Lung Cancer in Younger Patients

Carcinoma of the lung is rare in younger patients, but occasional reports of this condition have appeared in the literature. This article reviews the clinical and pathological patterns of bronchogenic carcinoma in 96 patients, 40 years old or younger seen at UCLA (University of California, Los Angeles) Hospital between 1956 and 1976. This review confirms the finding in other reports of a higher proportion of women among younger patients with lung cancer as well as a relatively low incidence of squamous cell carcinoma. Using comparative data from the UCLA and California tumor registries, we could find no significant difference in survival of the younger patients when compared with the general population of patients with lung cancer.     

黄石市30年3819例肺癌患者心理特点变化趋势分析

目的:探讨黄石市30年3819例肺癌患者心理变化特点,为相关决策提供理论依据。方法:收集1985-2014年30年间我院收治的新发肺癌患者3819例,以2000年为界,分为前15年(1985年-1999年)组828例和后15年(2000-2014年)组2991例,观察患者心理特点,比较对肿瘤放化疗的接受度及完成率。结果:后15年病例数是前15年的3.61倍,前15年很多癌症病人拒绝治疗以及许多病人家属选择隐瞒患者病情不送医院治疗,而后15年大多数癌症患者知晓病情并愿意积极住院接受治疗;患者对自己病情的知晓度明显提高,最近的一次病情问卷调查显示约91.96%患者知道自己罹患癌症;后15年患者接受化疗的意愿明显高于前15年,差异有统计学意义(P0.05),并且能顺利完成全程治疗的病人也明显多于后者,差异有统计学意义(P0.05);后15年患者接受放疗的意愿略高于前15年,但完成率明显高于于后者,差异有统计学意义(P0.05)。结论:随着肿瘤治疗水平的提高和时代的进步,患者对病情的知晓度和对放化疗的依从性普遍提高,这有利于肺癌患者的综合治疗的开展从而改善肺癌患者的疗效。     

EML-ALK突变阳性的肺癌患者EGFR突变检测及其临床特征

目的：检测表皮生长因子受体（epidermal growth factor receptor, EGFR）在间变性淋巴瘤激酶（anaplastic lymphoma kinase, ALK）融合基因突变的原发性肺癌（primary lung cancer）人群中的突变率,并分析其与病人临床病理特征间的关系。方法：入选的 106例病例均为中国西北五省人群,且经ALK 融合基因检测为阳性。将106 例患者的组织标本采用ARMS 方法检测EGFR基因 18-21 外显子的突变情况,统计分析双突变患者的临床病理特征。结果：106 例ALK 融合基因突变阳性的原发性肺癌患者的组织 标本,有7 例（6.6 %）同时存在EGFR突变,其中19 外显子缺失突变（19-del）的3 例（42.9 %）,L858R突变的2 例（28.5 %）,L861Q 和G719X 突变的各1 例（14.3 %）;7 例ALK 和双突变的患者中ALK 融合基因的突变均为EML4-ALK突变亚型1 （variant 1, V1）。7 例双阳性的患者中,6 例患者的年龄小于总体患者的中位年龄（53 岁),占85.7 %;男性患者4 例,占57.1 %;不吸 烟患者7 例,占100 %;腺癌患者4 例,占57.1 %,其中女性3例;肉瘤样癌2例,占28.6 %;粘液表皮样癌1例,占14.3 %。结论： EML4-ALK融合基因和EGFR突变能够共存,在EML4-ALK阳性的肺癌患者中,EGFR的突变率为6.6 %,双突变的患者大多年 轻且均无吸烟史,且双突变的女性患者均为腺癌。     

