Blast injuries to the lung: epidemiology and management

Lung injury is frequently a component of the polytrauma sustained by military personnel surviving blast on the battlefield. This article describes a case series of the military casualties admitted to University Hospital Birmingham's critical care services (role 4 facility), during the period 1 July 2008 to 15 January 2010. Of the 135 casualties admitted, 107 (79.2%) were injured by explosive devices. Plain chest films taken soon after arrival in the role 4 facility were reviewed in 96 of the 107 patients. In 55 (57.3%) films a tracheal tube was present. One or more radiological abnormalities was present in 66 (68.75%) of the films. Five patients met the consensus criteria for the definition of adult respiratory distress syndrome (ARDS). The majority of casualties with blast-related lung injury were successfully managed with conventional ventilatory support employing a lung protective strategy; only a small minority received non-conventional support at any time in the form of high-frequency oscillatory ventilation. Of those casualties who survived to be received by the role 4 facility, none subsequently died as a consequence of lung injury.     

Associations between season of birth and the risk of lung cancer: epidemiological findings from Hungary

Lung cancer is the leading cause of cancer deaths worldwide. Both incidence and mortality of lung cancer are especially high in Hungary. Several investigations suggested recently that month of birth (MOB) is associated with the risks of several nonmalignant disorders as well as some malignant disorders. Only a few studies investigated previously the association between MOB and risk of lung cancer, but they provided inconsistent results. We, therefore, decided to investigate this issue in a large sample of individuals who died from lung cancer. Accordingly, we determined the MOB-associated risk of death by lung cancer between the years 1970 and 2009 among all individuals born in Hungary between 1925 and 1934. The final sample included about two million people. A total of 61,904 deaths by lung cancer occurred in this sample during the period investigated. Using analysis of variance (ANOVA), we did not find significant association between MOB and risk of lung cancer death, either in the whole population investigated (F?=?1.492; p?=?.145) or in the female subpopulation (F?=?1.535; p?=?.129). However, those males born in late spring (May-June) had a lower risk of lung cancer development (F?=?2.577; p?=?.006). Results of the Edwards test also did not suggest consistent association between MOB and risk of lung cancer death in the whole investigated period (1925-1934) in any populations (i.e., whole population or male and female subpopulations). In conclusion, we did not find significant association between MOB and risk of lung cancer in our total sample (although results alluded to a weak association between MOB and risk of lung cancer development among males). The possible associations between MOB and the risk of lung cancer development (or smoking) would require confirmation (or refutation) in large studies from other populations.     

Beclin1、p53与肺癌恶性度及疗效预后的相关性研究

目的通过定量检测肺组织中Beclin1和p53表达水平,分析自噬蛋白Beclin1与凋亡蛋白P53在肺癌发生发展中的作用,研究二者之间及其与肺癌临床病理分期的关系、为肺癌早期诊断提供新的思路和实验依据。方法选取外科手术或纤维支气管镜肺组织56例,依据2003年UICC公布的肺癌TNM分期标准同时结合临床表现、胸部CT、X线检查、纤维支气管镜检查、腹部CT或B超等将入选的50例病例进行分组:其中Ⅰ期5例,Ⅱ期10例,Ⅲ期(ⅢA+ⅢB)26例,Ⅳ期9例,各组年龄、性别等控制情况基本匹配。组织病理学分级按2003年UICC标准:G17例,G219例,G324例。另取6例癌旁组织或者病理确诊为正常组织作为对照组织。采用流式细胞术检测和分析不同病理分期以及不同临床分期肺癌组织中Beclin1、p53的表达水平,对该表达情况与对应的分期进行样本均数两两对比式统计学分析,并与正常肺组织作对照。结果 P53蛋白阳性表达百分率:肿瘤患者(63.96±9.43)%显著高于正常对照组(24.90±4.68)%,t=49.46,P0.05;肿瘤转移者显著高于未转移者,P0.05;并且P53蛋白表达随患者临床分期和病理分级的增加而逐渐增高(P0.05)。Beclin1蛋白检出率的变化规律与P53蛋白检出率的变化相反:肿瘤患者Beclin1蛋白(31.72±20.53)%,显著低于正常对照组(92.26±4.51)%,t=35.84,P0.05;该指标随患者临床分期和病理分级的增加而逐渐降低(P0.05)。Beclin1蛋白与P53蛋白二者相关性分析,Beclin1与p53的表达呈负相关,r=-0.848,P0.05。结论 Beclin1与p53的联合检测可以作为肺癌诊断指标,为估计肺癌的恶性度及预后提供依据。Beclin1与P53蛋白表达水平与肺癌发生发展的关系密切,肿瘤发生过程中细胞自噬作用降低和抗凋亡作用增强同时并存,提高自噬能力成为肿瘤治疗的又一途径。     

