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Sample records for early stage lung

  1. Early diagnosis of early stage lung cancer

    Directory of Open Access Journals (Sweden)

    Andrej Debeljak

    2005-11-01

    Full Text Available Background: For the detection of premalignant changes of bronchial mucosa and early stages of lung cancer frequent chest X-ray, spiral low dose computed tomography, fluorescence bronchoscopy, sputum cytology (also with automated systems with genetic and molecular changes in the sputum cells and bronchial mucosa were used. These screening methods of the high-risk groups for lung cancer achieved: earlier diagnosis of lung cancer in lower stage, higher operability, longer 5-year survival, but without mortality reduction.Conclusions: In the clinical practice we can examine higher risk groups for lung cancer in randomised control trials with multimodality approach: frequent chest low-dose fast spiral computed tomography, sputum cytology with genetic and molecular examinations and fluorescence bronchoscopy. Smoking cessation remains the best means to achieve mortality reduction from lung cancer.

  2. Radiation Therapy for Early Stage Lung Cancer

    OpenAIRE

    Parashar, Bhupesh; Arora, Shruthi; Wernicke, A. Gabriella

    2013-01-01

    Radiation therapy for early stage lung cancer is a promising modality. It has been traditionally used in patients not considered candidates for standard surgical resection. However, its role has been changing rapidly since the introduction of new and advanced technology, especially in tumor tracking, image guidance, and radiation delivery. Stereotactic radiation therapy is one such advancement that has shown excellent local control rates and promising survival in early stage lung cancer. In a...

  3. Radiation Therapy for Early Stage Lung Cancer

    OpenAIRE

    Parashar, Bhupesh; Arora, Shruthi; Wernicke, A. Gabriella

    2013-01-01

    Radiation therapy for early stage lung cancer is a promising modality. It has been traditionally used in patients not considered candidates for standard surgical resection. However, its role has been changing rapidly since the introduction of new and advanced technology, especially in tumor tracking, image guidance, and radiation delivery. Stereotactic radiation therapy is one such advancement that has shown excellent local control rates and promising survival in early stage lung cancer. In a...

  4. An actuarial approach to comparing early stage and late stage lung cancer mortality and survival.

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    Goldberg, Sara W; Mulshine, James L; Hagstrom, Dale; Pyenson, Bruce S

    2010-02-01

    Comparing the mortality characteristics of different cohorts is an essential process in the life insurance industry. Pseudodisease, lead-time bias, and length bias, which are critical to determining the value of cancer screening, have close analogues in life insurance company management, including the temporal impact of underwriting. Ratios of all-cause mortality rates for cancer cohorts relative to standard population mortality rates can provide insights into early stage and late stage mortality differences, differences by age, sex, race, and histology, and allow modeling of biases associated with early stage detection or screening protocols. The Surveillance, Epidemiology and End Results (SEER) data set has characteristics that allow efficient application of actuarial techniques. We show the mortality burden associated with treated early stage lung cancer and that identifying all lung cancers at early stage could reduce US lung cancer deaths by over 70,000 per year.

  5. SBRT in operable early stage lung cancer patients.

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    Roesch, Johannes; Andratschke, Nicolaus; Guckenberger, Matthias

    2014-08-01

    Since decades the gold standard for treatment of early stage non-small cell lung cancer (NSCLC) is surgical lobectomy plus mediastinal lymph node dissection. Patients in worse health status are treated with sublobar resection or radiation treatment. With development of stereotactic-body-radiotherapy (SBRT), outcome of patients treated with radiation was substantially improved. Comparison of SBRT and surgical techniques is difficult due to the lack of randomized trials. However, all available evidence in form of case control studies of population based studies show equivalence between sublobar resection and SBRT indicating that SBRT-when performed by a trained and experienced team-should be offered to all high-risk surgical patients. For patients not willing to take the risk of lobectomy and therefore refusing surgery, SBRT is an excellent treatment option.

  6. Socioeconomic position and surgery for early-stage non-small-cell lung cancer

    DEFF Research Database (Denmark)

    Kærgaard Starr, Laila; Osler, Merete; Steding-Jessen, Marianne

    2013-01-01

    AIM: To examine possible associations between socioeconomic position and surgical treatment of patients with early-stage non-small-cell lung cancer (NSCLC). METHODS: In a register-based clinical cohort study, patients with early-stage (stages I-IIIa) NSCLC were identified in the Danish Lung Cancer...... in a health care system with free, equal access to health services, disadvantaged groups are less likely to receive surgery for lung cancer....... was associated with greater odds for no surgery in stage I and stage II patients as was living alone for stage I patients. Comorbidity, a short diagnostic interval and small diagnostic volume were all associated with higher odds for not undergoing surgery; but these factors did not appear to explain...

  7. Phylogenetic ctDNA analysis depicts early stage lung cancer evolution

    OpenAIRE

    Wilson, Gareth A.; Constantin, Tudor; Quesne, John Le; Moore, David A.; Kirkizlar, Eser; Fraioli, Francesco; Bakir, Maise Al; Zambrana, Francisco; Endozo, Raymondo; Bi, Wenya Linda; Fennessy, Fiona M.; Forster, Martin D.; Hafez, Dina; Ganguly, Apratim; Kareht, Stephanie

    2017-01-01

    The early detection of relapse following primary surgery for non-small cell lung cancer and the characterization of emerging subclones seeding metastatic sites might offer new therapeutic approaches to limit tumor recurrence. The potential to non-invasively track tumor evolutionary dynamics in ctDNA of early-stage lung cancer is not established. Here we conduct a tumour-specific phylogenetic approach to ctDNA profiling in the first 100 TRACERx (TRAcking non-small cell lung Cancer Evolution th...

  8. [Treatment of non-small cell lung carcinoma in early stages].

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    Meneses, José Carlos; Avila Martínez, Régulo J; Ponce, Santiago; Zuluaga, Mauricio; Bartolomé, Adela; Gámez, Pablo

    2013-12-01

    Treatment of lung carcinoma is multidisciplinary. There are different therapeutic strategies available, although surgery shows the best results in those patients with lung carcinoma in early stages. Other options such as stereotactic radiation therapy are relegated to patients with small tumors and poor cardiopulmonary reserve or to those who reject surgery. Adjuvant chemotherapy is not justified in patients with stage i of the disease and so double adjuvant chemotherapy should be considered. This adjuvant chemotherapy should be based on cisplatin after surgery in those patients with stages ii and IIIA.

  9. A robust prognostic gene expression signature for early stage lung adenocarcinoma

    DEFF Research Database (Denmark)

    Krzystanek, Marcin; Moldvay, Judit; Szüts, David;

    2016-01-01

    Stage I lung adenocarcinoma is usually not treated with adjuvant chemotherapy; however, around half of these patients do not survive 5 years. Therefore, a reliable prognostic biomarker for early stage patients would be critical to identify those most likely to benefit from early additional treatm...... not given adjuvant therapy. Seven genes consistently obtained statistical significance in Cox regression for overall survival. The combined signature has a weighted mean hazard ratio of 3.2 in all cohorts and 3.0 (C.I. 1.3-7.4, p ...... treatments. Several studies have searched for gene expression prognostic biomarkers for lung adenocarcinoma, but these have not yielded a widely accepted prognosticator. We analyzed gene expression from seven published lung adenocarcinoma cohorts for which we included only stage I and II patients who were...

  10. Phylogenetic ctDNA analysis depicts early stage lung cancer evolution

    DEFF Research Database (Denmark)

    Abbosh, Christopher; Birkbak, Nicolai Juul; Wilson, Gareth A.

    2017-01-01

    of early-stage lung cancer is not established. Here we conduct a tumour-specific phylogenetic approach to ctDNA profiling in the first 100 TRACERx (TRAcking non-small cell lung Cancer Evolution through therapy (Rx)) study participants, including one patient co-recruited to the PEACE (Posthumous Evaluation......The early detection of relapse following primary surgery for non-small cell lung cancer and the characterization of emerging subclones seeding metastatic sites might offer new therapeutic approaches to limit tumor recurrence. The potential to non-invasively track tumor evolutionary dynamics in ctDNA...... of Advanced Cancer Environment) post-mortem study. We identify independent predictors of ctDNA release and perform tumor volume limit of detection analyses. Through blinded profiling of post-operative plasma, we observe evidence of adjuvant chemotherapy resistance and identify patients destined to experience...

  11. Effect of body mass index on the survival of patients with early-stage small cell lung cancer after surgery

    OpenAIRE

    Kolesnik, A. P.

    2013-01-01

    Lung cancer is an important medico-social problem. It is connected with high level of incidence and mortality of lung cancer. Nowadays we know that obesity has significant influence on cancer development, including lung cancer. Multivariate analysis confirmed that histological type of tumour, kind of operation and body mass index (BMI) influence on prognosis in patients with early stages of mall cell lung cancer. So, now we can use BMI along with other significant prognostic criteria for dete...

  12. Expression analysis of Shh signaling members in early stages of chick lung development.

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    Moura, Rute Silva; Silva-Gonçalves, Carla; Vaz-Cunha, Patrícia; Correia-Pinto, Jorge

    2016-10-01

    Lung organogenesis is guided by epithelial-mesenchymal interactions that coordinate cellular events responsible for the formation of the respiratory system. Several signaling pathways have been implicated in this process; among them, sonic hedgehog (Shh) signaling has emerged as a crucial regulator of branching morphogenesis in the mammalian lung. Canonical Shh signaling requires the presence of patched (Ptch) and smoothened (Smo) transmembrane receptors in order to induce the activation of glioblastoma (Gli) zinc finger transcription factors that are the true effectors of the pathway. Signal transduction is finely regulated by Ptch1, Gli, and Hhip (hedgehog-interacting protein). The present work characterizes, for the first time, the expression pattern of shh, ptch1, smo, gli1, and hhip in early stages of the embryonic chick lung. In situ hybridization studies revealed that these genes are expressed in the same cellular compartments as their mammalian counterparts, although their proximo-distal distribution is slightly changed. Moreover, the molecular interactions between fibroblast growth factor (FGF) and Shh signaling pathway were assessed, in vitro, by grafting beads soaked in SU5402 (an FGF receptor inhibitor). In the chick lung, Shh signaling seems to have some features that are species specific since shh is not a downstream target of FGF signaling. Nonetheless and despite the observed differences, these findings suggest a role for Shh signaling in the epithelial-mesenchymal interactions that control chick lung morphogenesis.

  13. SSX2-4 expression in early-stage non-small cell lung cancer

    DEFF Research Database (Denmark)

    Greve, K B V; Pøhl, M; Olsen, K E

    2014-01-01

    The expression of cancer/testis antigens SSX2, SSX3, and SSX4 in non-small cell lung cancers (NSCLC) was examined, since they are considered promising targets for cancer immunotherapy due to their immunogenicity and testis-restricted normal tissue expression. We characterized three SSX antibodies...... was only detected in 5 of 143 early-stage NSCLCs, which is rare compared to other cancer/testis antigens (e.g. MAGE-A and GAGE). However, further studies are needed to determine whether SSX can be used as a prognostic or predictive biomarker in NSCLC....

  14. Robotic-Assisted Thoracic Surgery for Early-Stage Lung Cancer: A Review.

    Science.gov (United States)

    Brooks, Paula

    2015-07-01

    This review evaluates the benefits and disadvantages associated with the use of robotic-assisted technology in performing lobectomies in patients with early-stage lung cancer. The author conducted a literature search of Ovid®, MEDLINE®, PubMed®, and CINAHL® for articles published from 2005 to 2013. Search criteria included key terms such as robot, robotic, robotic-assisted lobectomy, and lung cancer. Of 922 articles, the author included a total of 12 research-based published studies in the analysis and incorporated the findings into an evidence table. Results showed that robotic-assisted lobectomies are feasible safe procedures for patients with stage 1A or 1B lung cancer; however, there is a steep learning curve and long-term randomized studies evaluating robotic-assisted lobectomy and conventional posterolateral thoracotomy or video-assisted thoracic lobectomy are needed. For patient safety, perioperative nurses should be aware of the length of time and experience required to perform these procedures, the costs, techniques, benefits, and disadvantages.

  15. Carbon Ion Therapy for Early-Stage Non-Small-Cell Lung Cancer

    Directory of Open Access Journals (Sweden)

    Yusuke Demizu

    2014-01-01

    Full Text Available Carbon ion therapy is a type of radiotherapies that can deliver high-dose radiation to a tumor while minimizing the dose delivered to the organs at risk; this profile differs from that of photon radiotherapy. Moreover, carbon ions are classified as high-linear energy transfer radiation and are expected to be effective for even photon-resistant tumors. Recently, high-precision radiotherapy modalities such as stereotactic body radiotherapy (SBRT, proton therapy, and carbon ion therapy have been used for patients with early-stage non-small-cell lung cancer, and the results are promising, as, for carbon ion therapy, local control and overall survival rates at 5 years are 80–90% and 40–50%, respectively. Carbon ion therapy may be theoretically superior to SBRT and proton therapy, but the literature that is currently available does not show a statistically significant difference among these treatments. Carbon ion therapy demonstrates a better dose distribution than both SBRT and proton therapy in most cases of early-stage lung cancer. Therefore, carbon ion therapy may be safer for treating patients with adverse conditions such as large tumors, central tumors, and poor pulmonary function. Furthermore, carbon ion therapy may also be suitable for dose escalation and hypofractionation.

  16. Four-arm robotic lobectomy for the treatment of early-stage lung cancer.

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    Veronesi, Giulia; Galetta, Domenico; Maisonneuve, Patrick; Melfi, Franca; Schmid, Ralph Alexander; Borri, Alessandro; Vannucci, Fernando; Spaggiari, Lorenzo

    2010-07-01

    We investigated the feasibility and safety of four-arm robotic lung lobectomy in patients with lung cancer and described the robotic lobectomy technique with mediastinal lymph node dissection. Over 21 months, 54 patients underwent robotic lobectomy for early-stage lung cancer at our institute. We used a da Vinci Robotic System (Intuitive Surgical, Inc, Mountain View, Calif) with three ports plus one utility incision to isolate hilum elements and perform vascular and bronchial resection using standard endoscopic staplers. Standard mediastinal lymph node dissection was performed subsequently. Surgical outcomes were compared with those in 54 patients who underwent open surgery over the same period and were matched to the robotic group using propensity scores for a series of preoperative variables. Conversion to open surgery was necessary in 7 (13%) cases. Postoperative complications (11/54, 20%, in each group) and median number of lymph nodes removed (17.5 robotic vs 17 open) were similar in the 2 groups. Median robotic operating time decreased by 43 minutes (P = .02) from first tertile (18 patients) to the second-plus-third tertile (36 patients). Median postoperative hospitalization was significantly shorter after robotic (excluding first tertile) than after open operations (4.5 days vs 6 days; P = .002). Robotic lobectomy with lymph node dissection is practicable, safe, and associated with shorter postoperative hospitalization than open surgery. From the number of lymph nodes removed it also appears oncologically acceptable for early lung cancer. Benefits in terms of postoperative pain, respiratory function, and quality of life still require evaluation. We expect that technologic developments will further simplify the robotic procedure. 2010 The American Association for Thoracic Surgery. Published by Mosby, Inc. All rights reserved.

  17. Drug Repositioning Discovery for Early- and Late-Stage Non-Small-Cell Lung Cancer

    Directory of Open Access Journals (Sweden)

    Chien-Hung Huang

    2014-01-01

    Full Text Available Drug repositioning is a popular approach in the pharmaceutical industry for identifying potential new uses for existing drugs and accelerating the development time. Non-small-cell lung cancer (NSCLC is one of the leading causes of death worldwide. To reduce the biological heterogeneity effects among different individuals, both normal and cancer tissues were taken from the same patient, hence allowing pairwise testing. By comparing early- and late-stage cancer patients, we can identify stage-specific NSCLC genes. Differentially expressed genes are clustered separately to form up- and downregulated communities that are used as queries to perform enrichment analysis. The results suggest that pathways for early- and late-stage cancers are different. Sets of up- and downregulated genes were submitted to the cMap web resource to identify potential drugs. To achieve high confidence drug prediction, multiple microarray experimental results were merged by performing meta-analysis. The results of a few drug findings are supported by MTT assay or clonogenic assay data. In conclusion, we have been able to assess the potential existing drugs to identify novel anticancer drugs, which may be helpful in drug repositioning discovery for NSCLC.

  18. Effect of body mass index on the survival of patients with early-stage small cell lung cancer after surgery

    Directory of Open Access Journals (Sweden)

    A. P. Kolesnik

    2013-04-01

    Full Text Available Lung cancer is an important medico-social problem. It is connected with high level of incidence and mortality of lung cancer. Nowadays we know that obesity has significant influence on cancer development, including lung cancer. Multivariate analysis confirmed that histological type of tumour, kind of operation and body mass index (BMI influence on prognosis in patients with early stages of mall cell lung cancer. So, now we can use BMI along with other significant prognostic criteria for detection of unfavorable prognostic group of patients.

  19. Circulating micro-RNA expression profiles in early stage nonsmall cell lung cancer.

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    Heegaard, Niels H H; Schetter, Aaron J; Welsh, Judith A; Yoneda, Mitsuhiro; Bowman, Elise D; Harris, Curtis C

    2012-03-15

    Circulating micro-RNA (miR) profiles have been proposed as promising diagnostic and prognostic biomarkers for cancer, including lung cancer. We have developed methods to accurately and reproducibly measure micro-RNA levels in serum and plasma. Here, we study paired serum and plasma samples from 220 patients with early stage nonsmall cell lung cancer (NSCLC) and 220 matched controls. We use qRT-PCR to measure the circulating levels of 30 different miRs that have previously been reported to be differently expressed in lung cancer tissue. Duplicate RNA extractions were performed for 10% of all samples, and micro-RNA measurements were highly correlated among those duplicates. This demonstrates high reproducibility of our assay. The expressions of miR-146b, miR-221, let-7a, miR-155, miR-17-5p, miR-27a and miR-106a were significantly reduced in the serum of NSCLC cases, while miR-29c was significantly increased. No significant differences were observed in plasma of patients compared with controls. Overall, expression levels in serum did not correlate well with levels in plasma. In secondary analyses, reduced plasma expression of let-7b was modestly associated with worse cancer-specific mortality in all patients, and reduced serum expression of miR-223 was modestly associated with cancer-specific mortality in stage IA/B patients. MiR profiles also showed considerable differences comparing African American and European Americans. In summary, we found significant differences in miR expression when comparing cases and controls and find evidence that expression of let-7b is associated with prognosis in NSCLC. Copyright © 2011 UICC.

  20. Targeting of Cancer Stem Cells and Their Microenvironment in Early-Stage Mutant K-ras Lung Cancer

    Science.gov (United States)

    2016-12-01

    1 Í AWARD NUMBER: W81XWH-14-1-0338 TITLE: Targeting of Cancer Stem Cells and Their Microenvironment in Early-Stage Mutant K-ras Lung... Cancer PRINCIPAL INVESTIGATOR: James Kim, MD. PhD CONTRACTING ORGANIZATION: UNIVERSITY OF TEXAS SOUTHWESTERN MEDICAL Dallas, TX 75390 REPORT DATE...15 Sep 2014 - 14 Sep 2016 4. TITLE AND SUBTITLE 5a. CONTRACT NUMBER Targeting of Cancer Stem Cells and Their Microenvironment in Early-Stage Mutant

  1. Stereotactic radiotherapy for early stage non-small cell lung cancer

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    Ricardi, Umberto; Badellino, Serena; Filippi, Andrea Riccardo [Dept. of Oncology, Radiation Oncology, University of Torino, Torino (Italy)

    2015-06-15

    Stereotactic body radiotherapy (SBRT) represents a consolidated treatment option for patients with medically inoperable early stage non-small cell lung cancer (NSCLC). The clinical evidence accumulated in the past decade supports its use as an alternative to surgery with comparable survival outcomes. Due to its limited toxicity, SBRT is also applicable to elderly patients with very poor baseline pulmonary function or other severe comorbidities. Recent comparative studies in operable patients raised the issue of the possible use of SBRT also for this subgroup, with quite promising results that still should be fully confirmed by prospective trials with long-term follow-up. Aim of this review is to summarize and discuss the major studies conducted over the years on SBRT and to provide data on the efficacy and toxicity of this radiotherapy technique for stage I NSCLC. Technical aspects and quality of life related issues are also discussed, with the goal to provide information on the current role and limitations of SBRT in clinical practice.

  2. SURVIVAL AND QUALITY OF LIFE AFTER STEREOTACTIC OR 3D-CONFORMAL RADIOTHERAPY FOR INOPERABLE EARLY-STAGE LUNG CANCER

    NARCIS (Netherlands)

    Widder, Joachim; Postmus, Douwe; Ubbels, Jan F.; Wiegman, Erwin M.; Langendijk, Johannes A.

    2011-01-01

    Purpose: To investigate survival and local recurrence after stereotactic ablative radiotherapy (SABR) or threedimensional conformal radiotherapy (3D-CRT) administered for early-stage primary lung cancer and to investigate longitudinal changes of health-related quality of life (HRQOL) parameters

  3. SURVIVAL AND QUALITY OF LIFE AFTER STEREOTACTIC OR 3D-CONFORMAL RADIOTHERAPY FOR INOPERABLE EARLY-STAGE LUNG CANCER

    NARCIS (Netherlands)

    Widder, Joachim; Postmus, Douwe; Ubbels, Jan F.; Wiegman, Erwin M.; Langendijk, Johannes A.

    2011-01-01

    Purpose: To investigate survival and local recurrence after stereotactic ablative radiotherapy (SABR) or threedimensional conformal radiotherapy (3D-CRT) administered for early-stage primary lung cancer and to investigate longitudinal changes of health-related quality of life (HRQOL) parameters afte

  4. Patterns of recurrence and second primary lung cancer in early-stage lung cancer survivors followed with routine computed tomography surveillance.

    Science.gov (United States)

    Lou, Feiran; Huang, James; Sima, Camelia S; Dycoco, Joseph; Rusch, Valerie; Bach, Peter B

    2013-01-01

    At present, there is no consensus on the optimal strategy for follow-up care after curative resection for lung cancer. We sought to understand the patterns of recurrence and second primary lung cancer, and their mode of detection, after resection for early-stage non-small cell lung cancer in patients who were followed by routine surveillance computed tomography scan. We reviewed the outcomes of consecutive patients who underwent resection for early-stage non-small cell lung cancer at Memorial Sloan-Kettering Cancer Center between 2004 and 2009. A total of 1294 consecutive patients with early-stage non-small cell lung cancer underwent resection. The median length of follow-up was 35 months. Recurrence was diagnosed in 257 patients (20%), and second primary lung cancer was diagnosed in 91 patients (7%). The majority of new primary cancers (85 [93%]) were identified by scheduled routine computed tomography scan, as were a smaller majority of recurrences (157 [61%]). During the first 4 years after surgery, the risk of recurrence ranged from 6% to 10% per person-year but decreased thereafter to 2%. Conversely, the risk of second primary lung cancer ranged from 3% to 6% per person-year and did not diminish over time. Additional testing after false-positive surveillance computed tomography scan results was performed for 329 patients (25%), but only 4 of these patients (0.3%) experienced complications as a result of subsequent invasive diagnostic procedures. Almost all second primary cancers and the majority of recurrences were detected by post-therapeutic surveillance computed tomography scan. The risk of recurrence for early-stage non-small cell lung cancer survivors persisted during the first 4 years after resection, and vigilance in surveillance should be maintained. Copyright © 2013 The American Association for Thoracic Surgery. Published by Mosby, Inc. All rights reserved.

  5. Methylation markers of early-stage non-small cell lung cancer.

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    Kaie Lokk

    Full Text Available BACKGROUND: Despite of intense research in early cancer detection, there is a lack of biomarkers for the reliable detection of malignant tumors, including non-small cell lung cancer (NSCLC. DNA methylation changes are common and relatively stable in various types of cancers, and may be used as diagnostic or prognostic biomarkers. METHODS: We performed DNA methylation profiling of samples from 48 patients with stage I NSCLC and 18 matching cancer-free lung samples using microarrays that cover the promoter regions of more than 14,500 genes. We correlated DNA methylation changes with gene expression levels and performed survival analysis. RESULTS: We observed hypermethylation of 496 CpGs in 379 genes and hypomethylation of 373 CpGs in 335 genes in NSCLC. Compared to adenocarcinoma samples, squamous cell carcinoma samples had 263 CpGs in 223 hypermethylated genes and 513 CpGs in 436 hypomethylated genes. 378 of 869 (43.5% CpG sites discriminating the NSCLC and control samples showed an inverse correlation between CpG site methylation and gene expression levels. As a result of a survival analysis, we found 10 CpGs in 10 genes, in which the methylation level differs in different survival groups. CONCLUSIONS: We have identified a set of genes with altered methylation in NSCLC and found that a minority of them showed an inverse correlation with gene expression levels. We also found a set of genes that associated with the survival of the patients. These newly-identified marker candidates for the molecular screening of NSCLC will need further analysis in order to determine their clinical utility.

  6. Staging of Lung Cancer

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    ... 2010. Online Version Reviewed September 2013 ATS Patient Education Series © 2010 American Thoracic Society LIVER BONE www.thoracic.org ATS PATIENT INFORMATION SERIES How will my lung cancer be staged? ...

  7. Effect of early chemoradiotherapy in patients with limited stage small cell lung cancer

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    Ha, In Bong; Jeong, Bae Kwon; Jeong, Ho Jin; Choi, Hoon Sik; Chai, Gyu Young; Kang, Myoung Hee; Kim, Hoon Gu; Lee, Gyeong Won; Na, Jae Beom; Kang, Ki Mun [Gyeongsang National University School of Medicine, Jinju (Korea, Republic of)

    2013-12-15

    We evaluated the effect of early chemoradiotherapy on the treatment of patients with limited stage small cell lung cancer (LS-SCLC). Between January 2006 and December 2011, thirty-one patients with histologically proven LS-SCLC who were treated with two cycles of chemotherapy followed by concurrent chemoradiotherapy and consolidation chemotherapy were retrospectively analyzed. The chemotherapy regimen was composed of etoposide and cisplatin. Thoracic radiotherapy consisted of 50 to 60 Gy (median, 54 Gy) given in 5 to 6.5 weeks. The follow-up period ranged from 5 to 53 months (median, 22 months). After chemoradiotherapy, 35.5% of the patients (11 patients) showed complete response, 61.3% (19 patients) showed partial response, 3.2% (one patient) showed progressive disease, resulting in an overall response rate of 96.8% (30 patients). The 1-, 2-, and 3-year overall survival (OS) rates were 66.5%, 41.0%, and 28.1%, respectively, with a median OS of 21.3 months. The 1-, 2-, and 3-year progression free survival (PFS) rates were 49.8%, 22.8%, and 13.7%, respectively, with median PFS of 12 months. The patterns of failure were: locoregional recurrences in 29.0% (nine patients), distant metastasis in 9.7% (three patients), and both locoregional and distant metastasis in 9.7% (three patients). Grade 3 or 4 toxicities of leukopenia, anemia, and thrombocytopenia were observed in 32.2%, 29.0%, and 25.8%, respectively. Grade 3 radiation esophagitis and radiation pneumonitis were shown in 12.9% and 6.4%, respectively. We conclude that early chemoradiotherapy for LS-SCLC provides feasible and acceptable local control and safety.

  8. Early stage lung cancer detection in systemic sclerosis does not portend survival benefit: a cross sectional study.

    Directory of Open Access Journals (Sweden)

    Jeremy B Katzen

    Full Text Available Systemic Sclerosis (SSc is a rare connective tissue disorder associated with an increased risk of malignancy including lung cancer.A single center review of all cases of lung cancer in patients with SSc was conducted. Clinical, radiographic, and detailed pathologic data was collected. Risk factors were compared with our center's SSc Registry. Cancer characteristics were compared with the National Cancer Institute SEER Cancer Statistics (NCI SEER data.17 cases were identified; the majority were females (82% with the lung cancers diagnosed after the onset of SSc (88%. Tobacco use was identified in 65% of cases. Serologic testing showed 50% of cases were Scl-70 positive. Twelve cases had radiographic evidence of SSc lung involvement, however only 6 had restrictive physiology on pulmonary function testing. Thirteen cases had pulmonary nodules preceding lung cancer. Thirteen of the cancers were adenocarcinoma. Ten underwent molecular mutational profiling: 2/8 had KRAS mutation and 1/10 had EGFR mutation. More of the non-small cell lung cancers were diagnosed at localized disease (56% than in the NCI SEER database. However, 5 years survival among the stage I cases was 25% versus an expected survival of 54%.The high proportion of adenocarcinomas seen in our study is different from that reported in the literature. Lung cancers were diagnosed at an early stage, likely due to our center's practice of radiographic screening for SSc associated lung involvement, however this did not confer a survival advantage. A high proportion of patients who developed lung cancer had interstitial lung disease.

  9. Differences in miRNA expression in early stage lung adenocarcinomas that did and did not relapse.

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    Mick D Edmonds

    Full Text Available Relapse of adenocarcinoma, the most common non-small cell lung cancer (NSCLC, is a major clinical challenge to improving survival. To gain insight into the early molecular events that contribute to lung adenocarcinoma relapse, and taking into consideration potential cell type specificity, we used stringent criteria for sample selection. We measured miRNA expression only from flash frozen stage I lung adenocarcinomas, excluding other NSCLC subtypes. We compared miRNA expression in lung adenocarcinomas that relapsed within two years to those that did not relapse within three years after surgical resection prior to adjuvant therapy. The most significant differences in mRNA expression for recurrent tumors compared to non-recurrent tumors were decreases in miR-106b*, -187, -205, -449b, -774* and increases in miR-151-3p, let-7b, miR-215, -520b, and -512-3p. A unique comparison between adjacent normal lung tissue from relapse and non-relapse groups revealed dramatically different miRNA expression, suggesting dysregulation of miRNA in the environment around the tumor. To assess patient-to-patient variability, miRNA levels in the tumors were normalized to levels in matched adjacent normal lung tissue. This analysis revealed a different set of significantly altered miRNA in tumors that recurred compared to tumors that did not. Together our analyses elucidated miRNA not previously linked to lung adenocarcinoma that likely have important roles in its development and progression. Our results also highlight the differences in miRNA expression in normal lung tissue in adenocarcinomas that do and do not recur. Most notably, our data identified those miRNA that distinguish early stage tumors likely to relapse prior to treatment and miRNA that could be further studied for use as biomarkers for prognosis, patient monitoring, and/or treatment decisions.

  10. Recurrence and Survival After Segmentectomy in Patients With Prior Lung Resection for Early-Stage Non-Small Cell Lung Cancer.

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    Brown, Lisa M; Louie, Brian E; Jackson, Nicole; Farivar, Alexander S; Aye, Ralph W; Vallières, Eric

    2016-10-01

    Lobectomy is the standard of care for patients with early-stage non-small cell lung cancer (NSCLC). However, the treatment of choice for patients with prior lung resection and a second primary NSCLC has not been established. We compared rates and patterns of recurrence and survival in patients with and without prior lung resection treated by segmentectomy and determined predictors of recurrence. This was a retrospective cohort study of 90 patients who underwent 91 consecutive segmentectomies for early-stage NSCLC between April 2004 and December 2014. Logistic regression was used to determine predictors of recurrence, and Kaplan-Meier curves were used to determine survival. Of the 91 segmentectomies, 21 (23%) had a prior lung cancer resection and 70 (77%) were primary resections. There were 18 recurrences (20%): 9 of 21 (43%) in those with prior lung resection and 9 of 70 (13%) in those without. The 90-day mortality was 0%. The recurrence-free survival and 5-year survival were 61% and 55% in those with prior lung resection (p = 0.09) and 84% and 65% in those without (p = 0.4). Close parenchymal margin and number of lymph nodes examined were significant modifiable predictors of recurrence. Segmentectomy is a reasonable option for patients with early-stage NSCLC who have had a prior lung resection. It results in similar survival but trends toward lower recurrence-free survival compared with patients undergoing primary resection. Copyright © 2016 The Society of Thoracic Surgeons. Published by Elsevier Inc. All rights reserved.

  11. Stereotactic body radiation therapy versus conventional radiation therapy in patients with early stage non-small cell lung cancer

    DEFF Research Database (Denmark)

    Jeppesen, Stefan Starup; Schytte, Tine; Jensen, Henrik R

    2013-01-01

    Abstract Introduction. Stereotactic body radiation therapy (SBRT) for early stage non-small cell lung cancer (NSCLC) is now an accepted and patient friendly treatment, but still controversy exists about its comparability to conventional radiation therapy (RT). The purpose of this single...... and SBRT predicted improved prognosis. However, staging procedure, confirmation procedure of recurrence and technical improvements of radiation treatment is likely to influence outcomes. However, SBRT seems to be as efficient as conventional RT and is a more convenient treatment for the patients....

  12. Fluid biopsy for circulating tumor cell identification in patients with early-and late-stage non-small cell lung cancer: a glimpse into lung cancer biology

    Science.gov (United States)

    Wendel, Marco; Bazhenova, Lyudmila; Boshuizen, Rogier; Kolatkar, Anand; Honnatti, Meghana; Cho, Edward H.; Marrinucci, Dena; Sandhu, Ajay; Perricone, Anthony; Thistlethwaite, Patricia; Bethel, Kelly; Nieva, Jorge; van den Heuvel, Michel; Kuhn, Peter

    2012-02-01

    Circulating tumor cell (CTC) counts are an established prognostic marker in metastatic prostate, breast and colorectal cancer, and recent data suggest a similar role in late stage non-small cell lung cancer (NSCLC). However, due to sensitivity constraints in current enrichment-based CTC detection technologies, there are few published data about CTC prevalence rates and morphologic heterogeneity in early-stage NSCLC, or the correlation of CTCs with disease progression and their usability for clinical staging. We investigated CTC counts, morphology and aggregation in early stage, locally advanced and metastatic NSCLC patients by using a fluid-phase biopsy approach that identifies CTCs without relying on surface-receptor-based enrichment and presents them in sufficiently high definition (HD) to satisfy diagnostic pathology image quality requirements. HD-CTCs were analyzed in blood samples from 78 chemotherapy-naïve NSCLC patients. 73% of the total population had a positive HD-CTC count (>0 CTC in 1 mL of blood) with a median of 4.4 HD-CTCs mL-1 (range 0-515.6) and a mean of 44.7 (±95.2) HD-CTCs mL-1. No significant difference in the medians of HD-CTC counts was detected between stage IV (n = 31, range 0-178.2), stage III (n = 34, range 0-515.6) and stages I/II (n = 13, range 0-442.3). Furthermore, HD-CTCs exhibited a uniformity in terms of molecular and physical characteristics such as fluorescent cytokeratin intensity, nuclear size, frequency of apoptosis and aggregate formation across the spectrum of staging. Our results demonstrate that despite stringent morphologic inclusion criteria for the definition of HD-CTCs, the HD-CTC assay shows high sensitivity in the detection and characterization of both early- and late-stage lung cancer CTCs. Extensive studies are warranted to investigate the prognostic value of CTC profiling in early-stage lung cancer. This finding has implications for the design of extensive studies examining screening, therapy and surveillance in

  13. Frequent silencing of the candidate tumor suppressor TRIM58 by promoter methylation in early-stage lung adenocarcinoma.

