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Pancreatic ductal adenocarcinoma: risk factors, screening, and early detection

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World Journal of Gastroenterology 2014年第32期20卷 11182-11198页

作者： andrew E Becker Yasmin G Hernandez Harold Frucht Aimee L Lucas Henry D. Janowitz Division of Gastroenterology Icahn School of Medicine at Mount Sinai New York NY 10029 United States Division of Digestive and Liver Diseases Columbia University College New York NY 10032 United States

Pancreatic cancer is the fourth most common cause of cancer-related deaths in the United States, with over 38000 deaths in 2013. The opportunity to detect pancreatic cancer while it is still curable is dependent on our ability to identify and screen high-risk populations before their symptoms arise. risk factors for developing pancreatic cancer include multiple genetic syndromes as well as modifiable risk factors. Genetic conditions include hereditary breast and ovarian cancer syndrome, Lynch Syndrome, familial adenomatous polyposis, Peutz-Jeghers Syndrome, familial atypical multiple mole melanoma syndrome, hereditary pancreatitis, cystic fibrosis, and ataxia-telangiectasia; having a genetic predisposition can raise the risk of developing pancreatic cancer up to 132-fold over the general population. Modifiable risk factors, which include tobacco exposure, alcohol use, chronic pancreatitis, diet, obesity, diabetes mellitus, as well as certain abdominal surgeries and infections, have also been shown to increase the risk of pancreatic cancer development. Several largevolume centers have initiated such screening protocols, and consensus-based guidelines for screening high-riskgroups have recently been published. The focus of this review will be both the genetic and modifiable risk factors implicated in pancreatic cancer, as well as a review of screening strategies and their diagnostic yields.

关键词： Pancreatic neoplasms Pancreas cancer screening Genetic predisposition to disease Hereditary breast and ovarian cancer syndrome Lynch syndrome Peutz-Jeghers BRCA PALB2 p16 Pancreatitis

The role of MDM2 and MDM4 in breast cancer development and prevention

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Journal of Molecular Cell Biology 2017年第1期9卷 53-61页

作者： Sue Haupt Reshma Vijayakumaran Panimaya Jeffreena Miranda andrew Burgess Elgene Lim Ygal Haup Tumour Suppression Laboratory Peter MacCallum Cancer Centre Melbourne 3000 Australia Sir Peter MacCallum Department of Oncology The University of Melbourne Melbourne 3000 Australia The Kinghorn Cancer Centre Garvan Institute of Medical Research Sydney New South Wales 2010 Australia St. Vincent's Clinical School Faculty of Medicine University of New South Wales Sydney New South Wales 2010 Australia Department of Pathology The University of Melbourne Parkville Victoria 3010 Australia Department of Biochemistry and Molecular Biology Monash University Clayton Australia

The major cause of death from breast cancer is not the primary turnout, but relapsing, drug-resistant, metastatic disease. Identifying factors that contribute to aggressive cancer offers important leads for therapy. Inherent defence against carcinogens depends on the individual molecular make-up of each person. Important molecular determinants of these responses are under the control of the mouse double minute （MDM） family： comprised of the proteins MDM2 and MDM4. In normal, healthy adult cells, the MDM family functions to critically regulate measured, cellular responses to stress and subsequent recovery. Proper function of the MDM family is vital for normal breast development, but also for preserving genomic fidelity. The MDM family members are best characterized for their negative regulation of the major tumour suppressor p53 to modulate stress responses. Their impact on other cellular regulators is emerging. Inappropriately elevated protein levels of the MDM family are highly associated with an increased risk of cancer incidence. Exploration of the MDM family members as cancer therapeutic targets is relerant for designing tailored anti-cancer treatments, but successful approaches must strategically consider the impact on both the target cancer and adjacent healthy ceils and tissues. This review focuses on recent findings pertaining to the role of the MDM family in normal and malignant breast cells.

