miRNA在宫颈癌早期诊断及预后中的研究进展

微小RNA(miRNA)在宫颈癌的发生、侵袭、转移和复发等过程中扮演重要角色,与其预后密切相关.宫颈癌患者血清中异常表达的miRNA可作为其无创诊断和预后判断的生物标志物,通过研究血清miRNA可以早期诊断宫颈癌,减少肿瘤的转移和复发,寻找治疗靶点,为宫颈癌的诊疗提供突破点.     

Understanding diagnosis of lung cancer in primary care: qualitative synthesis of significant event audit reports

Background

Most lung cancers present symptomatically, but the pathway to diagnosis in primary care can be complex and is poorly understood. Significant event audit (SEA) is a quality improvement technique widely used in UK general practice.

Aim

To gain insights into the diagnostic process for lung cancer, drawn from analysis of SEA documents.

Design and setting

Qualitative analysis of SEAs from 92 general practices in the North of England Cancer Network.

Method

Participating practices were provided with a standardised electronic template and asked to undertake a significant event audit related to the most recent diagnosis of lung cancer in the practice, even if that patient had since died. Reported accounts for 132 diagnoses were analysed using a modified framework approach.

Results

Most SEAs demonstrated timely recognition and referral. Where this had taken longer, there were often reasonable explanations, including: chest X-rays reported as normal or with benign findings; patient-mediated factors, such as delay in re-presenting or declining earlier referral; and presentation complicated by comorbidity. Some opportunities for earlier referral were also found. Lessons drawn from these events included limitations of chest X-ray as a diagnostic tool, the need for vigilance in patients with existing morbidity, and the importance of ‘safety-netting’.

Conclusion

Qualitative synthesis of SEAs offered considerable value in understanding circumstances surrounding the diagnostic process for lung cancer in primary care. The most common presentation was with cough or other symptoms indicative of infection, and it is by understanding more about these patients in particular that most can be gained.     

Metastatic lung cancer with occult primary site: a difficult diagnosis

Occult primary non-small cell lung cancer (OP-NSCLC) is a relatively rare entity that brings difficulties in diagnosis and treatment. Accurate diagnosis depends on biopsy specimens. Often, repeated biopsies are required. Here we report a patient who underwent 3 rounds of biopsy of her cervical superficial enlarged lymph nodes to get a final diagnosis of occult metastatic lung cancer. There was no evidence of primary lesions in the lung. The patient was treated with targeted chemotherapy and survived 4 years. We emphasize the importance of repeated biopsies or resection biopsy for a definitive diagnosis. Though molecular technologies and imaging may identify a primary site, some cases have occult primaries. Adjunct examination methods such as immunohistochemistry and/or molecular methods are valuable for definite diagnosis and guiding treatment.     

Cytodiagnostic aspects of lung adenocarcinoma manifesting with micropapillary pattern in sputum

The micropapillary pattern of lung adenocarcinoma was discussed in the 2004 World Health Organization classification and is now proposed as a distinct pattern in the new International Multidisciplinary Classification of Lung Adenocarcinoma Guidelines. The micropapillary pattern is histologically characterized by papillary tufts lacking a central fibrovascular core and is associated with an unfavorable prognosis. Herein, we report the cytological features of lung adenocarcinoma with the micropapillary pattern in a sputum specimen. A 75‐year‐old woman presented with a productive cough, blood‐tinged sputum, and some symptoms of upper respiratory tract infection. The initial impressions from her chest radiograph and computed tomography scan indicated pneumonia. However, the initial sputum cytology sample showed a few clusters of cells with abnormal three‐dimensional structure, interpreted as adenocarcinoma. These cells were small and had minimal cytologic atypia, demonstrating a potential diagnostic pitfall. The following biopsy confirmed lung adenocarcinoma with the micropapillary pattern. Here, we describe this case and discuss the differential diagnosis of pulmonary entities exhibiting similar morphologies. Diagn. Cytopathol. 2014;42:902–905. © 2014 Wiley Periodicals, Inc.     