    Science.gov (United States)

    Kajiura, Koichiro; Masuda, Kiyoshi; Naruto, Takuya; Kohmoto, Tomohiro; Watabnabe, Miki; Tsuboi, Mitsuhiro; Takizawa, Hiromitsu; Kondo, Kazuya; Tangoku, Akira; Imoto, Issei

    2017-01-10

    In this study, we aimed to identify novel drivers that would be epigenetically altered through aberrant methylation in early-stage lung adenocarcinoma (LADC), regardless of the presence or absence of tobacco smoking-induced epigenetic field defects. Through genome-wide screening for aberrantly methylated CpG islands (CGIs) in 12 clinically uniform, stage-I LADC cases affecting six non-smokers and six smokers, we identified candidate tumor-suppressor genes (TSGs) inactivated by hypermethylation. Through systematic expression analyses of those candidates in panels of additional tumor samples and cell lines treated or not treated with 5-aza-deoxycitidine followed by validation analyses of cancer-specific silencing by CGI hypermethylation using a public database, we identified TRIM58 as the most prominent candidate for TSG. TRIM58 was robustly silenced by hypermethylation even in early-stage primary LADC, and the restoration of TRIM58 expression in LADC cell lines inhibited cell growth in vitro and in vivo in anchorage-dependent and -independent manners. Our findings suggest that aberrant inactivation of TRIM58 consequent to CGI hypermethylation might stimulate the early carcinogenesis of LADC regardless of smoking status; furthermore, TRIM58 methylation might be a possible early diagnostic and epigenetic therapeutic target in LADC.

  14. Advances in Lymph Node Metastasis and the Modes of Lymph Node 
Dissection in Early Stage Non-small Cell Lung Caner

    Directory of Open Access Journals (Sweden)

    Ningning DING

    2016-06-01

    Full Text Available Lung cancer ranks the first position in morbidity and mortality among all malignances in China. Non-small cell lung cancer (NSCLC accounts for nearly 80% of all lung malignancies. Surgical resection is still the current major treatment method for early stage NSCLC. Lymph node stages together with the extent of lymph node dissection directly affect the prognosis. Anatomical lobectomy with systematic mediastinal lymph node dissection have been the standard surgical treatment for NSCLC. However, it is controversial in the extent of lymph node dissection for early stage NSCLC. Accurate nodes stage and the extent of mediatinal nodes dissection affect the peri-operative complications and the prognosis of NSCLC greatly. In the past decade, more and more surgeons demostrated that lobe-specific or selective mediastinal lymph node dissection is suitable for clinical stage I NSCLC, especially the stage Ia lesions, and may become the standard lymph node dissection mode in the future.

  15. [Advances in Lymph Node Metastasis and the Modes of Lymph Node 
Dissection in Early Stage Non-small Cell Lung Caner].

    Science.gov (United States)

    Ding, Ningning; Mao, Yousheng

    2016-06-20

    Lung cancer ranks the first position in morbidity and mortality among all malignances in China. Non-small cell lung cancer (NSCLC) accounts for nearly 80% of all lung malignancies. Surgical resection is still the current major treatment method for early stage NSCLC. Lymph node stages together with the extent of lymph node dissection directly affect the prognosis. Anatomical lobectomy with systematic mediastinal lymph node dissection have been the standard surgical treatment for NSCLC. However, it is controversial in the extent of lymph node dissection for early stage NSCLC. Accurate nodes stage and the extent of mediatinal nodes dissection affect the peri-operative complications and the prognosis of NSCLC greatly. In the past decade, more and more surgeons demostrated that lobe-specific or selective mediastinal lymph node dissection is suitable for clinical stage I NSCLC, especially the stage Ia lesions, and may become the standard lymph node dissection mode in the future.

  16. Scalpel or SABR for Treatment of Early-Stage Lung Cancer: Clinical Considerations for the Multidisciplinary Team

    Directory of Open Access Journals (Sweden)

    Joe Y. Chang

    2011-09-01

    Full Text Available Treatment options for early-stage (T1-2 N0 non-small cell lung cancer are often limited by the patient’s advanced age, poor performance status, and comorbidities. Despite these challenges, stereotactic ablative radiotherapy (SABR provides a highly effective and safe therapy for intrathoracic tumors and has become the standard of care for delivering definitive treatment in medically inoperable patients. High-quality treatment, which includes reliable immobilization, accurate tumor targeting, and precise verification of dose delivery, is essential both to achieve successful cure and to avoid debilitating toxicities. Generally, SABR is well tolerated in patients with peripherally located tumors, but even centrally or superiorly located lesions can be treated if there is adequate conformal avoidance of normal structures and/or modified fractionation to meet dose constraints. While several preliminary studies suggest that SABR is as efficacious as surgery in operable patients, results of randomized data will illuminate whether the indications for SABR can be expanded to include patients who are candidates for surgical resection. Herein, we review the rationale for using SABR and its application in treating different patient populations with early-stage lung cancer.

  17. Absence of toxicity with hypofractionated 3-dimensional radiation therapy for inoperable, early stage non-small cell lung cancer

    Directory of Open Access Journals (Sweden)

    Vuong Te

    2006-11-01

    Full Text Available Abstract Purpose Hypofractionated radiotherapy may overcome repopulation in rapidly proliferating tumors such as lung cancer. It is more convenient for the patients and reduces health care costs. This study reports our results on patients with medically inoperable, early stage, non-small cell lung cancer (NSCLC treated with hypofractionation. Materials and methods Stage T1-2N0 NSCLC patients were treated with hypofractionation alone, 52.5 Gy/15 fractions, in 3 weeks, with 3-dimensional conformal planning. T1-2N1 patients with the hilar lymphnode close to the primary tumor were also eligible for this treatment. We did not use any approach to reduce respiratory motion, but it was monitored in all patients. Elective nodal radiotherapy was not performed. Routine follow up included assessment for acute and late toxicity and radiological tumor response. Median follow up time was 29 months for the surviving patients. Results Thirty-two patients with a median age of 76 years, T1 = 15 and T2 = 17, were treated. Median planning target volume (PTV volume was 150cc and median V16 of both lungs was 13%. The most important finding of this study is that toxicity was minimal. Two patients had grade ≤ 2 acute pneumonitis and 3 had mild (grade 1 acute esophagitis. There was no late toxicity. Actuarial 1 and 2-year overall survival rates are 78% and 56%, cancer specific survival rates (CSS are 90% and 74%, and local relapse free survival rates are 93% and 76% respectively. Conclusion 3-D planning, involved field hypofractionation at a dose of 52.5 Gy in 15 daily fractions is safe, well tolerated and easy radiation treatment for medically inoperable lung cancer patients. It shortens by half the traditional treatment. Results compare favorably with previously published studies. Further studies are needed to compare similar technique with other treatments such as surgery and stereotactic radiotherapy.

  18. In the hunt for therapeutic targets: mimicking the growth, metastasis, and stromal associations of early-stage lung cancer using a novel orthotopic animal model.

    Science.gov (United States)

    Weiss, Ido D; Ella, Ezra; Dominsky, Omri; Smith, Yoav; Abraham, Michal; Wald, Hanna; Shlomai, Zippora; Zamir, Gideon; Feigelson, Sara W; Shezen, Elias; Bar-Shai, Amir; Alon, Ronen; Izhar, Uzi; Peled, Amnon; Shapira, Oz M; Wald, Ori

    2015-01-01

    The existing shortage of animal models that properly mimic the progression of early-stage human lung cancer from a solitary confined tumor to an invasive metastatic disease hinders accurate characterization of key interactions between lung cancer cells and their stroma. We herein describe a novel orthotopic animal model that addresses these concerns and consequently serves as an attractive platform to study tumor-stromal cell interactions under conditions that reflect early-stage lung cancer. Unlike previous methodologies, we directly injected small numbers of human or murine lung cancer cells into murine's left lung and longitudinally monitored disease progression. Next, we used green fluorescent protein-tagged tumor cells and immuno-fluorescent staining to determine the tumor's microanatomic distribution and to look for tumor-infiltrating immune cells and stromal cells. Finally, we compared chemokine gene expression patterns in the tumor and lung microenvironment. We successfully generated a solitary pulmonary nodule surrounded by normal lung parenchyma that grew locally and spread distally over time. Notably, we found that both fibroblasts and leukocytes are recruited to the tumor's margins and that distinct myeloid cell attracting and CCR2-binding chemokines are specifically induced in the tumor microenvironment. Our orthotopic lung cancer model closely mimics the pathologic sequence of events that characterizes early-stage human lung cancer propagation. It further introduces new means to monitor tumor-stromal cell interactions and offers unique opportunities to test therapeutic targets under conditions that reflect early-stage lung cancer. We argue that for such purposes our model is superior to lung cancer models that are based either on genetic induction of epithelial transformation or on ectopic transplantation of malignant cells.

  19. Recurrence Patterns and Second Primary Lung Cancers After Stereotactic Body Radiation Therapy for Early-Stage Non-Small-Cell Lung Cancer: Implications for Surveillance.

    Science.gov (United States)

    Spratt, Daniel E; Wu, Abraham J; Adeseye, Victoria; Din, Shaun U; Shaikh, Fauzia; Woo, Kaitlin M; Zhang, Zhigang; Foster, Amanda; Rosenzweig, Kenneth E; Gewanter, Richard; Huang, James; Rimner, Andreas

    2016-05-01

    Patients treated with stereotactic body radiation therapy (SBRT) for early-stage non-small-cell lung cancer (NSCLC) are subject to locoregional and distant recurrence, as well as the formation of second primary lung cancers (SPLCs). The optimal surveillance regimen for patients treated with SBRT for early-stage NSCLC remains unclear; we therefore investigated the posttreatment recurrence patterns and development of SPLCs. Three hundred sixty-six patients with pathologically proven inoperable early-stage NSCLC treated with SBRT between 2006 and 2013 were assessed. Patients underwent a computed tomographic (CT) scan of the chest every 3 months during years 1 and 2, every 6 months during years 3 and 4, and annually thereafter. Competing risk analysis was used for all time-to-event analyses. With a median follow-up of 23 months, the 2-year cumulative incidence of local, nodal, and distant treatment failures were 12.2%, 16.1%, and 15.5%, respectively. In patients with disease progression after SBRT (n = 108), 84% (n = 91) of cases occurred within the first 2 years. Five percent (n = 19) of patients experienced SPLCs. The median time to development of an SPLC was 16.5 months (range, 6.5-71.1 months), with 33% (n = 6) of these patients experiencing SPLCs after 2 years. None of the never smokers, but 4% of former tobacco smokers and 15% of current tobacco smokers, experienced an SPLC (P = .005). Close monitoring with routine CT scans within the first 2 years after SBRT is effective in detecting early disease progression. In contrast, the risk for the development of an SPLC remains elevated beyond 2 years, particularly in former and current smokers. Copyright © 2015 Elsevier Inc. All rights reserved.

  20. Detection of Recurrence Patterns After Wedge Resection for Early Stage Lung Cancer: Rationale for Radiologic Follow-Up.

    Science.gov (United States)

    Billè, Andrea; Ahmad, Usman; Woo, Kaitlin M; Suzuki, Kei; Adusumilli, Prasad; Huang, James; Jones, David R; Rizk, Nabil Pierre

    2016-10-01

    Wedge resection for selected patients with early stage non-small cell lung cancer is considered to be a valid treatment option. The aim of this study was to evaluate the recurrence patterns after wedge resection, to analyze the survival of patients under routine follow-up, and to recommend a follow-up regimen. A retrospective analysis was done of 446 consecutive patients between May 2000 and December 2012 who underwent a wedge resection for clinical stage I non-small cell lung cancer. All patients were followed up with a computed tomography scan with or without contrast. The recurrence was recorded as local (involving the same lobe of wedge resection), regional (involving mediastinal or hilar lymph nodes or a different lobe), or distant (including distant metastasis and pleural disease). Median follow-up for survivors (n = 283) was 44.6 months. In all, 163 patients died; median overall survival was 82.6 months. Thirty-six patients were diagnosed with new primary non-small cell lung cancer, and 152 with recurrence (79 local, 45 regional, and 28 distant). There was no difference in the incidence of recurrence detection detected by computed tomography scans with versus without contrast (p = 0.18). The cumulative incidence of local recurrences at 1, 2, and 3 years was higher than the cumulative incidence for local, regional, and distant recurrences: 5.2%, 11.1%, and 14.9% versus 3.7%, 6.6%, and 9.5% versus 2.3%, 4.7%, and 6.4%, respectively. Primary tumor diameter was associated with local recurrence in univariate analysis. Wedge resection for early stage non-small cell lung cancer is associated with a significant risk for local and regional recurrence. Long-term follow-up using noncontrast computed tomography scans at consistent intervals is appropriate to monitor for these recurrences. Copyright © 2016 The Society of Thoracic Surgeons. Published by Elsevier Inc. All rights reserved.

  1. Prevalence of and risk factors for postoperative pulmonary complications after lung cancer surgery in patients with early-stage COPD

    Directory of Open Access Journals (Sweden)

    Kim ES

    2016-06-01

    Full Text Available Eun Sun Kim,1 Young Tae Kim,2 Chang Hyun Kang,2 In Kyu Park,2 Won Bae,1 Sun Mi Choi,1 Jinwoo Lee,1 Young Sik Park,1 Chang-Hoon Lee,1 Sang-Min Lee,1 Jae-Joon Yim,1 Young Whan Kim,1 Sung Koo Han,1 Chul-Gyu Yoo1 1Division of Pulmonary and Critical Care Medicine, Department of Internal Medicine, 2Department of Thoracic and Cardiovascular Surgery, Seoul National University College of Medicine, Seoul, Republic of Korea Purpose: This study aimed to investigate whether the prevalence of postoperative pulmonary complications (PPCs in patients with non-small-cell lung cancer (NSCLC is even higher in the early stages of COPD than in such patients with normal lung function and to verify the usefulness of symptom- or quality of life (QoL-based scores in predicting risk for PPCs.Patients and methods: Patients undergoing pulmonary resection for NSCLC between July 2012 and October 2014 were prospectively enrolled. Preoperative measurements of lung function, dyspnea, and QoL, operative characteristics, PPCs, duration of postoperative hospitalization, and in-hospital mortality were assessed.Results: Among 351 consecutive patients with NSCLC, 343 patients with forced expiratory volume in 1 second (FEV1 ≥70% of predicted value were enrolled. At least one PPC occurred in 57 (16.6% patients. Prevalence of PPC was higher in patients with COPD (30.1% than in those with normal spirometry (10.0%; P<0.001. However, in patients with COPD, the prevalence of PPC was not different in patients with FEV1 ≥70% compared to those with FEV1 <70% and between group A (low risk and less symptoms and group B (low risk and more symptoms patients with COPD, based on the new Global initiative for chronic Obstructive Lung Disease 2011 guidelines. In patients with COPD, body mass index (odds ratio [OR]: 0.80, P=0.007, carbon monoxide diffusing capacity of the lung (DLCO, % predicted value (OR: 0.97, P=0.024, and operation time (OR: 1.01, P=0.003, but not COPD assessment test or St

  2. Telomere length of tumor tissues and survival in patients with early stage non-small cell lung cancer.

    Science.gov (United States)

    Jeon, Hyo-Sung; Choi, Yi Young; Choi, Jin Eun; Lee, Won Kee; Lee, Eungbae; Yoo, Seung Soo; Lee, Shin Yup; Lee, Jaehee; Cha, Seung Ick; Kim, Chang Ho; Park, Jae Yong

    2014-04-01

    Telomere shortening leads to genomic instability that drives oncogenesis through the activation of telomerase and the generation of other mutations necessary for tumor progression. This study was conducted to determine the impact of telomere shortening on the survival of patients with early stage non-small cell lung cancer (NSCLC). Relative telomere length in tumor tissues was measured by quantitative polymerase chain reaction in 164 patients with surgically resected NSCLC. The association between telomere length and overall survival (OS) and disease-free survival (DFS) was analyzed. When the patients were categorized into quartiles based on telomere length, those patients with the 1st quartile (shortest) of telomere length had a significantly worse OS and DFS compared to patients with the 2nd to the 4th quartiles of telomere length (adjusted hazard ratio for OS = 2.67, 95% confidence interval = 1.50-4.75, P = 0.001; and adjusted hazard ratio for DFS = 1.92, 95% confidence interval = 1.17-3.14, P = 0.01). An association between telomere length and survival outcome was more pronounced in squamous cell carcinomas than adenocarcinomas (P-value of test for homogeneity for OS and DFS = 0.05 and 0.02, respectively). Telomere length of tumor tissues is an independent prognostic factor in patients with surgically resected early stage NSCLC.

  3. Development of a Diagnostic Tool to Detect DNA Methylation Biomarkers for Early-Stage Lung Cancer

    Science.gov (United States)

    2015-02-01

    Lung Cancer PRINCIPAL INVESTIGATOR: Chongli Yuan CONTRACTING ORGANIZATION: Purdue University West Lafayette, IN 47907 REPORT DATE: February...DNA methylation with high spatial resolution. Task 2.1 Design a library of DNA constructs in which the location of the single methylated CpG site is...the impact on the development of the principal discipline of the project? This proposal aims to design and demonstrate proof-of-concept for these

  4. MYC and Human Telomerase Gene (TERC) Copy Number Gain in Early-stage Non–small Cell Lung Cancer

    Science.gov (United States)

    Flacco, Antonella; Ludovini, Vienna; Bianconi, Fortunato; Ragusa, Mark; Bellezza, Guido; Tofanetti, Francesca R.; Pistola, Lorenza; Siggillino, Annamaria; Vannucci, Jacopo; Cagini, Lucio; Sidoni, Angelo; Puma, Francesco; Varella-Garcia, Marileila; Crinò, Lucio

    2015-01-01

    Objectives We investigated the frequency of MYC and TERC increased gene copy number (GCN) in early-stage non–small cell lung cancer (NSCLC) and evaluated the correlation of these genomic imbalances with clinicopathologic parameters and outcome. Materials and Methods Tumor tissues were obtained from 113 resected NSCLCs. MYC and TERC GCNs were tested by fluorescence in situ hybridization (FISH) according to the University of Colorado Cancer Center (UCCC) criteria and based on the receiver operating characteristic (ROC) classification. Results When UCCC criteria were applied, 41 (36%) cases for MYC and 41 (36%) cases for TERC were considered FISH-positive. MYC and TERC concurrent FISH-positive was observed in 12 cases (11%): 2 (17%) cases with gene amplification and 10 (83%) with high polysomy. By using the ROC analysis, high MYC (mean ≥2.83 copies/cell) and TERC (mean ≥2.65 copies/cell) GCNs were observed in 60 (53.1%) cases and 58 (51.3%) cases, respectively. High TERC GCN was associated with squamous cell carcinoma (SCC) histology (P = 0.001). In univariate analysis, increased MYC GCN was associated with shorter overall survival (P = 0.032 [UCCC criteria] or P = 0.02 [ROC classification]), whereas high TERC GCN showed no association. In multivariate analysis including stage and age, high MYC GCN remained significantly associated with worse overall survival using both the UCCC criteria (P = 0.02) and the ROC classification (P = 0.008). Conclusions Our results confirm MYC as frequently amplified in early-stage NSCLC and increased MYC GCN as a strong predictor of worse survival. Increased TERC GCN does not have prognostic impact but has strong association with squamous histology. PMID:25806711

  5. FGFR1, 2 and 3 protein overexpression and molecular aberrations of FGFR3 in early stage non-small cell lung cancer

    NARCIS (Netherlands)

    Theelen, Willemijn Sme; Mittempergher, Lorenza; Willems, Stefan M; Bosma, Astrid J; Peters, Dennis Dgc; van der Noort, Vincent; Japenga, Eva J; Peeters, Ton; Koole, Koos; Šuštić, Tonći; Blaauwgeers, J L; van Noesel, Carel J; Bernards, René; van den Heuvel, Michel M

    2016-01-01

    This study aimed to determine protein expression levels of fibroblast growth factor receptors (FGFR) 1, 2 and 3 in early stage non-small cell lung cancer (NSCLC). Additionally, a screen to define the frequency of FGFR3-TACC3 translocation and FGFR3 amplification was performed. Archived tissues from

  6. Survival and Quality of Life After Stereotactic or 3D-Conformal Radiotherapy for Inoperable Early-Stage Lung Cancer

    Energy Technology Data Exchange (ETDEWEB)

    Widder, Joachim, E-mail: j.widder@rt.umcg.nl [Department of Radiation Oncology, University Medical Center Groningen, University of Groningen, Groningen (Netherlands); Postmus, Douwe [Department of Epidemiology, University Medical Center Groningen, University of Groningen, Groningen (Netherlands); Ubbels, Jan F.; Wiegman, Erwin M.; Langendijk, Johannes A. [Department of Radiation Oncology, University Medical Center Groningen, University of Groningen, Groningen (Netherlands)

    2011-11-15

    Purpose: To investigate survival and local recurrence after stereotactic ablative radiotherapy (SABR) or three-dimensional conformal radiotherapy (3D-CRT) administered for early-stage primary lung cancer and to investigate longitudinal changes of health-related quality of life (HRQOL) parameters after either treatment. Methods and Materials: Two prospective cohorts of inoperable patients with T1-2N0M0 primary lung tumors were analyzed. Patients received 70 Gy in 35 fractions with 3D-CRT or 60 Gy in three to eight fractions with SABR. Global quality of life (GQOL), physical functioning (PF), and patient-rated dyspnea were assessed using the respective dimensions of European Organization for Research and Treatment of Cancer Core Questionnaire-C30 and LC13. HRQOL was analyzed using multivariate linear mixed-effects modeling, survival and local control (LC) using the Kaplan-Meier method, Cox proportional hazards analysis, and Fine and Gray multivariate competing risk analysis as appropriate. Results: Overall survival (OS) was better after SABR compared with 3D-CRT with a HR of 2.6 (95% confidence interval [CI]: 1.5-4.8; p < 0.01). 3D-CRT conferred a subhazard ratio for LC of 5.0 (95% CI: 1.7-14.7; p < 0.01) compared with SABR. GQOL and PF were stable after SABR (p = 0.21 and p = 0.62, respectively). Dyspnea increased after SABR by 3.2 out of 100 points (95% CI: 1.0-5.3; p < 0.01), which is clinically insignificant. At 1 year, PF decreased by an excess of 8.7 out of 100 points (95% CI: 2.8-14.7; p < 0.01) after 3D-CRT compared with SABR. Conclusion: In this nonrandomized comparison of two prospective cohorts of medically inoperable patients with Stage I lung cancer, OS and LC were better after SABR. GQOL, PF, and patient-rated dyspnea were stable after SABR, whereas PF decreased after 3D-CRT approaching clinical significance already at 1 year.

  7. Digital tomosynthesis (DTS) for verification of target position in early stage lung cancer patients

    Energy Technology Data Exchange (ETDEWEB)

    Sörnsen de Koste, John R. van; Dahele, Max; Senan, Suresh; Weide, Lineke van der; Slotman, Ben J.; Verbakel, Wilko F. A. R. [Department of Radiation Oncology, VU University Medical Center (VUMC), Amsterdam, Noord-Holland 1081 HV (Netherlands); Mostafavi, Hassan [Varian Medical Systems, Palo Alto, California (United States)

    2013-09-15

    Purpose: The ability to verify intrafraction tumor position is clinically useful for hypofractionated treatments. Short arc kV digital tomosynthesis (DTS) could facilitate more frequent target verification. The authors used DTS combined with triangulation to determine the mean temporal position of small-volume lung tumor targets treated with stereotactic radiotherapy. DTS registration results were benchmarked against online clinical localization using registration between free-breathing cone-beam computed tomography (CBCT) and the average intensity projection (AvIP) of the planning 4DCT.Methods: In this retrospective study, 76 sets of kV-projection images from online CBCT scans of 13 patients were used to generate DTS image slices (CB-DTS) with nonclinical research software (DTS Toolkit, Varian Medical Systems). Three-dimensional tumor motion was 1.3–4 mm in six patients and 6.1–25.4 mm in seven patients on 4DCT (significant difference in the mean of the groups, P < 0.01). The 4DCT AvIP was used to digitally reconstruct the Reference-DTS. DTS registration and DTS registration combined with triangulation were investigated. Progressive shortening of total DTS arc lengths from 95° to 35° around 0° gantry position was evaluated for different scenarios: DTS registration using the entire arc; DTS registration plus triangulation using two nonoverlapping arcs; and for 55° and 45° total gantry rotation, DTS registration plus triangulation using two overlapping arcs. Finally, DTS registration plus triangulation performed at eight gantry angles, each separated by 45° was evaluated using full fan kV projection data for one patient with an immobile tumor and five patients with mobile tumors.Results: For DTS registration alone, shortening arc length did not influence accuracy in X- and Y-directions, but in Z-direction, mean deviations from online CBCT localization systematically increased for shorter arc length (P < 0.05). For example, using a 95° arc mean DTS

  8. Comparative effectiveness of 5 treatment strategies for early-stage non-small cell lung cancer in the elderly.

    Science.gov (United States)

    Shirvani, Shervin M; Jiang, Jing; Chang, Joe Y; Welsh, James W; Gomez, Daniel R; Swisher, Stephen; Buchholz, Thomas A; Smith, Benjamin D

    2012-12-01

    The incidence of early-stage non-small cell lung cancer (NSCLC) among older adults is expected to increase because of demographic trends and computed tomography-based screening; yet, optimal treatment in the elderly remains controversial. Using the Surveillance, Epidemiology, and End Results (SEER)-Medicare cohort spanning 2001-2007, we compared survival outcomes associated with 5 strategies used in contemporary practice: lobectomy, sublobar resection, conventional radiation therapy, stereotactic ablative radiation therapy (SABR), and observation. Treatment strategy and covariates were determined in 10,923 patients aged ≥ 66 years with stage IA-IB NSCLC. Cox regression, adjusted for patient and tumor factors, compared overall and disease-specific survival for the 5 strategies. In a second exploratory analysis, propensity-score matching was used for comparison of SABR with other options. The median age was 75 years, and 29% had moderate to severe comorbidities. Treatment distribution was lobectomy (59%), sublobar resection (11.7%), conventional radiation (14.8%), observation (12.6%), and SABR (1.1%). In Cox regression analysis with a median follow-up time of 3.2 years, SABR was associated with the lowest risk of death within 6 months of diagnosis (hazard ratio [HR] 0.48; 95% confidence interval [CI] 0.38-0.63; referent is lobectomy). After 6 months, lobectomy was associated with the best overall and disease-specific survival. In the propensity-score matched analysis, survival after SABR was similar to that after lobectomy (HR 0.71; 95% CI 0.45-1.12; referent is SABR). Conventional radiation and observation were associated with poor outcomes in all analyses. In this population-based experience, lobectomy was associated with the best long-term outcomes in fit elderly patients with early-stage NSCLC. Exploratory analysis of SABR early adopters suggests efficacy comparable with that of surgery in select populations. Evaluation of these therapies in randomized trials

  9. CLINICAL SIGNIFICANCE OF THE LYMPH NODE MICRO-METASTASIS IN PATEINTS WITH EARLY STAGE NON-SMALL-CELL LUNG CANCER

    Institute of Scientific and Technical Information of China (English)

    2000-01-01

    @@ The postoperative 5-year survival rate is about 50-85% in the patient with the stage I non-small-cell lung cancer (NSCLC). It is remains unclear how we should give these patients adjuvant radiotherapy and chemotherapy after operation. We performed a postspective study to assess the prognostic and treatment guiding significance of lymph nodes micrometastasis (LMM) in patients with completely resected NSCLC at stage I.

  10. Integrin expression profiling identifies integrin alpha5 and beta1 as prognostic factors in early stage non-small cell lung cancer

    Directory of Open Access Journals (Sweden)

    van Suylen Robert-Jan

    2010-06-01

    Full Text Available Abstract Background Selection of early stage non-small cell lung cancer patients with a high risk of recurrence is warranted in order to select patients who will benefit from adjuvant treatment strategies. We evaluated the prognostic value of integrin expression profiles in a retrospective study on frozen primary tumors of 68 patients with early stage non-small cell lung cancer. Methods A retrospective study was performed on frozen primary tumors of 68 early stage non-small cell lung cancer patients with a follow up of at least 10 years. From all tumor tissues, RNA was isolated and reverse transcribed into cDNA. qPCR was used to generate mRNA expression profiles including integrins alpha1, 2, 3, 4, 5, 6, 7, 11, and V as well as integrins beta1, 3, 4, 5, 6, and 8. Results The expression levels of integrins alpha5, beta1 and beta3 predicted overall survival and disease free survival in early stage NSCLC patients. There was no association between integrin expression and lymph node metastases. Comparison between the histological subtypes revealed a distinct integrin signature for squamous cell carcinoma while the profiles of adenocarcinoma and large cell carcinoma were largely the same. Conclusion Integrin expression in NSCLC is important for the development and behavior of the tumor and influences the survival of the patient. Determining the integrin expression profile might serve as a tool in predicting the prognosis of individual patients.

  11. Squamous cell carcinoma of pancreas: an unusual site of relapse from early-stage lung cancer: 12-month postsurgery

    Science.gov (United States)

    Sharma, Anand; Alfa-Wali, Maryam; Rodriguez-Justo, Manuel; Polychronis, Andreas

    2013-01-01

    A 57-year-old man presented with abdominal pain and backache, weight loss of 10 kg and irregular bowel movements. He was previously diagnosed with Stage IB squamous cell carcinoma of lung and had undergone lobectomy 12 months previously. Investigations including imaging revealed a cystic mass in the body and tail of the pancreas which was biopsied and it was confirmed to be a recurrence of the squamous lung cancer involving the pancreas. He was treated with systemic chemotherapy and has shown a partial response on repeat imaging. This case illustrates a rare and unusual site of relapse in lung cancer after adjuvant therapy and a key message for follow-up surveillance for these patients. PMID:23608858

  12. The cholesterol-binding protein NPC2 restrains recruitment of stromal macrophage-lineage cells to early-stage lung tumours.

    Science.gov (United States)

    Kamata, Tamihiro; Jin, Hong; Giblett, Susan; Patel, Bipin; Patel, Falguni; Foster, Charles; Pritchard, Catrin

    2015-07-16

    The tumour microenvironment is known to play an integral role in facilitating cancer progression at advanced stages, but its function in some pre-cancerous lesions remains elusive. We have used the (V600) (E)BRAF-driven mouse lung model that develop premalignant lesions to understand stroma-tumour interactions during pre-cancerous development. In this model, we have found that immature macrophage-lineage cells (IMCs) producing PDGFA, TGFβ and CC chemokines are recruited to the stroma of premalignant lung adenomas through CC chemokine receptor 1 (CCR1)-dependent mechanisms. Stromal IMCs promote proliferation and transcriptional alterations suggestive of epithelial-mesenchymal transition in isolated premalignant lung tumour cells ex vivo, and are required for the maintenance of early-stage lung tumours in vivo. Furthermore, we have found that IMC recruitment to the microenvironment is restrained by the cholesterol-binding protein, Niemann-Pick type C2 (NPC2). Studies on isolated cells ex vivo confirm that NPC2 is secreted from tumour cells and is taken up by IMCs wherein it suppresses secretion of the CCR1 ligand CC chemokine 6 (CCL6), at least in part by facilitating its lysosomal degradation. Together, these findings show that NPC2 secreted by premalignant lung tumours suppresses IMC recruitment to the microenvironment in a paracrine manner, thus identifying a novel target for the development of chemopreventive strategies in lung cancer.

  13. [Imaging protocols for the management of respiratory motions in the radiotherapy planning for early stage lung cancer patients].

    Science.gov (United States)

    Pócza, Tamás; Pesznyák, Csilla; Lövey, József; Bajcsay, András; Szilágyi, András; Almády, Balázs; Major, Tibor; Polgár, Csaba

    2015-06-01

    The aim of our work is to present the imaging techniques used at the National Institute of Oncology for taking into consideration the breathing motion at radiation therapy treatment planning. Internationally recommended imaging techniques, such as 4D CT, respiratory gating and ITV (Internal Target Volume) definition were examined. The different imaging techniques were analysed regarding the delivered dose during imaging, the required time to adapt the technique, and the necessary equipment. The differences in size of PTVs (Planning Target Volume) due to diverse volume defining methods were compared in 5 cases. For 4D CT breath monitoring is crucial, which requires special equipment. To decrease the relatively high exposure of 4D CT it is possible to scan only a few predefined breathing phases. The possible positions of the tumour can be well approximated with CT scans taken in the inhale maximum, the exhale maximum and in intermediate phase. The intermediate phase can be exchanged with an ordinary CT image set, and the extreme phase CT images can be ensured by given verbal instructions for the patient. This way special gating equipment is not required. Based on these 3 breathing phases an ITV can be defined. Using this ITV definition method the margin between the CTV (Clinical Target Volume) and the PTV can be reduced by 1 cm. Using this imaging protocol PTV can be reduced by 30%. A further 10% PTV reduction can be achieved with respiratory gating. In the routine clinical practice respiratory motion management with a 3-phase CT-imaging protocol the PTV for early-stage lung cancer can be significantly reduced without the use of 4D CT and/or respiratory gating. For special, high precision treatment techniques 4D CT is recommended.

  14. CT characteristics and pathological implications of early stage (T1N0M0) lung adenocarcinoma with pure ground-glass opacity

    Energy Technology Data Exchange (ETDEWEB)

    Jin, Xin; Zhao, Shao-hong; Wu, Jian; Wu, Chong-chong; Chang, Rui-ping; Ju, Hai-yue [Chinese PLA General Hospital, Department of Radiology, Beijing (China); Gao, Jie; Wang, Dian-jun [Chinese PLA General Hospital, Department of Pathology, Beijing (China)

    2015-09-15

    To analyze the CT characteristics and pathological classification of early lung adenocarcinoma (T1N0M0) with pure ground-glass opacity (pGGO). Ninety-four lesions with pGGO on CT in 88 patients with T1N0M0 lung adenocarcinoma were selected from January 2010 to December 2012. All lesions were confirmed by pathology. CT appearances were analyzed including lesion location, size, density, uniformity, shape, margin, tumour-lung interface, internal and surrounding malignant signs. Lesion size and density were compared using analysis of variance, lesion size also assessed using ROC curves. Gender of patients, lesion location and CT appearances were compared using χ2-test. There were no significant differences in gender, lesion location and density with histological invasiveness (P > 0.05). The ROC curve showed that the possibility of invasive lesion was 88.73 % when diameter of lesion was more than 10.5 mm. There was a significant difference between lesion uniformity and histological invasiveness (P = 0.01). There were significant differences in margin, tumour-lung interface, air bronchogram with histological invasiveness (P = 0.02,P = 0.00,P = 0.048). The correlation index of lesion size and uniformity was r = 0.45 (P = 0.00). The lesion size and uniformity, tumour-lung interface and the air bronchogram can help predict invasive extent of early stage lung adenocarcinoma with pGGO. (orig.)

