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91.
A. Dumont N. Bessières G. Razafindrafara M. Ravit A. Benbassa 《Revue d'épidémiologie et de santé publique》2019,67(2):120-125
Background
Testing for high-risk human papilloma virus (HR-HPV) is an effective approach to the prevention of cervical cancer. This study in the Atsinanana area of Madagascar aimed to compare the management of women screened by visual inspection after coloration with acetic acid (VIA) and the management of women screened by HPV with VIA as a triage test.Method
During the last two screening campaigns, the first patients (between 28 and 120 women par center) were sampled using a dry swab, just before the acetic acid application, to test 14 genotypes of HR-HPV using Roche Diagnostics Cobas® Test. We compared current management practices based on primary VIA to those that would have been implemented if the clinician had followed the recommendations of the World Health Organization for HPV-based primary screening. We used a regression Poisson model with random effect and robust variance.Results
Among the 250 screened-women, 28 (11.2%) had acidophilic lesions of the uterine cervix or suspected lesions of invasive cancer (IVA +). The HPV test was positive in 62 cases (24.8%). The HPV-based screening strategy would have reduced by 52% the number of women needing thermo-coagulation treatment: 24 women (9.6%) with primary VIA-based screening vs. 13 women (5.2%) with primary HPV-based screening; RR: 0.52 and 95%CI: 0.27–1.02. The diagnosis of severe dysplastic lesion or invasive cancer would not have changed.Conclusion
Primary HPV-based screening is a strategy that could be useful for low-resource countries like Madagascar. It would reduce the rate of false positives and unnecessary treatments compared to the current strategy based on primary IVA. The questions of the feasibility and cost-benefit of this strategy should be further explored. 相似文献92.
Shane R. Stecklein Simona F. Shaitelman Gildy V. Babiera Isabelle Bedrosian Dalliah M. Black Matthew T. Ballo Isadora Arzu Eric A. Strom Valerie K. Reed Tomas Dvorak Benjamin D. Smith Wendy A. Woodward Karen E. Hoffman Pamela J. Schlembach Steve M. Kirsner Christopher L. Nelson Jinzhong Yang William Guerra Elizabeth S. Bloom 《Practical radiation oncology》2019,9(1):e4-e13
Purpose
This study aimed to prospectively characterize toxicity and cosmesis after accelerated partial breast irradiation (APBI) with 3-dimensional conformal radiation therapy (CRT) or single-entry, multilumen, intracavitary brachytherapy.Methods and materials
A total of 281 patients with pTis, pT1N0, or pT2N0 (≤3.0 cm) breast cancer treated with segmental mastectomy were prospectively enrolled from December 2008 through August 2014. APBI was delivered using 3-dimensional CRT (n = 29) or with SAVI (n = 176), Contura (n = 56), or MammoSite (n = 20) brachytherapy catheters. Patients were evaluated at protocol-specified intervals, at which time the radiation oncologist scored cosmetic outcome, toxicities, and recurrence status using a standardized template.Results
The median follow-up time is 41 months. Grade 1 seroma and fibrosis were more common with brachytherapy than with 3-dimensional CRT (50.4% vs 3.4% for seroma; P < .0001 and 66.3% vs 44.8% for fibrosis; P = .02), but grade 1 edema was more common with 3-dimensional CRT than with brachytherapy (17.2% vs 5.6%; P = .04). Grade 2 to 3 pain was more common with 3-dimensional CRT (17.2% vs 5.2%; P = .03). Actuarial 5-year rates of fair or poor radiation oncologist-reported cosmetic outcome were 9% for 3-dimensional CRT and 24% for brachytherapy (P = .13). Brachytherapy was significantly associated with inferior cosmesis on mixed model analysis (P = .003). Significant predictors of reduced risk of adverse cosmetic outcome after brachytherapy were D0.1cc (skin) ≤102%, minimum skin distance >5.1 mm, dose homogeneity index >0.54, and volume of nonconformance ≤0.89 cc. The 5-year ipsilateral breast recurrence was 4.3% for brachytherapy and 4.2% for 3-dimensional CRT APBI patients (P = .95).Conclusions
Brachytherapy APBI is associated with higher rates of grade 1 fibrosis and seroma than 3-dimensional CRT but lower rates of grade 1 edema and grade 2 to 3 pain than 3-dimensional CRT. Rates of radiation oncologist-reported fair or poor cosmetic outcomes are higher with brachytherapy. We identified dosimetric parameters that predict reduced risk of adverse cosmetic outcome after brachytherapy-based APBI. Ipsilateral breast recurrence was equivalent for brachytherapy and 3-dimensional CRT. 相似文献93.
