intensities. In contrast, the effect of GSTM1-null genotype was not greater among smokers, regardless of intensity. Meta-analysis of the NAT2 associations with bladder cancer showed a highly significant relationship. Findings from this large USA population-based study provided evidence that the NAT2 slow acetylation genotype interacts with tobacco smoking as a function of exposure intensity.

Thyroid cancer risk in Belarus among children and adolescents exposed to radioiodine after the Chornobyl accident.

BACKGROUND: Previous studies showed an increased risk of thyroid cancer among children and adolescents exposed to radioactive iodines released after the Chornobyl (Chernobyl) accident, but the effects of screening, iodine deficiency, age at exposure and other factors on the dose-response are poorly understood. METHODS: We screened 11 970 individuals in Belarus aged 18 years or younger at the time of the accident who had estimated (131)I thyroid doses based on individual thyroid activity measurements and dosimetric data from questionnaires. The excess odds ratio per gray (EOR/Gy) was modelled using linear and linear-exponential functions. RESULTS: For thyroid doses <5 Gy, the dose-response was linear (n=85; EOR/Gy=2.15, 95% confidence interval: 0.81-5.47), but at higher doses the excess risk fell. The EOR/Gy was significantly increased among those with prior or screening-detected diffuse goiter, and larger for men than women, and for persons exposed before age 5 than those exposed between 5 and 18 years, although not statistically significant. A somewhat higher EOR/Gy was estimated for validated pre-screening cases. CONCLUSION: 10-15 years after the Chornobyl accident, thyroid cancer risk was significantly increased among individuals exposed to fallout as children or adolescents, but the risk appeared to be lower than in other Chornobyl studies and studies of childhood external irradiation.

Differential effects of smoking on lung cancer mortality before and after household stove improvement in Xuanwei, China.

BACKGROUND: In Xuanwei County, Yunnan Province, China, lung cancer mortality rates in both males and females are among the highest in China. METHODS: We evaluated differential effects of smoking on lung cancer mortality before and after household stove improvement with chimney to reduce exposure to smoky coal emissions in the unique cohort in Xuanwei, China. Effects of independent variables on lung cancer mortality were measured as hazard ratios and 95% confidence intervals using a multivariable Cox regression model that included separate time-dependent variables for smoking duration (years) before and after stove improvement. RESULTS AND CONCLUSION: We found that the effect of smoking on lung cancer risk becomes considerably stronger after chimney installation and consequent reduction of indoor coal smoke exposure.

Nanowire array composites.

Long, nanometer-size metallic wires can be synthesized by injection of the conducting melt into nanochannel insulating plates. Large-area arrays of parallel wires 200 nanometers in diameter and 50 micrometers long with a packing density of 5 x 10(8) per square centimeter have been fabricated in this way. When charged, the ends of the wires generate strong, short-range electric fields. The nanowire electric fields have been imaged at high spatial resolution with a scanning force microscope.

Brain metastases from epithelial ovarian cancer--report of cases.

Epithelial ovarian cancer is one of the gynecological malignancies most commonly diagnosed late and one of the principal causes of mortality among women. The majority of women present with advanced disease. However, 5-year survival of patients with ovarian cancer has improved in recent years. Brain metastases from epithelial ovarian cancer are rare but in the last few years the incidence of brain complications seems to be increasing. Among all patients registered as having epithelial ovarian cancer at the Department of Oncology, Division of Gynecological Oncology, Poznan University of Medical Sciences, Poland between August 1998 and March 2008, four patients (4/669) who developed central nervous system (CNS) metastases were identified. Patients with symptoms of the CNS were evaluated by a neurologist, with a CT scan of the brain. The most common symptom of brain metastases are headaches which occur in 40-50% of patients. Because of the rarity of these patients, the optimal treatment for brain metastases is ill-defined. Brain metastasis usually appears with a poor prognosis, however early diagnosis and aggressive multimodal treatment can improve the quality of life in patients.

Two cases of metachronic tumours: cancers of the ovary and endometrium in young women. Case presentation and review.

Ovarian and endometrial cancers seldom develop in females under 40 years of age. Manifestation of metachronic cancers before the age of 40 is of casuistic interest. Two cases are presented in whom metachronic cancers were detected: the first localisation involved the ovary, and the second the endometrium. One of the patients had earlier delivered a baby with multiple hereditary defects and was diagnosed with secondary infertility. The second patient was diagnosed with primary infertility. Immunohistochemical tests disclosed the presence of alpha and beta type estrogen receptors and progesterone receptors in the tumour cells of the ovary and endometrium. Neither of the patients carried mutations in the BRCA 1 or NOD 2 genes.

Activity of telomerase in ovarian cancer cells. Clinical implications.