关键词： MDM2 MDM4 TP53 p53 breast cancer

Vitamin D therapy in children with inflammatory bowel disease: A systematic review

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World Journal of Clinical Pediatrics 2019年第1期8卷 1-14页

作者： Tarah Rigterink Laura Appleton andrew S Day Vrije Universiteit Amsterdam Department of Paediatrics University of Otago Christchurch

BACKGROUND Vitamin D deficiency is highly prevalent in children with inflammatory bowel disease(IBD). This may contribute to an increased risk of poor bone health and may also influence the course of disease. An optimal treatment strategy of vitamin D therapy in children with IBD has not yet been *** To analyse the published intervention studies of vitamin D therapy in children with *** A systematic review was conducted of clinical studies involving children with IBD(including Crohn disease or ulcerative colitis) who had received vitamin D therapy. Studies up to March 31 st 2018 were identified through MEDLINE,PubMed, EMBASE and the Cochrane Library. Search terms included synonyms of the following terms: vitamin D, paediatric, supplementation, IBD. References of included articles based on abstract were searched for other relevant *** relevant articles were accessed and reviewed in full text. Studies fitting the set criteria were included and the remainder were *** Two hundred and seventy-seven discrete articles were identified. Following assessment of these articles included in the initial search and application of inclusion and exclusion criteria, ten published studies were included in this review. The included studies showed a heterogeneity in study design, inclusion and exclusion criteria, baseline demographics and treatment strategies. Treatment regimens differed in length, supplemented form of vitamin D and factors based upon which dosage was adjusted. Each of the reports included in this review concluded their vitamin D regimens to be safe and well-tolerated. Few of the included studies reported secondary outcomes on the efficacy of vitamin D treatment upon the clinical course of disease or markers of inflammation. Themajority of included trials were not sufficient in raising serum vitamin D levels to an adequate level(30 ng/mL) in children with IBD with vitamin D *** The included trials featured dive

关键词： Child Inflammatory bowel diseases Vitamin D Therapeutics Systemic review

Trunk Kinematics and Centre of Pressure Displacement during Lateral Lifting and Lowering

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中国运动医学杂志 2006年第4期25卷 428-434页

作者： Huang Qiangmin Alf Thorstensson andrew Cresswell Department of Sports Science Shanghai Institute of Physical EducationShanghaiChina 200438 Departments of Neuroscience Karolinska Institute and Sport and Health Sciences University College of Physical Education and Sports Stockholm Sweden

Lateral bending of the trunk has been specifically identified as a high risk factor for lower back disorders. However, few studies have presented in vivo kinematic data of the trunk while performing functional lateral bending tasks. Five healthy male subjects performed lateral lifting and lowering tasks under loading condition ranging from light (2kg) to 100 % of a maximum (ML) at a controlled velocity. Single lowering tasks were also performed at 125% and 150% of ML. Video based movement analysis was used to determine kinematics of the trunk, pelvis, shoulders and neck in the frontal plane. Centre of pressure (COP) data was also obtained from a force platform on which the subjects stood when performing the lifting and lowering tasks. Kinematics of the trunk revealed a smooth and relatively large change in angular displacement (between 69°to 55°) toward the unloaded side during the lifting phase. Trunk angular displacement significantly decreased with increasing lifting load. The trunk was additionally divided into four segments representing the lower and upper lumbar regions and the lower and upper thoracic regions. The greatest displacement in these segments took place at the upper lumbar and lower thoracic regions (ranging from 29°to 22°and 23°to 17°, respectively) with the least displacement occurring in the lower lumbar and upper thoracic regions (approx. 6° and 5°, respectively). Both the upper lumbar and lower thoracic segments showed significant decreases in angular displacement with increasing load. During the single lowering trials the trunk rotated toward the loaded side with slightly less magnitude to that recorded during the lowering phase of the heaviest lifting and lowering conditions. Angular displacements of the upper lumbar and lower thoracic segments also decreased with increasing load in single lowering. Identified changes in the COP displacement were also correlated to increasing lifting and lowering load. The main findings of this study indicat

关键词：运动分析运动医学侧弯曲侧提升

COVID-19 outbreak and endoscopy: Considerations in patients encountered in a foregut surgery practice