  15. Strategies of Individual Surgical Treatment for Early Stage Non-small Cell Lung Cancer and the Guidance of Intraoperative Frozen Pathology

    Directory of Open Access Journals (Sweden)

    Bin HU

    2016-06-01

    Full Text Available Early stage non-small cell lung cancer patients, especially those who presented small GGO on image, are increasing in Asia population. Retrospective clinical data indicated that the efficacy of sub-lobectomy for these patients may be non-inferior to that of lobectomy. Meanwhile, sub-lobectomy could preserve more pulmonary function for the patients. Researches have demonstrated that careful evaluation for the image manifestation is essential before sub-lobectomy and those who diagnosed as adenocarcinoma in situ or minimally invasive adenocarcinoma may be more appropriate for this procedure. Precise diagnosis of Intraoperative frozen section is an effective method toward personalization of surgical care for early-stage non-smallcell lung cancer.

  16. Robotic stereotactic body radiation therapy for elderly medically inoperable early-stage non-small cell lung cancer

    Directory of Open Access Journals (Sweden)

    Karam SD

    2013-08-01

    Full Text Available Sana D Karam,1 Zachary D Horne,1 Robert L Hong,1,2 Nimrah Baig,1 Gregory J Gagnon,4 Don McRae,2 David Duhamel,3 Nadim M Nasr1,21Department of Radiation Oncology, Georgetown University Hospital, Washington, DC, USA; 2Department of Radiation Oncology, Virginia Hospital Center, Arlington, VA, USA; 3Department of Pulmonary/Critical Care Medicine, Virginia Hospital Center, Arlington, VA, USA; 4Department of Radiation Oncology, Frederick Memorial Hospital, Frederick, MD, USAIntroduction: Stereotactic body radiation therapy (SBRT is being increasingly applied in the treatment of non-small cell lung cancer (NSCLC because of its high local efficacy. This study aims to examine survival outcomes in elderly patients with inoperable stage I NSCLC treated with SBRT.Methods: A total of 31 patients with single lesions treated with fractionated SBRT from 2008 to 2011 were retrospectively analyzed. A median prescribed dose of 48 Gy was delivered to the prescription isodose line, over a median of four treatments. The median biologically effective dose (BED was 105.6 (range 37.50–180, and the median age was 73 (65–90 years. No patient received concurrent chemotherapy.Results: With a median follow up of 13 months (range, 4–40 months, the actuarial median overall survival (OS and progression-free survival (PFS were 32 months, and 19 months, respectively. The actuarial median local control (LC time was not reached. The survival outcomes at median follow up of 13 months were 80%, 68%, and 70% for LC, PFS, and OS, respectively. Univariate analysis revealed a BED of >100 Gy was associated with improved LC rates (P = 0.02, while squamous cell histology predicted for worse LC outcome at median follow up time of 13 months (P = 0.04. Increased tumor volume was a worse prognostic indicator of both LC and OS outcomes (P < 0.05. Finally, female gender was a better prognostic factor for OS than male gender (P = 0.006. There were no prognostic indicators of PFS that reached

  17. Solid Predominant Histologic Subtype in Resected Stage I Lung Adenocarcinoma Is an Independent Predictor of Early, Extrathoracic, Multisite Recurrence and of Poor Postrecurrence Survival

    Science.gov (United States)

    Ujiie, Hideki; Kadota, Kyuichi; Chaft, Jamie E.; Buitrago, Daniel; Sima, Camelia S.; Lee, Ming-Ching; Huang, James; Travis, William D.; Rizk, Nabil P.; Rudin, Charles M.; Jones, David R.; Adusumilli, Prasad S.

    2015-01-01

    Purpose To examine the significance of the proposed International Association for the Study of Lung Cancer, American Thoracic Society, and European Respiratory Society (IASLC/ATS/ERS) histologic subtypes of lung adenocarcinoma for patterns of recurrence and, among patients who recur following resection of stage I lung adenocarcinoma, for postrecurrence survival (PRS). Patients and Methods We reviewed patients with stage I lung adenocarcinoma who had undergone complete surgical resection from 1999 to 2009 (N = 1,120). Tumors were subtyped by using the IASLC/ATS/ERS classification. The effects of the dominant subtype on recurrence and, among patients who recurred, on PRS were investigated. Results Of 1,120 patients identified, 188 had recurrent disease, 103 of whom died as a result of lung cancer. Among patients who recurred, 2-year PRS was 45%, and median PRS was 26.1 months. Compared with patients with nonsolid tumors, patients with solid predominant tumors had earlier (P = .007), more extrathoracic (P recurrences. Multivariable analysis of primary tumor factors revealed that, among patients who recurred, solid predominant histologic pattern in the primary tumor (hazard ratio [HR], 1.76; P = .016), age older than 65 years (HR, 1.63; P = .01), and sublobar resection (HR, 1.6; P = .01) were significantly associated with worse PRS. Presence of extrathoracic metastasis (HR, 1.76; P = .013) and age older than 65 years at the time of recurrence (HR, 1.7; P = .014) were also significantly associated with worse PRS. Conclusion In patients with stage I primary lung adenocarcinoma, solid predominant subtype is an independent predictor of early recurrence and, among those patients who recur, of worse PRS. Our findings provide a rationale for investigating adjuvant therapy and identify novel therapeutic targets for patients with solid predominant lung adenocarcinoma. PMID:26261257

  18. Genetic variants of the Wnt signaling pathway as predictors of recurrence and survival in early-stage non-small cell lung cancer patients.

    Science.gov (United States)

    Coscio, Angela; Chang, David W; Roth, Jack A; Ye, Yuanqing; Gu, Jian; Yang, Ping; Wu, Xifeng

    2014-06-01

    Early-stage non-small cell lung cancer (NSCLC) is potentially curative. Nevertheless, many patients will show disease recurrence after curative treatment. The Wnt signaling pathway is a developmental and stem cell pathway that plays an important role in tumorigenesis and may affect cancer progression. We hypothesize that genetic variants of the Wnt pathway may influence clinical outcome in early-stage NSCLC patients. We genotyped 441 functional and tagging single nucleotide polymorphisms (SNPs) from 54 genes of the Wnt pathway in 535 early-stage NSCLC patients treated with curative intent therapy including surgery and chemotherapy. For validation, 4 top SNPs were genotyped in 301 early-stage NSCLC patients from the Mayo Clinic. Cox proportional hazard model and combined SNP analyses were performed to identify significant SNPs correlated with recurrence-free and overall survival. Results from discovery group showed a total of 40 SNPs in 20 genes correlated with disease recurrence (P recurrence-free and overall survival. Joint SNP analyses identified predictive markers for recurrence stratified by treatment. Our findings suggest inherited genetic variation in the Wnt signaling pathway may contribute to variable clinical outcomes for patients with early-stage NSCLC. © The Author 2014. Published by Oxford University Press. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

  19. Lack of a Dose-Effect Relationship for Pulmonary Function Changes After Stereotactic Body Radiation Therapy for Early-Stage Non-Small Cell Lung Cancer

    Energy Technology Data Exchange (ETDEWEB)

    Guckenberger, Matthias, E-mail: Guckenberger_M@klinik.uni-wuerzburg.de [Department of Radiation Oncology, University Hospital Wuerzburg, Wuerzburg (Germany); Klement, Rainer J. [Department of Radiation Oncology, University Hospital Wuerzburg, Wuerzburg (Germany); Kestin, Larry L. [Department of Radiation Oncology, William Beaumont Hospital, Royal Oak, Michigan (United States); Hope, Andrew J. [Princess Margaret Hospital, University of Toronto, Toronto, ON (Canada); Belderbos, Jose [The Netherlands Cancer Institute–Antoni van Leeuwenhoek Hospital, Amsterdam (Netherlands); Werner-Wasik, Maria [Thomas Jefferson University Hospital, Philadelphia, Pennsylvania (United States); Yan, Di [Department of Radiation Oncology, William Beaumont Hospital, Royal Oak, Michigan (United States); Sonke, Jan-Jakob [The Netherlands Cancer Institute–Antoni van Leeuwenhoek Hospital, Amsterdam (Netherlands); Bissonnette, Jean-Pierre [Princess Margaret Hospital, University of Toronto, Toronto, ON (Canada); Xiao, Ying [Thomas Jefferson University Hospital, Philadelphia, Pennsylvania (United States); Grills, Inga S. [Department of Radiation Oncology, William Beaumont Hospital, Royal Oak, Michigan (United States)

    2013-03-15

    Purpose: To evaluate the influence of tumor size, prescription dose, and dose to the lungs on posttreatment pulmonary function test (PFT) changes after stereotactic body radiation therapy (SBRT) for early-stage non-small cell lung cancer (NSCLC). Methods and Materials: The analysis is based on 191 patients treated at 5 international institutions: inclusion criteria were availability of pre- and post-SBRT PFTs and dose-volume histograms of the lung and planning target volume (PTV); patients treated with more than 1 SBRT course were excluded. Correlation between early (1-6 months, median 3 months) and late (7-24 months, median 12 months) PFT changes and tumor size, planning target volume (PTV) dose, and lung doses was assessed using linear regression analysis, receiver operating characteristics analysis, and Lyman's normal tissue complication probability model. The PTV doses were converted to biologically effective doses and lung doses to 2 Gy equivalent doses before correlation analyses. Results: Up to 6 months after SBRT, forced expiratory volume in 1 second and carbon monoxide diffusion capacity changed by −1.4% (95% confidence interval [CI], −3.4% to 0) and −7.6% (95% CI, −10.2% to −3.4%) compared with pretreatment values, respectively. A modest decrease in PFTs was observed 7-24 months after SBRT, with changes of −8.1% (95% CI, −13.3% to −5.3%) and −12.4% (95% CI, −15.5% to −6.9%), respectively. Using linear regression analysis, receiver operating characteristic analysis, and normal tissue complication probability modeling, all evaluated parameters of tumor size, PTV dose, mean lung dose, and absolute and relative volumes of the lung exposed to minimum doses of 5-70 Gy were not correlated with early and late PFT changes. Subgroup analysis based on pre-SBRT PFTs (greater or equal and less than median) did not identify any dose-effect relationship. Conclusions: This study failed to demonstrate a significant dose-effect relationship for

  20. No Clinically Significant Changes in Pulmonary Function Following Stereotactic Body Radiation Therapy for Early- Stage Peripheral Non-Small Cell Lung Cancer: An Analysis of RTOG 0236

    Energy Technology Data Exchange (ETDEWEB)

    Stanic, Sinisa, E-mail: sinisa.stanic@carle.com [Carle Cancer Center and University of Illinois College of Medicine, Urbana, Illinois (United States); Paulus, Rebecca [Radiation Therapy Oncology Group Statistical Center, Philadelphia, Pennsylvania (United States); Timmerman, Robert D. [University of Texas Southwestern, Dallas, Texas (United States); Michalski, Jeff M. [Washington University, St. Louis, Missouri (United States); Barriger, Robert B. [Indiana University, Indianapolis, Indiana (United States); Bezjak, Andrea [Princess Margaret Cancer Center, Toronto, Ontario (Canada); Videtic, Gregory M.M. [Cleveland Clinic Foundation, Cleveland, Ohio (United States); Bradley, Jeffrey [Washington University, St. Louis, Missouri (United States)

    2014-04-01

    Purpose: To investigate pulmonary function test (PFT) results and arterial blood gas changes (complete PFT) following stereotactic body radiation therapy (SBRT) and to see whether baseline PFT correlates with lung toxicity and overall survival in medically inoperable patients receiving SBRT for early stage, peripheral, non-small cell lung cancer (NSCLC). Methods and Materials: During the 2-year follow-up, PFT data were collected for patients with T1-T2N0M0 peripheral NSCLC who received effectively 18 Gy × 3 in a phase 2 North American multicenter study (Radiation Therapy Oncology Group [RTOG] protocol 0236). Pulmonary toxicity was graded by using the RTOG SBRT pulmonary toxicity scale. Paired Wilcoxon signed rank test, logistic regression model, and Kaplan-Meier method were used for statistical analysis. Results: At 2 years, mean percentage predicted forced expiratory volume in the first second and diffusing capacity for carbon monoxide declines were 5.8% and 6.3%, respectively, with minimal changes in arterial blood gases and no significant decline in oxygen saturation. Baseline PFT was not predictive of any pulmonary toxicity following SBRT. Whole-lung V5 (the percentage of normal lung tissue receiving 5 Gy), V10, V20, and mean dose to the whole lung were almost identical between patients who developed pneumonitis and patients who were pneumonitis-free. Poor baseline PFT did not predict decreased overall survival. Patients with poor baseline PFT as the reason for medical inoperability had higher median and overall survival rates than patients with normal baseline PFT values but with cardiac morbidity. Conclusions: Poor baseline PFT did not appear to predict pulmonary toxicity or decreased overall survival after SBRT in this medically inoperable population. Poor baseline PFT alone should not be used to exclude patients with early stage lung cancer from treatment with SBRT.

  1. Metformin exposure is associated with improved progression-free survival in diabetic patients after resection for early-stage non-small cell lung cancer.

    Science.gov (United States)

    Medairos, Robert A; Clark, James; Holoubek, Simon; Kubasiak, John C; Pithadia, Ravi; Hamid, Fatima; Chmielewski, Gary W; Warren, William H; Basu, Sanjib; Borgia, Jeffrey A; Liptay, Michael J; Seder, Christopher W

    2016-07-01

    There are little clinical data assessing the antineoplastic effect of metformin in patients with non-small cell lung cancer. We hypothesized that in diabetic patients undergoing pulmonary resection for early-stage non-small cell lung cancer, metformin exposure is associated with improved survival. An institutional database was used to identify patients with stage I or II non-small cell lung cancer who underwent pulmonary resection between 2004 and 2013. Patients were divided into 3 cohorts: type II diabetic patients with metformin exposure (cohort A, n = 81), type II diabetic patients without metformin exposure (cohort B, n = 57), and nondiabetic individuals (cohort C, n = 77). Univariate, multivariate, and propensity-matched analyses were performed to assess progression-free and overall survivals between groups. A total of 215 patients with stage I and II non-small cell lung cancer treated with surgical resection were identified for analysis with a median follow-up of 19.5 months. Patients in cohort A had lower T- and N-stage tumors than those in cohorts B or C. However, on multivariate analysis adjusting for age, gender, and T and N stage, progression-free survival was greater for cohort A than cohort B (hazard ratio [HR], 0.410; 95% confidence interval, 0.199-0.874; P = .022) or cohort C (HR, 0.415; 95% confidence interval, 0.201-0.887; P = .017). Likewise, when propensity-matched analyses were performed, cohort A demonstrated a trend toward improved progression-free survival compared with cohort B (P = .057; HR, 0.44; c-statistic = 0.832) and improved progression-free survival compared with cohort C (P = .02; HR, 0.41; c-statistic = 0.843). No differences were observed in overall survival. Metformin exposure in diabetic patients with early-stage non-small cell lung cancer may be associated with improved progression-free survival, but no effect was seen on overall survival. Further studies are warranted to evaluate if there is a therapeutic

  2. An Immune Response Enriched 72-Gene Prognostic Profile for Early-Stage Non-Small-Cell Lung Cancer

    NARCIS (Netherlands)

    Roepman, P.; Jassem, J; Smit, E.F.; Muley, T.; Niklinski, J.; Vel, van de T.; Witteveen, A.T.; Rzyman, W.; Floore, A.; Burgers, S.; Giaccone, G.; Meister, M.; Dienemann, H.; Skrzypski, M.; Kozlowski, M.; Mooi, W.J.; Zandwijk, van N.

    2009-01-01

    0.01; n = 69). Genes in our prognostic signature were strongly enriched for genes associated with immune response. Conclusions: Our 72-gene signature is closely associated with recurrence-free and overall survival in early-stage NSCLC patients and may become a tool for patient selection for adjuvant

  3. Quantification of regional early stage gas exchange changes using hyperpolarized {sup 129}Xe MRI in a rat model of radiation-induced lung injury

    Energy Technology Data Exchange (ETDEWEB)

    Doganay, Ozkan, E-mail: ozkan.doganay@oncology.ox.ac.uk [Department of Medical Biophysics, Western University, London, Ontario N6A5C1 (Canada); Imaging Research Laboratories, Robarts Research Institute, London, Ontario N6A5C1 (Canada); Department of Oncology, University of Oxford, Old Road Campus Research Building, Roosevelt Drive, Oxford OX3 7DQ (United Kingdom); Stirrat, Elaine [Peter Gilgan Centre for Research and Learning, The Hospital for Sick Children, 555 University Avenue, Toronto, Ontario M5G1X8 (Canada); McKenzie, Charles [Department of Medical Biophysics, Western University, London, Ontario N6A5C1 (Canada); Imaging Research Laboratories, Robarts Research Institute, London, Ontario N6A5C1 (Canada); Schulte, Rolf F. [General Electric Global Research, Munich 85748 (Germany); Santyr, Giles E. [Department of Medical Biophysics, Western University, London, Ontario N6A5C1 (Canada); Imaging Research Laboratories, Robarts Research Institute, London, Ontario N6A5C1 (Canada); Peter Gilgan Centre for Research and Learning, The Hospital for Sick Children, 555 University Avenue, Toronto, Ontario M5G1X8 (Canada); Department of Medical Biophysics, University of Toronto, Toronto, Ontario M5G1L7 (Canada)

    2016-05-15

    Purpose: To assess the feasibility of hyperpolarized (HP) {sup 129}Xe MRI for detection of early stage radiation-induced lung injury (RILI) in a rat model involving unilateral irradiation by assessing differences in gas exchange dynamics between irradiated and unirradiated lungs. Methods: The dynamics of gas exchange between alveolar air space and pulmonary tissue (PT), PT and red blood cells (RBCs) was measured using single-shot spiral iterative decomposition of water and fat with echo asymmetry and least-squares estimation images of the right and left lungs of two age-matched cohorts of Sprague Dawley rats. The first cohort (n = 5) received 18 Gy irradiation to the right lung using a {sup 60}Co source and the second cohort (n = 5) was not irradiated and served as the healthy control. Both groups were imaged two weeks following irradiation when radiation pneumonitis (RP) was expected to be present. The gas exchange data were fit to a theoretical gas exchange model to extract measurements of pulmonary tissue thickness (L{sub PT}) and relative blood volume (V{sub RBC}) from each of the right and left lungs of both cohorts. Following imaging, lung specimens were retrieved and percent tissue area (PTA) was assessed histologically to confirm RP and correlate with MRI measurements. Results: Statistically significant differences in L{sub PT} and V{sub RBC} were observed between the irradiated and non-irradiated cohorts. In particular, L{sub PT} of the right and left lungs was increased approximately 8.2% and 5.0% respectively in the irradiated cohort. Additionally, V{sub RBC} of the right and left lungs was decreased approximately 36.1% and 11.7% respectively for the irradiated cohort compared to the non-irradiated cohort. PTA measurements in both right and left lungs were increased in the irradiated group compared to the non-irradiated cohort for both the left (P < 0.05) and right lungs (P < 0.01) confirming the presence of RP. PTA measurements also correlated with the

  4. Identification of early-stage usual interstitial pneumonia from low-dose chest CT scans using fractional high-density lung distribution

    Science.gov (United States)

    Xie, Yiting; Salvatore, Mary; Liu, Shuang; Jirapatnakul, Artit; Yankelevitz, David F.; Henschke, Claudia I.; Reeves, Anthony P.

    2017-03-01

    A fully-automated computer algorithm has been developed to identify early-stage Usual Interstitial Pneumonia (UIP) using features computed from low-dose CT scans. In each scan, the pre-segmented lung region is divided into N subsections (N = 1, 8, 27, 64) by separating the lung from anterior/posterior, left/right and superior/inferior in 3D space. Each subsection has approximately the same volume. In each subsection, a classic density measurement (fractional high-density volume h) is evaluated to characterize the disease severity in that subsection, resulting in a feature vector of length N for each lung. Features are then combined in two different ways: concatenation (2*N features) and taking the maximum in each of the two corresponding subsections in the two lungs (N features). The algorithm was evaluated on a dataset consisting of 51 UIP and 56 normal cases, a combined feature vector was computed for each case and an SVM classifier (RBF kernel) was used to classify them into UIP or normal using ten-fold cross validation. A receiver operating characteristic (ROC) area under the curve (AUC) was used for evaluation. The highest AUC of 0.95 was achieved by using concatenated features and an N of 27. Using lung partition (N = 27, 64) with concatenated features had significantly better result over not using partitions (N = 1) (p-value < 0.05). Therefore this equal-volume partition fractional high-density volume method is useful in distinguishing early-stage UIP from normal cases.

  5. Serum, liver, and lung levels of the major extracellular matrix components at the early stage of BCG-induced granulomatosis depending on the infection route.

    Science.gov (United States)

    Kim, L B; Shkurupy, V A; Putyatina, A N

    2015-01-01

    Experiments on the model of mouse BCG-induced granulomatous showed that the content of glycosaminoglycans and proteoglycans in the extracellular matrix of the liver and lungs are changed at the early stages of inflammation (days 3 and 30 postinfection) before cell destruction in the organs begins. This is related to degradation of extracellular matrix structures. Their high content in the blood and interstitium probably contributes to the formation of granulomas, fibroblast proliferation and organ fibrosis. These processes depend on the infection route that determines different conditions for generalization of the inflammation process. Intravenous method of vaccine injection is preferable to use when designing the experiments simulating tuberculosis granulomatosis, especially for the analysis of its early stages.

  6. Myeloid clusters are associated with a pro-metastatic environment and poor prognosis in smoking-related early stage non-small cell lung cancer.

    Directory of Open Access Journals (Sweden)

    Wang Zhang

    Full Text Available BACKGROUND: This study aimed to understand the role of myeloid cell clusters in uninvolved regional lymph nodes from early stage non-small cell lung cancer patients. METHODS: Uninvolved regional lymph node sections from 67 patients with stage I-III resected non-small cell lung cancer were immunostained to detect myeloid clusters, STAT3 activity and occult metastasis. Anthracosis intensity, myeloid cluster infiltration associated with anthracosis and pSTAT3 level were scored and correlated with patient survival. Multivariate Cox regression analysis was performed with prognostic variables. Human macrophages were used for in vitro nicotine treatment. RESULTS: CD68+ myeloid clusters associated with anthracosis and with an immunosuppressive and metastasis-promoting phenotype and elevated overall STAT3 activity were observed in uninvolved lymph nodes. In patients with a smoking history, myeloid cluster score significantly correlated with anthracosis intensity and pSTAT3 level (P<0.01. Nicotine activated STAT3 in macrophages in long-term culture. CD68+ myeloid clusters correlated and colocalized with occult metastasis. Myeloid cluster score was an independent prognostic factor (P = 0.049 and was associated with survival by Kaplan-Maier estimate in patients with a history of smoking (P = 0.055. The combination of myeloid cluster score with either lymph node stage or pSTAT3 level defined two populations with a significant difference in survival (P = 0.024 and P = 0.004, respectively. CONCLUSIONS: Myeloid clusters facilitate a pro-metastatic microenvironment in uninvolved regional lymph nodes and associate with occult metastasis in early stage non-small cell lung cancer. Myeloid cluster score is an independent prognostic factor for survival in patients with a history of smoking, and may present a novel method to inform therapy choices in the adjuvant setting. Further validation studies are warranted.

  7. Stereotactic Body Radiotherapy for Early-stage Non-small-cell Lung Cancer in Patients 80 Years and Older: A Multi-center Analysis.

    Science.gov (United States)

    Cassidy, Richard J; Patel, Pretesh R; Zhang, Xinyan; Press, Robert H; Switchenko, Jeffrey M; Pillai, Rathi N; Owonikoko, Taofeek K; Ramalingam, Suresh S; Fernandez, Felix G; Force, Seth D; Curran, Walter J; Higgins, Kristin A

    2017-09-01

    Stereotactic body radiotherapy (SBRT) is the standard of care for medically inoperable early-stage non-small-cell lung cancer. Despite the limited number of octogenarians and nonagenarians on trials of SBRT, its use is increasingly being offered in these patients, given the aging cancer population, medical fragility, or patient preference. Our purpose was to investigate the efficacy, safety, and survival of patients ≥ 80 years old treated with definitive lung SBRT. Patients who underwent SBRT were reviewed from 2009 to 2015 at 4 academic centers. Patients diagnosed at ≥ 80 years old were included. Kaplan-Meier and multivariate logistic regression and Cox proportional hazard regression analyses were performed. Recursive partitioning analysis was done to determine a subgroup of patients most likely to benefit from therapy. A total of 58 patients were included, with a median age of 84.9 years (range, 80.1-95.2 years), a median follow-up time of 19.9 months (range, 6.9-64.9 months), a median fraction size of 10.0 Gy (range, 7.0-20.0 Gy), and a median number of fractions of 5.0 (range, 3.0-8.0 fractions). On multivariate analysis, higher Karnofsky performance status (KPS) was associated with higher local recurrence-free survival (hazard ratio [HR], 0.92; P patients with KPS ≥ 75 had improved 3-year cancer-specific and overall survival (99.4% and 91.9%, respectively) compared with patients with KPS lung SBRT for early-stage non-small-cell lung cancer was efficacious and safe in patients ≥ 80 years old. Patients with a KPS of ≥ 75 derived the most benefit from therapy. Copyright © 2017 Elsevier Inc. All rights reserved.

  8. Volumetric Modulated Arc Radiotherapy for Early Stage Non-Small-Cell Lung Carcinoma: Is It Better Than the Conventional Static Beam Intensity Modulated Radiotherapy?

    Directory of Open Access Journals (Sweden)

    Vincent Wing Cheung Wu

    2014-01-01

    Full Text Available This study compared the performance of volumetric modulated arc therapy (VMAT techniques: single arc volumetric modulated arc therapy (SA-VMAT and double arc volumetric modulated arc therapy (DA-VMAT with the static beam conventional intensity modulated radiotherapy (C-IMRT for non-small-cell lung carcinoma (NSCLC. Twelve stage I and II NSCLC patients were recruited and their planning CT with contoured planning target volume (PTV and organs at risk (OARs was used for planning. Using the same dose constraints and planning objectives, the C-IMRT, SA-VMAT, and DA-VMAT plans were optimized. C-IMRT consisted of 7 static beams, while SA-VMAT and DA-VMAT plans consisted of one and two full gantry rotations, respectively. No significant difference was found among the three techniques in target homogeneity and conformity. Mean lung dose in C-IMRT plan was significantly lower than that in DA-VMAT plan P=0.04. The ability of OAR sparing was similar among the three techniques, with no significant difference in V20, V10, or V5 of normal lungs, spinal cord, and heart. Less MUs were required in SA-VMAT and DA-VMAT. Besides, SA-VMAT required the shortest beam on time among the three techniques. In treatment of early stage NSCLC, no significant dosimetric superiority was shown by the VMAT techniques over C-IMRT and DA-VMAT over SA-VMAT.

  9. The New Lung Cancer Staging System

    Institute of Scientific and Technical Information of China (English)

    Frank C. Detterbeck,MD, FCCP; Daniel J. Boffa, MD; Lynn T, Tanoue, MD, FCCP

    2009-01-01

    The International Association for the Study of Lung Cancer (IASLC) has conducted an extensive initiative to inform the revision of the lung cancer staging system. This involved development of an international database along with extensive analysis of a large population of patients and their prognoses. This article reviews the recommendations of the IASLC International Staging Committee for the definitions for the TNM descriptors and the stage grouping in the new non-small cell lung cancer staging system.

  10. Comprehensive dosimetric planning comparison for early-stage, non-small cell lung cancer with SABR: fixed-beam IMRT versus VMAT versus TomoTherapy.

    Science.gov (United States)

    Xhaferllari, Ilma; El-Sherif, Omar; Gaede, Stewart

    2016-09-08

    Volumetric-modulated arc therapy (VMAT) is emerging as a leading technology in treating early-stage, non-small cell lung cancer (NSCLC) with stereotactic ablative radiotherapy (SABR). However, two other modalities capable of deliver-ing intensity-modulated radiation therapy (IMRT) include fixed-beam and helical TomoTherapy (HT). This study aims to provide an extensive dosimetric compari-son among these various IMRT techniques for treating early-stage NSCLC with SABR. Ten early-stage NSCLC patients were retrospectively optimized using three fixed-beam techniques via nine to eleven beams (high and low modulation step-and-shoot (SS), and sliding window (SW)), two VMAT techniques via two partial arcs (SmartArc (SA) and RapidArc (RA)), and three HT techniques via three different fan beam widths (1 cm, 2.5 cm, and 5 cm) for 80 plans total. Fixed-beam and VMAT plans were generated using flattening filter-free beams. SS and SA, HT treatment plans, and SW and RA were optimized using Pinnacle v9.1, Tomoplan v.3.1.1, and Eclipse (Acuros XB v11.3 algorithm), respectively. Dose-volume histogram statistics, dose conformality, and treatment delivery efficiency were analyzed. VMAT treatment plans achieved significantly lower values for contralat-eral lung V5Gy (p ≤ 0.05) compared to the HT plans, and significantly lower mean lung dose (p VMAT techniques, a significant reduction in the total monitor units (p = 0.05) was found in the SA plans, while a significant decrease was observed in the dose falloff parameter, D2cm, (p = 0.05), for the RA treatments. The maximum cord dose was significantly reduced (p = 0.017) in grouped RA&SA plans com-pared to SS. Estimated treatment time was significantly higher for HT and fixed-beam plans compared to RA&SA (p VMAT is dosimetrically advantageous in treating early-stage NSCLC with SABR compared to fixed-beam, while providing significantly shorter treatment times.

  11. How Are Lung Carcinoid Tumors Staged?

    Science.gov (United States)

    ... in How Are Lung Carcinoid Tumors Diagnosed? The TNM staging system A staging system is a standard ... cancer – the American Joint Committee on Cancer (AJCC) TNM staging system. The TNM system describes 3 key ...

  12. Clinical Analysis of stereotactic body radiation therapy using extracranial gamma knife for patients with mainly bulky inoperable early stage non-small cell lung carcinoma

    Directory of Open Access Journals (Sweden)

    Tang Hanjun

    2011-07-01

    Full Text Available Abstract Purpose To evaluate the clinical efficacy and toxicity of stereotactic body radiation therapy (SBRT using extracranial gamma knife in patients with mainly bulky inoperable early stage non-small cell lung carcinoma (NSCLC. Materials and methods A total of 43 medically inoperable patients with mainly bulky Stage I/II NSCLC received SBRT using gamma knife were reviewed. The fraction dose and the total dose were determined by the radiation oncologist according to patients' general status, tumor location, tumor size and the relationship between tumor and nearby organ at risk (OAR. The total dose of 34~47.5 Gy was prescribed in 4~12 fractions, 3.5~10 Gy per fraction, one fraction per day or every other day. The therapeutic efficacy and toxicity were evaluated. Results The median follow-up was 22 months (range, 3-102 months. The local tumor response rate was 95.35%, with CR 18.60% (8/43 and PR 76.74% (33/43, respectively. The local control rates at 1, 2, 3, 5 years were 77.54%, 53.02%, 39.77%, and 15.46%, respectively, while the 1- and 2-year local control rates were 75% and 60% for tumor ≤3 cm; 84% and 71% for tumor sized 3~5 cm; 55% and 14.6% for tumor sized 5~7 cm; and 45%, 21% in those with tumor size of >7 cm. The overall survival rate at 1, 2, 3, 5 years were 92.04%, 78.04%, 62.76%, 42.61%, respectively. The toxicity of stereotactic radiation therapy was grade 1-2. Clinical stages were significantly important factor in local control of lung tumors (P = 0.000. Both clinical stages (P = 0.015 and chemotherapy (P = 0.042 were significantly important factors in overall survival of lung tumors. Conclusion SBRT is an effective and safe therapy for medically inoperable patients with early stage NSCLC. Clinical stage was the significant prognostic factors for both local tumor control and overall survival. The toxicity is mild. The overall local control for bulky tumors is poor. Tumor size is a poor prognostic factor, and the patients for

  13. Two-gene signature improves the discriminatory power of IASLC/ATS/ERS classification to predict the survival of patients with early-stage lung adenocarcinoma

    Directory of Open Access Journals (Sweden)

    Sun Y

    2016-07-01

    Full Text Available Yifeng Sun,1,* Likun Hou,2,* Yu Yang,1 Huikang Xie,2 Yang Yang,1 Zhigang Li,1 Heng Zhao,1 Wen Gao,3 Bo Su4 1Department of Thoracic Surgery, Shanghai Chest Hospital, Shanghai Jiaotong University, 2Department of Pathology, Shanghai Pulmonary Hospital, Tongji University School of Medicine, Shanghai, 3Department of Thoracic Surgery, Shanghai Huadong Hospital, Fudan University School of Medicine, Shanghai, 4Central Lab, Shanghai Pulmonary Hospital, Tongji University School of Medicine, Shanghai, People’s Republic of China *These authors contributed equally to this work Background: In this study, we investigated the contribution of a gene expression–based signature (composed of BAG1, BRCA1, CDC6, CDK2AP1, ERBB3, FUT3, IL11, LCK, RND3, SH3BGR to survival prediction for early-stage lung adenocarcinoma categorized by the new International Association for the Study of Lung Cancer (IASLC/the American Thoracic Society (ATS/the European Respiratory Society (ERS classification. We also aimed to verify whether gene signature improves the risk discrimination of IASLC/ATS/ERS classification in early-stage lung adenocarcinoma. Patients and methods: Total RNA was extracted from 93 patients with pathologically confirmed TNM stage Ia and Ib lung adenocarcinoma. The mRNA expression levels of ten genes in the signature (BAG1, BRCA1, CDC6, CDK2AP1, ERBB3, FUT3, IL11, LCK, RND3, and SH3BGR were detected using real-time polymerase chain reaction. Each patient was categorized according to the new IASLC/ATS/ERS classification by accessing hematoxylin–eosin-stained slides. The corresponding Kaplan–Meier survival analysis by the log-rank statistic, multivariate Cox proportional hazards modeling, and c-index calculation were conducted using the programming language R (Version 2.15.1 with the “risksetROC” package. Results: The multivariate analysis demonstrated that the risk factor of the ten-gene expression signature can significantly improve the discriminatory

  14. Analysis of GAGE, NY-ESO-1 and SP17 cancer/testis antigen expression in early stage non-small cell lung carcinoma.

    Science.gov (United States)

    Gjerstorff, Morten F; Pøhl, Mette; Olsen, Karen E; Ditzel, Henrik J

    2013-10-08

    The unique expression pattern and immunogenic properties of cancer/testis antigens make them ideal targets for immunotherapy of cancer. The MAGE-A3 cancer/testis antigen is frequently expressed in non-small cell lung cancer (NSCLC) and vaccination with MAGE-A3 in patients with MAGE-A3-positive NSCLC has shown promising results. However, little is known about the expression of other cancer/testis antigens in NSCLC. In the present study the expression of cancer/testis antigens GAGE, NY-ESO-1 and SP17 was investigated in patients with completely resected, early stage, primary NSCLC. Tumor biopsies from normal lung tissue and from a large cohort (n = 169) of NSCLC patients were examined for GAGE, NY-ESO-1 and SP17 protein expression by immunohistochemical analysis. The expression of these antigens was further matched to clinical and pathological features using univariate cox regression analysis. GAGE and NY-ESO-1 cancer/testis antigens were not expressed in normal lung tissue, while SP17 was expressed in ciliated lung epithelia. The frequency of GAGE, NY-ESO-1 and SP17 expression in NSCLC tumors were 26.0% (44/169), 11.8% (20/169) and 4.7% (8/169), respectively, and 33.1% (56/169) of the tumors expressed at least one of these antigens. In general, the expression of GAGE, NY-ESO-1 and SP17 was not significantly associated with a specific histotype (adenocarcinoma vs. squamous cell carcinoma), but high-level GAGE expression (>50%) was more frequent in squamous cell carcinoma (p = 0.02). Furthermore, the frequency of GAGE expression was demonstrated to be significantly higher in stage II-IIIa than stage I NSCLC (17.0% vs. 35.8%; p = 0.02). Analysis of the relation between tumor expression of GAGE and NY-ESO-1 and survival endpoints revealed no significant associations. Our study demonstrates that GAGE, NY-ESO-1 and SP17 cancer/testis antigens are candidate targets for immunotherapy of NSCLC and further suggest that multi-antigen vaccines may be beneficial.

