Background. Improvements in screening techniques have made significant contributions to the early detection of breast cancer. Physicians thus face the task of providing appropriate screening schedules for their patients. One group for whom this is particularly important are those women with a family history of breast cancer.

Methods. In this report, data from the Cancer and Steroid Hormone Study, a population-based, case-control study conducted by the Centers for Disease Control, are used to provide age-specific risk estimates of breast cancer for women with a family history of breast cancer. The data set includes 4730 patients with histologically confirmed breast cancer age 20–54 years and 4688 control subjects who were frequency matched to patients by geographic region and 5-year age intervals. The data set also includes family histories of breast cancer in mothers and sisters of both patients and control subjects.

Results. Genetic models fit previously to these data by the authors have provided evidence for a rare autosomal dominant allele that results in increased susceptibility to breast cancer. In addition, these models predict that women who carry the allele are at greater risk of developing breast cancer at any age than are women who do not carry the allele. The increase in risk in carriers versus noncarriers does, however, decrease with increasing age. Based on the parameters of this model, age-specific risks for a woman with one or more relatives affected with breast cancer at various ages at onset are given.

Conclusions. These tables can be used for the purpose of counseling women at high risk of breast cancer development, that is, women with a family history of breast cancer.

Autosomal Dominant Inheritance of Early-Onset Breast Cancer: Implications for Risk Prediction

Background The small intestinal epithelium is highly sensitive to radiation and is a major site of injury during radiation therapy and environmental overexposure Objective To examine probiotic bacteria as potential radioprotective agents in the intestine Methods 8-week-old C57BL/6 wild-type or knockout mice were administered probiotic by gavage for 3 days before 12 Gy whole body radiation The intestine was evaluated for cell-positional apoptosis (6 h) and crypt survival (84 h) Results Gavage of 5×10 7 Lactobacillus rhamnosus GG (LGG) improved crypt survival about twofold (p −/− , TLR-2 −/− and cyclo-oxygenase-2 −/− (COX-2) mice but not TLR-4 −/− mice LGG administration did not lead to increased jejunal COX-2 mRNA or prostaglandin E2 levels or a change in number of COX-2-expressing cells However, a location shift was observed in constitutively COX-2-expressing cells of the lamina propria from the villi to a position near the crypt base (villi to crypt ratio 80:20 for control and 62:38 for LGG; p Conclusions LGG or its CM reduce radiation-induced epithelial injury and improve crypt survival A TLR-2/MyD88 signalling mechanism leading to repositioning of constitutive COX-2-expressing mesenchymal stem cells to the crypt base is invoked

https://gut.bmj.com/content/gutjnl/61/6/829.full.pdf

Lactobacillus probiotic protects intestinal epithelium from radiation injury in a TLR-2/cyclo-oxygenase-2-dependent manner

Successful treatment of cancer remains a challenge, due to the unique pathophysiology of solid tumors, and the predictable emergence of resistance. Traditional methods for cancer therapy including radiotherapy, chemotherapy, and immunotherapy all have their own limitations. A novel approach is bacteriotherapy, either used alone, or in combination with conventional methods, has shown a positive effect on regression of tumors and inhibition of metastasis. Bacteria-assisted tumor-targeted therapy used as therapeutic/gene/drug delivery vehicles has great promise in the treatment of tumors. The use of bacteria only, or in combination with conventional methods was found to be effective in some experimental models of cancer (tumor regression and increased survival rate). In this article, we reviewed the major advantages, challenges, and prospective directions for combinations of bacteria with conventional methods for tumor therapy.

https://onlinelibrary.wiley.com/doi/pdf/10.1002/cam4.2148

Therapeutic bacteria to combat cancer; current advances, challenges, and opportunities.