《慢性疾病与转化医学(英文)》2019,5(4):258-266
Despite tremendous efforts to fight cancer, it remains a major public health problem and a leading cause of death worldwide. With increased knowledge of cancer pathways and improved technological platforms, precision therapeutics that specifically target aberrant cancer pathways have improved patient outcomes. Nevertheless, a primary cause of unsuccessful cancer therapy remains cancer drug resistance. In this review, we summarize the broad classes of resistance to cancer therapy, particularly pharmacokinetics, the tumor microenvironment, and drug resistance mechanisms. Furthermore, we describe how bacterial-mediated cancer therapy, a bygone mode of treatment, has been revitalized by synthetic biology and is uniquely suited to address the primary resistance mechanisms that confound traditional therapies. Through genetic engineering, we discuss how bacteria can be potent anticancer agents given their tumor targeting potential, anti-tumor activity, safety, and coordinated delivery of anti-cancer drugs. 相似文献
94.
《Vaccine》2019,37(31):4382-4391
Cancer-associated fibroblasts (CAFs), major components of the tumor microenvironment (TME), promote tumor growth and metastasis and inhibit the anti-tumor immune response. We previously constructed a DNA vaccine expressing human FAPα, which is highly expressed by CAFs, to target these cells in the TME, and observed limited anti-tumor effects in the 4T1 breast cancer model. When the treatment time was delayed until tumor nodes formed, the anti-tumor effect of the vaccine completely disappeared. In this study, to improve the safety and efficacy, we constructed a new FAPα-targeted vaccine containing only the extracellular domain of human FAPα with a tissue plasminogen activator signal sequence for enhanced antigen secretion and immunogenicity. The number of CAFs was more effectively reduced by CD8+ T cells induced by the new vaccine. This resulted in decreases in CCL2 and CXCL12 expression, leading to a significant decrease in the ratio of myeloid-derived suppressor cells in the TME. Moreover, when mice were treated after the establishment of tumors, the vaccine could still delay tumor growth. To facilitate the future application of the vaccine in clinical trials, we further optimized the gene codons and reduced the homology between the vaccine and the original sequence, which may be convenient for evaluating the vaccine distribution in the human body. These results indicated that the new FAPα-targeted vaccine expressing an optimized secreted human FAPα induced enhanced anti-tumor activity by reducing the number of FAPα+ CAFs and enhancing the recruitment of effector T cells in the 4T1 tumor model mice. 相似文献
95.
《Health & place》2019
The objective of this paper was to assess the link between premature mortality and a combination of neighbourhood contextual (environmental and health) and compositional (socioeconomic and demographic) characteristics. We statistically and spatially examined six environmental variables (ultrafine particles, carcinogenic and non-carcinogenic pollutants, pollution released to air, tree cover, and walkability index), six health service indicators (number health providers, breast, colorectal and cervical cancer screening uptake rates, student nutrition program uptake rates, and healthy food index), and eight socioeconomic indicators (total income, Gini coefficient, two age categories – below and above 40 years, proportion of females to males, visible minorities, Indigenous peoples, education, less than grade 9) among 140 neighbourhoods of the City of Toronto in Ontario (Canada). We applied principal component analysis to identify patterns and to reduce the number of explanatory variables into combined component axes that represent unique variation in these confounded and overlapping factors. We then applied regression analysis to model the relationship between the indices of enviro-health and socioeconomics and their potential relationship with premature mortality. Residual spatial analysis was used to investigate any remaining spatial structure (such as neighbourhoods with higher residual premature mortality rates). Neighbourhood Equity Index was correlated with our enviro-health and socioeconomic indices. Premature mortality within neighbourhoods was predicted by poor cancer screenings, pollution, lack of tree canopy, increased uptake of student nutrition programs and high walkability index. A negative association between premature mortality and pollution was associated low walkability index and presence of visible minorities within neighbourhoods. There was some unexplained residual spatial variation in our model of premature mortality - especially along the shores of Lake Ontario and in neighbourhoods with major highways or road corridors: premature mortality in Toronto neighbourhoods was higher than expected along highway-corridor neighbourhoods and shorelines. Our analysis revealed a significant relationship between neighbourhood contextual features – both environmental and health – and premature mortality, suggesting that these contextual components of neighbourhoods can predict rates of urban premature mortality in Toronto. 相似文献
96.
Anastasiia Panfilova Sarah E. Shelton Cristina Caresio Ruud J.G. van Sloun Filippo Molinari Hessel Wijkstra Paul A. Dayton Massimo Mischi 《Ultrasound in medicine & biology》2019,45(2):539-548
Dynamic contrast-enhanced ultrasound (DCE-US) has been proposed as a powerful tool for cancer diagnosis by estimation of perfusion and dispersion parameters reflecting angiogenic vascular changes. This work was aimed at identifying which vascular features are reflected by the estimated perfusion and dispersion parameters through comparison with acoustic angiography (AA). AA is a high-resolution technique that allows quantification of vascular morphology. Three-dimensional AA and 2-D DCE-US bolus acquisitions were used to monitor the growth of fibrosarcoma tumors in nine rats. AA-derived vascular properties were analyzed along with DCE-US perfusion and dispersion to investigate the differences between tumor and control and their evolution in time. AA-derived microvascular density and DCE-US perfusion exhibited good agreement, confirmed by their spatial distributions. No vascular feature was correlated with dispersion. Yet, dispersion provided better cancer classification than perfusion. We therefore hypothesize that dispersion characterizes vessels that are smaller than those visible with AA. 相似文献
97.
The natural compound amygdalin has gained high popularity among tumor patients as a complementary or alternative treatment option. However, due to metabolization of amygdalin to cyanide (HCN) following oral consumption, there could be a high risk of lactic acidosis caused by cyanide intoxication. The present retrospective study was undertaken to evaluate cyanide blood and lactate plasma levels of tumor patients (n = 55) before and after intravenous (i.v.) amygdalin infusion. All patients had also continuously ingested amygdalin tablets (3 x 500 mg/day), excepting on the days of i.v. administration. Each patient received one to five intravenous amygdalin treatments. The time period between each i.v. application ranged between 4–6 days. The initial i.v. dose was 6 mg (n = 28), 9 mg (n = 1), 15 mg (n = 1) or 18 mg (n = 25). The mean cyanide blood level before i.v. amygdalin administration was 34.74 μg/L, which increased significantly to a mean value of 66.20 μg/L after i. v. amygdalin application. In contrast, lactate decreased significantly from 1266 μmol/L pre-infusion to 868 μmol/L post-infusion. Increasing i.v. amygdalin by 1 mg was also associated with a significant increase in the cyanide level, while the lactate blood level significantly decreased. This is the first study evaluating cyanide levels under conditions employed by amygdalin administrators, i.e. after chronic oral amygdalin intake and then again after a closely subsequent intravenous amygdalin administration. Since lactate decreased, whilst cyanide increased, it is concluded that elevation of cyanide does not induce metabolic acidosis in terms of an increased lactate level. 相似文献
98.
Background/purpose
Necrotizing enterocolitis (NEC) is a devastating disease of prematurity that develops after feeding, often without warning, and results in diffuse intestinal necrosis leading to sepsis and death in many cases. The lack of improvement in overall survival is influenced by nonspecific diagnostic modalities as well as inexact and nonpersonalized treatment strategies.Methods/Results
Recently, we and others have shown that NEC develops in response to exaggerated bacterial signaling in the premature intestine, as a consequence of elevated expression and activity of the bacterial receptor toll-like receptor 4 (TLR4), which is important for normal gut development. Breast milk is a powerful TLR4 inhibitor, while mutations in TLR4 genes lead to increased NEC risk in humans, providing proof-of-concept for its role in NEC. Recently, a drug discovery approach has revealed a novel class of TLR4 inhibitors which are being developed for personalized approaches to NEC treatment.Conclusion
This review will highlight the current understanding of the role of bacterial signaling in NEC pathogenesis, and will describe advances in diagnosis, prevention and treatment of NEC that may hopefully improve survival for these most fragile patients.Systematic Review
Level of Evidence: Level II. 相似文献99.