  15. Postoperative pain and quality of life after lobectomy via video-assisted thoracoscopic surgery or anterolateral thoracotomy for early stage lung cancer

    DEFF Research Database (Denmark)

    Bendixen, Morten; Jørgensen, Ole Dan; Kronborg, Christian

    2016-01-01

    (1:1) to lobectomy via four-port VATS or anterolateral thoracotomy. After surgery, we applied identical surgical dressings to ensure masking of patients and staff. Postoperative pain was measured with a numeric rating scale (NRS) six times per day during hospital stay and once at 2, 4, 8, 12, 26...... died during the follow-up period (three in the VATS group and six in the thoracotomy group). INTERPRETATION: VATS is associated with less postoperative pain and better quality of life than is anterolateral thoracotomy for the first year after surgery, suggesting that VATS should be the preferred......BACKGROUND: Video-assisted thoracoscopic surgery (VATS) is used increasingly as an alternative to thoracotomy for lobectomy in the treatment of early-stage non-small-cell lung cancer, but remains controversial and worldwide adoption rates are low. Non-randomised studies have suggested that VATS...

  16. A Panel of Genetic Polymorphism for the Prediction of Prognosis in Patients with Early Stage Non-Small Cell Lung Cancer after Surgical Resection.

    Directory of Open Access Journals (Sweden)

    Shin Yup Lee

    Full Text Available This study was conducted to investigate whether a panel of eight genetic polymorphisms can predict the prognosis of patients with early stage non-small cell lung cancer (NSCLC after surgical resection.We selected eight single nucleotide polymorphisms (SNPs which have been associated with the prognosis of lung cancer patients after surgery in our previous studies. A total of 814 patients with early stage NSCLC who underwent curative surgical resection were enrolled. The association of the eight SNPs with overall survival (OS and disease-free survival (DFS was analyzed.The eight SNPs (CD3EAP rs967591, TNFRSF10B rs1047266, AKT1 rs3803300, C3 rs2287845, HOMER2 rs1256428, GNB2L1 rs3756585, ADAMTSL3 rs11259927, and CD3D rs3181259 were significantly associated with OS and/or DFS. Combining those eight SNPs, we designed a prognostic index to predict the prognosis of patients. According to relative risk of death, a score value was assigned to each genotype of the SNPs. A worse prognosis corresponded to a higher score value, and the sum of score values of eight SNPs defined the prognostic index of a patient. When we categorized the patients into two groups based on the prognostic index, high risk group was significantly associated with worse OS and DFS compared to low risk group (aHR for OS = 2.21, 95% CI = 1.69-2.88, P = 8.0 x 10-9, and aHR for DFS = 1.58, 95% CI = 1.29-1.94, P = 1.0 x 10-5.Prognostic index using eight genetic polymorphisms may be useful for the prognostication of patients with surgically resected NSCLC.

  17. Computed tomographic features predictive of local recurrence in patients with early stage lung cancer treated with stereotactic body radiation therapy.

    Science.gov (United States)

    Halpenny, Darragh; Ridge, Carole A; Hayes, Sara; Zheng, Junting; Moskowitz, Chaya S; Rimner, Andreas; Ginsberg, Michelle S

    2015-01-01

    The objective of this study is to identify computed tomography (CT) features of local recurrence (LR) after stereotactic body radiation therapy (SBRT) for lung cancer. Two hundred eighteen patients underwent SBRT for lung cancer from January 1st, 2006 to March 1st, 2011. Signs of LR recorded: opacity with new bulging margin, opacification of air bronchograms, enlarging pleural effusion, new or enlarging mass, and increased lung density at the treatment site. A new bulging margin at the treatment site was the only feature significantly associated with LR (P<.005). Most CT features classically associated with LR following conventional radiation therapy are unreliable for predicting LR following SBRT. Copyright © 2015 Elsevier Inc. All rights reserved.

  18. [Intraoperative methylene blue and (99m)Tc-sulfur colloid isotope tracing for sentinel node mapping in early-stage non-small cell lung cancer].

    Science.gov (United States)

    Hong, Bin; Shen, Xueyuan; Chen, Jiangyong

    2014-06-01

    To compare the accuracy of intaoperative methylene blue alone and in combination with (99m)Tc-sulfur colloid isotopic tracing for detection of sentinel lymph nodes (SLNs) in early-stage non-small cell lung cancer (NSCLC). Sixty-one patients with operable NSCLC who did not receive previous radiotherapy or chemotherapy were enrolled. Methylene blue and (99m)Tc-sulfur colloid were injected into the subserosal layer adjacent to the tumor, and SLNs were defined as those with blue staining or those containing 3 times more radioactivity than the surrounding tissue detected with a gamma probe. The SLN were removed with systematic lymph node dissection. All the removed lymph nodes were examined histopathologically with HE staining and immunohistochemistry. Methylene blue alone showed a low detection rate (60.0%) and sensitivity (58.33%) for SLNs compared with the combination of methylene blue and isotope tracing (96.15% and 92.86%, respectively). The combination of methylene blue and (99m)Tc-sulfur colloid isotopic tracing allows accurate detection of the SLNs in early-stage NSCLC.

  19. Transesophageal Ultrasonography for Lung Cancer Staging

    DEFF Research Database (Denmark)

    Konge, Lars; Annema, Jouke; Vilmann, Peter

    2013-01-01

    Accurate mediastinal nodal staging is essential for patients with resectable non-small-cell lung cancer and is achieved by combined endobronchial ultrasound and transesophageal endoscopic ultrasound (EUS). Training requirements for EUS-guided fine-needle aspiration (FNA) for lung cancer staging...

  20. Transesophageal Ultrasonography for Lung Cancer Staging

    DEFF Research Database (Denmark)

    Konge, Lars; Annema, Jouke; Vilmann, Peter

    2013-01-01

    Accurate mediastinal nodal staging is essential for patients with resectable non-small-cell lung cancer and is achieved by combined endobronchial ultrasound and transesophageal endoscopic ultrasound (EUS). Training requirements for EUS-guided fine-needle aspiration (FNA) for lung cancer staging...

  1. Long-term outcome of phase I/II prospective study of dose-escalated proton therapy for early-stage non-small cell lung cancer.

    Science.gov (United States)

    Chang, Joe Y; Zhang, Wencheng; Komaki, Ritsuko; Choi, Noah C; Chan, Shen; Gomez, Daniel; O'Reilly, Michael; Jeter, Melenda; Gillin, Michael; Zhu, Xiaorong; Zhang, Xiaodong; Mohan, Radhe; Swisher, Stephen; Hahn, Stephen; Cox, James D

    2017-02-01

    The aim of this phase I/II study was to assess the long-term clinical benefits and toxicities of proton beam therapy for medically inoperable early-stage non-small cell lung cancer (NSCLC). From June 2006 to September 2011, 35 patients with medically inoperable T1N0M0 (central or superior location, 12 patients) or T2-3N0M0 (any location, 23 patients) NSCLC were treated with 87.5Gy at 2.5Gy/fraction of proton therapy. Toxicities were scored according to the Common Terminology Criteria for Adverse Events, version 4.0. The median follow-up time was 83.1months (95% CI: 69.2-97.1months). For all 35 patients, the 1, 3, and 5-year overall survival rates were 85.7%, 42.9%, and 28.1%, respectively. The 5-year local recurrence-free, regional recurrence-free, and distant metastasis-free survival rates were 85.0%, 89.2%, and 54.4%, respectively. Different T stages had no effect on local and regional recurrence (p=0.499, p=1.00). However, with the increase in T stages, the distant metastasis rate increased significantly (p=0.006). The most common adverse effects were dermatitis (grade 2, 51.4%; grade 3, 2.9%) and radiation pneumonitis (grade 2, 11.4%; grade 3, 2.9%). Other grade 2 toxicities included esophagitis (2.9%), rib fracture (2.9%), heart toxicities (5.7%), and chest wall pain (2.9%). According to our long-term follow-up data, proton therapy with ablative doses is well tolerated and effective in medically inoperable early-stage NSCLC. Systemic therapy should be considered to reduce the rate of distant metastasis in cases of T2 and T3 lesions. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

  2. Salvage surgery for local failures after stereotactic ablative radiotherapy for early stage non-small cell lung cancer

    NARCIS (Netherlands)

    N. Verstegen (Naomi); A.W.P.M. Maat (Alex); F.J. Lagerwaard (Frank); M.A. Paul (Marinus); M. Versteegh (Michel); J.J. Joosten (Joris); W. Lastdrager (Willem); E.F. Smit (Egbert); B.J. Slotman (Ben); J.J.M.E. Nuyttens (Joost); S. Senan (Suresh)

    2016-01-01

    markdownabstract__Introduction:__ The literature on surgical salvage, i.e. lung resections in patients who develop a local recurrence following stereotactic ablative radiotherapy (SABR), is limited. We describe our experience with salvage surgery in nine patients who developed a local recurrence

  3. Targeting of Cancer Stem Cells and Their Microenvironment in Early-Stage MutantK-ras Lung Cancer

    Science.gov (United States)

    2015-10-01

    Ericson J, Morton S, Kawakami A, Roelink H, Jessell TM. Two critical periods of Sonic Hedgehog signaling required for the specification of motor...Non-small cell lung cancer, cancer stem cells, Hedgehog pathway, metastasis, tumor epithelial-stromal interactions 16. SECURITY CLASSIFICATION OF: 17...cancer cancer stem cells Hedgehog pathway metastasis tumor epithelial-stromal interactions ACCOMPLISHMENTS: I. Major Goals of the Project: AIM 1

  4. Effects of icotinib on early-stage non-small-cell lung cancer as neoadjuvant treatment with different epidermal growth factor receptor phenotypes

    Directory of Open Access Journals (Sweden)

    Wang T

    2016-03-01

    Full Text Available Tao Wang,1 Yang Liu,1 Bin Zhou,1 Zhi Wang,1 Naichao Liang,1 Yundong Zhang,1 Zhouhuan Dong,2 Jie Li2 1Department of Thoracic Surgery, 2Department of Pathology, People’s Liberation Army General Hospital, Beijing, People’s Republic of China Purpose: Epidermal growth factor receptor–tyrosine kinase inhibitors (EGFR–TKIs have demonstrated efficacy in treating advanced non-small-cell lung cancer (NSCLC. Preliminary findings suggested that EGFR–TKIs might also be beneficial in neoadjuvant therapy in treating NSCLC. Therefore, this study aimed to evaluate the efficacy and safety of neoadjuvant therapy with icotinib in patients with early-stage NSCLC.Patients and methods: We retrospectively reviewed the medical history of patients who were initially diagnosed with stage IA–IIIA NSCLC and were under icotinib administration before surgery between December 2011 and December 2014. Tumor assessment was conducted between the second and fourth week from initial icotinib treatment. The association between personal characteristics, smoking status, disease stage, EGFR mutation status, and clinical outcomes were investigated using multivariate logistic regression analysis.Results: A total of 67 patients with NSCLC were reviewed, and approximately half (38/67 of them were identified as having EGFR-mutant tumors. The overall response rate of all patients was 26.7% at 2–4 weeks’ assessment. Multivariate analysis showed that female sex (38.5% versus 10.7% in males, P=0.028 and EGFR mutation status (42.1% versus 6.9% in EGFR wild type, P=0.011 were independent predictive factors. The analysis also showed that the most common adverse effects were rash (43.3% and dry skin (34.4%, which were tolerable.Conclusion: Icotinib induced clinical response with minimal toxicity as neoadjuvant treatment in early NSCLC, especially in patients with common EGFR mutations. Further studies are warranted to confirm our findings. Keywords: non-small-cell lung cancer

  5. The potential role of respiratory motion management and image guidance in the reduction of severe toxicities following stereotactic ablative radiation therapy for patients with centrally located early stage non-small cell lung cancer or lung metastases

    Directory of Open Access Journals (Sweden)

    Alexander eChi

    2014-06-01

    Full Text Available Image guidance allows delivery of very high doses of radiation over a few fractions, known as stereotactic ablative radiotherapy (SABR. This treatment is associated with excellent outcome for early stage non-small cell lung cancer and metastases to the lungs. In the delivery of SABR, central location constantly poses a challenge due to the difficulty of adequately sparing critical thoracic structures that are immediately adjacent to the tumor if an ablative dose of radiation is to be delivered to the tumor target. As of current, various respiratory motion management and image guidance strategies can be used to ensure accurate tumor target localization prior and/ or during daily treatment, which allows for maximal and safe reduction of set up margins. The incorporation of both may lead to the most optimal normal tissue sparing and the most accurate SABR delivery. Here, the clinical outcome, treatment related toxicities, and the pertinent respiratory motion management/image guidance strategies reported in the current literature on SABR for central lung tumors are reviewed.

  6. Early treatment volume reduction rate as a prognostic factor in patients treated with chemoradiotherapy for limited stage small cell lung cancer

    Energy Technology Data Exchange (ETDEWEB)

    Lee, Joo Hwan; Lee, Jeong Shin; Lee, Chang Geol; Cho, Jae Ho [Dept. of Radiation Oncology, Yonsei Cancer Center, Yonsei University College of Medicine, Seoul (Korea, Republic of); Choi, Jin Hyun; Kim, Jun Won [Dept. of Radiation Oncology, Gangnam Severance Hospital, Yonsei University College of Medicine, Seoul (Korea, Republic of)

    2015-06-15

    To investigate the relationship between early treatment response to definitive chemoradiotherapy (CRT) and survival outcome in patients with limited stage small cell lung cancer (LS-SCLC). We retrospectively reviewed 47 patients with LS-SCLC who received definitive CRT between January 2009 and December 2012. Patients were treated with systemic chemotherapy regimen of etoposide/carboplatin (n = 15) or etoposide/cisplatin (n = 32) and concurrent thoracic radiotherapy at a median dose of 54 Gy (range, 46 to 64 Gy). Early treatment volume reduction rate (ETVRR) was defined as the percentage change in gross tumor volume between diagnostic computed tomography (CT) and simulation CT for adaptive RT planning and was used as a parameter for early treatment response. The median dose at adaptive RT planning was 36 Gy (range, 30 to 43 Gy), and adaptive CT was performed in 30 patients (63.8%). With a median follow-up of 27.7 months (range, 5.9 to 75.8 months), the 2-year locoregional progression-free survival (LRPFS) and overall survival (OS) rates were 74.2% and 56.5%, respectively. The mean diagnostic and adaptive gross tumor volumes were 117.9 mL (range, 5.9 to 447 mL) and 36.8 mL (range, 0.3 to 230.6 mL), respectively. The median ETVRR was 71.4% (range, 30 to 97.6%) and the ETVRR >45% group showed significantly better OS (p < 0.0001) and LRPFS (p = 0.009) than the other group. ETVRR as a parameter for early treatment response may be a useful prognostic factor to predict treatment outcome in LS-SCLC patients treated with CRT.

  7. Effect of tiotropium on lung function decline in early-stage of chronic obstructive pulmonary disease patients: propensity score-matched analysis of real-world data

    Directory of Open Access Journals (Sweden)

    Lee HY

    2015-10-01

    Full Text Available Ha Youn Lee,1,2 Sun Mi Choi,1,2 Jinwoo Lee,1,2 Young Sik Park,1,2 Chang-Hoon Lee,1,2 Deog Kyeom Kim,2,3 Sang-Min Lee,1,2 Ho Il Yoon,2,4 Jae-Joon Yim,1,2 Young Whan Kim,1,2 Sung Koo Han,1,2 Chul-Gyu Yoo1,2 1Division of Pulmonary and Critical Care Medicine, Department of Internal Medicine, Seoul National University Hospital, Seoul, Republic of Korea; 2Department of Internal Medicine, Seoul National University College of Medicine, Seoul, Republic of Korea; 3Department of Internal Medicine, Seoul Metropolitan Government-Seoul National University Boramae Medical Center, Seoul, Republic of Korea; 4Department of Internal Medicine, Seoul National University Bundang Hospital, Seongnam, Republic of Korea Background: Tiotropium failed to slow the annual rate of forced expiratory volume in 1 second (FEV1 decline in chronic obstructive pulmonary disease (COPD patients with <70% predicted FEV1. However, the rate of FEV1 decline is known to be faster at early stages, which suggests that the effects of tiotropium may be more prominent in early-stage of COPD patients. The aim of this study was to test the hypothesis that tiotropium modifies the rate of FEV1 decline in COPD patients with an FEV1≥70%.Methods: We retrospectively reviewed the records of COPD patients diagnosed between January 1, 2004, and July 31, 2012, at Seoul National University Hospital, Seoul National University Bundang Hospital, and Seoul Metropolitan Government-Seoul National University Boramae Medical Center. The inclusion criteria were as follows: age ≥40 years, postbronchodilator (BD FEV1≥70% of predicted and FEV1/FVC (forced vital capacity <0.70, and spirometry more than two times at certain times of the year. Conversely, the exclusion criteria were as follows: asthma, lung cancer, pulmonary tuberculosis, pulmonary resection, or long-term use of a short-acting muscarinic antagonist. The annual lung function decline in patients using tiotropium was compared with that in patients not

  8. Mid-radiotherapy PET/CT for prognostication and detection of early progression in patients with stage III non-small cell lung cancer.

    Science.gov (United States)

    Gensheimer, Michael F; Hong, Julian C; Chang-Halpenny, Christine; Zhu, Hui; Eclov, Neville C W; To, Jacqueline; Murphy, James D; Wakelee, Heather A; Neal, Joel W; Le, Quynh-Thu; Hara, Wendy Y; Quon, Andrew; Maxim, Peter G; Graves, Edward E; Olson, Michael R; Diehn, Maximilian; Loo, Billy W

    2017-08-19

    Pre- and mid-radiotherapy FDG-PET metrics have been proposed as biomarkers of recurrence and survival in patients treated for stage III non-small cell lung cancer. We evaluated these metrics in patients treated with definitive radiation therapy (RT). We also evaluated outcomes after progression on mid-radiotherapy PET/CT. Seventy-seven patients treated with RT with or without chemotherapy were included in this retrospective study. Primary tumor and involved nodes were delineated. PET metrics included metabolic tumor volume (MTV), total lesion glycolysis (TLG), and SUVmax. For mid-radiotherapy PET, both absolute value of these metrics and percentage decrease were analyzed. The influence of PET metrics on time to death, local recurrence, and regional/distant recurrence was assessed using Cox regression. 91% of patients had concurrent chemotherapy. Median follow-up was 14months. None of the PET metrics were associated with overall survival. Several were positively associated with local recurrence: pre-radiotherapy MTV, and mid-radiotherapy MTV and TLG (p=0.03-0.05). Ratio of mid- to pre-treatment SUVmax was associated with regional/distant recurrence (p=0.02). 5/77 mid-radiotherapy scans showed early out-of-field progression. All of these patients died. Several PET metrics were associated with risk of recurrence. Progression on mid-radiotherapy PET/CT was a poor prognostic factor. Copyright © 2017 Elsevier B.V. All rights reserved.

  9. Telomere length and recurrence risk after curative resection in patients with early-stage non-small-cell lung cancer: a prospective cohort study.

    Science.gov (United States)

    Kim, Eric S; Ye, Yuanqing; Vaporciyan, Ara A; Xing, Jinliang; Huang, Maosheng; Gu, Jian; Roth, Jack A; Lippman, Scott M; Wu, Xifeng

    2015-02-01

    We hypothesized that telomere length in peripheral blood would have significant predictive value for risk of recurrence after curative resection in non-small-cell lung cancer (NSCLC). This prospective study included 473 patients with histologically confirmed early stage NSCLC who underwent curative therapy at MD Anderson Cancer Center between 1995 and 2008. Relative telomere length (RTL) of peripheral leukocytes was measured by real-time polymerase chain reaction. The risk of recurrence was estimated as hazard ratios (HRs) and 95% confidence intervals (CIs) using a multivariable Cox proportional hazard regression model. Median duration of follow-up was 61 months, and 151 patients (32%) had developed recurrence at time of analysis. Patients who developed recurrence had significantly longer mean RTL compared with those without recurrence (1.13 versus 1.07, p = 0.046). A subgroup analysis indicates that women had longer RTL compared with men (1.12 versus 1.06, p = 0.025), and the patients with adenocarcinoma demonstrated longer RTL compared with those with other histologic types (1.11 versus 1.05, p = 0.042). To determine whether longer RTL in women and adenocarcinoma subgroup would predict risk of recurrence, multivariate Cox analysis adjusting for age, sex, stage, pack year and treatment regimens was performed. Longer telomeres were significantly associated with higher risk of developing recurrence in women (hazard ratio [HR], 2.25; 95% confidence interval [CI], 1.02-4.96, p = 0.044) and adenocarcinoma subgroups (HR, 2.19; 95% CI, 1.05-4.55, p = 0.036). The increased risk of recurrence due to long RTL was more apparent in women with adenocarcinoma (HR, 2.67; 95% CI, 1.19-6.03, p = 0.018). This is the first prospective study to suggest that long RTL is associated with recurrence in early stage NSCLC after curative resection. Women and adenocarcinoma seem to be special subgroups in which telomere biology may play an important role.

  10. The Impact of Tumor Size on Outcomes After Stereotactic Body Radiation Therapy for Medically Inoperable Early-Stage Non-Small Cell Lung Cancer

    Energy Technology Data Exchange (ETDEWEB)

    Allibhai, Zishan [Department of Radiation Oncology, Princess Margaret Cancer Centre, Toronto (Canada); Taremi, Mojgan [Department of Radiation Oncology, Stronach Regional Cancer Centre, Newmarket (Canada); Bezjak, Andrea; Brade, Anthony; Hope, Andrew J.; Sun, Alexander [Department of Radiation Oncology, Princess Margaret Cancer Centre, Toronto (Canada); Cho, B.C. John, E-mail: john.cho@rmp.uhn.on.ca [Department of Radiation Oncology, Princess Margaret Cancer Centre, Toronto (Canada)

    2013-12-01

    Purpose: Stereotactic body radiation therapy for medically inoperable early-stage non-small cell lung cancer (NSCLC) offers excellent control rates. Most published series deal mainly with small (usually <4 cm), peripheral, solitary tumors. Larger tumors are associated with poorer outcomes (ie, lower control rates, higher toxicity) when treated with conventional RT. It is unclear whether SBRT is sufficiently potent to control these larger tumors. We therefore evaluated and examined the influence of tumor size on treatment outcomes after SBRT. Methods and Materials: Between October 2004 and October 2010, 185 medically inoperable patients with early (T1-T2N0M0) NSCLC were treated on a prospective research ethics board-approved single-institution protocol. Prescription doses were risk-adapted based on tumor size and location. Follow-up included prospective assessment of toxicity (as per Common Terminology Criteria for Adverse Events, version 3.0) and serial computed tomography scans. Patterns of failure, toxicity, and survival outcomes were calculated using Kaplan-Meier method, and the significance of tumor size (diameter, volume) with respect to patient, treatment, and tumor factors was tested. Results: Median follow-up was 15.2 months. Tumor size was not associated with local failure but was associated with regional failure (P=.011) and distant failure (P=.021). Poorer overall survival (P=.001), disease-free survival (P=.001), and cause-specific survival (P=.005) were also significantly associated with tumor size (with tumor volume more significant than diameter). Gross tumor volume and planning target volume were significantly associated with grade 2 or worse radiation pneumonitis. However, overall rates of grade ≥3 pneumonitis were low and not significantly affected by tumor or target size. Conclusions: Currently employed stereotactic body radiation therapy dose regimens can provide safe effective local therapy even for larger solitary NSCLC tumors (up to 5.7 cm

  11. Early laparotomy after lung transplantation

    DEFF Research Database (Denmark)

    Bredahl, Pia; Zemtsovski, Mikhail; Perch, Michael;

    2014-01-01

    BACKGROUND: Gastrointestinal complications after lung transplantation have been reported with incidence rates ranging from 3% to 51%, but the reasons are poorly understood. We aimed to investigate the correlations between pulmonary diseases leading to lung transplantation and early gastrointestinal...... complications requiring laparotomy after transplantation with outcomes for patients at increased risk. METHODS: In this study we performed a retrospective analysis of data of patients who underwent lung transplantation at our institution from 2004 to 2012. The study period was limited to the first 90 days after...... for time on mechanical ventilation. Among pulmonary diseases and demographics of the patients, no other risk factors were identified for laparotomy. CONCLUSIONS: A1AD was the only significant risk factor identified for gastrointestinal complications that required laparotomy within 3 months after lung...

  12. Predicting Overall Survival After Stereotactic Ablative Radiation Therapy in Early-Stage Lung Cancer: Development and External Validation of the Amsterdam Prognostic Model

    Energy Technology Data Exchange (ETDEWEB)

    Louie, Alexander V., E-mail: Dr.alexlouie@gmail.com [Department of Radiation Oncology, VU University Medical Center, Amsterdam (Netherlands); Department of Radiation Oncology, London Regional Cancer Program, University of Western Ontario, London, Ontario (Canada); Department of Epidemiology, Harvard School of Public Health, Harvard University, Boston, Massachusetts (United States); Haasbeek, Cornelis J.A. [Department of Radiation Oncology, VU University Medical Center, Amsterdam (Netherlands); Mokhles, Sahar [Department of Cardio-Thoracic Surgery, Erasmus University Medical Center, Rotterdam (Netherlands); Rodrigues, George B. [Department of Radiation Oncology, London Regional Cancer Program, University of Western Ontario, London, Ontario (Canada); Stephans, Kevin L. [Department of Radiation Oncology, Taussig Cancer Institute, Cleveland Clinic, Cleveland, Ohio (United States); Lagerwaard, Frank J. [Department of Radiation Oncology, VU University Medical Center, Amsterdam (Netherlands); Palma, David A. [Department of Radiation Oncology, London Regional Cancer Program, University of Western Ontario, London, Ontario (Canada); Videtic, Gregory M.M. [Department of Radiation Oncology, Taussig Cancer Institute, Cleveland Clinic, Cleveland, Ohio (United States); Warner, Andrew [Department of Radiation Oncology, London Regional Cancer Program, University of Western Ontario, London, Ontario (Canada); Takkenberg, Johanna J.M. [Department of Cardio-Thoracic Surgery, Erasmus University Medical Center, Rotterdam (Netherlands); Reddy, Chandana A. [Department of Radiation Oncology, Taussig Cancer Institute, Cleveland Clinic, Cleveland, Ohio (United States); Maat, Alex P.W.M. [Department of Cardio-Thoracic Surgery, Erasmus University Medical Center, Rotterdam (Netherlands); Woody, Neil M. [Department of Radiation Oncology, Taussig Cancer Institute, Cleveland Clinic, Cleveland, Ohio (United States); Slotman, Ben J.; Senan, Suresh [Department of Radiation Oncology, VU University Medical Center, Amsterdam (Netherlands)

    2015-09-01

    Purpose: A prognostic model for 5-year overall survival (OS), consisting of recursive partitioning analysis (RPA) and a nomogram, was developed for patients with early-stage non-small cell lung cancer (ES-NSCLC) treated with stereotactic ablative radiation therapy (SABR). Methods and Materials: A primary dataset of 703 ES-NSCLC SABR patients was randomly divided into a training (67%) and an internal validation (33%) dataset. In the former group, 21 unique parameters consisting of patient, treatment, and tumor factors were entered into an RPA model to predict OS. Univariate and multivariate models were constructed for RPA-selected factors to evaluate their relationship with OS. A nomogram for OS was constructed based on factors significant in multivariate modeling and validated with calibration plots. Both the RPA and the nomogram were externally validated in independent surgical (n=193) and SABR (n=543) datasets. Results: RPA identified 2 distinct risk classes based on tumor diameter, age, World Health Organization performance status (PS) and Charlson comorbidity index. This RPA had moderate discrimination in SABR datasets (c-index range: 0.52-0.60) but was of limited value in the surgical validation cohort. The nomogram predicting OS included smoking history in addition to RPA-identified factors. In contrast to RPA, validation of the nomogram performed well in internal validation (r{sup 2}=0.97) and external SABR (r{sup 2}=0.79) and surgical cohorts (r{sup 2}=0.91). Conclusions: The Amsterdam prognostic model is the first externally validated prognostication tool for OS in ES-NSCLC treated with SABR available to individualize patient decision making. The nomogram retained strong performance across surgical and SABR external validation datasets. RPA performance was poor in surgical patients, suggesting that 2 different distinct patient populations are being treated with these 2 effective modalities.

  13. Surgical Management of Early-Stage Non-small Cell Lung Carcinoma and the Present and Future Roles of Adjuvant Therapy: A Review for the Radiation Oncologist

    Energy Technology Data Exchange (ETDEWEB)

    Medford-Davis, Laura [Department of Emergency Medicine, Ben Taub General Hospital, Houston, TX (United States); DeCamp, Malcom [Division of Thoracic Surgery, Department of Surgery, Northwestern Memorial Hospital, Northwestern University Feinberg School of Medicine, Chicago, Illinois (United States); Recht, Abram [Department of Radiation Oncology, Beth Israel Deaconess Medical Center, Boston, Massachusetts (United States); Flickinger, John [Department of Radiation Oncology, Pittsburgh Cancer Institute, Pittsburgh, Pennsylvania (United States); Belani, Chandra P. [Department of Medical Oncology, Penn State Hershey Cancer Institute, Hershey, Pennsylvania (United States); Varlotto, John, E-mail: jvarlotto@hmc.psu.edu [Division of Radiation Oncology, Penn State Hershey Cancer Institute, Hershey, Pennsylvania (United States)

    2012-12-01

    We review the evidence for optimal surgical management and adjuvant therapy for patients with stages I and II non-small cell lung cancer (NSCLC) along with factors associated with increased risks of recurrence. Based on the current evidence, we recommend optimal use of mediastinal lymph node dissection, adjuvant chemotherapy, and post-operative radiation therapy, and make suggestions for areas to explore in future prospective randomized clinical trials.