Rapid diagnosis of coccidioidomycosis by nested PCR assay of sputum

Coccidioidomycosis is a deep infection caused by two dimorphic fungi, Coccidioides immitis and Coccidioides posadasii. Diagnosis of the disease requires culture of suspicious clinical samples on mycological media. However, as these species are virulent pathogens, handling of their cultures is a high-risk activity, and is limited to Biosafety Level 3 laboratories. This study describes the direct detection of C. posadasii DNA in an inappropriate sputum sample by PCR amplification of the highly specific Ag2/PRA antigen gene. The results obtained suggest that direct detection of the Ag2/PRA sequence in sputum is an excellent method for rapid and specific diagnosis of coccidioidomycosis.     

Effective use of bronchoscopy and sputa in the diagnosis of lung cancer

The records of 134 patients who underwent bronchoscopy at the Forbes Health System hospitals between January 1, 1982 and December 31, 1983 were reviewed. The number of pre- and postbronchoscopy sputa obtained on each patient, final diagnosis, and follow-up for 6 to 30 months were obtained. Tissue obtained at bronchoscopy yielded a diagnosis of malignancy in 71 of 84 (84.5%) patients who received that final diagnosis. Addition of postbronchoscopy sputa examination increased the yield to 73 of 84 (86.9%). Prebronchoscopy sputa contributed no diagnoses beyond those made by bronchoscopically obtained material. The cost to the patient of examining pre- and postbronchoscopy sputa in addition to bronchoscopically obtained cytologic and biopsy material is 70% higher than that of examining bronchoscopically obtained material alone. Indirect costs of increased hospital stay may also be significant. We propose early bronchoscopy without prebronchoscopy sputa in cases where there is clinical suspicion of lung cancer. Postbronchoscopy sputa should be obtained, but only processed for microscopic examination if the bronchoscopically obtained material does not yield a diagnosis.     

肺癌合并肺部真菌感染的诊疗进展

随着肺癌发病率的增加,肺癌合并肺部真菌感染的病人在临床上已经越来越常见,因其临床表现缺乏特异性又合并原发疾病,针对这部分的病人在早期诊断、治疗上仍然存在一定的困难.本文将从常见致病真菌、影像学表现和常用抗真菌药物、抗真菌治疗的研究进展等方面讨论肺癌病人合并肺部真菌感染的诊断和治疗.     

与肺癌相关的靶基因研究简介

肺癌是目前全世界发病率最高的恶性肿瘤,其病死率也居于前列。因此,肺癌的早期诊断及早期治疗对于降低肺癌患者的病死率以及改善患者生存质量至关重要。近年来有关肺癌早期诊断、治疗及预后的分子标志物的研究愈来愈受到关注。在肺癌中,非小细胞肺癌(non-small cell lung cancer,NSCLC)占绝大多数。针对晚期NSCLC,肿瘤分子靶向治疗日趋重要。因此,从分子水平研究肺癌的发病机制和诊断,对肺癌的防治有重大意义。近些年,对基因水平方面的研究也取得了很大进展。现对与肺癌相关的靶基因最新研究进行展综述如下。     

Effectiveness of sputum cytology using ThinPrep method for evaluation of lung cancer

Sputum cytology is a non-invasive test for evaluating lung cancer. But, its sensitivity is yet lower than other tests. ThinPrep (TP) is an automated cytopreparatory method that has mucolytic and hemolysing effects. We compared 955 sputum specimens that were prepared by both TP and conventional preparation (CP). The nuclear details were more preserved on the TP slides, while the obscuring materials were more eliminated on the TP slides as compared with the CP. The cytologic rates of TP were 2.7% unsatisfactory, 4.7% normal, 81.0% benign, 2.4% suspicious, and 9.1% malignancy. The rates of CP were 7.9% unsatisfactory, 1.6% normal, 84.8% benign, 1.8% suspicious, and 4.0% malignancy. The false negative rates, relative to the histologic data for 352 cases which the tissue diagnosis was available, were 49.6% (TP) and 69.4% (CP). Sputum cytology using the TP method improves the diagnostic accuracy for evaluating lung cancer by reducing the unsatisfactory and false-negative rates.     

Developing a complex intervention to reduce time to presentation with symptoms of lung cancer

Background

Lung cancer is the commonest cause of cancer in Scotland and is usually advanced at diagnosis. Median time between symptom onset and consultation is 14 weeks, so an intervention to prompt earlier presentation could support earlier diagnosis and enable curative treatment in more cases.

Aim

To develop and optimise an intervention to reduce the time between onset and first consultation with symptoms that might indicate lung cancer.