70 岁以上老年原发性肝癌患者临床特点

目的:探讨70岁以上高龄原发性肝癌患者临床表现、诊治方法和预后特点。方法:回顾性研究我院2000～2010年间70例原发性肝癌患者(PLC)临床资料,比较两组患者(≥70岁,高龄组;和<70岁,低龄组)的临床特点和预后。结果:≥70岁患者36例(51.4%),<70岁34例(48.6%)。与低龄组相比,高龄组心脏病(50.0%vs 17.6%)和糖尿病(41.7%vs 14.7%)显著增高(P=0.004-0.012);而乙型病毒性肝炎感染率低(50.0%vs 88.2%,P=0.016),发病时平均肿瘤直径小(3.4±2.3cm vs 5.8±4.4cm,P=0.02)。两组男性发病率、饮酒、脑血管病、首发症状和体征、肝硬化、肿瘤位置、肿瘤形态、AFP、发病时Child分级、组织学类型两组无显著差异(P>0.05)。总体(59,84.3%)以肝动脉化疗栓塞(TACE)治疗为主,平均治疗3.2±3.1次,两组接受TACE治疗患者和次数无差异。平均随访28.9月,生存分析显示两组死亡率(63.9%vs 58.8%,p=0.66)和中位生存时间(25.5月vs 20.5月,P=0.88)无显著差异。结论:≥70岁高龄PLC患者有较高的心脏病和糖尿病合并率,但多数可耐受系统性TACE治疗,从而有效延长老年患者的平均生存时间。     

Profiling Critical Cancer Gene Mutations in Clinical Tumor Samples

Background

Detection of critical cancer gene mutations in clinical tumor specimens may predict patient outcomes and inform treatment options; however, high-throughput mutation profiling remains underdeveloped as a diagnostic approach. We report the implementation of a genotyping and validation algorithm that enables robust tumor mutation profiling in the clinical setting.

Methodology

We developed and implemented an optimized mutation profiling platform (“OncoMap”) to interrogate ∼400 mutations in 33 known oncogenes and tumor suppressors, many of which are known to predict response or resistance to targeted therapies. The performance of OncoMap was analyzed using DNA derived from both frozen and FFPE clinical material in a diverse set of cancer types. A subsequent in-depth analysis was conducted on histologically and clinically annotated pediatric gliomas. The sensitivity and specificity of OncoMap were 93.8% and 100% in fresh frozen tissue; and 89.3% and 99.4% in FFPE-derived DNA. We detected known mutations at the expected frequencies in common cancers, as well as novel mutations in adult and pediatric cancers that are likely to predict heightened response or resistance to existing or developmental cancer therapies. OncoMap profiles also support a new molecular stratification of pediatric low-grade gliomas based on BRAF mutations that may have immediate clinical impact.

Conclusions

Our results demonstrate the clinical feasibility of high-throughput mutation profiling to query a large panel of “actionable” cancer gene mutations. In the future, this type of approach may be incorporated into both cancer epidemiologic studies and clinical decision making to specify the use of many targeted anticancer agents.     

Clock Gene Expression Levels and Relationship With Clinical and Pathological Features in Colorectal Cancer Patients

The clock gene machinery controls cellular metabolism, proliferation, and key functions, such as DNA damage recognition and repair. Dysfunction of the circadian clock is involved in tumorigenesis, and altered expression of some clock genes has been found in cancer patients. The aim of this study was to evaluate the expression levels of core clock genes in colorectal cancer (CRC). Quantitative real-time polymerase chain reaction (qPCR) was used to examine ARNTL1, CLOCK, PER1, PER2, PER3, CRY1, CRY2, Timeless (TIM), TIPIN, and CSNK1Ε expression levels in the tumor tissue and matched apparently healthy mucosa of CRC patients. In the tumor tissue of CRC patients, compared to their matched healthy mucosa, expression levels of ARNTL1 (p?=?.002), PER1 (p?=?.002), PER2 (p?=?.011), PER3 (p?=?.003), and CRY2 (p?=?.012) were lower, whereas the expression level of TIM (p?=?.044) was higher. No significant difference was observed in the expression levels of CLOCK (p?=?.778), CRY1 (p?=?.600), CSNK1Ε (p?=?.903), and TIPIN (p?=?.136). As to the clinical and pathological features, a significant association was found between low CRY1 expression levels in tumor mucosa and age (p?=?.026), and female sex (p?=?.005), whereas high CRY1 expression levels in tumor mucosa were associated with cancer location in the distal colon (p?=?.015). Moreover, high TIM mRNA levels in the tumor mucosa were prevalent whenever proximal lymph nodes were involved (p?= .013) and associated with TNM stages III–IV (p?=?.005) and microsatellite instability (p?=?.015). Significantly poorer survival rates were evidenced for CRC patients with lower expression in the tumor tissue of PER1 (p?=?.010), PER3 (p?= .010), and CSNKIE (p?=?.024). In conclusion, abnormal expression levels of core clock genes in CRC tissue may be related to the process of tumorigenesis and exert an influence on host/tumor interactions. (Author correspondence: g.mazzoccoli@tin.it)     