  14. Dosimetric rationale and early experience at UFPTI of thoracic proton therapy and chemotherapy in limited-stage small cell lung cancer

    Energy Technology Data Exchange (ETDEWEB)

    Colaco, Rovel J.; Huh, Soon; Nichols, Romaine; Morris, Christopher G.; Flampouri, Stella; Li, Zuofeng; Hoppe, Bradford S. [Univ. of Florida Proton Therapy Inst., Jacksonville (United States)], e-mail: bhoppe@floridaproton.org; D' Agostino, Harry [Dept. of Thoracic Surgery, Univ. of Florida Coll. of Medicine, Gainesville (United States); Pham, Dat C. [Dept. of Hematology and Medical Oncology, Univ. of Florida Coll. of Medicine, Gainesville (United States); Bajwa, Abubakr A. [Dept. of Medicine, Univ. of Florida Coll. of Medicine, Gainesville (United States)

    2013-04-15

    Background: Concurrent chemoradiotherapy (CRT) is the standard of care in patients with limited-stage small cell lung cancer (SCLC). Treatment with conventional x-ray therapy (XRT) is associated with high toxicity rates, particularly acute grade 3+ esophagitis and pneumonitis. We present outcomes for the first known series of limited-stage SCLC patients treated with proton therapy and a dosimetric comparison of lung and esophageal doses with intensity-modulated radiation therapy (IMRT). Material and methods: Six patients were treated; five concurrently and one sequentially. Five patients received 60-66 CGE in 30-34 fractions once daily and one patient received 45 CGE in 30 fractions twice daily. All six patients received prophylactic cranial irradiation. Common Terminology Criteria for Adverse Events, v3.0, was used to grade toxicity. IMRT plans were also generated and compared with proton plans. Results: The median follow-up was 12.0 months. The one-year overall and progression-free survival rates were 83% and 66%, respectively. There were no cases of acute grade 3+ esophagitis or acute grade 2+ pneumonitis, and no other acute grade 3+ non-hematological toxicities were seen. One patient with a history of pulmonary fibrosis and atrial fibrillation developed worsening symptoms four months after treatment requiring oxygen. Three patients died; two of progressive disease and one after a fall. The latter patient was disease-free at 36 months after treatment. Another patient recurred and is alive, while two patients remain disease-free at 12 months of follow-up. Proton therapy proved superior to IMRT across all esophageal and lung dose volume points. Conclusion. In this small series of SCLC patients treated with proton therapy with radical intent, treatment was well tolerated with no cases of acute grade 3+ esophagitis or acute grade 2+ pneumonitis. Dosimetric comparison showed better sparing of lung and esophagus with proton therapy. Proton therapy merits further

  15. Early COPD patients with lung hyperinflation associated with poorer lung function but better bronchodilator responsiveness

    Directory of Open Access Journals (Sweden)

    Chen C

    2016-10-01

    Full Text Available Chunlan Chen,* Wenhua Jian,* Yi Gao, Yanqing Xie, Yan Song, Jinping Zheng State Key Laboratory of Respiratory Disease, China National Clinical Research Center for Respiratory Disease, Guangzhou Institute of Respiratory Diseases, First Affiliated Hospital of Guangzhou Medical University, Guangzhou, People’s Republic of China *These authors contributed equally to this work Background: It is unknown whether aggressive medication strategies should be used for early COPD with or without lung hyperinflation. We aimed to explore the characteristics and bronchodilator responsiveness of early COPD patients (stages I and II with/without lung hyperinflation.Methods: Four hundred and six patients with COPD who performed both lung volume and bronchodilation tests were retrospectively analyzed. Residual volume to total lung capacity >120% of predicted values indicated lung hyperinflation. The characteristics and bronchodilator responsiveness were compared between the patients with and without lung hyperinflation across all stages of COPD.Results: The percentages of patients with lung hyperinflation were 72.7% in the entire cohort, 19.4% in stage I, 68.5% in stage II, 95.3% in stage III, and 100.0% in stage IV. The patients with lung hyperinflation exhibited poorer lung function but better bronchodilator responsiveness of both forced expiratory volume in 1 second and forced vital capacity than those without lung hyperinflation during early COPD (t=2.21–5.70, P=0.000–0.029, especially in stage I, while age, body mass index, smoking status, smoking history, and disease duration were similar between the two subgroups in the same stages. From stages I to IV of subgroups with lung hyperinflation, stage I patients had the best bronchodilator responsiveness. Use of bronchodilator responsiveness of forced vital capacity to detect the presence of lung hyperinflation in COPD patients showed relatively high sensitivities (69.5%–75.3% and specificities (70.3%

  16. Support Vector Machine-Based Prediction of Local Tumor Control After Stereotactic Body Radiation Therapy for Early-Stage Non-Small Cell Lung Cancer

    Energy Technology Data Exchange (ETDEWEB)

    Klement, Rainer J., E-mail: rainer_klement@gmx.de [Department of Radiation Oncology, University of Würzburg (Germany); Department of Radiotherapy and Radiation Oncology, Leopoldina Hospital, Schweinfurt (Germany); Allgäuer, Michael [Department of Radiotherapy, Barmherzige Brüder Regensburg, Regensburg (Germany); Appold, Steffen [Department of Radiation Oncology, Technische Universität Dresden (Germany); Dieckmann, Karin [Department of Radiotherapy, Medical University of Vienna (Austria); Ernst, Iris [Department of Radiotherapy, University Hospital Münster (Germany); Ganswindt, Ute [Department of Radiation Oncology, Ludwigs-Maximilians-University Munich, München (Germany); Holy, Richard [Department of Radiation Oncology, RWTH Aachen University, Aachen (Germany); Nestle, Ursula [Department of Radiation Oncology, University Hospital Freiburg, Freiburg i Br (Germany); Nevinny-Stickel, Meinhard [Department of Therapeutic Radiology and Oncology, Innsbruck Medical University (Austria); Semrau, Sabine [Department of Radiation Oncology, Friedrich-Alexander University Erlangen-Nuremberg, Erlangen (Germany); Sterzing, Florian [Department of Radiation Oncology, University Hospital Heidelberg (Germany); Wittig, Andrea [Department of Radiotherapy and Radiation Oncology, Philipps-University Marburg (Germany); Andratschke, Nicolaus [Department of Radiation Oncology, Technische Universität München (Germany); Guckenberger, Matthias [Department of Radiation Oncology, University of Würzburg (Germany)

    2014-03-01

    Background: Several prognostic factors for local tumor control probability (TCP) after stereotactic body radiation therapy (SBRT) for early stage non-small cell lung cancer (NSCLC) have been described, but no attempts have been undertaken to explore whether a nonlinear combination of potential factors might synergistically improve the prediction of local control. Methods and Materials: We investigated a support vector machine (SVM) for predicting TCP in a cohort of 399 patients treated at 13 German and Austrian institutions. Among 7 potential input features for the SVM we selected those most important on the basis of forward feature selection, thereby evaluating classifier performance by using 10-fold cross-validation and computing the area under the ROC curve (AUC). The final SVM classifier was built by repeating the feature selection 10 times with different splitting of the data for cross-validation and finally choosing only those features that were selected at least 5 out of 10 times. It was compared with a multivariate logistic model that was built by forward feature selection. Results: Local failure occurred in 12% of patients. Biologically effective dose (BED) at the isocenter (BED{sub ISO}) was the strongest predictor of TCP in the logistic model and also the most frequently selected input feature for the SVM. A bivariate logistic function of BED{sub ISO} and the pulmonary function indicator forced expiratory volume in 1 second (FEV1) yielded the best description of the data but resulted in a significantly smaller AUC than the final SVM classifier with the input features BED{sub ISO}, age, baseline Karnofsky index, and FEV1 (0.696 ± 0.040 vs 0.789 ± 0.001, P<.03). The final SVM resulted in sensitivity and specificity of 67.0% ± 0.5% and 78.7% ± 0.3%, respectively. Conclusions: These results confirm that machine learning techniques like SVMs can be successfully applied to predict treatment outcome after SBRT. Improvements over traditional TCP

  17. Analysis of GAGE, NY-ESO-1 and SP17 cancer/testis antigen expression in early stage non-small cell lung carcinoma

    DEFF Research Database (Denmark)

    Gjerstorff, Morten F; Pøhl, Mette; Olsen, Karen E

    2013-01-01

    NSCLC has shown promising results. However, little is known about the expression of other cancer/testis antigens in NSCLC. In the present study the expression of cancer/testis antigens GAGE, NY-ESO-1 and SP17 was investigated in patients with completely resected, early stage, primary NSCLC....

  18. Morphogenesis of early stage melanoma

    Science.gov (United States)

    Chatelain, Clément; Amar, Martine Ben

    2015-08-01

    Melanoma early detection is possible by simple skin examination and can insure a high survival probability when successful. However it requires efficient methods for identifying malignant lesions from common moles. This paper provides an overview first of the biological and physical mechanisms controlling melanoma early evolution, and then of the clinical tools available today for detecting melanoma in vivo at an early stage. It highlights the lack of diagnosis methods rationally linking macroscopic observables to the microscopic properties of the tissue, which define the malignancy of the tumor. The possible inputs of multiscale models for improving these methods are shortly discussed.

  19. Keratin 34betaE12/keratin7 expression is a prognostic factor of cancer-specific and overall survival in patients with early stage non-small cell lung cancer

    DEFF Research Database (Denmark)

    Pøhl, Mette; Olsen, Karen Ege; Holst, Rene

    2016-01-01

    BACKGROUND: Carcinomas and their metastases often retain the keratin patterns of their epithelial origin, and are therefore useful as lineage-specific markers in diagnostic pathology. Recently, it has become clear that intermediate filaments composed by keratins play a role in modulation of cell...... proliferation, migration, and possibly cancer invasion, factors impacting prognosis in early stage non-small cell lung cancer (NSCLC). MATERIAL AND METHODS: Tumor tissue from a retrospective Danish cohort of 177 patients with completely resected NSCLC, stage I-IIIA tumors, were analyzed for keratin 7 (K7......) and keratin 34βE12 expression by immunohistochemistry and validated in a comparable independent Norwegian cohort of 276 stage I-IIIA NSCLC patients. RESULTS: Based on keratin 34βE12/K7 expression, three subgroups with significantly different median cancer-specific survival rates were identified (34βE12+/K7...

  20. 早期非小细胞肺癌立体定向消融放疗现状%Current Status of Stereotactic Ablative Radiotherapy (SABR) for Early-stage Non-small Cell Lung Cancer

    Institute of Scientific and Technical Information of China (English)

    石安辉; 朱广迎

    2016-01-01

    目前比较立体定向消融放疗(stereotactic ablative radiotherapy, SABR)与手术治疗早期非小细胞肺癌(non-small cell lung cancer, NSCLC)的随机研究证据尚不多,高水平的循证医学证据更是缺乏。尽管STARS和ROSEL两项随机研究结果荟萃分析显示SABR较手术耐受性更好,生存不劣于手术,但是目前仍仅推荐拒绝手术或不可手术的早期NSCLC首选SABR,期待着正在进行的随机研究VALOR(Veterans Affairs Lung Cancer Surgery or Stereotactic Ra-diotherapy in the US)和SABRTooth(SABRTooth study in the United Kingdom)的结果。许多回顾性的研究和病例对照研究显示了SABR治疗的安全性和有效性(局部控制率达90%以上,5年生存率达70%),但是由于肿瘤分期定义、如何决定可否手术及手术患者采用手术方式(开胸或胸腔镜辅助)等不同,很难比较SABR和手术的优劣,尽管大部分结论是两种方法疗效相似,但难以成为循证医学证据,因此争论热点是哪一种方法更安全、创伤更小。本文将就以上争论热点进行述评。%High level evidence from randomized studies comparing stereotactic ablative radiotherapy (SABR) to surgery is lacking. Although the results of pooled analysis of two randomized trials for STARS and ROSEL showed that SABR is better tolerated and might lead to better overall survival than surgery for operable clinical stage I non-small cell lung cancer (NSCLC), SABR, however, is only recommended as a preferred treatment option for early stage NSCLC patients who cannot or will not undergo surgery. We, therefore, are waiting for the results of the ongoing randomized studies [Veterans af-fairs lung cancer surgery or stereotactic radiotherapy in the US (VALOR) and the SABRTooth study in the United Kingdom (SABRTooths)]. Many retrospective and case control studies showed that SABR is safe and effective (local control rate higher than 90%, 5 years survival rate

  1. [Lung and heart-lung transplantation in Rabin medical center: early experience with 70 cases].

    Science.gov (United States)

    Kramer, Mordechai R; Saute, Milton; Eidelman, Leonid; Aravot, Dan; Fink, Gershon; Shitrit, David; Izbicky, Gabriel; Izvicky, Gavriel; Dayan, Daniel Ben; Bakal, Ilana; Kogan, Alex; Gendel, Boris; Vidne, Bernardo; Sahar, Gideon

    2004-01-01

    Lung transplantation is a relatively new field in solid organ transplantation. We present our early experience with the first 70 cases at the Rabin Medical Center during the years 1997-2003. Forty seven patients underwent single lung, eight double lung and eight heart-lung transplantations. The patients treated included 49 men and 21 women aged 5-66 years. There were 26 cases with emphysema COPD. 30 patients with pulmonary fibrosis. 5 patients with pulmonary hypertension/Eisenmenger and 9 patients with cystic fibrosis and bronchiectasis. Although early results (1997-1999) showed 1 and 3 year survival of only 50%, in the last 3 years (2000-2003), survival reached 84% and 82% at 1 and 3 years respectively. Improvement in the success rate is due to better patient selection, new immunosuppressive regimen and, most importantly, excellent teamwork. We conclude that lung transplantation is a viable option for selected patients with end-stage lung disease.

  2. The early diagnosis of lung cancer.

    Science.gov (United States)

    Petty, T L

    2001-06-01

    Lung cancer is the most common fatal malignancy in both men and women, both in the United States and elsewhere in the world. Today, lung cancer is most often diagnosed on the basis of symptoms of advanced disease or when chest x-rays are taken for a variety of purposes unrelated to lung cancer detection. Unfortunately, in the United States no society or governmental agency recommends screening, even for patients with high risks, such as smokers with airflow obstruction or people with occupational exposures, including asbestos. The origins of this negative attitude toward lung cancer screening are found in 3 studies sponsored by the National Cancer Institute in the mid-1970s and conducted at Johns Hopkins University School of Medicine, the Mayo Clinic, and the Memorial Sloan-Kettering Center. These studies concluded that early identification of lung cancer through chest x-rays and cytologic diagnosis of sputum did not alter disease-specific mortality. However, patients with earlier stage disease were found through screening, which resulted in a higher resectability rate and improved survival in the screening group compared with a control group of patients receiving ordinary care. Patients in the control group often received annual chest x-rays during the course of this study, which was the standard of care at the time. Thus no true nonscreening control group resulted. The patients at highest risk were not enrolled in this study. No specific amount of pack-years of smoking intensity was required. Only men were screened. The studies were inadequately powered to show an improvement in mortality rate of less than 50%. Ninety percent of lung cancer occurs in smokers. The prevalence of lung cancer is 4 to 6 times greater when smokers have airflow obstruction than with normal airflow, when all other background factors, including smoking history, occupational risk, and family history, are the same. Screening heavy smokers (ie, > or = 30 pack-years) with airflow obstruction

  3. Staging Lung Cancer: Current Controversies and Strategies

    Directory of Open Access Journals (Sweden)

    Riyad Karmy-Jones

    1997-01-01

    Full Text Available A consistent approach to staging is required for the rational management of lung cancer. This paper was prepared at the request of the Standards Committee of the Canadian Thoracic Society, and reviews and discusses the relative merits of the available methods of staging. Whichever methods are chosen by a particular institution, the following points must be stressed. No patient can be considered automatically "unresectable" when chest radiography and/ or computed tomography demonstrate adenopathy or only suggest local invasion. Clinical and/or radiographical evidence suggesting extensive local or metastatic disease should be evaluated as completely as possible before subjecting the patient to a possible "nontherapeutic" thoracotomy. Finally, in some cases thoracotomy is required to decide whether the lesion is "completely" resectable.

  4. Preclinical lung disease in early rheumatoid arthritis.

    Science.gov (United States)

    Robles-Perez, Alejandro; Luburich, Patricio; Rodriguez-Sanchon, Benigno; Dorca, Jordi; Nolla, Joan Miquel; Molina-Molina, Maria; Narvaez-Garcia, Javier

    2016-02-01

    Early detection and treatment of lung disease in patients with rheumatoid arthritis (RA) may ameliorate disease progression. The objectives of this study were to investigate the frequency of asymptomatic lung abnormalities in early RA patients and the potential association of positive RA blood reactive biomolecules with lung involvement. A prospective observational study was performed in a cohort of patients with early RA (joint symptoms disease with a baseline chest radiograph (CR) and complete pulmonary function tests (PFTs). In those patients with lung abnormalities on the CR or PFTs, a high-resolution chest computed tomography scan (HRCT) was performed. We included 40 patients (30 women). Altered PFTs were detected in 18 (45%) of these patients. These cases had a diffusion lung transfer capacity of carbon monoxide (DLCO) of disease is present in up to 45% of early RA patients and can be determined by PFTs and ACPA levels.

  5. Early Lung Cancer Diagnosis by Biosensors

    Directory of Open Access Journals (Sweden)

    Lianhui Wang

    2013-07-01

    Full Text Available Lung cancer causes an extreme threat to human health, and the mortality rate due to lung cancer has not decreased during the last decade. Prognosis or early diagnosis could help reduce the mortality rate. If microRNA and tumor-associated antigens (TAAs, as well as the corresponding autoantibodies, can be detected prior to clinical diagnosis, such high sensitivity of biosensors makes the early diagnosis and prognosis of cancer realizable. This review provides an overview of tumor-associated biomarker identifying methods and the biosensor technology available today. Laboratorial researches utilizing biosensors for early lung cancer diagnosis will be highlighted.

  6. Volatile signature for the early diagnosis of lung cancer.

    Science.gov (United States)

    Gasparri, Roberto; Santonico, Marco; Valentini, Claudia; Sedda, Giulia; Borri, Alessandro; Petrella, Francesco; Maisonneuve, Patrick; Pennazza, Giorgio; D'Amico, Arnaldo; Di Natale, Corrado; Paolesse, Roberto; Spaggiari, Lorenzo

    2016-02-09

    Exhaled breath contains hundreds of volatile organic compounds (VOCs). Several independent researchers point out that the breath of lung cancer patients shows a characteristic VOC-profile which can be considered as lung cancer signature and, thus, used for diagnosis. In this regard, the analysis of exhaled breath with gas sensor arrays is a potential non-invasive, relatively low-cost and easy technique for the early detection of lung cancer. This clinical study evaluated the gas sensor array response for the identification of the exhaled breath of lung cancer patients. This study involved 146 individuals: 70 with lung cancer confirmed by computerized tomography (CT) or positron emission tomography-(PET) imaging techniques and histology (biopsy) or with clinical suspect of lung cancer and 76 healthy controls. Their exhaled breath was measured with a gas sensor array composed of a matrix of eight quartz microbalances (QMBs), each functionalized with a different metalloporphyrin. The instrument produces, for each analyzed sample, a vector of signals encoding the breath (breathprint). Breathprints were analyzed with multivariate analysis in order to correlate the sensor signals to the disease. Breathprints of the lung cancer patients were differentiated from those of the healthy controls with a sensitivity of 81% and specificity of 91%. Similar values were obtained in patients with and without metabolic comorbidities, such as diabetes, obesity and dyslipidemia (sensitivity 85%, specificity 88% and sensitivity 76%, specificity 94%, respectively). The device showed a large sensitivity to lung cancer at stage I with respect to stage II/III/IV (92% and 58% respectively). The sensitivity for stage I did not change for patients with or without metabolic comorbidities (90%, 94%, respectively). Results show that this electronic nose can discriminate the exhaled breath of the lung cancer patients from those of the healthy controls. Moreover, the largest sensitivity is observed

  7. Radiation Pneumonitis After Stereotactic Body Radiation Therapy for Early Stage Non-small Cell Lung Cancer%早期非小细胞肺癌立体定向放射治疗后的放射性肺炎

    Institute of Scientific and Technical Information of China (English)

    陈露; 赵娅琴; 许峰

    2014-01-01

    With the development of radiation technology, stereotactic body radiation therapy (SBRT) has been widely used in early stage non-small cell lung cancer (NSCLC). It is not only the standard therapy for medically inoperable early-stage NSCLC, but also one of the therapies for operable early-stage NSCLC. Radiation pneumonitis (RP) is one of the most common adverse effects atfer SBRT, it may reduce the patients’ quality of life, even cause treatment failure. hTerefore, in order to improve the patients’ quality of life and enhance local control rate of tumor, it is important to reduce the risk of RP. hTe unique fractionation schemes and the dose distribution of SBRT make it not only different from conventional fraction radiation therapy in treatment outcomes, but also in the incidence of radiation pneumonitis. hTis article reviews the applying of SBRT for early stage NSCLC, the incidence of radiation pneumonitis, radiological appearance atfer SBRT and predictive factors.%随着放疗技术的进步,立体定向放射治疗(stereotactic body radiation therapy, SBRT)在早期非小细胞肺癌(non-small cell lung cancer, NSCLC)中得到了广泛应用,其不仅是不可手术的早期NSCLC的标准治疗方法,也是可手术的早期NSCLC的治疗方法之一。放射性肺炎(radiation pneumonitis, RP)是SBRT治疗后最常见的并发症。SBRT独特的分割计划和剂量分布使其不仅在治疗效果上和常规分割放疗不同,而且治疗后引起的RP和常规分割放疗引起的RP也有所不同。RP的发生可降低患者的生活质量,甚至导致治疗失败。因此,降低RP的风险对提高患者的生活质量和肿瘤的控制率有重要意义。本文就SBRT在早期NSCLC治疗中应用、治疗后RP的发生率、影像学表现以及预测因素方面作一综述。

  8. A Gene Signature Combining the Tissue Expression of Three Angiogenic Factors is a Prognostic Marker in Early-stage Non-small Cell Lung Cancer

    National Research Council Canada - National Science Library

    Sanmartín, Elena; Sirera, Rafael; Usó, Marta; Blasco, Ana; Gallach, Sandra; Figueroa, Santiago; Martínez, Nieves; Hernando, Cristina; Honguero, Antonio; Martorell, Miguel; Guijarro, Ricardo; Rosell, Rafael; Jantus-Lewintre, Eloisa; Camps, Carlos

    .... The aim of this study was to analyze relative expression levels of angiogenic markers in resectable non-small cell lung cancer patients in order to asses a prognostic signature that could improve...

  9. High-Dose Hypofractionated Proton Beam Radiation Therapy Is Safe and Effective for Central and Peripheral Early-Stage Non-Small Cell Lung Cancer: Results of a 12-Year Experience at Loma Linda University Medical Center

    Energy Technology Data Exchange (ETDEWEB)

    Bush, David A., E-mail: dbush@llu.edu [Department of Radiation Oncology, Loma Linda University Medical Center, Loma Linda, California (United States); Cheek, Gregory [Department of Pulmonary Medicine, Loma Linda University Medical Center, Loma Linda, California (United States); Zaheer, Salman; Wallen, Jason [Department of Thoracic Surgery, Loma Linda University Medical Center, Loma Linda, California (United States); Mirshahidi, Hamid [Department of Medical Oncology, Loma Linda University Medical Center, Loma Linda, California (United States); Katerelos, Ari; Grove, Roger; Slater, Jerry D. [Department of Radiation Oncology, Loma Linda University Medical Center, Loma Linda, California (United States)

    2013-08-01

    Purpose: We update our previous reports on the use of hypofractionated proton beam radiation therapy for early-stage lung cancer patients. Methods and Materials: Eligible subjects had biopsy-proven non-small cell carcinoma of the lung and were medically inoperable or refused surgery. Clinical workup required staging of T1 or T2, N0, M0. Subjects received hypofractionated proton beam therapy to the primary tumor only. The dose delivered was sequentially escalated from 51 to 60 Gy, then to 70 Gy in 10 fractions over 2 weeks. Endpoints included toxicity, pulmonary function, overall survival (OS), disease-specific survival (DSS), and local control (LC). Results: One hundred eleven subjects were analyzed for treatment outcomes. The patient population had the following average characteristics; age 73.2 years, tumor size 3.6 cm, and 1.33 L forced expiratory volume in 1 second. The entire group showed improved OS with increasing dose level (51, 60, and 70 Gy) with a 4-year OS of 18%, 32%, and 51%, respectively (P=.006). Peripheral T1 tumors exhibited LC of 96%, DSS of 88%, and OS of 60% at 4 years. Patients with T2 tumors showed a trend toward improved LC and survival with the 70-Gy dose level. On multivariate analysis, larger tumor size was strongly associated with increased local recurrence and decreased survival. Central versus peripheral location did not correlate with any outcome measures. Clinical radiation pneumonitis was not found to be a significant complication, and no patient required steroid therapy after treatment for radiation pneumonitis. Pulmonary function was well maintained 1 year after treatment. Conclusions: High-dose hypofractionated proton therapy achieves excellent outcomes for lung carcinomas that are peripherally or centrally located. The 70-Gy regimen has been adopted as standard therapy for T1 tumors at our institution. Larger T2 tumors show a trend toward improved outcomes with higher doses, suggesting that better results could be seen with

  10. A treatment planning comparison between modulated tri-cobalt-60 teletherapy and linear accelerator–based stereotactic body radiotherapy for central early-stage non−small cell lung cancer

    Energy Technology Data Exchange (ETDEWEB)

    Merna, Catherine; Rwigema, Jean-Claude M.; Cao, Minsong; Wang, Pin-Chieh; Kishan, Amar U.; Michailian, Argin; Lamb, James; Sheng, Ke; Agazaryan, Nzhde; Low, Daniel A.; Kupelian, Patrick; Steinberg, Michael L.; Lee, Percy, E-mail: percylee@mednet.ucla.edu

    2016-04-01

    We evaluated the feasibility of planning stereotactic body radiotherapy (SBRT) for large central early-stage non−small cell lung cancer with a tri-cobalt-60 (tri-{sup 60}Co) system equipped with real-time magnetic resonance imaging (MRI) guidance, as compared to linear accelerator (LINAC)–based SBRT. In all, 20 patients with large central early-stage non−small cell lung cancer who were treated between 2010 and 2015 with LINAC-based SBRT were replanned using a tri-{sup 60}Co system for a prescription dose of 50 Gy in 4 fractions. Doses to organs at risk were evaluated based on established MD Anderson constraints for central lung SBRT. R{sub 100} values were calculated as the total tissue volume receiving 100% of the dose (V{sub 100}) divided by the planning target volume and compared to assess dose conformity. Dosimetric comparisons between LINAC-based and tri-{sup 60}Co SBRT plans were performed using Student's t-test and Wilcoxon Ranks test. Blinded reviews by radiation oncologists were performed to assess the suitability of both plans for clinical delivery. The mean planning target volume was 48.3 cc (range: 12.1 to 139.4 cc). Of the tri-{sup 60}Co SBRT plans, a mean 97.4% of dosimetric parameters per patient met MD Anderson dose constraints, whereas a mean 98.8% of dosimetric parameters per patient were met with LINAC-based SBRT planning (p = 0.056). R{sub 100} values were similar between both plans (1.20 vs 1.21, p = 0.79). Upon blinded review by 4 radiation oncologists, an average of 90% of the tri-{sup 60}Co SBRT plans were considered acceptable for clinical delivery compared with 100% of the corresponding LINAC-based SBRT plans (p = 0.17). SBRT planning using the tri-{sup 60}Co system with built-in MRI is feasible and achieves clinically acceptable plans for most central lung patients, with similar target dose conformity and organ at risk dosimetry. The added benefit of real-time MRI-guided therapy may further optimize tumor targeting while

  11. SU-E-T-338: Dosimetric Study of Volumetric Modulated Arc Therapy (VMAT) and Intensity Modulated Radiation Therapy (IMRT) for Stereotactic Body Radiation Therapy (SBRT) in Early Stage Lung Cancer

    Energy Technology Data Exchange (ETDEWEB)

    Ahmad, I; Quinn, K; Seebach, A; Wang, H [OSF Saint Anthony Medical Center, Rockford, IL (United States); Yah, R [University of Illinois College of Medicine at Rockford, Rockford, IL (United States)

    2015-06-15

    Purpose: This study evaluates the dosimetric differences using volumetric modulated arc therapy (VMAT) in patients previously treated with intensity modulated radiation therapy IMRT for stereotactic body radiotherapy (SBRT) in early stage lung cancer. Methods: We evaluated 9 consecutive medically inoperable lung cancer patients at the start of the SBRT program who were treated with IMRT from November 2010 to October 2011. These patients were treated using 6 MV energy. The 9 cases were then re-planned with VMAT performed with arc therapy using 6 MV flattening filter free (FFF) energy with the same organs at risk (OARS) constraints. Data collected for the treatment plans included target coverage, beam on time, dose to OARS and gamma pass rate. Results: Five patients were T1N0 and four patients were T2N0 with all tumors less than 5 cm. The average GTV was 13.02 cm3 (0.83–40.87) and average PTV was 44.65 cm3 (14.06–118.08). The IMRT plans had a mean of 7.2 angles (6–9) and 5.4 minutes (3.6–11.1) per plan. The VMAT plans had a mean of 2.8 arcs (2–3) and 4.0 minutes (2.2–6.0) per plan. VMAT had slightly more target coverage than IMRT with average increase in D95 of 2.68% (1.24–5.73) and D99 of 3.65% (0.88–8.77). VMAT produced lower doses to all OARs. The largest reductions were in maximum doses to the spinal cord with an average reduction of 24.1%, esophagus with an average reduction of 22.1%, and lung with an average reduction in the V20 of 16.3% The mean gamma pass rate was 99.8% (99.2–100) at 3 mm and 3% for VMAT with comparable values for IMRT. Conclusion: These findings suggest that using VMAT for SBRT in early stage lung cancer is superior to IMRT in terms of dose coverage, OAR dose and a lower treatment delivery time with a similar gamma pass rate.

  12. Stages of Small Cell Lung Cancer

    Science.gov (United States)

    ... lung cancer is a disease in which malignant (cancer) cells form in the tissues of the lung. The ... diagnosed, tests are done to find out if cancer cells have spread within the chest or to other ...

  13. A comparative study of the target volume definition in radiotherapy with «Slow CT Scan» vs. 4D PET/CT Scan in early stages non-small cell lung cancer.

    Science.gov (United States)

    Molla, M; Anducas, N; Simó, M; Seoane, A; Ramos, M; Cuberas-Borros, G; Beltran, M; Castell, J; Giralt, J

    To evaluate the use of 4D PET/CT to quantify tumor respiratory motion compared to the «Slow»-CT (CTs) in the radiotherapy planning process. A total of 25 patients with inoperable early stage non small cell lung cancer (NSCLC) were included in the study. Each patient was imaged with a CTs (4s/slice) and 4D PET/CT. The adequacy of each technique for respiratory motion capture was evaluated using the volume definition for each of the following: Internal target volume (ITV) 4D and ITVslow in relation with the volume defined by the encompassing volume of 4D PET/CT and CTs (ITVtotal). The maximum distance between the edges of the volume defined by each technique to that of the total volume was measured in orthogonal beam's eye view. The ITV4D showed less differences in relation with the ITVtotal in both the cranio-caudal and the antero-posterior axis compared to the ITVslow. The maximum differences were 0.36mm in 4D PET/CTand 0.57mm in CTs in the antero-posterior axis. 4D PET/CT resulted in the definition of more accurate (ITV4D/ITVtotal 0.78 vs. ITVs/ITVtotal 0.63), and larger ITVs (19.9 cc vs. 16.3 cc) than those obtained with CTs. Planning with 4D PET/CT in comparison with CTs, allows incorporating tumor respiratory motion and improving planning radiotherapy of patients in early stages of lung cancer. Copyright © 2016 Elsevier España, S.L.U. y SEMNIM. All rights reserved.

  14. Early Detection of Lung Cancer Using Neural Network Techniques

    Directory of Open Access Journals (Sweden)

    Prashant Naresh

    2014-08-01

    Full Text Available Effective identification of lung cancer at an initial stage is an important and crucial aspect of image processing. Several data mining methods have been used to detect lung cancer at early stage. In this paper, an approach has been presented which will diagnose lung cancer at an initial stage using CT scan images which are in Dicom (DCM format. One of the key challenges is to remove white Gaussian noise from the CT scan image, which is done using non local mean filter and to segment the lung Otsu’s thresholding is used. The textural and structural features are extracted from the processed image to form feature vector. In this paper, three classifiers namely SVM, ANN, and k-NN are applied for the detection of lung cancer to find the severity of disease (stage I or stage II and comparison is made with ANN, and k-NN classifier with respect to different quality attributes such as accuracy, sensitivity(recall, precision and specificity. It has been found from results that SVM achieves higher accuracy of 95.12% while ANN achieves 92.68% accuracy on the given data set and k-NN shows least accuracy of 85.37%. SVM algorithm which achieves 95.12% accuracy helps patients to take remedial action on time and reduces mortality rate from this deadly disease.

  15. Low-Dose Acetylsalicylic Acid in Treating Patients With Stage I-III Non-Small Cell Lung Cancer

    Science.gov (United States)

    2016-06-28

    Adenocarcinoma of the Lung; Recurrent Non-small Cell Lung Cancer; Stage IA Non-small Cell Lung Cancer; Stage IB Non-small Cell Lung Cancer; Stage IIA Non-small Cell Lung Cancer; Stage IIB Non-small Cell Lung Cancer; Stage IIIA Non-small Cell Lung Cancer; Stage IIIB Non-small Cell Lung Cancer

  16. Early lung function abnormalities in acromegaly.

    Science.gov (United States)

    Benfante, A; Ciresi, A; Bellia, M; Cannizzaro, F; Bellia, V; Giordano, C; Scichilone, N

    2015-06-01

    Acromegaly is an insidious disorder caused by a pituitary growth hormone (GH)-secreting adenoma resulting in high circulating levels of GH and insulin-like growth factor I (IGF-I). Respiratory disorders are common complications in acromegaly, and can severely impact on quality of life, eventually affecting mortality. The present study aimed to explore structural and functional lung alterations of acromegalic subjects. We enrolled 10 consecutive patients (M/F: 5/5) affected by acromegaly. In all patients, magnetic resonance imaging (MRI) revealed the presence of pituitary tumor. All patients underwent clinical, lung functional, biological, and radiological assessments. Ten healthy age-matched subjects also served as controls. No statistically significant differences in lung function were detected between acromegalic and healthy subjects (p ≥ 0.05 for all analyses). However, the diffusing capacity for CO (TLCO) was significantly lower in the acromegalic group than in healthy subjects (TLCO% predicted: 78.1 ± 16 vs. 90 ± 6 %, respectively, p = 0.04; KCO% predicted: 77 ± 16 vs. 93 ± 5 %, p = 0.02, respectively). None of the lung function parameters correlated with duration of the disease, or with inflammatory marker of the airways. In acromegalics, biological (exhaled NO concentrations) and imaging (total lung volume, TLV, and mean lung density, MLD) evaluations were within normal values. The TLV measured by HRCT was 3540 ± 1555 ml in acromegalics, and the MLD was -711 ± 73 HU. None of the lung functional, radiological, and biological findings correlated with GH or IGF-I levels, and no correlation was found with duration of disease. In the current study, lung function evaluation allowed to detect early involvement of lung parenchyma, as assessed by TLCO and KCO, even in the absence of parenchymal density alterations of the lung by HRCT. These findings suggest to routinely include the carbon monoxide diffusing capacity in the lung function assessment for an

  17. Expression Levels of Some Antioxidant and Epidermal Growth Factor Receptor Genes in Patients with Early-Stage Non-Small Cell Lung Cancer

    Science.gov (United States)

    De Palma, Giuseppe; Mozzoni, Paola; Acampa, Olga; Internullo, Eveline; Carbognani, Paolo; Rusca, Michele; Goldoni, Matteo; Corradi, Massimo; Tiseo, Marcello; Apostoli, Pietro; Mutti, Antonio

    2010-01-01

    This study was aimed at: (i) investigating the expression profiles of some antioxidant and epidermal growth factor receptor genes in cancerous and unaffected tissues of patients undergoing lung resection for non-small cell lung cancer (NSCLC) (cross-sectional phase), (ii) evaluating if gene expression levels at the time of surgery may be associated to patients' survival (prospective phase). Antioxidant genes included heme oxygenase 1 (HO-1), superoxide dismutase-1 (SOD-1), and -2 (SOD-2), whereas epidermal growth factor receptor genes consisted of epidermal growth factor receptor (EGFR) and v-erb-b2 erythroblastic leukaemia viral oncogene homolog 2 (HER-2). Twenty-eight couples of lung biopsies were obtained and gene transcripts were quantified by Real Time RT-PCR. The average follow-up of patients lasted about 60 months. In the cancerous tissues, antioxidant genes were significantly hypo-expressed than in unaffected tissues. The HER-2 transcript levels prevailed in adenocarcinomas, whereas EGFR in squamocellular carcinomas. Patients overexpressing HER-2 in the cancerous tissues showed significantly lower 5-year survival than the others. PMID:20700416

  18. Expression levels of some antioxidant and epidermal growth factor receptor genes in patients with early-stage non-small cell lung cancer.

    Science.gov (United States)

    De Palma, Giuseppe; Mozzoni, Paola; Acampa, Olga; Internullo, Eveline; Carbognani, Paolo; Rusca, Michele; Goldoni, Matteo; Corradi, Massimo; Tiseo, Marcello; Apostoli, Pietro; Mutti, Antonio

    2010-01-01

    THIS STUDY WAS AIMED AT: (i) investigating the expression profiles of some antioxidant and epidermal growth factor receptor genes in cancerous and unaffected tissues of patients undergoing lung resection for non-small cell lung cancer (NSCLC) (cross-sectional phase), (ii) evaluating if gene expression levels at the time of surgery may be associated to patients' survival (prospective phase). Antioxidant genes included heme oxygenase 1 (HO-1), superoxide dismutase-1 (SOD-1), and -2 (SOD-2), whereas epidermal growth factor receptor genes consisted of epidermal growth factor receptor (EGFR) and v-erb-b2 erythroblastic leukaemia viral oncogene homolog 2 (HER-2). Twenty-eight couples of lung biopsies were obtained and gene transcripts were quantified by Real Time RT-PCR. The average follow-up of patients lasted about 60 months. In the cancerous tissues, antioxidant genes were significantly hypo-expressed than in unaffected tissues. The HER-2 transcript levels prevailed in adenocarcinomas, whereas EGFR in squamocellular carcinomas. Patients overexpressing HER-2 in the cancerous tissues showed significantly lower 5-year survival than the others.