Estimation of telomerase activity in cell nuclei of ovarian malignant tumours may provide an independent prognostic index. The test for telomerase activity in tumour cell nuclei may be accepted as a useful diagnostic test with application for differential diagnoses of benign ovarian tumours vs tumours of a borderline or malignant character.

Improving handover between the transport team and neonatal intensive care unit staff in neonatal transports using the plan-do-study-act tool.

OBJECTIVES: The aim was to achieve 100% effective handover from the critical care transport team to the neonatal intensive care unit (NICU) medical team. STUDY DESIGN: All patients transferred from referring hospitals by the critical care transport team to the Level IV NICU were included. Data for each infant was collected prospectively. The percentage of transported patients for which medical team and nursing handover occurred was recorded. A quality improvement project was launched using the Plan-Do-Study-Act (PDSA) tool. We implemented several processes including call from the transport team before arrival and the completion of a transfer of care form on arrival to the NICU. The process measures and the outcome measure of completion of handover were monitored. Run charts of process measures and the outcome measure were analyzed. RESULTS: Completion of medical handover increased from 95% (baseline) to 100% after 3 PDSA cycles and this has been maintained for 18 consecutive months. CONCLUSION: Medical handover from the critical care transport team to the NICU medical staff has been achieved and sustained for all neonatal transports.

Autoimmune thyroiditis and exposure to iodine 131 in the Ukrainian cohort study of thyroid cancer and other thyroid diseases after the Chornobyl accident: results from the first screening cycle (1998-2000).

CONTEXT: Due to the Chornobyl accident, millions were exposed to radioactive isotopes of iodine and some received appreciable iodine 131 (131I) doses. A subsequent increase in thyroid cancer has been largely attributed to this exposure, but evidence concerning autoimmune thyroiditis (AIT) remains inconclusive. OBJECTIVE: The objective of the study was to quantify risk of AIT after 131I exposure. DESIGN/SETTING/PARTICIPANTS: Baseline data were collected from the first screening cycle (1998-2000) of a large cohort of radiation-exposed individuals (n = 12,240), residents of contaminated, iodine-deficient territories of Ukraine. Study individuals were under the age of 18 yr on April 26, 1986, and had thyroid radioactivity measurements made shortly after the accident. OUTCOMES: AIT was defined a priori based on various combinations of elevated antibodies to thyroid peroxidase (ATPO), TSH, and clinical findings; elevated ATPO were considered to be an indicator of thyroid autoimmunity. RESULTS: No significant association was found between 131I thyroid dose estimates and AIT, but prevalence of elevated ATPO demonstrated a modest, significant association with 131I that was well described by several concave models. This relationship was apparent in individuals with moderately elevated ATPO and euthyroid, thyroid disease-free individuals. CONCLUSIONS: Twelve to 14 yr after the Chornobyl accident, no radiation-related increase in prevalence of AIT was found in a large cohort study, the first in which 131I thyroid doses were estimated using individual radioactivity measurements. However, a dose-response relationship with ATPO prevalence raises the possibility that clinically important changes may occur over time. Thus, further follow-up and analysis of prospective data in this cohort are necessary.

Post-Chernobyl thyroid cancers in Ukraine. Report 2: risk analysis.

On April 26, 1986, the worst nuclear reactor accident to date occurred at the Chornobyl (Chernobyl) power plant in Ukraine. Millions of people in Ukraine, Belarus and Russia were exposed to radioactive nuclides, especially (131)I. Since then, research has been conducted on various subgroups of the exposed population, and it has been demonstrated that the large increase in thyroid cancer is related to the (131)I exposure. However, because of study limitations, quantified risk estimates are limited, and there remains a need for additional information. We conducted an ecological study to investigate the relationship between (131)I thyroid dose and the diagnosis of thyroid cancer in three highly contaminated oblasts in Northern Ukraine. The study population is comprised of 301,907 persons who were between the ages of 1 and 18 at the time of the Chornobyl accident and were living in 1,293 rural settlements in the three study oblasts. Twenty-four percent of the study population had individual thyroid dose estimates and the other 76% had "individualized" estimates of thyroid dose based on direct thyroid measurements taken from a person of the same age and gender living in the same or nearby settlement. Cases include 232 thyroid cancers diagnosed from January 1990 through December 2001, and all were confirmed histologically. Dose-response analyses took into account differences in the rate of ultrasound examinations conducted in the three study oblasts. The estimated excess relative risk per gray was 8.0 (95% CI = 4.6-15) and the excess absolute risk per 10,000 person-year gray was estimated to be 1.5 (95% CI = 1.2-1.9). In broad terms, these estimates are compatible with results of other studies from the contaminated areas, as well as studies of external radiation exposure.

Lung cancer risk from residential radon: meta-analysis of eight epidemiologic studies.

BACKGROUND: Studies of underground miners exposed to radioactive radon and its decay products have found that exposure increases risk of lung cancer. Consequently, when radon was found to accumulate in houses, there was concern about the public health impact from exposure to a known carcinogen. Estimates on the basis of studies of underground miners suggest that indoor radon may account for 6000-36,000 lung cancer deaths each year in the United States. Because of differences between working in underground mines and living in houses, estimates are subject to major uncertainties. Numerous case-control studies were launched to assess directly the lung cancer risk from indoor radon. Some studies report positive or weakly positive findings, while others report no increased risk. Thus, the potential hazard from indoor radon remains answered only indirectly through miner studies, experimental animal studies, and cellular studies. PURPOSE: To provide more information on the risk of lung cancer from indoor radon, we conducted a meta-analysis of all case-control studies that included at least 200 case subjects each and that used long-term indoor radon measurements. METHODS: Eight studies were available and included a total of 4263 lung cancer case subjects and 6612 control subjects. From the published results of each study, confounder-adjusted relative risk (RR) estimates and 95% confidence intervals (CIs) for categories of radon concentration were obtained, and weighted linear regression analyses were performed. RESULTS: The combined trend in the RR was significantly different from zero (two-sided P = .03), and an estimated RR of 1.14 (95% CI = 1.0-1.3) at 150 Bq/m3 was found. An influence analysis indicated that no single study dominated the combined results. The exposure-response trend was similar to model-based extrapolations from miners and to RRs computed directly from miners with low cumulative exposures. However, there were significant differences in the study-specific estimates of the exposure response (two-sided P < .001), which were not explained by study differences in percent of the defined exposure interval covered by radon measurements, mean number of residences per subject, and other factors. CONCLUSIONS: Meta-analyses are valuable for identifying differences among studies and for summarizing results, but they should be interpreted cautiously when expected RRs are low as with indoor radon exposure, when there is study heterogeneity and where there is the potential for confounding and exposure misclassification. Nonetheless, the results of this meta-analysis suggest that the risk from indoor radon is not likely to be markedly greater than that predicted from miners and indicate that the negative exposure response reported in some ecologic studies is likely due to model misspecification or uncontrolled confounding and can be rejected. IMPLICATIONS: Until ongoing case-control studies of indoor radon are completed and the data are pooled and analyzed, the studies of underground miners remain the best source of data to use to assess risk from indoor radon. This meta-analysis provides support for their general validity.

Assessment of lung cancer risk factors by histologic category.

The patterns of risk by histologic type of lung cancer were analyzed with the use of data from a large hospital-based case-control study (7,804 cases and 15,207 controls) of lung cancer performed in Western Europe. Relative risks (RR) increased with duration of cigarette use for all histologic types, although the gradients of risk were greater for Kreyberg I cell types, particularly squamous cell carcinoma (SCC), than for adenocarcinoma (AC). Risks also declined more sharply with years since cessation of smoking for all Kreyberg I cell types, in particular for SCC, rather than for AC. After adjustment for duration of use, the RR associated with number of cigarettes smoked per day, frequency and depth of inhalation, and fraction of cigarette consumed were not consistently different by cell type, suggesting that intensity-related measures of cigarette exposure have less effect on cell type than duration-related factors. Among those who never smoked there were marked cell type differences by sex, with a greater proportion of AC compared to SCC for females (45 vs. 25%) than for males (35 vs. 33%). Review of limited work histories indicated that occupational associations also were more strongly related to Kreyberg I than to Kreyberg II tumors.

Dark tobacco and lung cancer in Cuba.

A retrospective epidemiologic study of 826 cytologically and/or histologically confirmed lung cancer cases (219 females and 607 males), 979 hospital controls, and 539 neighborhood controls was undertaken in Havana, Cuba, to investigate whether the high lung cancer mortality rates in this country could be explained by the cigarette and cigar consumption habits, including the smoking of dark-tobacco cigarettes. Relative risk(s)(RR) of lung cancer among cigarette smokers were 7.3 in women and 14.1 in men and increased consistently with various measures of exposure to smoke. The findings suggested that duration of smoking, daily number of cigarettes consumed, and inhalation practices have independent effects. Most Cubans smoked dark tobacco. RR were higher for dark-tobacco users than for light-tobacco users (RR = 8.6 vs. 4.6 for women and 14.3 vs. 11.3 for men), but the differences were reduced after adjustment for amount smoked. Cigarette smoking was associated with all histologic types of lung cancer, although the risk for adenocarcinoma was lower than that for the other types. Men who smoked exclusively cigars had a fourfold risk of lung cancer. Mixed smokers (i.e., cigar and cigarette smoker) had a greater RR than cigarette-only smokers (15.0 vs. 14.1), which was perhaps related to the unusually deep and frequent inhalation of cigar smoke. The data support the hypothesis that smoking patterns account for the higher lung cancer mortality in Cuba than in other Latin American countries.