应用寡核苷酸微阵列检测肺癌样品中的P53和K-ras基因点突变

对影响寡核苷酸微阵列检测点突变的敏感性和特异性的各种因素,如杂交液,杂交温度,标记引物浓度及其比例等,进行了研究,采用不对称PCR扩增有利于敏感性提高,多重不对称PCR不影响杂交的特异性,且敏感性有所增加,对30例肺癌标本进行寡核苷酸微阵列检测,发现12例标本发生了P53基因来点突变,K-ras突变有5例,与测序结果相比,P53基因突变符合率达到80％,由于检测样本较少且检测位点不完全,因而未得到K－ras和P53基因突变与肿瘤的种类,病期及吸烟之间的明显相关性。     

应用寡核苷酸微阵列检测肺癌样品中的P53和K-ras基因点突变

对影响寡核苷酸微阵列检测点突变的敏感性和特异性的各种因素,如杂交液、杂交温度、标记引物浓度及其比例等,进行了研究。采用不对称PCR扩增有利于敏感性提高;多重不对称PCR不影响杂交的特异性,且敏感性有所增加。对30例肺癌标本进行寡核苷酸微阵列检测,发现12例标本发生了P53基因点突变,K-ras突变有5例。与测序结果相比,P53基因突变符合率达到80%。由于检测样本较少且检测位点不完全,因而未得到K-ras和P53基因突变与肿瘤的种类、病期及吸烟之间的明显相关性。     

一组有或无基因突变的特发性扩张型心肌病患者临床发病及预后的分析

目的:分析携带基因突变和未携带基因突变的特发性扩张型心肌病(IDCM)患者的临床发病及预后的差异性。方法:收集2011年01月-2014年09月于南京鼓楼医院就诊的IDCM患者115例,经靶向二代测序鉴定后分为基因突变组和未突变组,出院后对两组患者进行定期随访,将两组患者的临床资料及随访结果进行统计学分析。结果:两组患者的一般临床特征(如性别比例、首发症状年龄、血压、糖尿病比例等)无显著差异(P0.05);辅助检查特征(如左室射血分数、左室舒张末内径、室壁厚度、QRS-T夹角和血肌酐水平等)无显著差异(P0.05);治疗情况(如药物和器械治疗)无差异(P0.05);随访资料(如再入院和生存分析)亦无统计学差异(P0.05,Log rank P=0.12);将性别比例、是否吸烟、是否合并糖尿病、是否植入器械、是否发生突变等临床参数进行Cox回归分析,发现上述参数未影响患者的临床预后(P0.05)。结论:本组资料显示携带基因突变的IDCM患者临床发病及预后较未携带突变者无显著差异。     

35 岁以下年轻乳腺癌患者的临床特征及预后因素分析

目的:探讨年轻乳腺癌患者的临床病理特点及影响其预后的相关因素。方法:选取潍坊市人民医院2005年11月至2011年11月收治的年龄不高于35岁的137例年轻乳腺癌患者的临床资料,其中共有116例入组,初步分析年轻乳腺癌患者的临床病理特征及对预后产生的影响。结果:116例患者中位随访时间为46.0个月。3年OS和PFS为94.6%和79.1%。单因素、多因素分析结果显示淋巴结转移情况和Ki67水平与预后的显著相关(P0.05),淋巴结转数目、Ki67水平与预后呈负相关。结论:年轻乳腺癌患者的生物学行为、病理及预后较为特殊。淋巴结转移情况、Ki67水平是影响预后的关键因素。     