Objective Radiation proctitis (RP) is a complication of pelvic radiotherapy which affects both the host and microbiota. Herein we assessed the radiation effect on microbiota and its relationship to tissue damage using a rectal radiation mouse model. Design We evaluated luminal and mucosa-associated dysbiosis in irradiated and control mice at two postradiation time points and correlated it with clinical and immunological parameters. Epithelial cytokine response was evaluated using bacterial–epithelial co-cultures. Subsequently, germ-free (GF) mice were colonised with postradiation microbiota and controls and exposed to radiation, or dextran sulfate-sodium (DSS). Interleukin (IL)-1β correlated with tissue damage and was induced by dysbiosis. Therefore, we tested its direct role in radiation-induced damage by IL-1 receptor antagonist administration to irradiated mice. Results A postradiation shift in microbiota was observed. A unique microbial signature correlated with histopathology. Increased colonic tumor necrosis factor (TNF)α, IL-1β and IL-6 expression was observed at two different time points. Adherent microbiota from RP differed from those in uninvolved segments and was associated with tissue damage. Using bacterial–epithelial co-cultures, postradiation microbiota enhanced IL-1β and TNFα expression compared with naive microbiota. GF mice colonisation by irradiated microbiota versus controls predisposed mice to both radiation injury and DSS-induced colitis. IL-1 receptor antagonist administration ameliorated intestinal radiation injury. Conclusions The results demonstrate that rectal radiation induces dysbiosis, which transmits radiation and inflammatory susceptibility and provide evidence that microbial-induced radiation tissue damage is at least in part mediated by IL-1β. Environmental factors may affect the host via modifications of the microbiome and potentially allow for novel interventional approaches via its manipulation.

https://gut.bmj.com/content/gutjnl/67/1/97.full.pdf

Radiation induces proinflammatory dysbiosis: transmission of inflammatory susceptibility by host cytokine induction

A risk prediction model is a statistical tool for estimating the probability that a currently healthy individual with specific risk factors will develop a condition in the future such as breast cancer. Reliably accurate prediction models can inform future disease burdens, health policies and individual decisions. Breast cancer prediction models containing modifiable risk factors, such as alcohol consumption, BMI or weight, condom use, exogenous hormone use and physical activity, are of particular interest to women who might be considering how to reduce their risk of breast cancer and clinicians developing health policies to reduce population incidence rates. We performed a systematic review to identify and evaluate the performance of prediction models for breast cancer that contain modifiable factors. A protocol was developed and a sensitive search in databases including MEDLINE and EMBASE was conducted in June 2010. Extensive use was made of reference lists. Included were any articles proposing or validating a breast cancer prediction model in a general female population, with no language restrictions. Duplicate data extraction and quality assessment were conducted. Results were summarised qualitatively, and where possible meta-analysis of model performance statistics was undertaken. The systematic review found 17 breast cancer models, each containing a different but often overlapping set of modifiable and other risk factors, combined with an estimated baseline risk that was also often different. Quality of reporting was generally poor, with characteristics of included participants and fitted model results often missing. Only four models received independent validation in external data, most notably the 'Gail 2' model with 12 validations. None of the models demonstrated consistently outstanding ability to accurately discriminate between those who did and those who did not develop breast cancer. For example, random-effects meta-analyses of the performance of the 'Gail 2' model showed the average C statistic was 0.63 (95% CI 0.59-0.67), and the expected/observed ratio of events varied considerably across studies (95% prediction interval for E/O ratio when the model was applied in practice was 0.75-1.19). There is a need for models with better predictive performance but, given the large amount of work already conducted, further improvement of existing models based on conventional risk factors is perhaps unlikely. Research to identify new risk factors with large additionally predictive ability is therefore needed, alongside clearer reporting and continual validation of new models as they develop.

A systematic review of breast cancer incidence risk prediction models with meta-analysis of their performance.

Effects of probiotics on radiation-induced intestinal injury in rats

Objective: Radiotherapy is an important aspect of multimodal cancer therapy, but radiation- induced acute intestinal injury is a common and serious problem. Disruption of morphologic mucosal integrity and normal bacterial microflora after abdominal radiation leads to malabsorption and bacterial translocation. Methods: Lactobacillus bulgaricus strain isolated from yogurt was given as a probiotic to rats subjected to radiotherapy. On postradiation day 8 rats were killed. Mesenteric lymph nodes, liver, and spleen were excised for microbiologic examinations. Segments of jejunum, ileum, and colon were evaluated for the presence of inflammation, vascularity, and mucus cells. Results: The results of this study suggest that probiotics may have a protective effect on intestinal mucosa.