  19. Aberrant p16 promoter hypermethylation in bronchial mucosae as a biomarker for the early detection of lung cancer

    Institute of Scientific and Technical Information of China (English)

    XIE Guang-shun; HOU Ai-rong; LI Long-yun; GAO Yan-ning; CHENG Shu-jun

    2006-01-01

    @@ Lung cancer is the leading cause of cancer related death in the world and its mortality could be greatly reduced by diagnosis and treatment in its early stages. Effective tools for the early detection of lung cancer and its high risk factors remain a major challenge. Biomarkers that detect lung cancer in its early stages or identify its pretumour lesions,enabling early therapeutic intervention, would be invaluable to improve its dismal prognosis.

  20. Stereotactic body radiation therapy versus conventional radiation therapy in patients with early stage non-small cell lung cancer - An updated retrospective study on local failure and survival rates

    Energy Technology Data Exchange (ETDEWEB)

    Jeppesen, Stefan S. [Dept. of Oncology, Odense Univ. Hospital, Odense (Denmark)], e-mail: Stefan.Jeppesen@rsyd.dk; Schytte, Tine; Hansen, Olfred [Dept. of Oncology, Odense Univ. Hospital, Odense (Denmark); Inst. of Clinical Research, Univ. of Southern Denmark, Odense (Denmark); Jensen, Henrik R. [Lab. of Radiation Physics, Odense Univ. Hospital, Odense (Denmark); Brink, Carsten [Lab. of Radiation Physics, Odense Univ. Hospital, Odense (Denmark); Inst. of Clinical Research, Univ. of Southern Denmark, Odense (Denmark)

    2013-10-15

    Introduction: Stereotactic body radiation therapy (SBRT) for early stage non-small cell lung cancer (NSCLC) is now an accepted and patient friendly treatment, but still controversy exists about its comparability to conventional radiation therapy (RT). The purpose of this single-institutional report is to describe survival outcome for medically inoperable patients with early stage NSCLC treated with SBRT compared with high dose conventional RT. Material and methods: From August 2005 to June 2012, 100 medically inoperable patients were treated with SBRT at Odense Univ. Hospital. The thoracic RT consisted of 3 fractions (F) of 15-22 Gy delivered in nine days. For comparison a group of 32 medically inoperable patients treated with conventional RT with 80 Gy/35-40 F (5 F/week) in the period of July 1998 to August 2011 were analyzed. All tumors had histological or cytological proven NSCLC T1-2N0M0. Results: The median overall survival was 36.1 months versus 24.4 months for SBRT and conventional RT, respectively (p = 0.015). Local failure-free survival rates at one year were in SBRT group 93 % versus 89 % in the conventional RT group and at five years 69 % versus 66 %, SBRT and conventional RT respectively (p = 0.99). On multivariate analysis, female gender and performance status of 0-1 and SBRT predicted improved prognosis. Conclusion: In a cohort of patients with NSCLC there was a significant difference in overall survival favoring SBRT. Performance status of 0-1, female gender and SBRT predicted improved prognosis. However, staging procedure, confirmation procedure of recurrence and technical improvements of radiation treatment is likely to influence outcomes. However, SBRT seems to be as efficient as conventional RT and is a more convenient treatment for the patients.

  1. Endoscopic ultrasound in the diagnosis and staging of lung cancer

    DEFF Research Database (Denmark)

    Colella, Sara; Vilmann, Peter; Konge, Lars

    2014-01-01

    We reviewed the role of endobronchial ultrasound-guided transbronchial needle aspiration (EBUS-TBNA) and esophageal ultrasound guided fine needle aspiration (EUS-FNA) in the pretherapeutic assessment of patients with proven or suspected lung cancer. EUS-FNA and EBUS-TBNA have been shown to have...... a good diagnostic accuracy in the diagnosis and staging of lung cancer. In the future, these techniques in combination with positron emission tomography/computed tomographic may replace surgical staging in patients with suspected and proven lung cancer, but until then surgical staging remains the gold...

  2. Preoperative staging of lung cancer with combined PET-CT

    DEFF Research Database (Denmark)

    Fischer, Barbara; Lassen, Ulrik; Mortensen, Jann

    2009-01-01

    BACKGROUND: Fast and accurate staging is essential for choosing treatment for non-small-cell lung cancer (NSCLC). The purpose of this randomized study was to evaluate the clinical effect of combined positron-emission tomography and computed tomography (PET-CT) on preoperative staging of NSCLC...... one of the following: a thoracotomy with the finding of pathologically confirmed mediastinal lymph-node involvement (stage IIIA [N2]), stage IIIB or stage IV disease, or a benign lung lesion; an exploratory thoracotomy; or a thoracotomy in a patient who had recurrent disease or death from any cause...

  3. 机器人手术系统在早期肺癌治疗中的应用%Application of robotic surgery system in the treatment of early-stage lung cancer

    Institute of Scientific and Technical Information of China (English)

    李德闽

    2015-01-01

    The robotic surgical system for surgical resection of early-stage non-small cell lung cancer is the one of new tech-niques of minimally invasive surgery in the last decade.Compare to the traditional video-assisted thoracoscopic surgery(VATS),the technique provides more intuitive movements, greater flexibility, higher definition 3-dimentional vision, and the Endowrist instrument system in addition to the advantages of minimally invasiveness.Through man-machine communication,its seven degrees of freedom and two degrees of axial rotation replicate the synchronous movement of eye and hand in open surgery.This raises the minimal invasive sur-gical technique to a new level.The article reviewed the recent advances of robotic surgical system in the treatment of early non-small cell lung cancer.%机器人手术系统用于早期肺癌治疗是近10年发展起来的一项新的微创治疗技术。与传统的电视胸腔镜( vide-o-assisted thoracoscopic surgery,VATS)比较,除具有VATS微创的基本优点外,其3D高清成像,高倍数放大,符合人体工程学的仿真机械臂及多自由度转腕功能( Endowrist)等,通过人机交流还原了开放式手术中术者眼与器械、手与器械的同步运动,将微创外科技术提高到了一个新的境界。本文就机器人手术系统在早期肺癌治疗中的应用现状做一简述。

  4. Dislocation generation during early stage sintering.

    Science.gov (United States)

    Sheehan, J. E.; Lenel, F. V.; Ansell, G. S.

    1973-01-01

    Discussion of the effects of capillarity-induced stresses on dislocations during early stage sintering. A special version of Hirth's (1963) theoretical calculation procedures modified to describe dislocation nucleation on planes meeting the sintering body's neck surface obliquely is shown to predict plastic flow at stress levels know to exist between micron size metal particles in the early stages of sintering.

  5. The monitoring and management for patients following lung transplatation surgery during early stage in intensive care unit: 9 cases report%肺移植术后早期的重症监护及处理

    Institute of Scientific and Technical Information of China (English)

    李强; 马旭晨; 卢家凯; 张京岚

    2012-01-01

    目的 总结同种异体原位肺移植术后早期监护与治疗经验,以提高肺移植手术的成功率.方法 对2005年5月至2011年5月9例原位肺移植术患者的临床资料进行回顾性分析.结果 本组男5例,女4例;年龄21 ~ 67岁,平均(46.1 ±14.1)岁;生存6例.病因为肺纤维化4例,肺淋巴管平滑肌瘤病3例,双侧支气管扩张(支扩)2例;行单纯左肺移植1例,右肺移植3例,双侧单肺序贯式肺移植5例.术后呼吸机辅助2 ~32天;监护室停留3~42天;术后住院3~60天;术后并发急性排斥反应2例.肺感染4例(3例使用体外膜氧合辅助治疗);死亡3例,死因为感染2例,循环衰竭1例.6例生存,生存率66.7%.结论 肺移植术后早期处理应重视血流动力学监测和处理,合理应用血管活性药和利尿药物,通过药物和通气调整肺循环阻力,应用肺保护机械通气策略,降低机械通气和带管时间,控制术后肺感染的患病率,对于肺移植患者安全度过围术期至关重要.%Objective To summarize the experience during early stage of postoperative monitoring and treatment for the patients follwing lung transplantation in surgical intensive care unit,and to improve the patient's outcome of lung transplantation.Methods A retrospective analysis of 9 cases of orthotopic lung transplantation admitted to surgical intensive care unit (SICU) of Beijing Anzhen Hospital from May 2005 to May 2011 was made.Results There 5 male patients and 4 female patients with the age 21 -67 (46.1 ± 14.1 ) years old in present group,and among them 6 patients survived (survival rate:66.7% ).The etiological indication of admission were idiopathic pulmonary fibrosis (n =4),pulmonary lymphangioleiomyomatosis ( n =3 ),and bronehiectasis ( n =2).Bilateral sequential lung transplantation ( n =5 ),single left lung transplantation ( n =1 ) and single rigbt lung transplantation ( n =3) were performed.The postoperative duration of mechanical ventilation

  6. Lymph node micrometastases are associated with disease recurrence and poor survival for early-stage non-small cell lung cancer patients: a meta-analysis.

    Science.gov (United States)

    Deng, Xu Feng; Jiang, Li; Liu, Quan Xing; Zhou, Dong; Hou, Bing; Cui, Kefan; Min, Jia Xin; Dai, Ji Gang

    2016-02-16

    We performed a meta-analysis to clarify whether the molecular detection of tumor cells or micrometastases in the lymph node (LN) indicates a high risk of disease recurrence and poor survival in negative pathologic lymph node status non-small cell lung cancer (NSCLC). A literature search was performed using relevant keywords. We searched relevant studies from PubMed, Embase, and the Cochrane Library. Direct and indirect meta-estimates were generated using Review Manager software with fixed effects for the study. Study-to-study heterogeneity was summarized using I (2) statistics and predictive intervals (PIs). Our analysis of eight eligible studies revealed that patients with lymph node micrometastases (LNMM) were associated with poor overall survival (OS) (HR, 1.98; 95 % CI, 1.50 to 2.62; p recurrence and poor survival in patients with negative pathologic node negative NSCLC. Thus, these patients need to be carefully followed up after the initial pulmonary resection.

  7. Chest wall and rib irradiation and toxicities of early-stage lung cancer patients treated with CyberKnife stereotactic body radiotherapy.

    Science.gov (United States)

    Podder, Tarun; Biswas, Tithi; Yao, Min; Zhang, Yuxia; Kim, Ellen; Ellis, Rodney J; Lo, Simon S; Machtay, Mitchell

    2014-12-01

    The aim of the study is to evaluate the chest wall and rib toxicities in primary lung cancer patients treated with CyberKnife-based stereotactic body radiotherapy. In this study, data were collected from the 118 patients, of which 25 patients who had longer follow-up (mean: 21.9 months) were considered. Studied parameters were maximum point dose, doses to 1-100 cm(3) of chest wall and 1-10 cm(3) of ribs. Three patients developed chest wall pain (grade I). 25 studied patients, on average, received 27.7 Gy to 30 cm(3) of chest wall and 50.4 Gy to 1 cm(3) of rib. Nine patients had more than 30 Gy dose to 30 cm(3) of chest wall. No rib bone fracture was found. No correlations of chest wall pain and volume of irradiation were found.

  8. Feasibility report of image guided stereotactic body radiotherapy (IG-SBRT) with tomotherapy for early stage medically inoperable lung cancer using extreme hypofractionation

    Energy Technology Data Exchange (ETDEWEB)

    Hodge, Wes; Tome, Wolfgang A.; Jaradat, Hazim A.; Orton, Nigel P.; Khuntia, Deepak; Mehta, Minesh P. [Univ. of Wisconsin School of Medicine and Public Health, Madison, WI (United States). Dept. of Human Oncology; Traynor, Anne [Univ. of Wisconsin School of Medicine and Public Health, Madison, WI (United States). Dept. of Medicine; Weigel, Tracey [Univ. of Wisconsin School of Medicine and Public Health, Madison, WI (United States). Dept. of Surgery

    2006-09-15

    We report on the technical feasibility, dosimetric aspects, and daily image-guidance capability with megavoltage CT (MVCT) of stereotactic body radiotherapy (SBRT) using helical tomotherapy for medically inoperable T1/2 N0 M0 non-small cell lung cancer. Nine patients underwent treatment planning with 4D-CT in a double vacuum based immobilization system to minimize tumor motion and to define a lesion-specific 4D-motion envelope. Patients received 60 Gy in 5 fractions within 10 days to a PTV defined by a motion envelope plus a 6 mm expansion for microscopic extension and setup error using tomotherapy, with daily pretreatment MVCT image guidance. The primary endpoint was technical feasibility. Secondary endpoints were defining the acute and sub-acute toxicities and tumor response. Forty three of 45 fractions were successfully delivered, with an average delivery time of 22 minutes. MVCT provided excellent tumor visualization for daily image guidance. No significant tumor regression was observed on MVCT in any patient during therapy. Median mean normalized total doses were: tumor 117 Gy{sub 10}; residual lung 9 Gy{sub 3}. Maximum fraction-size equivalent dose values were: esophagus 5 Gy{sub 3}{sup 9}; cord 7 Gy{sub 3}{sup 6}. No patient experienced = grade 2 pulmonary toxicity. 3 complete, 4 partial and 2 stable responses were observed, with <3 months median follow-up. The mean tumor regression is 72%. SBRT using tomotherapy proved to be feasible, safe and free of major technical limitations or acute toxicities. Daily pretreatment MVCT imaging allows for precise daily tumor targeting with the patient in the actual treatment position, and therefore provides for precise image guidance.

  9. Methoxyamine, Pemetrexed Disodium, Cisplatin, and Radiation Therapy in Treating Patients With Stage IIIA-IV Non-small Cell Lung Cancer

    Science.gov (United States)

    2016-10-05

    Metastatic Malignant Neoplasm in the Brain; Stage IIIA Large Cell Lung Carcinoma; Stage IIIA Lung Adenocarcinoma; Stage IIIA Non-Small Cell Lung Cancer; Stage IIIB Large Cell Lung Carcinoma; Stage IIIB Lung Adenocarcinoma; Stage IIIB Non-Small Cell Lung Cancer; Stage IV Large Cell Lung Carcinoma; Stage IV Lung Adenocarcinoma; Stage IV Non-Small Cell Lung Cancer

  10. Expression of miR-29c, miR-93, and miR-429 as potential biomarkers for detection of early stage non-small lung cancer.

    Directory of Open Access Journals (Sweden)

    Wangyu Zhu

    Full Text Available BACKGROUND: Altered expression of miRNA expression contributes to human carcinogenesis. This study was designed to detect aberrant miRNA expressions as a potential biomarker for early detection and prognosis prediction of non-small cell lung cancer (NSCLC. METHODS: miRNA array was used to profile differentially expressed miRNAs and Taqman-based quantitative RT-PCR assays were used to analyze levels of miR-29c, miR-93, and miR-429 expression in NSCLC tissue samples, corresponding normal tissue samples, and serum samples from 70 NSCLC patients as well as in serum samples from 48 healthy controls. RESULTS: Levels of miR-29c and miR-93 expression were upregulated in NSCLC tissues, while serum levels of miR-29c were also upregulated, but levels of serum miR-429 were decreased in NSCLC. Moreover, the levels of miR-429 expression in NSCLC tissues were associated with those in serum samples. Receiver operating characteristic (ROC curve analysis showed that at the optimal cut-off point, the areas under the ROC curve for serum levels of miR-29c and miR-429 were 0.723 and 0.727, respectively, levels which are higher than that of carcinoma embryonic antigen (0.534 in diagnosis of stage I NSCLC. In addition, serum levels of miR-429 were associated with poor overall survival of NSCLC patients. Both univariate and multivariate analyses showed that serum miR-429 level was an independent prognostic predictor for NSCLC. CONCLUSIONS: The results of the current study suggest that detection of serum miR-29c and miR-429 expression should be further evaluated as a novel, non-invasive biomarker for early stage NSCLC.

  11. Proteomic patterns analysis with multivariate calculations as a promising tool for prompt differentiation of early stage lung tissue with cancer and unchanged tissue material

    Directory of Open Access Journals (Sweden)

    Grodzki Tomasz

    2011-03-01

    Full Text Available Abstract Background Lung cancer diagnosis in tissue material with commonly used histological techniques is sometimes inconvenient and in a number of cases leads to ambiguous conclusions. Frequently advanced immunostaining techniques have to be employed, yet they are both time consuming and limited. In this study a proteomic approach is presented which may help provide unambiguous pathologic diagnosis of tissue material. Methods Lung tissue material found to be pathologically changed was prepared to isolate proteome with fast and non selective procedure. Isolated peptides and proteins in ranging from 3.5 to 20 kDa were analysed directly using high resolution mass spectrometer (MALDI-TOF/TOF with sinapic acid as a matrix. Recorded complex spectra of a single run were then analyzed with multivariate statistical analysis algorithms (principle component analysis, classification methods. In the applied protocol we focused on obtaining the spectra richest in protein signals constituting a pattern of change within the sample containing detailed information about its protein composition. Advanced statistical methods were to indicate differences between examined groups. Results Obtained results indicate changes in proteome profiles of changed tissues in comparison to physiologically unchanged material (control group which were reflected in the result of principle component analysis (PCA. Points representing spectra of control group were located in different areas of multidimensional space and were less diffused in comparison to cancer tissues. Three different classification algorithms showed recognition capability of 100% regarding classification of examined material into an appropriate group. Conclusion The application of the presented protocol and method enabled finding pathological changes in tissue material regardless of localization and size of abnormalities in the sample volume. Proteomic profile as a complex, rich in signals spectrum of proteins

  12. Identification of serum biomarkers for diagnosing stagelung adenocarcinoma by MALDI-TOF mass spectrometry

    Institute of Scientific and Technical Information of China (English)

    2009-01-01

    Objective To identify specific biomarkers that could improve early diagnosis of lung adenocarcinoma using matrix-assisted laser desorption/ionization (MALDI) technology. Methods Serum samples were isolated from 17 patients with stagelung adenocarcinoma and 17 age-and sex-matched healthy controls,and the serum proteomic profiles were obtained by matrix-assisted laser desorption ionization time of flight (MALDI-TOF) mass spectrometry. Results Compared with healthy control group,two highly expressed potenti...

  13. Identification of Subtype-Specific Prognostic Genes for Early-Stage Lung Adenocarcinoma and Squamous Cell Carcinoma Patients Using an Embedded Feature Selection Algorithm.

    Directory of Open Access Journals (Sweden)

    Suyan Tian

    Full Text Available The existence of fundamental differences between lung adenocarcinoma (AC and squamous cell carcinoma (SCC in their underlying mechanisms motivated us to postulate that specific genes might exist relevant to prognosis of each histology subtype. To test on this research hypothesis, we previously proposed a simple Cox-regression model based feature selection algorithm and identified successfully some subtype-specific prognostic genes when applying this method to real-world data. In this article, we continue our effort on identification of subtype-specific prognostic genes for AC and SCC, and propose a novel embedded feature selection method by extending Threshold Gradient Descent Regularization (TGDR algorithm and minimizing on a corresponding negative partial likelihood function. Using real-world datasets and simulated ones, we show these two proposed methods have comparable performance whereas the new proposal is superior in terms of model parsimony. Our analysis provides some evidence on the existence of such subtype-specific prognostic genes, more investigation is warranted.

  14. Screening and early detection of lung cancer.

    Science.gov (United States)

    Van't Westeinde, Susan C; van Klaveren, Rob J

    2011-01-01

    Lung cancer with an estimated 342,000 deaths in 2008 (20% of total) is the most common cause of death from cancer, followed by colorectal cancer (12%), breast cancer (8%), and stomach cancer (7%) in Europe. In former smokers, the absolute lung cancer risk remains higher than in never-smokers; these data therefore call for effective secondary preventive measures for lung cancer in addition to smoking cessation programs. This review presents and discusses the most recent advances in the early detection and screening of lung cancer.An overview of randomized controlled computerized tomography-screening trials is given, and the role of bronchoscopy and new techniques is discussed. Finally, the approach of (noninvasive) biomarker testing in the blood, exhaled breath, sputum, and bronchoscopic specimen is reviewed.

  15. Metabolomics provide new insights on lung cancer staging and discrimination from chronic obstructive pulmonary disease.

    Science.gov (United States)

    Deja, Stanislaw; Porebska, Irena; Kowal, Aneta; Zabek, Adam; Barg, Wojciech; Pawelczyk, Konrad; Stanimirova, Ivana; Daszykowski, Michal; Korzeniewska, Anna; Jankowska, Renata; Mlynarz, Piotr

    2014-11-01

    Chronic obstructive pulmonary disease (COPD) and lung cancer are widespread lung diseases. Cigarette smoking is a high risk factor for both the diseases. COPD may increase the risk of developing lung cancer. Thus, it is crucial to be able to distinguish between these two pathological states, especially considering the early stages of lung cancer. Novel diagnostic and monitoring tools are required to properly determine lung cancer progression because this information directly impacts the type of the treatment prescribed. In this study, serum samples collected from 22 COPD and 77 lung cancer (TNM stages I, II, III, and IV) patients were analyzed. Then, a collection of NMR metabolic fingerprints was modeled using discriminant orthogonal partial least squares regression (OPLS-DA) and further interpreted by univariate statistics. The constructed discriminant models helped to successfully distinguish between the metabolic fingerprints of COPD and lung cancer patients (AUC training=0.972, AUC test=0.993), COPD and early lung cancer patients (AUC training=1.000, AUC test=1.000), and COPD and advanced lung cancer patients (AUC training=0.983, AUC test=1.000). Decreased acetate, citrate, and methanol levels together with the increased N-acetylated glycoproteins, leucine, lysine, mannose, choline, and lipid (CH3-(CH2)n-) levels were observed in all lung cancer patients compared with the COPD group. The evaluation of lung cancer progression was also successful using OPLS-DA (AUC training=0.811, AUC test=0.904). Based on the results, the following metabolite biomarkers may prove useful in distinguishing lung cancer states: isoleucine, acetoacetate, and creatine as well as the two NMR signals of N-acetylated glycoproteins and glycerol.

  16. Lung clearance index for monitoring early lung disease in alpha-1-antitrypsin deficiency.

    Science.gov (United States)

    Fuchs, Susanne I; Schwerk, Nicolaus; Pittschieler, Klaus; Ahrens, Frank; Baden, Winfried; Bals, Robert; Fähndrich, Sebastian; Gleiber, Wolfgang; Griese, Matthias; Hülskamp, Georg; Köhnlein, Thomas; Reckling, Ludmilla; Rietschel, Ernst; Staab, Doris; Gappa, Monika

    2016-07-01

    Patients with alpha-1-antitrypsin deficiency (AATD) and a PI-ZZ genotype are at high risk to develop severe emphysema during adulthood. However, little is known about early stages of emphysema and disease manifestation in other PI-types. Spirometry is commonly used for monitoring although early manifestation of emphysema is suspected within the peripheral airways that are not accessible by forced expiratory manoeuvres. We hypothesized that the Lung Clearance Index (LCI) derived from multiple breath nitrogen-washout (N2-washout) is useful to bridge this diagnostic gap. Patients from age 4 years onward and different PI-types performed N2-washout and spirometry. Results were compared to controls. 193 patients (4-79 years, 75% PI-ZZ) and 33 controls (8-60 years) were included. Mean (SD) LCI in patients was 9.1 (3.1) and 6.3 (0.6) in controls (p ≤ 0.001). 47% of adult patients with other than PI-ZZ genotypes and 39% of all patients with normal spirometry had abnormal LCIs. The LCI measured by N2-washout discriminates between patients with AATD and controls, reflects AATD related lung disease in all stages and appears to identify early peripheral lung changes in younger age than spirometry. We conclude that a normal spirometry does not exclude presence of AATD related lung disease even in genotypes other than PI-ZZ.

  17. Computed tomography-based anatomic assessment overestimates local tumor recurrence in patients with mass-like consolidation after stereotactic body radiotherapy for early-stage non-small cell lung cancer.

    Science.gov (United States)

    Dunlap, Neal E; Yang, Wensha; McIntosh, Alyson; Sheng, Ke; Benedict, Stanley H; Read, Paul W; Larner, James M

    2012-12-01

    To investigate pulmonary radiologic changes after lung stereotactic body radiotherapy (SBRT), to distinguish between mass-like fibrosis and tumor recurrence. Eighty consecutive patients treated with 3- to 5-fraction SBRT for early-stage peripheral non-small cell lung cancer with a minimum follow-up of 12 months were reviewed. The mean biologic equivalent dose received was 150 Gy (range, 78-180 Gy). Patients were followed with serial CT imaging every 3 months. The CT appearance of consolidation was defined as diffuse or mass-like. Progressive disease on CT was defined according to Response Evaluation Criteria in Solid Tumors 1.1. Positron emission tomography (PET) CT was used as an adjunct test. Tumor recurrence was defined as a standardized uptake value equal to or greater than the pretreatment value. Biopsy was used to further assess consolidation in select patients. Median follow-up was 24 months (range, 12.0-36.0 months). Abnormal mass-like consolidation was identified in 44 patients (55%), whereas diffuse consolidation was identified in 12 patients (15%), at a median time from end of treatment of 10.3 months and 11.5 months, respectively. Tumor recurrence was found in 35 of 44 patients with mass-like consolidation using CT alone. Combined with PET, 10 of the 44 patients had tumor recurrence. Tumor size (hazard ratio 1.12, P=.05) and time to consolidation (hazard ratio 0.622, P=.03) were predictors for tumor recurrence. Three consecutive increases in volume and increasing volume at 12 months after treatment in mass-like consolidation were highly specific for tumor recurrence (100% and 80%, respectively). Patients with diffuse consolidation were more likely to develop grade ≥ 2 pneumonitis (odds ratio 26.5, P=.02) than those with mass-like consolidation (odds ratio 0.42, P=.07). Incorporating the kinetics of mass-like consolidation and PET to the current criteria for evaluating posttreatment response will increase the likelihood of correctly identifying

  18. Computed Tomography-Based Anatomic Assessment Overestimates Local Tumor Recurrence in Patients With Mass-like Consolidation After Stereotactic Body Radiotherapy for Early-Stage Non-Small Cell Lung Cancer

    Energy Technology Data Exchange (ETDEWEB)

    Dunlap, Neal E. [Department of Radiation Oncology, University of Louisville, Louisville, KY (United States); Yang Wensha [Department of Radiation Oncology, Cedars Sinai Medical Center, Los Angeles, CA (United States); McIntosh, Alyson [Department of Radiation Oncology, John and Dorothy Morgan Cancer Center, Lehigh Valley Hospital, Allentown, PA (United States); Sheng, Ke [Department of Radiation Oncology, David Geffen School of Medicine at University of California Los Angeles, Los Angeles, CA (United States); Benedict, Stanley H.; Read, Paul W. [Department of Radiation Oncology, University of Virginia, Charlottesville, VA (United States); Larner, James M., E-mail: jml2p@virginia.edu [Department of Radiation Oncology, University of Virginia, Charlottesville, VA (United States)

    2012-12-01

    Purpose: To investigate pulmonary radiologic changes after lung stereotactic body radiotherapy (SBRT), to distinguish between mass-like fibrosis and tumor recurrence. Methods and Materials: Eighty consecutive patients treated with 3- to 5-fraction SBRT for early-stage peripheral non-small cell lung cancer with a minimum follow-up of 12 months were reviewed. The mean biologic equivalent dose received was 150 Gy (range, 78-180 Gy). Patients were followed with serial CT imaging every 3 months. The CT appearance of consolidation was defined as diffuse or mass-like. Progressive disease on CT was defined according to Response Evaluation Criteria in Solid Tumors 1.1. Positron emission tomography (PET) CT was used as an adjunct test. Tumor recurrence was defined as a standardized uptake value equal to or greater than the pretreatment value. Biopsy was used to further assess consolidation in select patients. Results: Median follow-up was 24 months (range, 12.0-36.0 months). Abnormal mass-like consolidation was identified in 44 patients (55%), whereas diffuse consolidation was identified in 12 patients (15%), at a median time from end of treatment of 10.3 months and 11.5 months, respectively. Tumor recurrence was found in 35 of 44 patients with mass-like consolidation using CT alone. Combined with PET, 10 of the 44 patients had tumor recurrence. Tumor size (hazard ratio 1.12, P=.05) and time to consolidation (hazard ratio 0.622, P=.03) were predictors for tumor recurrence. Three consecutive increases in volume and increasing volume at 12 months after treatment in mass-like consolidation were highly specific for tumor recurrence (100% and 80%, respectively). Patients with diffuse consolidation were more likely to develop grade {>=}2 pneumonitis (odds ratio 26.5, P=.02) than those with mass-like consolidation (odds ratio 0.42, P=.07). Conclusion: Incorporating the kinetics of mass-like consolidation and PET to the current criteria for evaluating posttreatment response will

  19. The airway microbiota in early cystic fibrosis lung disease.

    Science.gov (United States)

    Frayman, Katherine B; Armstrong, David S; Grimwood, Keith; Ranganathan, Sarath C

    2017-08-16

    Infection plays a critical role in the pathogenesis of cystic fibrosis (CF) lung disease. Over the past two decades, the application of molecular and extended culture-based techniques to microbial analysis has changed our understanding of the lungs in both health and disease. CF lung disease is a polymicrobial disorder, with obligate and facultative anaerobes recovered alongside traditional pathogens in varying proportions, with some differences observed to correlate with disease stage. While healthy lungs are not sterile, differences between the lower airway microbiota of individuals with CF and disease-controls are already apparent in childhood. Understanding the evolution of the CF airway microbiota, and its relationship with clinical treatments and outcome at each disease stage, will improve our understanding of the pathogenesis of CF lung disease and potentially inform clinical management. This review summarizes current knowledge of the early development of the respiratory microbiota in healthy children and then discusses what is known about the airway microbiota in individuals with CF, including how it evolves over time and where future research priorities lie. © 2017 Wiley Periodicals, Inc.

  20. QUALITY ASSURANCE OF 4D-CT SCAN TECHNIQUES IN MULTICENTER PHASE III TRIAL OF SURGERY VERSUS STEREOTACTIC RADIOTHERAPY (RADIOSURGERY OR SURGERY FOR OPERABLE EARLY STAGE (STAGE 1A) NON-SMALL-CELL LUNG CANCER [ROSEL] STUDY)

    NARCIS (Netherlands)

    Hurkmans, Coen W.; van Lieshout, Maarten; Schuring, Danny; van Heumen, Marielle J. T.; Cuijpers, Johan P.; Lagerwaard, Frank J.; Widder, Joachim; van der Heide, Uulke A.; Senan, Suresh

    2011-01-01

    Purpose: To determine the accuracy of four-dimensional computed tomography (4D-CT) scanning techniques in institutions participating in a Phase III trial of surgery vs. stereotactic radiotherapy (SBRT) for lung cancer. Methods and Materials: All 9 centers performed a 4D-CT scan of a motion phantom (

  1. Pathological study at the early stage of acute lung injury induced by paraquat in rabbits%百草枯致兔急性肺损伤早期的病理研究

    Institute of Scientific and Technical Information of China (English)

    陈高飞; 宋祖军; 尹文; 曹建霞; 敖国昆; 袁小东

    2013-01-01

    目的 研究百草枯(PQ)致兔急性肺损伤(ALI)早期的病理生理改变.方法 20只新西兰白兔随机分为对照组和百草枯组.百草枯组以35 mg/kg剂量一次性腹腔注射百草枯,建立ALI模型,对照组以等体积生理盐水注射.实验各组分别于建模2、4、6h时间点行320排CT扫描胸腔,得到灌注图像的CTP(CT Perfusion)参数[包括局部血流量(regional blood flower,rBF)、局部血容量(regional blood volume,rBV)、毛细血管通透性(permeability surface,rPS)],测定血清血管内皮生长因子(VEGF)质量浓度.6h后用空气栓塞法处死动物,取肺组织行病理观察.结果 分析百草枯组CTP参数和血清VEGF质量浓度,rBF和rBV随实验延长逐渐降低,rPS和血清VEGF质量浓度随时间延长逐渐升高,各个时间点与对照组比较差异均有统计学意义(P<0.05).病理观察显示,光镜下百草枯组炎细胞浸润明显,肺泡上皮细胞增生,弥漫性肺泡间隔增宽,可见灶性出血.结论 PQ致兔ALI早期时肺灌注不良,血清VEGF质量浓度升高,结合病理结果提示,ALI早期时肺血管通透性增加.%Objective To study the pathophysiological changes at the early stage of acute lung injury (ALI) induced by paraquat (PQ) in rabbits. Methods 20 New Zealand white rabbits were randomly divided into control group and PQ group. The rabbits in PQ group were treated with PQ at 35 mg/kg through intraperitoneal injection,then would be made the model of ALI . The rats in control group were treated with the same volume of saline. In experimental groups, chest was scanned by 320 - slice CT for CT perfusion (CTP) parameters including the regional blood flower (rBF) , the regional blood volume(rBV) and the permeability surface(rPS) , and the vascular endothelial growth factor (VEGF) mass concentration was measured in serum on 2, 4, 6 h respectively after building models. Animals were sacrificed by air embolism and the lung tissues were obtained for pathological

  2. Differential expression of microRNAs in early-stage neoplastic transformation in the lungs of F344 rats chronically treated with the tobacco carcinogen 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone.

    Science.gov (United States)

    Kalscheuer, Stephen; Zhang, Xiaoxiao; Zeng, Yan; Upadhyaya, Pramod

    2008-12-01

    While numerous microRNAs (miRNAs) have been reported to alter their expression levels in human lung cancer tissues compared with normal tissues, the function of these miRNAs and their contribution to the long process of lung cancer development remains largely unknown. We applied a tobacco-specific carcinogen-induced cancer model to investigate the involvement of miRNAs in early lung cancer development, which could also provide information on potential, early biomarkers of lung cancers. Male F344 rats were first chronically treated with 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone (NNK), a carcinogen present in tobacco products, for up to 20 weeks. The expression profiles of miRNAs in rat lungs were then determined. As measured by miRNA microarrays and confirmed by Northern blot and real-time polymerase chain reaction analyses, NNK treatment reduced the expression of a number of miRNAs, such as miR-101, miR-126*, miR-199 and miR-34. Significantly, these miRNAs overlap with previously published reports on altered miRNA expression in human lung cancer samples. These miRNAs might, therefore, represent early-response miRNAs that signify the molecular changes associated with pulmonary tumorigenesis. Moreover, we identified cytochrome P450 (CYP) 2A3, a critical enzyme in rat lungs that activates NNK to render it carcinogenic, as a potential target of miR-126*. NNK treatment in rats repressed miR-126* but induced CYP2A3 expression, a mechanism that may potentiate the oncogenic effects of NNK.