EGFR Mutations in Indian Lung Cancer Patients: Clinical Correlation and Outcome to EGFR Targeted Therapy

Screening for EGFR mutation is a key molecular test for management of lung cancer patients. Outcome of patients with mutation receiving EGFR tyrosine kinase inhibitor is known to be better across different ethnic populations. However, frequency of EGFR mutations and the clinical response in most other ethnic populations, including India, remains to be explored. We conducted a retrospective analysis of Indian lung cancer patients who were managed with oral tyrosine kinase inhibitors. Majority of the patients in the study had adenocarcinoma and were non-smokers. 39/111 patients tested positive for EGFR kinase domain mutations determined by Taqman based real time PCR. The overall response to oral TKI therapy was 30%. Patients with an activating mutation of EGFR had a response rate of 74%, while the response rate in patients with wild type EGFR was 5%, which was a statistically significant difference. Progression free survival of patients with EGFR mutations was 10 months compared to 2 months for EGFR mutation negative patients. Overall survival was 19 months for EGFR mutation patients and 13 months for mutation negative patients. This study emphasizes EGFR mutation as an important predictive marker for response to oral tyrosine kinase inhibitors in the Indian population.     

Clinicopathologic Features of Patients with Non-Small Cell Lung Cancer Harboring the EML4-ALK Fusion Gene: A Meta-Analysis

Background

The frequencies of EML4-ALK fusion gene in non-small cell lung cancer (NSCLC) with different clinicopathologic features described by previous studies are inconsistent. The key demographic and pathologic features associated with EML4-ALK fusion gene have not been definitively established. This meta-analysis was conducted to compare the frequency of the EML4-ALK fusion gene in patients with different clinicopathologic features and to identify an enriched population of patients with NSCLC harboring EML4-ALK fusion gene.

Methods

The Pubmed and Embase databases for all studies on EML4-ALK fusion gene in NSCLC patients were searched up to July 2014. A criteria list and exclusion criteria were established to screen the studies. The frequency of the EML4-ALK fusion gene and the clinicopathologic features, including smoking status, pathologic type, gender, and EGFR status were abstracted.

Results

Seventeen articles consisting of 4511 NSCLC cases were included in this meta-analysis. A significant lower EML4-ALK fusion gene positive rate was associated with smokers (pooled OR = 0.40, 95% CI = 0.30–0.54, P<0.00001). A significantly higher EML4-ALK fusion gene positivity rate was associated with adenocarcinomas (pooled OR = 2.53, 95% CI = 1.66–3.86, P<0.0001) and female (pooled OR = 0.61, 95% CI = 0.41–0.90, P = 0.01). We found that a significantly lower EML4-ALK fusion gene positivity rate was associated with EGFR mutation (pooled OR = 0.07, 95% CI = 0.03–0.19, P<0.00001). No publication bias was observed in any meta-analysis (all P value of Egger''s test >0.05); however, because of the small sample size, no results were in the meta-analysis regarding EGFR gene status.

Conclusion

This meta-analysis revealed that the EML4-ALK fusion gene is highly correlated with a never/light smoking history, female and the pathologic type of adenocarcinoma, and is largely mutually exclusive of EGFR.     

Distinct Clinical and Experimental Characteristics in the Patients Younger than 60 Years Old with Myelodysplastic Syndromes

Myelodysplastic syndromes (MDS) mainly occur in elderly individuals in Western countries. However, MDS is commonly found in young individuals (<60 years) in Asia. The reason for the high incidence in younger individuals is still unclear, and the differences in disease features between young and elderly patients with MDS have been not well recognized. To explore these issues, in this study, we analyzed the clinical and experimental characteristics of MDS in the patients younger and older than 60 years old and characterized the potential age-associated differences. The results showed that over half of the patients with MDS (61.9%) were younger than 60 years old upon the first diagnosis. The younger patients were more likely to be female, who have lower risk and less advanced MDS. The occurrence of trisomy 8 and bone marrow failure were more frequent in the younger patients than the older ones. The marrow CD34+ cells in the younger patients showed lower proliferation and higher apoptosis in comparison with that in the older ones. Obvious amplification of T cells and low CFU formation could be found in the younger patients. CFU formation was significantly increased in the younger patients after the removal of activated T cells. In addition, the younger patients had a lower frequency of p15^INK4B methylation, longer survival expectancy and less AML transformation. In summary, the younger patients with MDS in China may show more benign disease features than the older ones. Enhanced immunological response may be involved in the pathogenesis of MDS in the patients younger than 60 years.     