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World Journal of Gastrointestinal Surgery 2020年第5期12卷 197-202页

作者： Tanya Olszewski andrew D Grubic Shahin Ayazi Blair A Jobe Esophageal and Lung Institute Department of SurgeryAllegheny Health NetworkPittsburghPA 15224United States

Severe acute respiratory syndrome coronavirus has become a critical challenge to global *** the arrival of coronavirus disease 2019 in the United States,several government agencies and professional societies have issued guidelines to healthcare systems and medical *** is a substantial portion of the practice of many general surgeons in the United *** upper endoscopy,manipulation of the upper aerodigestive tract can turn the droplets to an aerosolized form and increase the likelihood of transmission and therefore is considered a high-risk *** this article we review some aspects of the coronavirus disease 2019 outbreak that are relevant to practice of surgical *** emphasis of this communication is on the mode of transmission,previous experiences during other coronavirus outbreaks and society *** then highlight the changes that we have made to our practice to incorporate these factors to improve the safety of patients,health care providers,and community as a whole.

关键词： SARS-CoV-2 COVID-19 Endoscopy Pandemic Best practice Personal protection equipment

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阿司匹林用于结直肠癌预防(英文)

化学进展 2013年第9期25卷 1450-1453页

作者： andrew T.Chan Division of Gastroenterology Massachusetts General Hospital

一直以来,实验室研究、流行病学调查和最近的随机对照临床试验都表明阿司匹林可以降低结直肠癌的风险。出于对潜在的副作用如胃肠道出血的考虑,此前美国预防医学工作组的专家曾经建议对于处于平均风险的普通人群不要常规使用阿司匹林来... 详细信息

一直以来,实验室研究、流行病学调查和最近的随机对照临床试验都表明阿司匹林可以降低结直肠癌的风险。出于对潜在的副作用如胃肠道出血的考虑,此前美国预防医学工作组的专家曾经建议对于处于平均风险的普通人群不要常规使用阿司匹林来预防结直肠癌。然而,最近的高质量证据表明,阿司匹林不仅可以预防结直肠癌,对其它癌症也有预防作用。因此,值得重新考虑阿司匹林是否可常规用于癌症预防这个问题。本文总结了这些支持阿司匹林化学预防功效的有力证据,认为阿司匹林广泛的抗癌效应加上它在预防心血管疾病中的作用可能推动阿司匹林在众多患者中的长期应用。

关键词：阿司匹林结直肠癌随机对照试验非阿司匹林非甾体抗炎药化学预防

Microbiome and colorectal carcinogenesis:Linked mechanisms and racial differences

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World Journal of Gastrointestinal Oncology 2022年第2期14卷 375-395页

作者： Sofia C Tortora Vimal M Bodiwala andrew Quinn Laura A Martello Shivakumar Vignesh Department of Medicine and Division of Gastroenterology&Hepatology SUNY Downstate Health Sciences UniversityBrooklynNY 11203United States

Various studies have shown the interplay between the intestinal microbiome,environmental factors,and genetic changes in colorectal cancer(CRC)*** this review,we highlight the various gut and oral microbiota associated with CRC and colorectal adenomas,and their proposed molecular mechanisms in relation to the processes of“the hallmarks of cancer”,and differences in microbial diversity and abundance between race/*** with CRC showed increased levels of Bacteroides,Prevotella,Escherichia coli,enterotoxigenic Bacteroides fragilis,Streptococcus gallolyticus,Enterococcus faecalis,Fusobacterium nucleatum(***)and Clostridium *** levels of Bacteroides have been found in African American(AA)compared to Caucasian American(CA)***-inflammatory bacteria such as *** and Enterobacter species were significantly higher in ***,AA patients have been shown to have decreased microbial diversity compared to CA *** studies have shown that using microbiome profiles in conjunction with certain risk factors such as age,race and body mass index may help predict healthy colon vs one with adenomas or *** is one of the most common bacterial infections in humans and is more prevalent in Non-Hispanic-Blacks as compared to Non-Hispanic *** condition causes increased systemic inflammation,immune dysregulation,gut microbiota dysbiosis and thereby possibly influencing colorectal ***-associated bacteria such as Fusobacterium,Prevotella,Bacteroides and Porphyromonas have been found in CRC tissues and in feces of CRC ***,a deeper understanding of the association between oral and gastrointestinal bacterial profile,in addition to identifying prevalent bacteria in patients with CRC and the differences observed in ethnicity/race,may play a pivotal role in predicting incidence,prognosis,and lead to the development of new treatments.