  3. Endobronchial Photoacoustic Microscopy for Staging of Lung Cancer

    Science.gov (United States)

    2016-08-01

    optical absorber which is important for PA imaging. To image the lymph node, the dye or absorber is necessary to generate the acoustic signals for...SUPPLEMENTARY NOTES Photoacoustic imaging, photoacoustic microscopy, lung cancer 14. ABSTRACT This research is aimed at developing a new endoscopic...imaging approach, called “photoacoustic microscopy (PAM)”, for lung cancer staging. The project will develop imaging hardware and conduct phantom

  4. Severity of lung fibrosis affects early surgical outcomes of lung cancer among patients with combined pulmonary fibrosis and emphysema.

    Science.gov (United States)

    Mimae, Takahiro; Suzuki, Kenji; Tsuboi, Masahiro; Ikeda, Norihiko; Takamochi, Kazuya; Aokage, Keiju; Shimada, Yoshihisa; Miyata, Yoshihiro; Okada, Morihito

    2016-07-01

    Combined pulmonary fibrosis and emphysema (CPFE) is defined as upper lobe emphysema and lower lobe fibrosis, which are representative lung disorders that increase the prevalence of lung cancer. This unique disorder may affect the morbidity and mortality during the early period after surgery. The present study aimed to identify which clinicopathological features significantly affect early surgical outcomes after lung resection in nonsmall cell lung cancer (NSCLC) patients and in those with CPFE.We retrospectively assessed 2295 patients with NSCLC and found that 151 (6.6%) had CPFE. All were surgically treated between January 2008 and December 2010 at 4 institutions.The postoperative complication rates for patients with and without CPFE were 39% and 17%, respectively. The 90-day mortality rates were higher among patients with than without CPFE (7.9% vs 1%). Acute exacerbation of interstitial pneumonia was the main cause of death among 12 patients with CPFE who died within 90 days after surgery. Multivariate logistic regression analysis selected CPFE, gender, age, and clinical stage as independent predictive factors for postoperative complications, and CPFE, clinical stage, and sex for 90-day mortality. The severity of lung fibrosis on preoperative CT images was an independent predictive factor for 90-day mortality among patients with CPFE.The key predictive factor for postoperative mortality and complications of lung resection for NSCLC was CPFE. The severity of lung fibrosis was the principal predictor of early outcomes after lung surgery among patients with CPFE and NSCLC.

  5. Patterns of failure in limited-stage small cell lung cancer: Implications of TNM stage for prophylactic cranial irradiation.

    Science.gov (United States)

    Wu, Abraham J; Gillis, Andrea; Foster, Amanda; Woo, Kaitlin; Zhang, Zhigang; Gelblum, Daphna Y; Downey, Robert J; Rosenzweig, Kenneth E; Ong, Leonard; Perez, Carmen A; Pietanza, M Catherine; Krug, Lee; Rudin, Charles M; Rimner, Andreas

    2017-08-01

    The relationship between tumor-node-metastasis (TNM) stage and patterns of failure in limited-stage small cell lung cancer (LS-SCLC) remains unclear. We hypothesized that TNM stage predicts brain metastasis risk, and could inform the use of prophylactic cranial irradiation. We reviewed 283 patients with stage I-IIIB SCLC. Competing-risks regression was used to analyze local, distant, and brain failure. Multivariate analysis was used to evaluate the effect of treatment and clinical factors on failure and OS. Patients with stage I or II SCLC (35% of cohort) had significantly better survival and lower risk of distant and brain metastasis, compared with stage III patients. The 5-year cumulative incidence of brain metastasis for stage I/II and III were 12% and 26%, respectively. Stage had no correlation with local failure. On multivariate analysis, stage was independently prognostic for survival, distant metastasis risk, and brain metastasis risk. TNM staging predicts likelihood of distant metastasis, brain metastasis, and survival in LS-SCLC. This supports the routine use of TNM staging in clinical practice. The lower risk of brain metastasis in stage I and II SCLC suggests that prophylactic cranial irradiation could play a more limited role in treatment of early-stage disease. Copyright © 2017 Elsevier B.V. All rights reserved.

  6. Aberrant Signaling through the HER2-ERK1/2 Pathway is Predictive of Reduced Disease-Free and Overall Survival in Early Stage Non-Small Cell Lung Cancer (NSCLC) Patients.

    Science.gov (United States)

    Scrima, Marianna; Zito Marino, Federica; Oliveira, Duarte Mendes; Marinaro, Cinzia; La Mantia, Elvira; Rocco, Gaetano; De Marco, Carmela; Malanga, Donatella; De Rosa, Nicla; Rizzuto, Antonia; Botti, Gerardo; Franco, Renato; Zoppoli, Pietro; Viglietto, Giuseppe

    2017-01-01

    Background: Purpose of this study was to evaluate the contribution of the Extracellular-regulated protein kinase (ERK)-1/2 pathway to oncogenic signaling elicited by the tyrosine kinase receptor HER2 in Non-Small Cell Lung Cancer (NSCLC) and to assess the prognostic value of these oncoproteins in NSCLC patients. Methods: Immunohistochemistry was performed to determine expression and activation of HER2 and ERK1/2 (detected by phosphorylation of Y1248 and T202/Y204, respectively) using Tissue Micro Arrays (TMA) containing matched normal and neoplastic tissues from 132 NSCLC patients. Survival analysis was carried out using the Kaplan-Meier method. Univariate and multivariate analysis were used to evaluate the prognostic value of pERK1/2, pHER2 and a combination thereof with clinical-pathological parameters such as age, lymph node status (N), size (T), stage (TNM) and grade. Results: We found that HER2 was overexpressed in 33/120 (27%) and activated in 41/114 (36%) cases; ERK1/2 was activated in 44/102 (43%) cases. A direct association was found between pERK1/2 and pHER2 (23/41; p=0.038). In addition, patients positive for pERK1/2 and for both pHER2 and pERK1/2 showed significantly worse overall survival (OS) and disease-free survival (DFS) compared with negative patients. Univariate and multivariate analysis of patients' survival revealed that positivity for pHER2-pERK1/2 and for pERK1/2 alone were independent prognostic factors of poor survival in NSCLC patients. In particular, this association was significantly important for DFS in stage I+II patients. Conclusion: This study provides evidence that activated ERK1/2 and/or the combined activation of HER2 and ERK1/2 are good indicators of poor prognosis in NSCLC patients, not only in unselected patients but also in early stage disease.

  7. Urticaria as the initial presentation of early stage Bronchioloalveolar carcinoma: a case report

    Institute of Scientific and Technical Information of China (English)

    HU Hui-hui; YING Ke-jing; WU Xiao-hong; CHAI Ying

    2012-01-01

    Bronchioloalveolar carcinoma is a subtype of the lung adenocarcinoma.Early stage bronchioloalveolar carcinoma is usually asymptomatic,especially in the peripheral lung.Rarely,urticaria has been described occurring with lung cancer,usually small-cell lung cancer,but no case has been reported of the bronchioloalveolar carcinoma yet.We report here a unique and initial urticaria on a patient,lasting for 6 months,who finally was diagnosed as early stage bronchioloalveolar carcinoma (T1aNOMo).After treatment of surgery,the symptom of urticaria disappeared and did not recur.Therefore,we consider that utricaria is a oossibly clinical manifestation in early stage bronchioloalveolar carcinoma.

  8. [Organisational aspects and existing problems in prevention and early diagnostics of lung cancer].

    Science.gov (United States)

    Dzhorbenadze, R A

    2005-10-01

    Thorough study of advanced stages of lung cancer has been held. Delayed detection of most of the malignant tumours (IV stages) points to a number of problems existing in Georgia in terms of primary prevention and early detection of oncologic diseases. Hence, elaboration of strategy for prevention and early detection of oncologic diseases is of great importance for our country. Activities aimed at early detection of lung cancer under the conditions of low-level resources primarily imply education of population and professionals, as well as implementation of screening procedures. Cheap and effective methods should be applied for early diagnosis of one or two most widespread malignant tumours.

  9. A treatment planning and delivery comparison of volumetric modulated arc therapy with or without flattening filter for gliomas, brain metastases, prostate, head/neck and early stage lung cancer.

    Science.gov (United States)

    Gasic, Daniel; Ohlhues, Lars; Brodin, N Patrik; Fog, Lotte S; Pommer, Tobias; Bangsgaard, Jens P; Munck Af Rosenschöld, Per

    2014-08-01

    Flattening filter-free (FFF) beams are an emerging technology that has not yet been widely implemented as standard practice in radiotherapy centers. To facilitate the clinical implementation of FFF, we attempted to elucidate the difference in plan quality and treatment delivery time compared to flattening filter beams (i.e. standard, STD) for several patient groups. We hypothesize that the treatment plan quality is comparable while the treatment delivery time of volumetric modulated arc therapy (VMAT) is considerably shorter using FFF beams, especially for stereotactic treatments. A total of 120 patients treated for head and neck (H&N) tumors, high-grade glioma, prostate cancer, early stage lung cancer and intra-cranial metastatic disease (both single and multiple metastases) were included in the study. For each cohort, 20 consecutive patients were selected. The plans were generated using STD- and FFF-VMAT for both 6 MV and 10 MV, and were compared with respect to plan quality, monitor units and delivery time using Wilcoxon signed rank tests. For H&N and high-grade gliomas, there was a significant difference in homogeneity index in favor for STD-VMAT (p delivery time compared to STD-VMAT plans (p < 0.001) for higher dose per fraction, on average 54.5% for 6 MV and 71.4% for 10 MV. FFF-VMAT generally required a higher number of MU/Gy (p < 0.001), on average 7.0% for 6 MV and 8.4% for 10 MV. It was generally possible to produce FFF-VMAT plans with the same target dose coverage and doses to organs at risk as STD-VMAT plans. Target dose homogeneity tended to be somewhat inferior for FFF-VMAT for the larger targets investigated. For stereotactic radiotherapy, FFF-VMAT resulted in a considerable time gain while maintaining similar plan quality compared to STD beams.

  10. DART-bid: dose-differentiated accelerated radiation therapy, 1.8 Gy twice daily. High local control in early stage (I/II) non-small-cell lung cancer

    Energy Technology Data Exchange (ETDEWEB)

    Zehentmayr, Franz; Wurstbauer, Karl; Deutschmann, Heinz; Sedlmayer, Felix [Landeskrankenhaus Salzburg, Univ.-Klinik fuer Radiotherapie und Radio-Onkologie, Univ.-Klinikum der Paracelsus Medizinischen Privatuniversitaet, Salzburg (Austria); Paracelsus Medizinische Privatuniversitaet, Institute for Research and Development of Advanced Radiation Technologies (radART), Salzburg (Austria); Fussl, Christoph; Kopp, Peter; Dagn, Karin; Fastner, Gerd [Landeskrankenhaus Salzburg, Univ.-Klinik fuer Radiotherapie und Radio-Onkologie, Univ.-Klinikum der Paracelsus Medizinischen Privatuniversitaet, Salzburg (Austria); Porsch, Peter; Studnicka, Michael [Landeskrankenhaus Salzburg, Univ.-Klinik fuer Pneumologie, Univ.-Klinikum der Paracelsus Medizinischen Privatuniversitaet, Salzburg (Austria)

    2014-09-23

    While surgery is considered standard of care for early stage (I/II), non-small-cell lung cancer (NSCLC), radiotherapy is a widely accepted alternative for medically unfit patients or those who refuse surgery. International guidelines recommend several treatment options, comprising stereotactic body radiation therapy (SBRT) for small tumors, conventional radiotherapy ≥ 60 Gy for larger sized especially centrally located lesions or continuous hyperfractionated accelerated RT (CHART). This study presents clinical outcome and toxicity for patients treated with a dose-differentiated accelerated schedule using 1.8 Gy bid (DART-bid). Between April 2002 and December 2010, 54 patients (median age 71 years, median Karnofsky performance score 70 %) were treated for early stage NSCLC. Total doses were applied according to tumor diameter: 73.8 Gy for < 2.5 cm, 79.2 Gy for 2.5-4.5 cm, 84.6 Gy for 4.5-6 cm, 90 Gy for > 6 cm. The median follow-up was 28.5 months (range 2-108 months); actuarial local control (LC) at 2 and 3 years was 88 %, while regional control was 100 %. There were 10 patients (19 %) who died of the tumor, and 18 patients (33 %) died due to cardiovascular or pulmonary causes. A total of 11 patients (20 %) died intercurrently without evidence of progression or treatment-related toxicity at the last follow-up, while 15 patients (28 %) are alive. Acute esophagitis ≤ grade 2 occurred in 7 cases, 2 patients developed grade 2 chronic pulmonary fibrosis. DART-bid yields high LC without significant toxicity. For centrally located and/or large (> 5 cm) early stage tumors, where SBRT is not feasible, this method might serve as radiotherapeutic alternative to present treatment recommendations, with the need of confirmation in larger cohorts. (orig.) [German] Die Standardbehandlung fuer nichtkleinzellige Bronchialkarzinome (NSCLC) im Stadium I/II ist die Operation, wobei Radiotherapie fuer Patienten, die nicht operabel sind oder die Operation ablehnen, als Alternative

  11. Surgery in limited stage small cell lung cancer

    DEFF Research Database (Denmark)

    Lassen, U; Hansen, H H

    1999-01-01

    The role of surgery in small cell lung cancer (SCLC) is controversial. Surgery has several potential advantages because it may reduce the frequency of local relapses, it does not impede the intensity of chemotherapy, it does not affect the bone marrow, and surgical staging may be of prognostic...

  12. [Treatment of early stage Hodgkin disease

    DEFF Research Database (Denmark)

    Specht, Lena; Carde, P.; Mauch, P.

    1993-01-01

    In early stage Hodgkin's disease the optimal choice of treatment is still an unresolved issue. Twenty-two randomized trials of radiotherapy alone versus radiotherapy plus combination chemotherapy have been carried out world-wide. The preliminary results of a global meta-analysis of these trials...

  13. Radiotherapy versus combined modality in early stages

    DEFF Research Database (Denmark)

    Specht, L.; Carde, P.; Mauch, P.;

    1992-01-01

    In early stage Hodgkin's disease the optimal choice of treatment for the individual patient is still an unresolved issue. So far, twenty-two randomized trials of radiotherapy alone versus radiotherapy plus combination chemotherapy have been carried out worldwide. The preliminary results of a glob...

  14. A Phase I Trial of an Immune Checkpoint Inhibitor Plus Stereotactic Ablative Radiotherapy in Patients with Inoperable Stage I Non-Small Cell Lung Cancer

    Science.gov (United States)

    2016-10-01

    with Inoperable Stage I Non-Small Cell Lung Cancer PRINCIPAL INVESTIGATOR: Karen Kelly, MD CONTRACTING ORGANIZATION: University of California...Checkpoint Inhibitor Plus Stereotactic Ablative Radiotherapy in Patients with Inoperable Stage I Non-Small Cell Lung Cancer 5b. GRANT NUMBER W81XWH-15...checkpoint inhibitor MPDL3280A (atezolizumab) in early stage inoperable non-small cell lung cancer. The trial is comprised of a traditional 3 + 3 phase I

  15. Carboplatin and Paclitaxel With or Without Bevacizumab and/or Cetuximab in Treating Patients With Stage IV or Recurrent Non-Small Cell Lung Cancer

    Science.gov (United States)

    2015-09-01

    Recurrent Large Cell Lung Carcinoma; Recurrent Lung Adenocarcinoma; Recurrent Squamous Cell Lung Carcinoma; Stage IV Large Cell Lung Carcinoma; Stage IV Lung Adenocarcinoma; Stage IV Squamous Cell Lung Carcinoma

  16. Canonical Sonic Hedgehog Signaling in Early Lung Development

    Directory of Open Access Journals (Sweden)

    Hugo Fernandes-Silva

    2017-03-01

    Full Text Available The canonical hedgehog (HH signaling pathway is of major importance during embryonic development. HH is a key regulatory morphogen of numerous cellular processes, namely, cell growth and survival, differentiation, migration, and tissue polarity. Overall, it is able to trigger tissue-specific responses that, ultimately, contribute to the formation of a fully functional organism. Of all three HH proteins, Sonic Hedgehog (SHH plays an essential role during lung development. In fact, abnormal levels of this secreted protein lead to severe foregut defects and lung hypoplasia. Canonical SHH signal transduction relies on the presence of transmembrane receptors, such as Patched1 and Smoothened, accessory proteins, as Hedgehog-interacting protein 1, and intracellular effector proteins, like GLI transcription factors. Altogether, this complex signaling machinery contributes to conveying SHH response. Pulmonary morphogenesis is deeply dependent on SHH and on its molecular interactions with other signaling pathways. In this review, the role of SHH in early stages of lung development, specifically in lung specification, primary bud formation, and branching morphogenesis is thoroughly reviewed.

  17. Positron emission tomography in the diagnosis and staging of lung cancer

    DEFF Research Database (Denmark)

    Fischer, B M; Mortensen, J; Højgaard, L

    2001-01-01

    positron emission tomography (PET) and gamma-camera PET in the diagnostic investigation of non-small-cell lung cancer (NSCLC). A systematic literature search was carried out in the MEDLINE and EMBASE databases and the Cochrane Controlled Trials Register. We identified 55 original works on the diagnostic......Lung cancer is the cause of 32% of all male cancer deaths and 25% of all female cancer deaths. Because the prognosis depends on early diagnosis and staging, continuous evaluation of the diagnostic tools available is important. The aim of this study was to assess the diagnostic value of dedicated...

  18. Current innovations in sentinel lymph node mapping for the staging and treatment of resectable lung cancer.

    Science.gov (United States)

    Hachey, Krista J; Colson, Yolonda L

    2014-01-01

    Despite surgical resectability, early-stage lung cancer remains a challenge to cure. Survival outcomes are hindered by variable performance of adequate lymphadenectomy and the limitations of current pathologic nodal staging. Sentinel lymph node (SLN) mapping, a mainstay in the management of breast cancer and melanoma, permits targeted nodal sampling for efficient and accurate staging that can influence both intraoperative and adjuvant treatment decisions. Unfortunately, standard SLN identification techniques with blue dye and radiocolloid tracers have not been shown to be reproducible in lung cancer. In more recent years, intraoperative near-infrared image-guided lung SLN mapping has emerged as promising technology for the identification of the tumor-associated lymph nodes most likely to contain metastatic disease. Additionally, the clinical relevance of SLN mapping for lung cancer remains pressing, as the ability to identify micrometastatic disease in SLNs could facilitate trials to assess chemotherapeutic response and the clinical effect of occult nodal disease. This review outlines the status of lung cancer lymphatic mapping and techniques in development that may help close the gap between translational research in this field and routine clinical practice.

  19. Endobronchial Photoacoustic Microscopy for Staging of Lung Cancer

    Science.gov (United States)

    2015-06-01

    whereas chemotherapy and radiotherapy could be more effective when contralateral metastases are confirmed by staging. Computed tomography (CT) or...positron emission tomography ( PET ) can only yield presumptive clinical diagnosis for lung cancer, and invasive biopsy is necessary to be carried out for...accurate and minimally invasive method for the biopsy of lymph node. However, the ultrasound-based imaging has an inherently low imaging contrast owning to

  20. Is surgery still the best management option for early stage NSCLC?

    OpenAIRE

    Ottlakan, Aurel; Martucci, Nicola; Rocco, Gaetano

    2014-01-01

    Under the formidable thrust of alternative management options for early stage lung cancer, the role of surgery in this disease subset has been questioned. Stereotactic body radiotherapy (SBRT) has been advocated as an ideal substitute for surgery not only in high risk patients or for the ones who refuse surgery but also in lieu of sublobar resection in otherwise fit patients. The therapeutic modalities for early stage NSCLC were compared as to warranting local control, enabling adequate tissu...

  1. Prevalence of gastroesophageal reflux in end-stage lung disease candidates for lung transplant.

    Science.gov (United States)

    D'Ovidio, Frank; Singer, Lianne G; Hadjiliadis, Denis; Pierre, Andrew; Waddell, Thomas K; de Perrot, Marc; Hutcheon, Micheal; Miller, Linda; Darling, Gail; Keshavjee, Shaf

    2005-10-01

    Aspiration secondary to gastroesophageal reflux has been postulated to be a contributing factor in bronchiolitis obliterans after lung transplantation. It is not clear whether gastroesophageal reflux is a preexisting condition or secondary to intraoperative vagal injury or drug-induced prolonged gastric emptying. The prevalence of gastroesophageal reflux was examined in 78 consecutive end-stage lung disease patients assessed for lung transplantation: emphysema, 21; cystic fibrosis, 5; idiopathic pulmonary fibrosis, 26; scleroderma, 10; and miscellaneous diseases, 16. All underwent esophageal manometry. Two-channel esophageal 24-hour pH testing was completed in 76 patients. Gastric emptying studies were conducted in 36 patients. Typical gastroesophageal reflux symptoms were documented in 63% of patients. The lower esophageal sphincter was hypotensive in 72% of patients, and 33% had esophageal body dysmotility. Prolonged gastric emptying was documented in 44%, and 38% had abnormal pH testing. The overall DeMeester score was above normal in 32% of patients, and 20% had abnormal proximal pH probe readings. Gastroesophageal reflux is highly prevalent in end-stage lung disease patients who are candidates for lung transplantation. Further investigation is needed to study the prevalence of gastroesophageal reflux after lung transplantation and its contribution to chronic allograft dysfunction.

  2. Radiotherapy versus combined modality in early stages

    DEFF Research Database (Denmark)

    Specht, L; Carde, P; Mauch, P;

    1992-01-01

    In early stage Hodgkin's disease the optimal choice of treatment for the individual patient is still an unresolved issue. So far, twenty-two randomized trials of radiotherapy alone versus radiotherapy plus combination chemotherapy have been carried out worldwide. The preliminary results of a global...... be kept at a minimum. Recently, trials have been carried out testing chemotherapy alone. The results of these trials are however conflicting. In order not to jeopardize the good results achieved with the standard treatments developed over the last three decades, newer treatment approaches should...... be carefully tested in large randomized trials before being implemented for general clinical use....

  3. Early Stage of Pulsed Discharge in Water

    Institute of Scientific and Technical Information of China (English)

    卢新培; 潘垣; 刘克富; 刘明海; 张寒虹

    2001-01-01

    The bubble radius at the early stage of discharge in water is investigated using high-speed photography. Some simulation results on the bubble radius are presented, which are in agreement with the experimental results, with a maximum difference of about 10%. The reasons why the peak pressure of the first shock wave is only related to the energy released in the bubble during the first half period are addressed. The energy released in the bubble after the first half period increases the bubble pulsation period, but it produces no more than 10% under the peak pressure of the second shock wave.

  4. Dupuytren contracture. Radiotherapy of early stages

    Energy Technology Data Exchange (ETDEWEB)

    Herbst, M.; Regler, G.

    1985-03-01

    Conventional radiotherapy is the treatment of choice for the early stages of theDupuytren contracture. The conventional semi-deep therapy is more favorable than the soft ray technique and the moulage technique. 62 patients have been treated at Erlangen; 33 out of them (46 irradiated hands) with a minimum observation time of 18 months have been evaluated. The pathologic process was stopped in 98% of the cases. 85% of the patients showed an improvement of troubles by regression of tubercules and cords, pains and sensation of pressure. A recurrence was obseved only in one patient at the edge of the irradiated volume.

  5. Lung cancer stage at diagnosis: Individual associations in the prospective VITamins and lifestyle (VITAL cohort

    Directory of Open Access Journals (Sweden)

    Au David H

    2011-06-01

    Full Text Available Abstract Background Lung cancer is the leading cause of cancer death in the United States. Identifying factors associated with stage of diagnosis can improve our understanding of biologic and behavioral pathways of lung cancer development and detection. We used data from a prospective cohort study to evaluate associations of demographic, health history, and health behaviors with early versus late stage at diagnosis of non-small cell lung cancer (NSCLC. Methods We calculated odds ratios (ORs for the association of patient-level characteristics with advanced stage of diagnosis for NSCLC. The OR's were then adjusted for age, gender, race/ethnicity, smoking status, income, education, chronic obstructive pulmonary disease, and a comorbidity index. Results We identified 612 cases of NSCLC among 77,719 adults, aged 50 to 76 years from Washington State recruited in 2000-2002, with followup through December 2007. In univariate analyses, subjects who quit smoking Conclusions Smoking status, education, and a screening activity were associated with stage at diagnosis of NSCLC. These results may guide future studies of the underlying mechanisms that influence how NSCLC is detected and diagnosed.

  6. Patterns of recurrence and survival after surgery or stereotactic radiotherapy for early stage NSCLC

    NARCIS (Netherlands)

    van den Berg, Liseth L.; Klinkenberg, Theo J.; Groen, Harry J. M.; Widder, Joachim

    Introduction: Surgery is the standard treatment for early stage non-small-cell lung cancer (NSCLC). For medically inoperable patients, stereotactic ablative radiotherapy (SABR) has emerged as widely used standard treatment. The aim of this study was to analyze survival and patterns of tumor

  7. Patterns of recurrence and survival after surgery or stereotactic radiotherapy for early stage NSCLC

    NARCIS (Netherlands)

    van den Berg, Liseth L.; Klinkenberg, Theo J.; Groen, Harry J. M.; Widder, Joachim

    2015-01-01

    Introduction: Surgery is the standard treatment for early stage non-small-cell lung cancer (NSCLC). For medically inoperable patients, stereotactic ablative radiotherapy (SABR) has emerged as widely used standard treatment. The aim of this study was to analyze survival and patterns of tumor recurren

  8. Deformable image registration for multimodal lung-cancer staging

    Science.gov (United States)

    Cheirsilp, Ronnarit; Zang, Xiaonan; Bascom, Rebecca; Allen, Thomas W.; Mahraj, Rickhesvar P. M.; Higgins, William E.

    2016-03-01

    Positron emission tomography (PET) and X-ray computed tomography (CT) serve as major diagnostic imaging modalities in the lung-cancer staging process. Modern scanners provide co-registered whole-body PET/CT studies, collected while the patient breathes freely, and high-resolution chest CT scans, collected under a brief patient breath hold. Unfortunately, no method exists for registering a PET/CT study into the space of a high-resolution chest CT scan. If this could be done, vital diagnostic information offered by the PET/CT study could be brought seamlessly into the procedure plan used during live cancer-staging bronchoscopy. We propose a method for the deformable registration of whole-body PET/CT data into the space of a high-resolution chest CT study. We then demonstrate its potential for procedure planning and subsequent use in multimodal image-guided bronchoscopy.

  9. Early Detection of Lung Cancer : “A Role for Serum Biomarkers?”

    NARCIS (Netherlands)

    I. Broodman (Ingrid)

    2016-01-01

    markdownabstractLung cancer has the highest mortality rate among cancer patients in the world, in particular because most patients are only diagnosed at an advanced and non-curable stage. Computed tomography (CT) screening on high-risk individuals has shown that early detection could reduce the mort

  10. Detection of Early lung Cancer Among Military Personnel (DECAMP)

    Science.gov (United States)

    2016-10-01

    Award Number: W81XWH-11-2-0161 TITLE: Detection of Early lung Cancer Among Military Personnel (DECAMP) PRINCIPAL INVESTIGATOR: Avrum E. Spira...W81XWH-11-2-0161 Detection of Early lung Cancer Among Military Personnel (DECAMP) 5b. GRANT NUMBER W81XWH-11-2-0161 5c. PROGRAM ELEMENT NUMBER 6...bodily fluids, which may be used for the early detection of lung cancer among military personnel and veterans. Over the course of the fifth year of

  11. Identification of serum biomarkers for diagnosing stage I lung adenocarcinoma by MALDI-TOF mass spectrometry

    Institute of Scientific and Technical Information of China (English)

    Xin-ju Li; Da-lin He; Jun-ke Fu; Jing-ren Liang

    2009-01-01

    Objectire To identify specific biomarkers that could improve early diagnsis of lung adenuearcinoma using matrix-assisted laser desorptian/ionization (MALDI) technology. Methods Serum samples were isolated from 17 patients with stage I lung adenuearcinoma and 17 age- and sex-matched healthy controls, and the serum proteomic profiles were obtained by matrix-assistcd laser desorption ionization time of flight (MALDI-TOF) mass spectrometry. Results Compared with healthy control group, two highly expressed potential biomarkers were identified with the relative molecular weights of 6 631.64 Da and 4 964. 21 Da. The two best novel protein peaks were automatically chosen for the system training and the development of the constructed model. The constructed model was then used to test an independent set of masked serum samples from 15 lung adenocarcinoma patients and 22 healthy individuals. The analysis yielded a sensitivity of 93.3 %, and a specificity of 95.5 %. Conclusion These results suggest that MALDI-TOF-MS ProteinChip technology is a quick, convenient, and high-output analyzing method that is capable of selecting several relatively potential biomarkers from the serum of lung adenocarcinoma patients and may have a clinical value in the future, and will provide clues to identifying new serologic btomarkers of lung adenocarcinoma.

  12. Stereotactic Ablative Radiation Therapy for Centrally Located Early Stage or Isolated Parenchymal Recurrences of Non-Small Cell Lung Cancer: How to Fly in a “No Fly Zone”

    Energy Technology Data Exchange (ETDEWEB)

    Chang, Joe Y., E-mail: jychang@mdanderson.org [Department of Radiation Oncology, The University of Texas MD Anderson Cancer Center, Houston, Texas (United States); Li, Qiao-Qiao; Xu, Qing-Yong; Allen, Pamela K.; Rebueno, Neal; Gomez, Daniel R. [Department of Radiation Oncology, The University of Texas MD Anderson Cancer Center, Houston, Texas (United States); Balter, Peter [Department of Radiation Physics, The University of Texas MD Anderson Cancer Center, Houston, Texas (United States); Komaki, Ritsuko [Department of Radiation Oncology, The University of Texas MD Anderson Cancer Center, Houston, Texas (United States); Mehran, Reza; Swisher, Stephen G.; Roth, Jack A. [Department of Thoracic and Cardiovascular Surgery, The University of Texas MD Anderson Cancer Center, Houston, Texas (United States)

    2014-04-01

    Purpose: We extended our previous experience with stereotactic ablative radiation therapy (SABR; 50 Gy in 4 fractions) for centrally located non-small cell lung cancer (NSCLC); explored the use of 70 Gy in 10 fractions for cases in which dose-volume constraints could not be met with the previous regimen; and suggested modified dose-volume constraints. Methods and Materials: Four-dimensional computed tomography (4DCT)-based volumetric image-guided SABR was used for 100 patients with biopsy-proven, central T1-T2N0M0 (n=81) or isolated parenchymal recurrence of NSCLC (n=19). All disease was staged with positron emission tomography/CT; all tumors were within 2 cm of the bronchial tree, trachea, major vessels, esophagus, heart, pericardium, brachial plexus, or vertebral body. Endpoints were toxicity, overall survival (OS), local and regional control, and distant metastasis. Results: At a median follow-up time of 30.6 months, median OS time was 55.6 months, and the 3-year OS rate was 70.5%. Three-year cumulative actuarial local, regional, and distant control rates were 96.5%, 87.9%, and 77.2%, respectively. The most common toxicities were chest-wall pain (18% grade 1, 13% grade 2) and radiation pneumonitis (11% grade 2 and 1% grade 3). No patient experienced grade 4 or 5 toxicity. Among the 82 patients receiving 50 Gy in 4 fractions, multivariate analyses showed mean total lung dose >6 Gy, V{sub 20} >12%, or ipsilateral lung V{sub 30} >15% to independently predict radiation pneumonitis; and 3 of 9 patients with brachial plexus D{sub max} >35 Gy experienced brachial neuropathy versus none of 73 patients with brachial D{sub max} <35 Gy (P=.001). Other toxicities were analyzed and new dose-volume constraints are proposed. Conclusions: SABR for centrally located lesions produces clinical outcomes similar to those for peripheral lesions when normal tissue constraints are respected.

  13. (18)F-FDG PET during stereotactic body radiotherapy for stage I lung tumours cannot predict outcome : a pilot study

    NARCIS (Netherlands)

    Wiegman, Erwin M.; Pruim, Jan; Ubbels, Jan F.; Groen, Harry J. M.; Langendijk, Johannes A.; Widder, Joachim

    2011-01-01

    (18)F-Fluorodeoxyglucose positron emission tomography (FDG PET) has been used to assess metabolic response several months after stereotactic body radiotherapy (SBRT) for early-stage non-small cell lung cancer. However, whether a metabolic response can be observed already during treatment and thus ca

  14. Multidetector Computed Tomography Findings in the Revised Tumor, Nodal and Metastasis Staging of Non-Small Cell Carcinoma of the Lung: APictorial Essay

    Directory of Open Access Journals (Sweden)

    N. S. Mahmood

    2010-06-01

    Full Text Available Non-small cell carcinoma of the lung is one of the leading causes of cancer deaths. Early diagnosis and accurate staging is hence crucial. Through this pictorial essay, we aim to create awareness regarding the revised staging system for this lung tumor and CT findings of different stages of non-small cell carcinoma of the lung."nMDCT with its multiplanar imaging capability plays an important role not only in making the diagnosis but also in accurate staging which determines the prognosi

  15. Urinary biomarkers at early ADPKD disease stage.

    Directory of Open Access Journals (Sweden)

    Katja Petzold

    Full Text Available Autosomal dominant polycystic kidney disease (ADPKD is characterized by a decline in renal function at late disease stage when the majority of functional renal parenchyma is replaced by cystic tissue. Thus, kidney function, assessed by estimated glomerular filtration rate (eGFR does not well represent disease burden in early disease. Here, we investigated various urinary markers for tubular injury and their association with disease burden in ADPKD patients at early disease course.ADPKD patients between 18 and 40 years with an eGFR greater or equal to 70 ml per min per 1.73m2 were eligible for this cross-sectional study. Urinary Neutrophil Gelatinase-Associated Lipocalin (NGAL, Kidney Injury Molecule-1 (KIM-1, and Uromodulin (UMOD were investigated by Enzyme-Linked Immunosorbent Assay. Clara Cell Protein 16 (CC16 was investigated by Latex Immuno Assay. Cryoscopy was performed to assess urine osmolality and Urinary Albumin-to-Creatinine Ratio (UACR was calculated. The association and the predictive properties of the markers on eGFR and height adjusted total kidney volume (htTKV was evaluated using multiple regression analysis, incorporating different control variables for adjustment. Internal bootstrapping validated the obtained results.In 139 ADPKD patients (age 31 ±7 years, mean eGFR of 93 ± 19 ml per min per 1.73 m2 the total kidney volume was negatively correlated with eGFR and UMOD and positive associated with age, UACR, KIM-1 and urine osmolality after adjustment for possible confounders. Urine osmolality and htTKV were also associated with eGFR, whereas no association of CC16, NGAL and UMOD with eGFR or htTKV was found.UACR and urinary KIM-1 are independently associated with kidney size but not with renal function in our study population. Urine osmolality was associated with eGFR and kidney volume following adjustment for multiple confounders. Despite statistical significance, the clinical value of our results is not yet conceivable

  16. Staging in Patients with Small-Cell Lung Carcinoma; PET-CT versus Standard Staging Procedures

    Directory of Open Access Journals (Sweden)

    Burcu Yalçın

    2016-12-01

    Full Text Available Objective: The most important factor for accurate treatment of patients with small cell lung carcinoma (SCLC is accuracy of the initial staging. The aim of this study was to determine how often patients, staged as local or local-advanced disease by standard staging procedures (SSPs, would be staged to have a metastatic disease based on the findings of the positron emission tomography–computed tomography (PET-CT scan. Methods: Patients with SCLC who were staged as I, II, or III disease by SSPs (according to the American Joint Committee on Cancer Staging, 7th edition formed the study population. SSPs included computed tomography of chest, abdomen, brain (or magnetic resonance imaging of brain, and bone scintigraphy. These patients were re-staged with 18F-FDG PET-CT scan. Results: Between 2013 and 2015, 27 patients were prospectively studied. Of these patients, 92.5% were male and the median age was 61. Among 27 patients, distant metastasis was detected by PET-CT in 7 (25.9% patients. Two of 7 patients were determined as stage IIIA by SSPs and 5 of 17 patients that were determined as stage IIIB by SSPs were upstaged to metastatic disease by PET-CT. All of the 7 patients had bone metastasis by PET-CT. But bone metastasis could not be detected with bone scintigraphy. Conclusion: PET-CT detected distant metastasis in one quarter of SCLC stage III patients by SSPs. Patients who staged local-advanced SCLC with CT of the chest have to be assessed by PET-CT for extracranial distant metastasis.