《European journal of surgical oncology》2019,45(12):2289-2294
IntroductionDespite the excellent prognosis associated with pathological complete response (pCR) to neoadjuvant chemotherapy (NAC), some patients still develop recurrence. Here, we investigated the outcomes of breast cancer patients with pCR, as well as the clinical and pathological predictors of cancer recurrence in these patients.Materials and methodsOf the 1599 breast cancer patients treated with NAC, we evaluated 394 patients who achieved pCR between January 2007 and December 2016. pCR was defined as no evidence of invasive cancer in breast. Residual in situ ductal and axillary lymph node diseases were not considered. We analyzed the outcomes using the Kaplan–Meier method. We assessed the association of clinical and pathological predictors with cancer recurrence using the cox proportional hazards regression model.ResultsThe median follow-up time was 63 months. The 5-year disease-free survival rate was 92.3%. Cancer recurrence was observed in 28 patients (7.1%): local recurrence 8 patients (2.0%), visceral metastasis 10 patients (2.5%), and brain metastasis 10 patients (2.5%). Brain metastases were found in patients with HER2 type breast cancer. The significant predictors of cancer recurrence were HER2 positivity (p = 0.04), clinical tumor size (p < 0.01), and lymph node metastasis (p < 0.01) before NAC on univariate analysis and only lymph node metastasis on multivariate analysis.ConclusionPatients achieving pCR to NAC showed excellent outcomes. Advanced clinical stage, large tumor size, presence of lymph node metastasis, and HER2 positivity before NAC were identified as significant predictors of cancer recurrence. Residual in situ ductal and lymph node diseases after NAC were not significant predictors. 相似文献
100.
Qiao Wei Xiyi Li Zhengfei Zhu Weiwei Yu Guangqi Qin Huan Chen Yanzi Gu Kuaile Zhao Xiaolong Fu Menghong Sun 《Pathology, research and practice》2019,215(12):152645
BackgroundForkhead box protein P1 (FOXP1) has been suggested as a prognostic marker in several malignant tumors. However, the significance of FOXP1 in esophageal squamous cell carcinoma (ESCC) is still unclear. The purpose of this study was to investigate the expression pattern of FOXP1 in normal esophageal tissue and ESCC and to analyze the clinicopathological significance and prognostic value of FOXP1 in ESCC.MethodsFOXP1 was detected by immunohistochemistry using tissue microarrays containing tumor tissues and adjacent normal tissues from 270 ESCC patients with oncological follow-up data.ResultsNormal esophageal tissues predominantly showed an exclusive nuclear FOXP1 (n-FOXP1) expression pattern, and no exclusive cytoplasmic FOXP1 (c-FOXP1) staining was found. In ESCC, the expression rates of exclusive n-FOXP1-positive, exclusive c-FOXP1-positive, both nuclear and cytoplasmic positive and complete negative were 14.4%, 28.9%, 10.4% and 46.3%, respectively. High n-FOXP1 expression was significantly correlated with decreased postoperative recurrence and distant metastasis (P < 0.05). Furthermore, elevated c-FOXP1 expression was significantly associated with regional lymph node metastasis and distant metastasis (P < 0.05). High c-FOXP1 expression had an effect on shorter overall survival (OS) time, but the difference was not statistically significant (P > 0.05). Kaplan–Meier analysis showed that ESCC patients with high n-FOXP1 expression survived significantly longer than patients with low n-FOXP1 expression. Multivariate analysis confirmed that patients with high n-FOXP1 staining exhibit good prognosis and n-FOXP1 was an independent factor for ESCC prognosis.ConclusionsOur results suggest that FOXP1 plays an essential role in ESCC progression and prognosis and may be a useful biomarker for predicting survival. 相似文献