Prostate cancer: epidemiology, screening, and biomarkers

Carcinoma of the prostate continues to be a major health problem in the United States. Beginning in 1988, a marked increase in detection of prostate cancer occurred due to the development of a test for prostate-specific antigen (PSA). Controversy exists, however, about the value of PSA as a tumor marker. Although it has prognostic significance both before and after definitive therapy for prostate cancer, it is unclear whether routine PSA screening will translate into a survival advantage for patients. Because of its limitations, PSA may not ultimately be a good enough marker to be used as a screening tool. However, molecular biology has led to a rapid rise in the number of potential new prostate tumor markers, which may eventually overcome the weaknesses of PSA. Considerable progress has occurred in the diagnosis and management of prostate cancer: more is understood about the risk factors for the disease, possible ways to prevent it, and new ways to diagnose and monitor it. These developments have already translated into better patient care, while also identifying where further improvements are needed.     

The alcoholic lung: epidemiology, pathophysiology, and potential therapies

Epidemiological evidence gathered only in the past decade reveals that alcohol abuse independently increases the risk of developing the acute respiratory distress syndrome by as much as three- to fourfold. Experimental models and clinical studies are beginning to elucidate the mechanisms underlying this previously unrecognized association and are revealing for the first time that chronic alcohol abuse causes discrete changes, particularly within the alveolar epithelium, that render the lung susceptible to acute edematous injury in response to sepsis, trauma, and other inflammatory insults. Recent studies in relevant animal models as well as in human subjects are identifying common mechanisms by which alcohol abuse targets both the alveolar epithelium and the alveolar macrophage, such that the risks for acute lung injury and pulmonary infections are inextricably linked. Specifically, chronic alcohol ingestion decreases the levels of the antioxidant glutathione within the alveolar space by as much as 80-90%, and, as a consequence, impairs alveolar epithelial surfactant production and barrier integrity, decreases alveolar macrophage function, and renders the lung susceptible to oxidant-mediated injury. These changes are often subclinical and may not manifest as detectable lung impairment until challenged by an acute insult such as sepsis or trauma. However, even otherwise healthy alcoholics have evidence of severe oxidant stress in the alveolar space that correlates with alveolar epithelial and macrophage dysfunction. This review focuses on the epidemiology and the pathophysiology of alcohol-induced lung dysfunction and discusses potential new treatments suggested by recent experimental findings.     

Research on smoking and lung cancer: a landmark in the history of chronic disease epidemiology

This paper describes the history of the epidemiologic research on lung cancer prior to 1970 and its effect on chronic disease epidemiology. In the 1930s, epidemiology was largely concerned with acute infectious diseases. As the evidence grew that the incidence of lung cancer was increasing among men, however, epidemiologists undertook research into the etiology of the disease. In 1950, Doll and Hill, in England, and Wynder and Graham, in the United States, published substantial case-control studies that implicated the use of tobacco as a major risk factor for the disease. A controversy developed over the credibility of this finding and was increased in 1954 when a cohort study by Doll and Hill and another by Hammond and Horn each gave estimates that the risk of lung cancer was greatly increased among smokers relative to the risk among comparable non-smokers. An account is given of the disputes surrounding these and related studies. The controversy had a stimulating effect in fostering the developing discipline of chronic disease and epidemiology.     