  17. Genetic Circuit for the Early Warning of Lung Cancer using iBioSim

    OpenAIRE

    2016-01-01

    With the development of molecular biology and gene-engineering technology, gene diagnosis has been an emerging approach for modern life sciences. Biological marker, recognized as the hot topic in the molecular and gene fields, has important values in early diagnosis, malignant tumour stage, treatment and therapeutic efficacy evaluation. The design of markers detection genetic circuit system for lung cancer is presented as a new method to provide basis for early warning and therapy. The system...

  18. Mediastinal staging for lung cancer: the influence of biopsy volume

    DEFF Research Database (Denmark)

    Nelson, Elof; Pape, Christian; Jørgensen, Ole Dan

    2010-01-01

    OBJECTIVE: Mediastinal staging is of paramount importance prior to surgery for non-small-cell lung cancer (NSCLC) to identify patients with N2-disease. Mediastinoscopy remains the gold standard, and sampling from at least three lymph node stations is generally recommended. It is unknown whether...... of demonstrating N2-disease (psampling from several lymph node stations was significantly associated with a decreased probability of demonstrating N2-disease (p=0.015) and volume was significantly larger per station when fewer stations were sampled (p... nodes during mediastinoscopy was significantly associated with the probability of demonstrating N2-disease; however, contrary to common belief, sampling from several lymph node stations was not associated with an increased probability of detecting N2-disease. Although purely speculative, these findings...

  19. Palliative Care Intervention in Improving Symptom Control and Quality of Life in Patients With Stage II-IV Non-small Cell Lung Cancer and Their Family Caregivers

    Science.gov (United States)

    2016-10-13

    Caregiver; Psychological Impact of Cancer and Its Treatment; Recurrent Non-small Cell Lung Cancer; Stage IIA Non-small Cell Lung Cancer; Stage IIB Non-small Cell Lung Cancer; Stage IIIA Non-small Cell Lung Cancer; Stage IIIB Non-small Cell Lung Cancer; Stage IV Non-small Cell Lung Cancer

  20. PET-Adjusted Intensity Modulated Radiation Therapy and Combination Chemotherapy in Treating Patients With Stage II-IV Non-small Cell Lung Cancer

    Science.gov (United States)

    2017-01-23

    Metastatic Malignant Neoplasm in the Brain; Recurrent Non-Small Cell Lung Carcinoma; Stage IIA Non-Small Cell Lung Carcinoma; Stage IIB Non-Small Cell Lung Carcinoma; Stage IIIA Non-Small Cell Lung Cancer; Stage IIIB Non-Small Cell Lung Cancer; Stage IV Non-Small Cell Lung Cancer

  1. Early Impairment of Lung Mechanics in a Murine Model of Marfan Syndrome

    Science.gov (United States)

    Uriarte, Juan J.; Meirelles, Thayna; Gorbenko del Blanco, Darya; Nonaka, Paula N.; Campillo, Noelia; Sarri, Elisabet; Navajas, Daniel; Egea, Gustavo; Farré, Ramon

    2016-01-01

    Early morbidity and mortality in patients with Marfan syndrome (MFS) -a connective tissue disease caused by mutations in fibrillin-1 gene- are mainly caused by aorta aneurysm and rupture. However, the increase in the life expectancy of MFS patients recently achieved by reparatory surgery promotes clinical manifestations in other organs. Although some studies have reported respiratory alterations in MFS, our knowledge of how this connective tissue disease modifies lung mechanics is scarce. Hence, we assessed whether the stiffness of the whole lung and of its extracellular matrix (ECM) is affected in a well-characterized MFS mouse model (FBN1C1039G/+). The stiffness of the whole lung and of its ECM were measured by conventional mechanical ventilation and atomic force microscopy, respectively. We studied 5-week and 9-month old mice, whose ages are representative of early and late stages of the disease. At both ages, the lungs of MFS mice were significantly more compliant than in wild type (WT) mice. By contrast, no significant differences were found in local lung ECM stiffness. Moreover, histopathological lung evaluation showed a clear emphysematous-like pattern in MFS mice since alveolar space enlargement was significantly increased compared with WT mice. These data suggest that the mechanism explaining the increased lung compliance in MFS is not a direct consequence of reduced ECM stiffness, but an emphysema-like alteration in the 3D structural organization of the lung. Since lung alterations in MFS are almost fully manifested at an early age, it is suggested that respiratory monitoring could provide early biomarkers for diagnosis and/or follow-up of patients with the Marfan syndrome. PMID:27003297

  2. Preoperative PET/CT in early-stage breast cancer

    DEFF Research Database (Denmark)

    Bernsdorf, M; Berthelsen, A K; Wielenga, V T;

    2012-01-01

    The aim of this study was to assess the diagnostic and therapeutic impact of preoperative positron emission tomography and computed tomography (PET/CT) in the initial staging of patients with early-stage breast cancer.......The aim of this study was to assess the diagnostic and therapeutic impact of preoperative positron emission tomography and computed tomography (PET/CT) in the initial staging of patients with early-stage breast cancer....

  3. An Analysis of Immunoreactive Signatures in Early Stage Hepatocellular Carcinoma

    Directory of Open Access Journals (Sweden)

    Yu Hong

    2015-05-01

    Interpretation: Tumor-associated autoimmune reactions may be triggered by early stage HCCs. Measurement of serum autoantibody to TAAs may be complementary to AFP measurements and improve diagnosis of early HCC.

  4. Primary Treatment Options for High-Risk/Medically Inoperable Early Stage NSCLC Patients.

    Science.gov (United States)

    Jones, Guy C; Kehrer, Jason D; Kahn, Jenna; Koneru, Bobby N; Narayan, Ram; Thomas, Tarita O; Camphausen, Kevin; Mehta, Minesh P; Kaushal, Aradhana

    2015-11-01

    Lung cancer is among the most common cancers worldwide and is the leading cause of cancer death in both men and women. For patients with early stage (American Joint Committee on Cancer T1-2, N0) non-small-cell lung cancer, the current standard of care is lobectomy with systematic lymph node evaluation. Unfortunately, patients with lung cancer often have medical comorbities, which may preclude the option of surgical resection. In such cases, a number of minimally invasive to noninvasive treatment options have gained popularity in the treatment of these high-risk patients. These modalities provide significant advantages, including patient convenience, treatment in an outpatient setting, and acceptable toxicities, including reduced impact on lung function and a modest risk of postprocedure chest wall pain. We provide a comprehensive review of the literature, including reported outcomes, complications, and limitations of sublobar resection with or without intraoperative brachytherapy, radiofrequency ablation, microwave ablation, percutaneous cryoablation, photodynamic therapy, and stereotactic body radiotherapy.

  5. Prognostic impact of serum albumin levels on the recurrence of stage I non-small cell lung cancer.

    Science.gov (United States)

    Jin, Ying; Zhao, Li; Peng, Fang

    2013-05-01

    Patients with stage I non-small cell lung cancer who have undergone complete surgical resection harbor a 30% risk for tumor recurrence. Thus, the identification of factors that are predictive for tumor recurrence is urgently needed. The aim of this study was to test the prognostic value of serum albumin levels on tumor recurrence in patients with stage I non-small cell lung cancer. Stage I non-small cell lung cancer patients who underwent complete surgical resection of the primary tumor at Zhejiang Hospital were analyzed in this study. Serum albumin levels were measured before surgery and once again after surgery in 101 histologically diagnosed non-small cell lung cancer patients. Correlations between the pre- and post-operative serum albumin levels and various clinical demographics and recurrence-free survival rates were analyzed. Patients with pre-operative hypoalbuminemia (recurrence. Serum albumin levels appear to be a significant independent prognostic factor for tumor recurrence in patients with stage I non-small cell lung cancer who have undergone complete resection. Patient pre-treatment and post-treatment serum albumin levels provide an easy and early means of discrimination between patients with a higher risk for recurrence and patients with a low risk of recurrence.

  6. Very early stages of massive stars

    Science.gov (United States)

    Vasyunina, Tatiana

    2010-12-01

    The goal of this thesis work is to investigate the initial conditions and the early phases of the formation of high-mass stars by means of dedicated observational studies. We consider two object classes: infrared dark clouds (IRDCs), and a subsequent stage characterized by the presence of young embedded (proto-)stellar clusters. First, we estimate masses and column densities for a completely new sample of southern IRDCs, utilizing our own millimeter continuum emission maps as well as Spitzer satellite data. The parameters we derive show that IRDCs from our sample have the potential to form not only low- and intermediate-mass stars, but can also be the birth places of massive stars. In particular, the comparison of our results with previously obtained data for low-mass starless cores shows a clear trend for IRDCs to have systematically higher column densities. The interpolated IRDC peak column densities exceed the threshold for the onset of massive star formation previously advocated by theoretical studies. We also critically evaluate the limitations of the applied emission and extinction methods. Second, we investigate the physical conditions and the chemical composition of the dense gas within the IRDCs of our sample by means of a multi-line molecular spectroscopy analysis. All the clouds have complex HCO+ line pro les, and we detect SiO emission in some clouds. These ndings mark the presence of infall and out ow motions in at least some parts of the IRDCs, and hence, ongoing star formation. In comparison with low-mass starless cores, the IRDCs have broader and more intense lines. Thus, they may be characterised by more turbulent conditions. Nevertheless, we nd a tendency for the IRDCs to have molecular abundances similar to the case of low-mass starless cores. This indicates similar chemical initial conditions for low- and high-mass star-forming regions. Finally, we study the stellar composition and environmental conditions in the young embedded cluster IRAS

  7. Beyond two-stage models for lung carcinogenesis in the Mayak workers: implications for plutonium risk.

    Directory of Open Access Journals (Sweden)

    Sascha Zöllner

    Full Text Available Mechanistic multi-stage models are used to analyze lung-cancer mortality after Plutonium exposure in the Mayak-workers cohort, with follow-up until 2008. Besides the established two-stage model with clonal expansion, models with three mutation stages as well as a model with two distinct pathways to cancer are studied. The results suggest that three-stage models offer an improved description of the data. The best-fitting models point to a mechanism where radiation increases the rate of clonal expansion. This is interpreted in terms of changes in cell-cycle control mediated by bystander signaling or repopulation following cell killing. No statistical evidence for a two-pathway model is found. To elucidate the implications of the different models for radiation risk, several exposure scenarios are studied. Models with a radiation effect at an early stage show a delayed response and a pronounced drop-off with older ages at exposure. Moreover, the dose-response relationship is strongly nonlinear for all three-stage models, revealing a marked increase above a critical dose.

  8. Management of Anorexia-Cachexia in Late Stage Lung Cancer Patients.

    Science.gov (United States)

    Del Ferraro, Catherine; Grant, Marcia; Koczywas, Marianna; Dorr-Uyemura, Laura A

    2012-08-01

    Nutritional deficiencies are experienced by most adults with advanced lung cancer during the course of their disease and treatment. Well-nourished individuals tolerate cancer treatment with less morbidity, mortality, and increased response to treatment as compared to those who are malnourished. Novel anti-cancer therapies cause many deficits that impact nutritional and functional status during the treatment process. Nutritional deficits include weight loss, malnutrition, and anorexia-cachexia. Anorexia-Cachexia is complex, not well understood and seen in many solid tumors in late stage disease. Assessing adequate nutrition is one of the most challenging problems for nurses, their patients and patient's families. The purpose of this review is to define and describe cancer anorexia-cachexia in late stage lung cancer, through case presentation, and to describe palliative strategies for prevention, assessment, and management in the palliative care setting. Early assessment for nutritional imbalances must be done regularly with re-evaluation for intervention effectiveness and should continue throughout the illness trajectory. Management of adverse effects of cancer and cancer-related treatment is critical to improving quality of life. Palliative care and hospice nurses play a critical role in early assessment, education and prevention to support nutritional needs for patients and their families.

  9. Treatment Options by Stage (Small Cell Lung Cancer)

    Science.gov (United States)

    ... lung cancer is a disease in which malignant (cancer) cells form in the tissues of the lung. The ... diagnosed, tests are done to find out if cancer cells have spread within the chest or to other ...

  10. Treatment Options by Stage (Non-Small Cell Lung Cancer)

    Science.gov (United States)

    ... Lung Cancer Screening Research Non-Small Cell Lung Cancer Treatment (PDQ®)–Patient Version General Information About Non-Small ... clinical trials before, during, or after starting their cancer treatment. Some clinical trials only include patients who have ...

  11. A prospective study of PET/CT in initial staging of small-cell lung cancer

    DEFF Research Database (Denmark)

    Fischer, B M; Mortensen, J; Langer, S W

    2007-01-01

    BACKGROUND: Small-cell lung cancer (SCLC) accounts for 15%-20% of all lung cancer cases. Accurate and fast staging is mandatory when choosing treatment, but current staging procedures are time consuming and lack sensitivity. PATIENTS AND METHODS: A prospective study was designed to examine the ro...

  12. The Optimality of Different Strategies for Supplemental Staging of Non–Small-Cell Lung Cancer

    DEFF Research Database (Denmark)

    Søgaard, Rikke; Fischer, Barbara Malene B; Mortensen, Jann;

    2013-01-01

    To assess the expected costs and outcomes of alternative strategies for staging of lung cancer to inform a Danish National Health Service perspective about the most cost-effective strategy.......To assess the expected costs and outcomes of alternative strategies for staging of lung cancer to inform a Danish National Health Service perspective about the most cost-effective strategy....

  13. Analysis of factors responsible for the image in early stage emphysema and research concerning the diagnosis

    Energy Technology Data Exchange (ETDEWEB)

    Nakanishi, Hirotaka [Wakayama Medical Coll. (Japan)

    1998-11-01

    To clarify the utility of the CT image to a clinical diagnosis of the early stage emphysema, the relation of CT value to the level of the lung destruction, the change in the lung density and pulmonary function was examined. Experimental pulmonary emphysema model in canine was produced by inhalation of aerosolized papain solution. In this model, the relationship between the destruction in lung tissues and the analysis of CT images was investigated. Changes in the alveolar surface area per unit lung volume well reflected those in mean CT value in the lung parenchyma. Also, it was clarified that the degree of the lung destruction in this model corresponded to that in patients with the early stage emphysema. Mean CT value in the area that formed lowest 5th percentile of the CT value histogram (mCT (5%ile)) was developed to analyze CT images in emphysema. To develop this study, changes of the mCT (5%ile) at the respiratory level from 5% to 95% inspiratory vital capacity (mCT (5%ile (5-95%VC))) was examined. In experimental studies, there was statistical significance between control and emphysema model. In clinical study using 14 patients with emphysema, the mCT (5%ile (5-95%VC)) reflected well the values of pulmonary function tests which indicated air flow limitation such as %pred. FEV 1.0 and MMF. The present studies demonstrated that it might be useful to detect the pathological and functional impairment in the early stage emphysema by using mCT (5%ile (5-95%VC)). (author)

  14. Chemotherapy and Radiation Therapy With or Without Metformin Hydrochloride in Treating Patients With Stage III Non-small Cell Lung Cancer

    Science.gov (United States)

    2016-06-17

    Adenosquamous Lung Carcinoma; Bronchioloalveolar Carcinoma; Large Cell Lung Carcinoma; Lung Adenocarcinoma; Non-Small Cell Lung Carcinoma; Recurrent Non-Small Cell Lung Carcinoma; Squamous Cell Lung Carcinoma; Stage IIIA Non-Small Cell Lung Cancer; Stage IIIB Non-Small Cell Lung Cancer

  15. Effects of early bronchoalveolar lavage fluid collected from dogs with smoke inhalation injury on the lungs of rats

    Institute of Scientific and Technical Information of China (English)

    NIE Fa-chuan; SU Dong; YANG Zong-cheng; BI Min; HUANG Yue-sheng

    2004-01-01

    Objective: Whether early massive bronchoalveolar lavage can remove the harmful substances from the lungs injured with smoke inhalation remains uncertain. This study was designed to observe the effects of early massive bronchoalveolar lavage fluid (BALF) on the healthy lungs in rats. Methods: Mongrel dogs were inflicted with severe smoke inhalation injury. The injured lungs were lavaged with large amount of normal saline in the first hour after injury and the BALF was collected. The BALF was injected into the healthy lungs of 30 rats (group C) in the dosage of 5 ml/kg. The functions and pathological changes of the lungs were observed 24 h after perfusion with the BALF. The data were compared with those of 23 rats (group B) whose lungs were perfused with the BALF collected from normal dogs and those of 21 rats (group A)whose lungs were perfused with normal saline. Results: The mortality rate 24 h after lung perfusion was higher in group C than in groups A and B. The survivors of group C exhibited fluctuation of respiratory rate (RR), remarkable decrease of PaO2, significantly higher content of lung water, decrease of total static pulmonary compliance and pulmonary expansion index, and increasse of inflammatory cytokines in the tissues of lungs. Only slight mechanic obstructive effect on the airway was observed in rats of group A and B. The pathological changes of the lungs of the rats in group C were similar to those of the dogs with actual smoke inhalation injury. Conclusion: Our findings indicate that the BALF collected from dogs with acute severe smoke inhalation injury in the early stage after injury injured the normal lungs of rats with the bioactive substances in the BALF. These findings show us that it is a valuable therapeutic procedure to apply massive bronchoalveolar fluid lavage in the early stage after inhalation injury.

  16. Pancreatic Perfusion CT in Early Stage of Severe Acute Pancreatitis

    Directory of Open Access Journals (Sweden)

    Yoshihisa Tsuji

    2012-01-01

    Full Text Available Early intensive care for severe acute pancreatitis is essential for improving SAP mortality rates. However, intensive therapies for SAP are often delayed because there is no ideal way to accurately evaluate severity in the early stages. Currently, perfusion CT has been shown useful to predict prognosis of SAP in the early stage. In this presented paper, we would like to review the clinical usefulness and limitations of perfusion CT for evaluation of local and systemic complications in early stage of SAP.

  17. The seventh tumour-node-metastasis staging system for lung cancer: Sequel or prequel?

    Science.gov (United States)

    van Meerbeeck, Jan P; Janssens, Annelies

    2013-09-01

    , Epidemiology and End Results (SEER) database. The ten modifications and the mediastinal lymph-node map - which were proposed in 2007 and adopted by the AJCC and IUCC in their respective seventh revision of the TNM system - were implemented as of 2010 and were rapidly adopted by the thoracic oncology community and cancer registries. As expected, not all controversies could be fully addressed, and the need for a prospective data set containing more granular information was felt early on. This data set of 25,000 consecutive incident cases will form the base for the eighth revision in 2017 and is currently being collected. Other threats are the role of stage migration and the increasing number of biological factors interfering with disease extent for prognostication. The latter issue will be addressed by the creation of a prognostic index, including several prognostic factors, of which stage will be one. For the time being, the seventh TNM classification is considered the gold standard for the description of disease extent, initial treatment allocation and the reporting of treatment results. The uniform use of the TNM descriptors and the lymph-node map by all involved in lung cancer care is to be considered a process indicator of quality.

  18. Ethics and decision making in end stage lung disease.

    Science.gov (United States)

    Simonds, A K

    2003-03-01

    Most physicians believe they do more good than harm, and these duties of helping and not harming the patient are rooted in the Hippocratic oath, the good Samaritan tradition, and the Order of the Knight Hospitallers founded in the 11th century to care for pilgrims and those wounded in the Crusades.(1) In recent times the simple principles of beneficence and non-maleficence have been augmented and sometimes challenged by a rising awareness of patient/consumer rights, and the public expectation of greater involvement in medical, social and scientific affairs which affect them. In a publicly funded healthcare system in which rationing (explicit or otherwise) is inevitable, the additional concepts of utility and distributive justice can easily come into conflict with the individual's right to autonomy. Possible treatment options for end stage lung disease include transplantation and long term invasive ventilation which are challenging in resource terms. Other interventions such as pulmonary rehabilitation and palliative care are relatively low cost but not uniformly accessible.

  19. Time-varying pattern of postoperative recurrence risk of early-stage (T1a-T2bN0M0) non-small cell lung cancer (NSCLC): results of a single-center study of 994 Chinese patients.

    Science.gov (United States)

    Zhu, Jian-fei; Feng, Xing-yu; Zhang, Xue-wen; Wen, Ying-sheng; Lin, Peng; Rong, Tie-hua; Cai, Ling; Zhang, Lan-jun

    2014-01-01

    The aim of this study was to analyze the time-varying pattern of recurrence risk of early-stage (T1a-T2bN0M0) non-small cell lung cancer (NSCLC) after surgery using the hazard function and identify patients who might benefit from adjuvant chemotherapy. This retrospective study enrolled 994 patients with early-stage NSCLC who underwent radical surgical resection between January 1999 and October 2009. Survival curves were generated using the Kaplan-Meier method, and the annual recurrence hazard was estimated using the hazard function. The median recurrence-free survival (RFS) was 8.8 years. The life table survival analysis showed that the 1-year, 3-year, 5-year and 10-year recurrence rates were 82.0%, 67.0%, 59.0% and 48.0%, respectively. Approximately 256 (25.7%) patients experienced relapse [locoregional: 32 (3.2%) and distant: 224 (22.5%)], and 162 patients died from cancer. The annual recurrence hazard curve for the entire population showed that the first major recurrence surge reached a maximum 1.6 years after surgery. The curve subsequently declined until reaching a nadir at 7.2 years. A second peak occurred at 8.8 years. An analysis of clinical-pathological factors demonstrated that this double-peaked pattern was present in several subgroups. The presence of a double-peaked pattern indicates that there is a predictable temporal distribution of the recurrence hazard of early-stage NSCLC. The annual recurrence hazard may be an effective method of selecting patients at high risk of recurrence, who may benefit from adjuvant therapy.

  20. Solcoseryl prevents early postradiation changes in the lungs.

    Science.gov (United States)

    Starosławska, E; Chyczewski, L; Peszyński, J; Sobolewski, K; Bańkowski, E; Chyczewska, E; Nikliński, J; Donica, H; Kojtych, A

    1994-01-01

    The aim of the study was to test the influence of Solcoseryl on early postradiation changes in the lungs of rats. The chests of the rats were irradiated with Co-60, fractional dose 250 cGy/DT, total dose 2500 cGy/DT. Solcoseryl was given intraperitoneally in quantities of 0,1ml daily, during 60 days of the experiment. Morphological examinations of the lungs revealed that Solcoseryl decreased significantly the effects of early postradiation damage of the respiratory organ in rats.

  1. What is the Optimum Screening Strategy for the Early Detection of Lung Cancer.

    Science.gov (United States)

    Baldwin, D R; Callister, M E J

    2016-11-01

    Early diagnosis of lung cancer is currently the most effective way of reducing lung cancer mortality other than quitting smoking because the treatment of late stage disease has little impact. Improving the awareness of the risk of lung cancer and warning symptoms, recognition and prompt referral, and screening with low dose computed tomography (LDCT) are potential ways to improve early diagnosis. Currently the evidence is strongest for LDCT, where one large trial, the US National Lung Screening Trial (NLST), showed a 20% relative reduction in lung cancer-related mortality and a 6.7% reduction in all-cause mortality in patients who had LDCT compared with chest X-ray. Although many questions remain about optimal methodology and cost-effectiveness, lung cancer screening is now being implemented in the USA using the NLST screening criteria. Many of these questions are being answered by on-going European trials that are reporting their findings. Here we review the research evidence for LDCT screening and explore the important issues that need to be addressed to optimise effectiveness.

  2. Transient early wheeze and lung function in early childhood associated with chronic obstructive pulmonary disease genes

    NARCIS (Netherlands)

    Kerkhof, Marjan; Boezen, Hendrika; Granell, Raquel; Wijga, Alet H.; Brunekreef, Bert; Smit, Henriette A.; de Jongste, Johan C.; Thijs, Carel; Mommers, Monique; Penders, John; Henderson, John; Koppelman, Gerard H.; Postma, Dirkje S.

    2014-01-01

    Background: It has been hypothesized that a disturbed early lung development underlies the susceptibility to chronic obstructive pulmonary disease (COPD). Little is known about whether subjects genetically predisposed to COPD show their first symptoms or reduced lung function in childhood. Objective

  3. [An unexpected stage of alkalosis in the dynamics of the early posthemorrhagic period].

    Science.gov (United States)

    Beliaev, A V

    2000-01-01

    A study was made on acid-base metabolism in early posthemorrhagic period as exemplified by examination of patients presenting with gastrointestinal hemorrhage. It has been ascertained that hemorrhage is accompanied by a mixed variant of the acid-base state (ABS) deviation, namely metabolic lactate-acidosis and respiratory alkalosis. In the time-related course of posthemorrhagic period such deviations persist in patients with lethal outcome; with the disease running a favourable course the above deviations are found to return to normal quite soon. The development of complications leads to staging in ABC, its stages being as follows: stage I--the initial stage, stage II--persisting metabolic acidosis and respiratory alkalosis, stage III--alkalosis, stage IV--normalization, with stage III of ABS being encouraged by hypocapnia caused by function disorders of the lungs in early posthemorrhagic period, normalization of cell metabolism, increase in the rate of urination as a reflection of the third earlier identified stage of water metabolism, with the H+ excretion in the urine at the previous level. The identified ABS stage III threatens coming trouble, being accompanied by metabolic deviations together with a risk of function disorder of the myocardium.

  4. Stages of Non-Small Cell Lung Cancer

    Science.gov (United States)

    ... leaking from the lung into the chest. Enlarge Fine-needle aspiration biopsy of the lung. The patient lies on a ... nodes , or other areas. Enlarge Endoscopic ultrasound-guided fine-needle aspiration biopsy. An endoscope that has an ultrasound probe and ...

  5. Image-Guided Hypofractionated Radiation Therapy With Stereotactic Body Radiation Therapy Boost and Combination Chemotherapy in Treating Patients With Stage II-III Non-Small Cell Lung Cancer That Cannot Be Removed By Surgery

    Science.gov (United States)

    2017-06-12

    Adenocarcinoma of the Lung; Adenosquamous Cell Lung Cancer; Large Cell Lung Cancer; Recurrent Non-small Cell Lung Cancer; Squamous Cell Lung Cancer; Stage IIA Non-small Cell Lung Cancer; Stage IIB Non-small Cell Lung Cancer; Stage IIIA Non-small Cell Lung Cancer; Stage IIIB Non-small Cell Lung Cancer

  6. Proteasomes in lungs from organ donors and patients with end-stage pulmonary diseases.

    Science.gov (United States)

    Baker, T A; Bach, H H; Gamelli, R L; Love, R B; Majetschak, M

    2014-01-01

    Proteasomes appear to be involved in the pathophysiology of various acute and chronic lung diseases. Information on the human lung proteasome in health and disease, however, is sparse. Therefore, we studied whether end-stage pulmonary diseases are associated with alterations in lung 20S/26S proteasome content, activity and 20S subunit composition. Biopsies were obtained from donor lungs (n=7) and explanted lungs from patients undergoing lung transplantation because of end stage chronic obstructive pulmonary disease (COPD; n=7), idiopathic pulmonary fibrosis (IPF, n=7) and pulmonary sarcoidosis (n=5). 20S/26S proteasomes in lung extracts were quantified by ELISA, chymotrypsin-like proteasome peptidase activities measured and 20S proteasome beta subunits analyzed by Western blot. As compared with donor lungs, proteasome content was increased in IPF and sarcoidosis, but not in COPD. The relative distribution of free 20S and 26S proteasomes was similar; 20S proteasome was predominant in all extracts. Proteasome peptidase activities in donor and diseased lungs were indistinguishable. All extracts contained a mixed composition of inducible 20S beta immuno-subunits and their constitutive counterparts; a disease associated distribution could not be identified. A higher content of lung proteasomes in IPF and pulmonary sarcoidosis may contribute to the pathophysiology of human fibrotic lung diseases.

  7. Current concepts in the mediastinal lymph node staging of nonsmall cell lung cancer

    NARCIS (Netherlands)

    Kramer, H; Groen, HJM

    2003-01-01

    Objective: To review the current concepts in the mediastinal staging of nonsmall cell lung cancer (NSCLC), evaluating traditional and modem staging modalities. Summary Background Data: Staging of NSCLC includes the assessment of mediastinal lymph nodes. Traditionally, computed tomography (CT) and me

  8. Recurrence Risk Factors Analysis for Stage I Non-small Cell Lung Cancer.

    Science.gov (United States)

    Wu, Ching-Feng; Fu, Jui-Ying; Yeh, Chi-Ju; Liu, Yun-Hen; Hsieh, Ming-Ju; Wu, Yi-Cheng; Wu, Ching-Yang; Tsai, Ying-Huang; Chou, Wen-Chi

    2015-08-01

    Lung cancer is the leading cause of cancer-related death worldwide. Even early-stage patients might encounter disease recurrence with relative high risk. Effective postoperative therapy is based on an accurate assessment of treatment failure after surgery. The aim of this study is to construct a disease-free survival (DFS) prediction model and stratify patients into different risk score groups.A total of 356 pathological stage I patients (7th American Joint Committee on Cancer) who underwent lung resection from January 2005 through June 2011 were retrospectively reviewed. Of these patients, 63 patients were eliminated for this study. A total of 293 p-stage I patients were included for further univariate and multivariate analysis. Clinical, surgical, and pathological factors associated with high risk of recurrence were analyzed, including age, gender, smoking status, additional primary malignancy (APM), operation method, histology, visceral pleural invasion, angiolymphatic invasion, tumor necrosis, and tumor size.Of the 293 p-stage I non-small cell lung cancer (NSCLC) patients examined, 143 were female and 150 were male, with a mean age of 62.8-years old (range: 25-83-years old). The 5-year DFS and overall survival rates after surgery were 58.9% and 75.3%, respectively. On multivariate analysis, current smoker (hazards ratio [HR]: 1.63), APM (HR: 1.86), tumor size (HR: 1.54, 2.03), nonanatomic resections (HR: 1.81), adenocarcinoma histology (HR: 2.07), visceral pleural invasion (HR: 1.54), and angiolymphatic invasion (HR: 1.53) were found to be associated with a higher risk of tumor recurrence. The final model showed a fair discrimination ability (C-statistic = 0.68). According to the difference risk group, we found patients with intermediate or higher risk group had a higher distal relapse tendency as compared with low risk group (P = 0.016, odds ratio: 3.31, 95% confidence interval: 1.21-9.03).Greater than 30% of disease recurrences occurred after surgery

  9. New procedures. Comprehensive staging of lung cancer by MRI; Neue Verfahren. Umfassendes Staging des Lungenkarzinoms mit der MRT

    Energy Technology Data Exchange (ETDEWEB)

    Hintze, C. [Universitaetsklinikum Schleswig-Holstein, Campus Kiel, Klinik fuer Diagnostische Radiologie, Kiel (Germany); Deutsches Krebsforschungszentrum (DKFZ) Heidelberg, Abteilung Radiologie (E010), Heidelberg (Germany); Dinkel, J. [Deutsches Krebsforschungszentrum (DKFZ) Heidelberg, Abteilung Radiologie (E010), Heidelberg (Germany); Biederer, J. [Universitaetsklinikum Schleswig-Holstein, Campus Kiel, Klinik fuer Diagnostische Radiologie, Kiel (Germany); Heussel, C.P. [Thoraxklinik Heidelberg, Abteilung Diagnostische und Interventionelle Radiologie, Heidelberg (Germany); Puderbach, M. [Deutsches Krebsforschungszentrum (DKFZ) Heidelberg, Abteilung Radiologie (E010), Heidelberg (Germany); Thoraxklinik Heidelberg, Abteilung Diagnostische und Interventionelle Radiologie, Heidelberg (Germany)

    2010-08-15

    Lung cancer staging according to the TNM system is based on morphological assessment of the primary cancer, lymph nodes and metastases. All aspects of this important oncological classification are measurable with MRI. Pulmonary nodules can be detected at the clinically relevant size of 4-5 mm in diameter. The extent of mediastinal, hilar and supraclavicular lymph node affection can be assessed at the same time. The predominant metastatic spread to the adrenal glands and spine can be detected in coronal orientation during dedicated MRI of the lungs. Search focused whole body MRI completes the staging. Various additional MR imaging techniques provide further functional and clinically relevant information during a single examination. In the oncological context the most important techniques are imaging of perfusion and tumor motion. Functional MRI of the lungs complements the pure staging and improves surgical approaches and radiotherapy planning. (orig.) [German] Das Staging des Lungenkarzinoms nach dem TNM-System basiert auf der morphologischen Einschaetzung des Primarius, der Lymphknoten und Metastasen. Alle Aspekte dieser onkologisch wichtigen Beurteilung lassen sich mit der MRT erfassen. Pulmonale Rundherde sind ab der klinisch relevanten Groesse von 4-5 mm Durchmesser sicher erkennbar. Die Groesse der mediastinalen, hilaeren und supraklavikulaeren Lymphknoten kann in einem Untersuchungsgang bestimmt werden. In der koronaren Schichtfuehrung der dedizierten MRT der Lunge werden die Bereiche der bevorzugten Metastasierung in Nebennieren und weite Teile der Wirbelsaeule miterfasst. