Background
Women and their health care providers need a reliable answer to this important question: If a woman chooses to participate in regular mammography screening, then how much will this choice ...improve her chances of avoiding a death from breast cancer compared with women who choose not to participate?
Methods
To answer this question, we used comprehensive registries for population, screening history, breast cancer incidence, and disease‐specific death data in a defined population in Dalarna County, Sweden. The annual incidence of breast cancer was calculated along with the annual incidence of breast cancers that were fatal within 10 and within 11 to 20 years of diagnosis among women aged 40 to 69 years who either did or did not participate in mammography screening during a 39‐year period (1977‐2015). For an additional comparison, corresponding data are presented from 19 years of the prescreening period (1958‐1976). All patients received stage‐specific therapy according to the latest national guidelines, irrespective of the mode of detection.
Results
The benefit for women who chose to participate in an organized breast cancer screening program was a 60% lower risk of dying from breast cancer within 10 years after diagnosis (relative risk, 0.40; 95% confidence interval, 0.34‐0.48) and a 47% lower risk of dying from breast cancer within 20 years after diagnosis (relative risk, 0.53; 95% confidence interval, 0.44‐0.63) compared with the corresponding risks for nonparticipants.
Conclusions
Although all patients with breast cancer stand to benefit from advances in breast cancer therapy, the current results demonstrate that women who have participated in mammography screening obtain a significantly greater benefit from the therapy available at the time of diagnosis than do those who have not participated.
After 20 years of follow‐up, women who participate in mammography screening have a 47% lower risk of dying from breast cancer. Although all patients with breast cancer potentially can benefit from advances in breast cancer therapy, women who participate in mammography screening obtain a significantly greater benefit from the therapy available at the time of diagnosis than those who do not participate.
To estimate the long-term (29-year) effect of mammographic screening on breast cancer mortality in terms of both relative and absolute effects.
This study was carried out under the auspices of the ...Swedish National Board of Health and Welfare. The board determined that, because randomization was at a community level and was to invitation to screening, informed verbal consent could be given by the participants when they attended the screening examination. A total of 133 065 women aged 40-74 years residing in two Swedish counties were randomized into a group invited to mammographic screening and a control group receiving usual care. Case status and cause of death were determined by the local trial end point committees and, independently, by an external committee. Mortality analysis was performed by using negative binomial regression.
There was a highly significant reduction in breast cancer mortality in women invited to screening according to both local end point committee data (relative risk RR = 0.69; 95% confidence interval: 0.56, 0.84; P < .0001) and consensus data (RR = 0.73; 95% confidence interval: 0.59, 0.89; P = .002). At 29 years of follow-up, the number of women needed to undergo screening for 7 years to prevent one breast cancer death was 414 according to local data and 519 according to consensus data. Most prevented breast cancer deaths would have occurred (in the absence of screening) after the first 10 years of follow-up.
Invitation to mammographic screening results in a highly significant decrease in breast cancer-specific mortality. Evaluation of the full impact of screening, in particular estimates of absolute benefit and number needed to screen, requires follow-up times exceeding 20 years because the observed number of breast cancer deaths prevented increases with increasing time of follow-up.
Background
It is of paramount importance to evaluate the impact of participation in organized mammography service screening independently from changes in breast cancer treatment. This can be done by ...measuring the incidence of fatal breast cancer, which is based on the date of diagnosis and not on the date of death.
Methods
Among 549,091 women, covering approximately 30% of the Swedish screening‐eligible population, the authors calculated the incidence rates of 2473 breast cancers that were fatal within 10 years after diagnosis and the incidence rates of 9737 advanced breast cancers. Data regarding each breast cancer diagnosis and the cause and date of death of each breast cancer case were gathered from national Swedish registries. Tumor characteristics were collected from regional cancer centers. Aggregated data concerning invitation and participation were provided by Sectra Medical Systems AB. Incidence rates were analyzed using Poisson regression.