Animal models in carotenoids research and lung cancer prevention

Numerous epidemiological studies have consistently demonstrated that individuals who eat more fruits and vegetables (which are rich in carotenoids) and who have higher serum β-carotene levels have a lower risk of cancer, especially lung cancer. However, two human intervention trials conducted in Finland and in the United States have reported contrasting results with high doses of β-carotene supplementation increasing the risk of lung cancer among smokers. The failure of these trials to demonstrate actual efficacy has resulted in the initiation of animal studies to reproduce the findings of these two studies and to elucidate the mechanisms responsible for the harmful or protective effects of carotenoids in lung carcinogenesis. Although these studies have been limited by a lack of animal models that appropriately represent human lung cancer induced by cigarette smoke, ferrets and A/J mice are currently the most widely used models for these types of studies. There are several proposed mechanisms for the protective effects of carotenoids on cigarette smoke-induced lung carcinogenesis, and these include antioxidant/prooxidant effects, modulation of retinoic acid signaling pathway and metabolism, induction of cytochrome P450, and molecular signaling involved in cell proliferation and/or apoptosis. The technical challenges associated with animal models include strain-specific and diet-specific effects, differences in the absorption and distribution of carotenoids, and differences in the interactions of carotenoids with other antioxidants. Despite the problems associated with extrapolating from animal models to humans, the understanding and development of various animal models may provide useful information regarding the protective effects of carotenoids against lung carcinogenesis.     

Colon cancer stem cells: implications for prevention and therapy

The recent identification of colon cancer tumor-initiating cells adds further support to the cancer stem cell hypothesis. Ongoing basic and translational research efforts are aimed at gaining an increased understanding of the biology of these cells, as well as methods of targeting them. In addition, the relationship between colon carcinogenesis and inflammatory conditions, such as longstanding colitis and inherited syndromes, might be linked to the effect of the processes on stem cells in the colon. This review summarizes current literature on colon cancer stem cells and proposes strategies aimed at targeting these cells for colon cancer prevention and therapy.     

Studies on biomarkers in cancer etiology and prevention: a summary and challenge of 20 years of interdisciplinary research

Sensitive, specific methods have been developed that allow quantitative measurements of the metabolites of carcinogen metabolites and of DNA and protein adducts in humans exposed occupationally, environmentally and endogenously to genotoxic agents. The interrelationship between exposure to carcinogens, host risk factors and the responses of biomarkers has been examined in cross-sectional, ecological and case-control studies which provided new insights into the causes of cancer and the mechanisms of carcinogenesis. The identification of hitherto unknown DNA-reactive chemicals formed in the human body from dietary precursors and of carcinogenic components of complex mixtures has increased the possibility of establishing causal relationships in etiology. The identification of individuals and subgroups heavily exposed to carcinogens has led to the development of measures for avoiding or decreasing exposure to carcinogenic risk factors. New, ultrasensitive methods for measuring DNA adducts allow the quantification and structural elucidation of specific DNA damage in humans arising from oxidative stress and lipid peroxidation (LPO), which have been found to be the driving forces in several human malignancies. Background DNA damage in "unexposed" individuals has been shown unequivocally to be due to LPO products, and a significant interindividual variation in adduct levels has been shown in individuals with comparable exposure to carcinogens. Thus, pharmacogenetic variants with higher susceptibility to carcinogenic insults, due to genetic polymorphism in xenobiotic-metabolizing enzymes, have been characterized by a combination of genotyping and measurements of macromolecular adducts. Dosimetry has been used in human studies to evaluate the efficacy of interventions with chemopreventive agents like ascorbic acid, dietary phenols and green tea. Advances in the application of selected biomarkers in human studies are reviewed and illustrated by examples from the author's research conducted during the past two decades.     