Design and setting

Iterative development of complex healthcare intervention according to the MRC Framework conducted in Northeast Scotland.

Method

The study produced a complex intervention to promote early presentation of lung cancer symptoms. An expert multidisciplinary group developed the first draft of the intervention based on theory and existing evidence. This was refined following focus groups with health professionals and high-risk patients.

Results

First draft intervention components included: information communicated persuasively, demonstrations of early consultation and its benefits, behaviour change techniques, and involvement of spouses/partners. Focus groups identified patient engagement, achieving behavioural change, and conflict at the patient–general practice interface as challenges and measures were incorporated to tackle these. Final intervention delivery included a detailed self-help manual and extended consultation with a trained research nurse at which specific action plans were devised.

Conclusion

The study has developed an intervention that appeals to patients and health professionals and has theoretical potential for benefit. Now it requires evaluation.     

Plasma microRNAs as novel biomarkers for early detection of lung cancer

A diagnosis of lung cancer at its early stages is vital for improving the survival rate of patients. MicroRNAs (miRNAs), a family of 19- to 25-nucleotide non-coding small RNAs, are frequently dysregulated in lung cancer. The objective of this study was to investigate the potential of circulating miRNAs for early detection of lung cancer. We searched the published literature for the miRNA microarray data of primary lung cancer and selected 15 miRNAs that were most frequently up-regulated in lung cancer tissues. Total plasma RNA including miRNAs was isolated, polyadenylated and reverse-transcribed into cDNAs. The levels of miRNAs were determined by real-time RT-PCR in 74 lung cancer patients and 68 age-matched cancer-free controls. We found that the levels of miR-155, miR-197, and miR-182 in the plasma of lung cancer including stage I patients were significantly elevated compared with controls (P<0.001). The combination of these 3 miRNAs yielded 81.33% sensitivity and 86.76% specificity in discriminating lung cancer patients from controls. The levels of miR-155 and miR-197 were higher in the plasma from lung cancer patients with metastasis than in those without metastasis (P<0.05) and were significantly decreased in responsive patients during chemotherapy (P<0.001). These results indicate that miR-155, miR-197, and miR-182 can be potential non-invasive biomarkers for early detection of lung cancer.     

Lung cancer samples preserved in liquid medium: One step beyond cytology

Lung cancer is one of the most common cancer types in men and women worldwide with a high mortality rate. World Health Organization (WHO) classification has accepted biopsy as the primary sample for lung cancer diagnosis, pathological classification and molecular testing for management of patients, yet, the use of alternative sampling procedures is highly encouraged. Bronchial cytological samples require a less invasive collection technique and may be suitable for pathological and molecular analysis and storage in liquid medium. Furthermore, the molecular analysis of bronchial cytological samples allows the detection of molecular biomarkers, which may be useful for the selection of molecular targeted therapies. Thus, the purpose of this review is to describe the usefulness of bronchial cytological samples preserved in liquid medium from lung cancer patients for pathological diagnosis and molecular investigation.     

低剂量螺旋CT扫描联合血清p16基因甲基化检测在肺癌早期诊断中的应用

目的研究在无症状的肺癌高危人群中利用低剂量CT（LDCT）联合血清p16基因甲基化检测进行肺癌早期诊断的可行性。方法肺癌高危人群入组标准：男性，年龄55～75岁；吸烟指数≥400支／年，目前仍在吸烟或戒烟不超过10年。共893例受检者被随机分为两组。一组为447例（LDCT—p16组），平均年龄66岁，进行LDCT联合血清p16基因甲基化检测；另一组为446例（CXR组），平均年龄67岁，接受后前位胸片检查。两组检查阳性病例将接受进一步组织病理学检查。并分别统计两组阳性结节检出率及肺癌检出率，并行X2检验。结果LDCT—p16组与CXR组分别有96．8％和92．8％的受检者完成了检查。LDCT—p16组中1113％病人可疑肺癌，明显高于CXR组的6．5％（P〈0．05）。其中LDCT—p16组中有7例，CXR组中有2例确诊为肺癌。LDCT—p16组肺癌检出率高于CXR组，但无统计学意义（P〉0．05）。结论低剂量CT联合血清p16基因甲基化检测是一种敏感、安全、可行的筛查早期肺癌的方法，能够取代胸片筛查早期肺癌。     