Results
Women who participated in mammography screening had a statistically significant 41% reduction in their risk of dying of breast cancer within 10 years (relative risk, 0.59; 95% CI, 0.51‐0.68 P < .001) and a 25% reduction in the rate of advanced breast cancers (relative risk, 0.75; 95% CI, 0.66‐0.84 P < .001).
Conclusions
Substantial reductions in the incidence rate of breast cancers that were fatal within 10 years after diagnosis and in the advanced breast cancer rate were found in this contemporaneous comparison of women participating versus those not participating in screening. These benefits appeared to be independent of recent changes in treatment regimens.
Substantial and significant reductions in the incidence rates of fatal breast cancer and advanced breast cancer with 10 years of follow‐up are observed in this analysis of greater than one‐half million Swedish women participating and not participating in breast cancer screening. These comparisons are contemporaneous, and thus are not influenced by changes in therapeutic regimens.
Current clinical challenges of prostate cancer management are to restrict tumor growth and prohibit metastasis. AICAR (5-aminoimidazole-4-carbox-amide-1-β-d-ribofuranoside), an AMP-activated protein ...kinase (AMPK) agonist, has demonstrated antitumor activities for several types of cancers. However, the activity of AICAR on the cell growth and metastasis of prostate cancer has not been extensively studied. Herein we examine the effects of AICAR on the cell growth and metastasis of prostate cancer cells. Cell growth was performed by MTT assay and soft agar assay; cell apoptosis was examined by Annexin V/propidium iodide (PI) staining and poly ADP ribose polymerase (PARP) cleavage western blot, while cell migration and invasion were evaluated by wound-healing assay and transwell assay respectively. Epithelial-mesenchymal transition (EMT)-related protein expression and AMPK/mTOR-dependent signaling axis were analyzed by western blot. In addition, we also tested the effect of AICAR on the chemosensitivity to docetaxel using MTT assay. Our results indicated that AICAR inhibits cell growth in prostate cancer cells, but not in non-cancerous prostate cells. In addition, our results demonstrated that AICAR induces apoptosis, attenuates transforming growth factor (TGF)-β-induced cell migration, invasion and EMT-related protein expression, and enhances the chemosensitivity to docetaxel in prostate cancer cells through regulating the AMPK/mTOR-dependent pathway. These findings support AICAR as a potential therapeutic agent for the treatment of prostate cancer.
Abstract
Amantadine hydrochloride (HCl) is commonly prescribed for treating influenza A virus infection and Parkinson’s disease. Recently, several studies have indicated that the use of amantadine ...HCl is associated with corneal edema; however, the cytotoxic effect of amantadine HCl has not been investigated. In the present study, the effects of amantadine HCl on cell growth, proliferation, and apoptosis in bovine cornea endothelial cells, and in vitro endothelial permeability were examined. Results showed that lower doses of amantadine HCl do not affect cell growth (≤ 20 μΜ), whereas higher doses of amantadine HCl inhibits cell growth (≥ 50 μΜ), induces apoptosis (2000 μΜ), increases sub-G1 phase growth arrest (2000 μΜ), causes DNA damage (≥ 1000 μΜ), and induces endothelial hyperpermeability (≥ 1000 μΜ) in bovine cornea endothelial cells; additionally, we also found that amantadine HCl attenuates the proliferation (≥ 200 μΜ) and arrests cell cycle at G1 phase (≥ 200 μΜ) in bovine cornea endothelial cells. In the present study, we measured the cytotoxic doses of amantadine HCl on cornea endothelial cells, which might be applied in evaluating the association of corneal edema.
Background and Aim
Currently, some countries still acknowledge double‐contrast barium enema (DCBE) as a backup confirmatory examination when colonoscopy is not feasible or incomplete in colorectal ...cancer (CRC) screening programs. This study aims to compare the performance of colonoscopy and DCBE in terms of the risk of incident CRC after negative results in the fecal immunochemical test (FIT)‐based Taiwan Colorectal Cancer Screening Program.
Methods
Subjects who had positive FITs and received confirmatory exams, either colonoscopy or DCBE, without the findings of neoplastic lesions from 2004 to 2013 in the screening program comprised the study cohort. Both the colonoscopy and DCBE subcohorts were followed until the end of 2018 and linked to the Taiwan Cancer Registry to identify incident CRC cases. Multivariate analysis was conducted to compare the risk of incident CRC in both subcohorts after controlling for potential confounders.
Results
A total of 102 761 colonoscopies and 5885 DCBEs were performed after positive FITs without neoplastic findings during the study period. By the end of 2018, 2113 CRCs (2.7 per 1000 person‐years) and 368 CRCs (7.6 per 1000 person‐years) occurred in the colonoscopy and DCBE subcohorts, respectively. After adjusting for major confounders, DCBE had a significantly higher risk of incident CRC than colonoscopy, with an adjusted HR of 2.81 (95% CI = 2.51–3.14).
Conclusions
In the FIT screening program, using DCBE as a backup examination was associated with a nearly threefold risk of incident CRC compared with colonoscopy, demonstrating that it is no longer justified as a backup examination for incomplete colonoscopy.
Mass screening with abdominal ultrasonography (AUS) has been suggested as a tool to control adult hepatocellular carcinoma (HCC) in individuals, but its efficacy in reducing HCC mortality has never ...been demonstrated. This study aimed to assess the effectiveness of reducing HCC mortality by mass AUS screening for HCC based on a program designed and implemented in the Changhua Community‐based Integrated Screening (CHCIS) program with an efficient invitation scheme guided by the risk score. We invited 11,114 (27.0%) of 41,219 eligible Taiwanese subjects between 45 and 69 years of age who resided in an HCC high‐incidence area to attend a risk score‐guided mass AUS screening between 2008 and 2010. The efficacy of reducing HCC mortality was estimated. Of the 8,962 AUS screening attendees (with an 80.6% attendance rate), a total of 16 confirmed HCC cases were identified through community‐based ultrasonography screening. Among the 16 screen‐detected HCC cases, only two died from HCC, indicating a favorable survival. The cumulative mortality due to HCC (per 100,000) was considerably lower in the invited AUS group (17.26) compared with the uninvited AUS group (42.87) and the historical control group (47.51), yielding age‐ and gender‐adjusted relative mortality rates of 0.69 (95% confidence interval CI: 0.56‐0.84) and 0.63 (95% CI: 0.52‐0.77), respectively. Conclusion: The residents invited to community‐based AUS screening for HCC, compared with those who were not invited, showed a reduction in HCC mortality by ∼31% among subjects aged 45‐69 years who had not been included in the nationwide vaccination program against hepatitis B virus infection. (Hepatology 2014;59:1840–1849)
Few studies quantify a cascade of dynamic transitions on the detailed components of metabolic syndrome (MetS) and subsequent progressions to cardiovascular disease (CVD) and its death. A total of ...47,495 subjects repeatedly attending a community-based integrated screening program in Taiwan were recruited. The refined MetS-related classification (RMRC) in relation to five criteria of MetS was defined as free of metabolic disorder (FMD, none of any criteria), mild metabolic disorder (MMD, 1-2 criteria) and MetS. A multistate Markov model was used for modelling such a multistate process. The estimated progression rate from FMD to MMD was 44.82% (95% CI 42.95-46.70%) whereas the regression rate was estimated as 29.11% (95% CI 27.77-30.45%). The progression rate from MMD to MetS was estimated as 6.15% (95% CI 5.89-6.42%). The estimated annual incidence rates of CVD increased with the severity of RMRC, being 1.62% (95% CI 1.46-1.79%) for FMD, 4.74% (95% CI 4.52-4.96%) for MMD, to 20.22% (95% CI 19.52-20.92%) for MetS. The estimated hazard rate of CVD death was 6.1 (95% CI 4.6-7.7) per thousand. Elucidating the dynamics of MetS-related transition and quantifying the incidence and prognosis of CVD provide a new insight into the design and the evaluation of intervention programs for CVD.
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