Beyond chemotherapy and targeted therapy: adoptive cellular therapy in non-small cell lung cancer

Non-small cell lung cancer (NSCLC) is an intractable disease for which effective treatment approaches are urgently needed. The ability to induce antigen-specific immune responses in patients with lung cancer has led to the development of immunotherapy as a novel concept for the treatment of NSCLC. Adoptive cellular therapy (ACT) represents an important advancement in cancer immunotherapy with the utilization of tumor infiltrating lymphocytes, cytokine-induced killer cells, natural killer cells and γδ T cells. In this study, we review recent advances in ACT for NSCLC in clinical trials and provide a perspective on the improvement in ACT and potential therapeutic approaches using engineered T cell therapy for NSCLC.     

Cigarette tar yields in relation to mortality from lung cancer in the cancer prevention study II prospective cohort, 1982-8

Objective To assess the risk of lung cancer in smokers of medium tar filter cigarettes compared with smokers of low tar and very low tar filter cigarettes.Design Analysis of the association between the tar rating of the brand of cigarette smoked in 1982 and mortality from lung cancer over the next six years. Multivariate proportional hazards analyses used to assess hazard ratios, with adjustment for age at enrolment, race, educational level, marital status, blue collar employment, occupational exposure to asbestos, intake of vegetables, citrus fruits, and vitamins, and, in analyses of current and former smokers, for age when they started to smoke and number of cigarettes smoked per day.Setting Cancer prevention study II (CPS-II).Participants 364 239 men and 576 535 women, aged ≥ 30 years, who had either never smoked, were former smokers, or were currently smoking a specific brand of cigarette when they were enrolled in the cancer prevention study.Main outcome measure Death from primary cancer of the lung among participants who had never smoked, former smokers, smokers of very low tar (≤ 7 mg tar/cigarette) filter, low tar (8-14 mg) filter, high tar (≥ 22 mg) non-filter brands and medium tar conventional filter brands (15-21 mg).Results Irrespective of the tar level of their current brand, all current smokers had a far greater risk of lung cancer than people who had stopped smoking or had never smoked. Compared with smokers of medium tar (15-21 mg) filter cigarettes, risk was higher among men and women who smoked high tar (≥ 22 mg) non-filter brands (hazard ratio 1.44, 95% confidence interval 1.20 to 1.73, and 1.64, 1.26 to 2.15, respectively). There was no difference in risk among men who smoked brands rated as very low tar (1.17, 0.95 to 1.45) or low tar (1.02, 0.90 to 1.16) compared with those who smoked medium tar brands. The same was seen for women (0.98, 0.80 to 1.21, and 0.95, 0.82 to 1.11, respectively).Conclusion The increase in lung cancer risk is similar in people who smoke medium tar cigarettes (15-21 mg), low tar cigarettes (8-14 mg), or very low tar cigarettes (≤ 7 mg). Men and women who smoke non-filtered cigarettes with tar ratings ≥ 22 mg have an even higher risk of lung cancer.     

Incidence, risk factors and prevention of cisplatin-induced nephrotoxicity in patients with lung cancer

High-dose (75 mg/m2) cisplatin is baseline chemotherapy in lung cancer. To prevent nephrotoxicity, patients generally receive saline infusion on the day of chemotherapy prior to and following cisplatin (total of 3.5-4.0 liters during 3-4 hours). Despite these measures nephrotoxicity has remained frequent, especially among patients also suffering from cardiovascular disease or diabetes mellitus. Since 2005 several international recommendations have been formed about prevention of cisplatin nephrotoxicity. According to these recommendations: 1) renal function should not be evaluated by serum creatinine concentration; 2) evaluation of renal function should be based on calculated creatinine clearance (e.g. by the Cockcroft-Gault equation); 3) patients to be treated by high-dose cisplatin should be euvolemic and should have saline diuresis (urine NaCl concentration ~1%) of at least 100 ml/hour prior to, during and several days following the administration of cisplatin. Keeping these recommendations ensures prolonged cisplatin treatability of lung cancer patients. Moreover, decreased renal function will not limit the full dose administration of several other cytotoxic agents. Losonczy G, Máthé C, Müller V, Szondy K, Moldvay J. Incidence, risk factors and prevention of cisplatin-induced nephrotoxicity in patients with lung cancer.