Basic nutritional investigation Effects of probiotics on radiation-induced intestinal injury in rats

The Gail model is considered the best available means for estimating risk of breast cancer development, but it has not yet been applied systematically and validated in Turkish female population. This study was designed to evaluate the performance of the Gail model for Turkish female population. Additionally duration of breastfeeding was examined as a possible risk factor. Our analysis included 650 patients with invasive breast carcinoma (group 1) and 640 women with negative results who had undergone a screening mammography on visiting a mammary care unit (group 2). Two groups were compared with regard to individual risk factors included in the Gail model and also duration of breastfeeding. The Gail model was used to predict 5-year risk for each woman. Age and first live birth ≥30 years were associated with an increased relative risk for breast cancer development. Age at menarche, previous breast biopsy, atypical hyperplasia, and number of first degree relatives with breast cancer were found to be non-significant. The Gail model showed 13.3% sensitivity and 92% specificity in estimating the risk of breast cancer development in Turkish women. Positive predictive value was 63%, negative predictive value was 51.9%, and validity index was 53.1%. Duration of breastfeeding was significantly longer in group 1 than 2 (median 17 vs. 13 months). The proportion of parous women with no breastfed was higher in group 1 than 2. The currently used Gail model does not seem to be an appropriate breast cancer risk assessment tool for Turkish female population.

Applicability of the Gail model for breast cancer risk assessment in Turkish female population and evaluation of breastfeeding as a risk factor.

ABSTRACT BACKGROUND: This study aims to determine the uncommon causes of acute appendicitis in analyzed post appendectomy specimens. METHODS: Histopathology reports of 6785 removed appendices were analyzed retrospectively in order to confirm the uncommon cause of acute appendicitis in single tertiary institution. RESULTS: Unusual cause of acute appendicitis was found in 98 (1.44%) samples (40 female and rest 58 male patients). Neuroendocrine tumor of the appendix was the most common pathology, followed by serrated adenoma, low-grade appendicular mucinous neoplasm, hyperplastic polyp and intestinal parasite. In four patients (0.05%), appendicular adenocarcinoma was confirmed with an overall mortality of 75%. Age was significantly higher in uncommon acute appendectomies than in ordinary appendectomies. Survival analysis of unusual appendectomies showed that advanced age is of prognostic importance (Kaplan Meier p<0.0001). There was also a difference in survival between different disease groups in unusual appendectomies, but Cox multifactorial analysis showed that these two factors were not statistically significant. CONCLUSION: Although rare, unusual causes are the etiological factor responsible for acute appendicitis. These reasons should be kept in mind in the older age group and the diagnosis of appendicitis should be made carefully.

Uncommon causes of acute appendicitis: Retrospective analysis of 6785 histopathological findings in a tertiary center

Tumour budding (TB) in cancer is a phenomenon of tumour cells forming clusters, and it is associated with an epithelial-mesenchymal transition into the extracellular matrix of the tumour. It has been shown that the presence of TB in colorectal cancer (CRC) is associated with worse overall survival, higher possibility for vessel invasion, lymph node involvement, and distant metastases appearance. In this retrospective study TB presence in operated patients for CRC is analysed. In the data from 81 patients, 26 presented with TB. Analysis revealed high statistical significance of the effect of TB presence on the number of metastatic lymph nodes, and the lymphovascular and perineural invasion. A statistically meaningful correlation was found between the presence of TB and CRC survival ( p = 0.016). Patients with right-sided colon cancer presented with worse overall survival ( p = 0.011). The patients who presented lymph node metastases and TB presence had worse overall survival ( p = 0.026 and p = 0.021, respectively). Tumour budding, tumour location, and age over 64 years are found to be the independent prognostic factors in CRC patients. Tumour budding is an important prognostic factor in CRC patients that will contribute to treatment. Pathological examination must consider TB in detail.

/pdf/tumour-budding-an-additional-prognostic-factor-in-colorectal-kuxskwna.pdf

Tumour budding - an additional prognostic factor in colorectal cancer survival.

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