肺癌生物标志物研究现状与资助趋势

肺癌是全球发病率和病死率最高的恶性肿瘤之一,早期诊断、治疗、转移与预后相关的生物标志物研究是目前最活跃的研究领域。本文就肺癌相关生物标志物的研究现状进行综述,并分析了近10年国内外肺癌标志物领域的基金资助情况,为肺癌生物标志物的基础研究和临床转化医学研究提供方向。     

Consistent mutation status within histologically heterogeneous lung cancer lesions

Mattsson J S M, Imgenberg‐Kreuz J, Edlund K, Botling J & Micke P
(2012) Histopathology  61, 744–748 Consistent mutation status within histologically heterogeneous lung cancer lesions Aims: Activating epidermal growth factor receptor (EGFR) and KRAS mutations characterize molecular subgroups of non‐small‐cell lung cancer (NSCLC) with a strong predictive value for response to EGFR inhibitor therapy. However, the temporal occurrence and clonal stability of these mutations during the course of cancer progression are debated. The aim of this study was to characterize the presence of EGFR and KRAS mutations in histologically different areas of primary NSCLC lesions. Methods and results: Formalin‐fixed paraffin‐embedded cancer specimens from six cases with EGFR mutations and five cases with KRAS mutations were selected from a pool of primary resected NSCLC patients. From each tumour, three morphologically distinct areas were manually microdissected and analysed for the presence of mutations. The results demonstrated consistent EGFR and KRAS mutation status in the different histological areas of all primary tumours. Conclusions: The results support the concept that activating EGFR and KRAS mutations are oncogenic events that are consistently present throughout the primary tumour independently of histological heterogeneity. Thus, for molecular diagnostics, any part of the tumour is likely to be representative for EGFR and KRAS mutation testing.     

Metastatic pulmonary leiomyosarcoma: Cytopathologic diagnosis on sputum examination

Pulmonary metastasis of sarcomas is not uncommon. Rarely, endobronchial involvement may result in exfoliation of diagnostic cells in sputum. This case report is of a 71-yr-old man with a history of lower leg leiomyosarcoma who developed multiple lung metastases. Sputum examination revealed malignant cells with pleomorphic, elongated, and cigar-shaped nuclei and occasional bipolar cytoplasmic processes. Immunoperoxidase studies on the smears using desmin and smooth muscle actin were strongly positive, consistent with leiomyosarcoma. Confirmation of metastatic lung disease by sputum cytology not only has prognostic importance but also obviates the need for further investigations. Diagn. Cytopathol. 1998;18:280–283. © 1998 Wiley-Liss, Inc.     

高龄早期非小细胞肺癌单纯放射治疗临床观察

目的观察分析70岁以上早期（Ⅰ、Ⅱ期）非小细胞肺癌患者接受单纯放射治疗后的临床疗效及死亡原因。方法选择1992年至2003年48例70岁以上早期非小细胞肺癌患者，均为男性，年龄70～94岁，平均年龄78岁。Ⅰ期患者38例，Ⅱ期10例。既往有肺部阻塞性疾病26例，心血管疾病18例．糖尿病18例，脑血管疾病2例．共有15例（31．3％）患者同时合并两种或以上疾病。全部患者接受放射治疗，照射剂量60～66Gv（平均64Gy）／30～33次，常规分割照射2Gy／次。结果治疗后总有效率为58．3％。存活时间3～90个月（平均30．5个月），1、2、3年存活率分别为56．3％、45．8％、39．6％，平均疾病专项生存时间34．0个月，1、2、3年疾病专项生存率分别为62．6％、53．0％、45．8％。6例（12．5％）老年患者在放射治疗结束后3～6个月出现局灶性放射性肺炎，27例（56．3％）患者出现2级以下自限性的放射性食管反应。死亡的30例患者中，16例（53．3％）死于肺部感染、呼吸衰竭；9例（30．0％）死于肿瘤局部复发或广泛转移；3例（10．0％）死于心脑血管疾病；1例（3．3％）死于消化道大出血：1例（3．3％）死于甲状腺未分化癌。结论单纯放射治疗高龄早期非小细胞肺癌的临床疗效可靠且毒副反应较小．并且不会降低患者生活质量。对于高龄患者尤其是对于不能耐受或拒绝手术的高龄患者是很好的选择。从死亡原因分析．肺部感染仍是致死的重要因素。