Validation of an Ion Torrent Sequencing Platform for the Detection of Gene Mutations in Biopsy Specimens from Patients with Non-Small-Cell Lung Cancer

Background

Treatment for patients with advanced non-small cell lung cancer (NSCLC) is often determined by the presence of biomarkers that predict the response to agents targeting specific molecular pathways. Demands for multiplex analysis of the genes involved in the pathogenesis of NSCLC are increasing.

Methods

We validated the Ion Torrent Personal Genome Machine (PGM) system using the Ion AmpliSeq Cancer Hotspot Panel and compared the results with those obtained using the gold standard methods, conventional PCR and Sanger sequencing. The cycleave PCR method was used to verify the results.

Results and Conclusion

The Ion Torrent PGM resulted in a similar level of accuracy in identifying multiple genetic mutations in parallel, compared with conventional PCR and Sanger sequencing; however, the Ion Torrent PGM was superior to the other sequencing methods in terms of increased ease of use, even when taking into account the small amount of DNA that was obtained from formalin-fixed paraffin embedded (FFPE) biopsy specimens.     

肺炎型肺癌的影像学特点及误诊分析

目的:探讨肺炎型肺癌影像学特点,深入肺炎型肺癌认识,提高诊断水平,降低临床误诊率。方法:随机选取2013年1月份至2014年2月份我院胸外科住院治疗的36例肺炎型肺癌患者作为研究对象,回顾性分析全部患者的影像学资料及病理检查结果。结果:患者病变部位在各肺段均有分布,局限性及弥漫性分布均可见,其中局灶性分布较大,未出现跨越肺段侵袭肺叶的病例。影像表现主要为边缘不清云絮状肿块影、云絮状影伴结节、肺段实变影、肺实变伴空泡及蜂窝状影、肺炎纤维样化及混合阴影。其中,单纯性磨玻璃影10例;磨玻璃结节肿块10例;肺段分布实变影7例;肺叶及肺段实变伴空泡或蜂窝状影6例;肺炎样纤维化及肿块10例;混合阴影(4种或4种以上阴影并存)3例。结论:肺炎型肺癌患者影像学检查结果多具有肺炎样改变,极易误诊肺炎性疾病,临床诊断中结合活检检查技术,有利于改善临床诊断正确率。     

Diagnosis of Distant Metastasis of Lung Cancer: Based on Clinical and Radiomic Features

OBJECTIVES: To analyze the distant metastasis possibility based on computed tomography (CT) radiomic features in patients with lung cancer. METHODS: This was a retrospective analysis of 348 patients with lung cancer enrolled between 2014 and February 2015. A feature set containing clinical features and 485 radiomic features was extracted from the pretherapy CT images. Feature selection via concave minimization (FSV) was used to select effective features. A support vector machine (SVM) was used to evaluate the predictive ability of each feature. RESULTS: Four radiomic features and three clinical features were obtained by FSV feature selection. Classification accuracy by the proposed SVM with SGD method was 71.02%, and the area under the curve was 72.84% with only the radiomic features extracted from CT. After the addition of clinical features, 89.09% can be achieved. CONCLUSION: The radiomic features of the pretherapy CT images may be used as predictors of distant metastasis. And it also can be used in combination with the patient's gender and tumor T and N phase information to diagnose the possibility of distant metastasis in lung cancer.     

Gene Polymorphism of Toll-Like Receptors and Lung Function at Five to Seven Years of Age after Infant Bronchiolitis

Aim

Toll-like receptors (TLR) play a crucial role in innate immunity, protecting the host from pathogens such as viruses. Genetic variations in TLRs have been associated with the severity of viral bronchiolitis in infancy and with the later occurrence of post-bronchiolitis asthma. The aim of the present study was to evaluate if there are any exploratory associations between TLR gene polymorphisms and lung function at 5 to 7 years of age in former bronchiolitis patients.