关键词： Colorectal cancer Oral microbiome Gut microbiome Hallmarks of cancer Racial/ethnic microbial diversity

Nutrition in alcohol-related liver disease:Physiopathology and management

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World Journal of Gastroenterology 2020年第22期26卷 2916-2930页

作者： Umair Kamran Jennifer Towey Amardeep Khanna Abhishek Chauhan Neil Rajoriya andrew Holt The Liver Unit Queen Elizabeth Hospital BirminghamBirmingham B152GWUnited Kingdom Department of Dietetics Queen Elizabeth Hospital BirminghamBirmingham B152GWUnited Kingdom Centre for Liver Research Institute of Immunology and Inflammationand National Institute for Health Research(NIHR)Birmingham Biomedical Research CentreThe Medical SchoolUniversity of BirminghamBirmingham B152TTUnited Kingdom

Malnutrition encompassing both macro-and micro-nutrient deficiency,remains one of the most frequent complications of alcohol-related liver disease(ArLD).Protein-energy malnutrition can cause significant complications including sarcopenia,frailty and immunodepression in cirrhotic *** reduces patient’s survival and negatively affects the quality of life of individuals with ***,nutritional deficit increases the likelihood of hepatic decompensation in *** recognition of at-risk individuals,early diagnosis and treatment of malnutrition remains a key component of ArLD *** this review,we describe the pathophysiology of malnutrition in ArLD,review the screening tools available for nutritional assessment and discuss nutritional management strategies relevant to the different stages of ArLD,ranging from acute alcoholic hepatitis through to decompensated end stage liver disease.

关键词： Malnutrition Sarcopenia Alcohol-related liver disease Nutritional assessment Nutrition support Micronutrients

Dynamic failure in coal seams Implications of coal composition for bump susceptibility

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International Journal of Mining Science and Technology 2016年第1期26卷 3-8页

作者： Lawson Heather Weakley andrew Miller Arthur Office of Mine Safety and Health Research NIOSHSpokane 99207USA Department of Chemical and Materials Engineering University of IdahoBoise 83705USA

As a contributing factor in the dynamic failure(bumping) of coal pillars,a bump-prone coal seam has been described as one that is ‘‘uncleated or poorly cleated,strong...that sustains high stresses."Despite extensive research regarding engineering controls to help reduce the risk for coal bumps,there is a paucity of research related to the properties of coal itself and how those properties might contribute to the mechanics of failures. Geographic distribution of reportable dynamic failure events reveals a highly localized clustering of incidents despite widespread mining activities. This suggests that unique,contributing geologic characteristics exist within these regions that are less prevalent elsewhere. To investigate a new approach for identifying coal characteristics that might lead to bumping,a principal component analysis(PCA) was performed on 306 coal records from the Pennsylvania State Coal Sample database to determine which characteristics were most closely linked with a positive history of reportable bumping. Selected material properties from the data records for coal samples were chosen as variables for the PCA and included petrographic,elemental,and molecular properties. Results of the PCA suggest a clear correlation between low organic sulfur content and the occurrence of dynamic failure,and a secondary correlation between volatile matter and dynamic failure phenomena. The ratio of volatile matter to sulfur in the samples shows strong correlation with bump-prone regions,with a minimum threshold value of approximately 20,while correlations determined for other petrographic and elemental variables were more ambiguous. Results suggest that the composition of the coal itself is directly linked to how likely a coal is to have experienced a reportable dynamic failure event. These compositional controls are distinct from other previously established engineering and geologic criteria and represent a missing piece to the bump prediction puzzle.

关键词： CoalBumpBounceDynamic failurePillar burst