Methods

We performed impulse oscillometry (IOS) at the median age of 6.3 years for 103 children who had been hospitalized for bronchiolitis at less than six months of age. The main parameters evaluated were airway resistance and reactance at 5Hz in baseline and post-exercise measurements. Data on single nucleotide polymorphisms (SNP) of TLR1 rs5743618, TLR2 rs5743708, TLR6 rs5743810 and TLR10 rs4129009 (TLR2 subfamily) and TLR3 rs3775291, TLR4 rs4986790, TLR7 rs179008, TLR8 rs2407992 and TLR 9 rs187084 were available for analyses.

Results

The TLR4 rs4986790 wild genotype A/A was associated with a greater Rrs5 response (0.72 vs. -0.42, p = 0.03) to exercise. In TLR6 rs5743810, the minor allele T was associated with greater Rrs5 response (0.80 vs. -0.03, p = 0.04) to exercise. In TLR7 rs179008, the major allele A was associated with baseline decline in dRrs/df (-1.03 vs 0.61, p = 0.01) and increased Fres (2.28 vs. 0.89, p = 0.01) in girls.

Conclusion

Among the nine studied TLRs, only TLR7 rs179008 showed some exploratory associations with post-bronchiolitis lung function deficiency, and polymorphisms of TLR4 rs4986790, and TLR6 rs5743810 in particular, with airway reactivity. These findings call for further confirmatory studies.     

Clinicopathologic Features and Prognosis of Type 2 Diabetes Mellitus and Diabetic Nephropathy in Different Age Groups: More Attention to Younger Patients

Objective: Our study sought to investigate the clinicopathologic features and renal prognosis of patients with type 2 diabetes mellitus (T2DM) and diabetic nephropathy (DN) in different age groups.Methods: A total of 315 patients with T2DM and biopsy-proven DN were enrolled and divided into three groups by age: the Youth group (≤44 years old), the Middle-aged group (45 to 59 years old), and the Elderly group (≥60 years old).Results: The Youth group, Middle-aged group, and Elderly group accounted for 19.05% (60/315), 59.37% (187/315), and 21.59% (68/315) of the patients in our study, respectively. The patients in the Youth group had a higher estimated glomerular filtration rate (calculated using the Chronic Kidney Disease–Epidemiology collaboration formula) (P<.001), a higher incidence of diabetic retinopathy (P = .044), and a higher incidence of being in the lower-risk chronic kidney disease heat map category (P = .046) but lower duration of diabetes (P = .016). Histologically, patients in the Youth group had the highest incidence of glomerular classification in class I (P = .006) and arteriolar hyalinosis score of 0 (P = .005). The renal survival among the three groups was comparable (P>.05).Conclusion: This study indicated that there were different clinicopathologic features among Chinese DN patients in different age groups. Although the Youth group had a relatively lower rapid kidney disease progression rate, there were no significant differences in renal survival rate among the three groups, which calls more attention to early supervision and prevention for younger DN patients.Abbreviations: CKD = chronic kidney disease; DN = diabetic nephropathy; DR = diabetic retinopathy; eGFR = estimated glomerular filtration rate; ESRD = end-stage renal disease; G&Y&O = green and yellow and orange; IFTA = interstitial fibrosis and tubular atrophy; T2DM = type 2 diabetes mellitus     

微流控芯片检测肺癌患者血浆中p16基因异常甲基化在临床应用的评价

肺癌是常见的恶性肿瘤之一,其死亡率和发病率在世界范围的肿瘤性疾病中均居高不下.p16基因启动子区异常甲基化被认为是肺癌发生中的一起早期事件.为了提高检测异常甲基化方法的灵敏度及特异性,利用微流控芯片检测p16基因的异常甲基化,通过对肺癌患者血浆标本的检测,使病人血浆中的p16基因甲基化的异常改变可能成为辅助肺癌早期诊断和高危人群筛选的分子标记物,以期建立一种崭新而可靠的早期肺癌临床诊断方法.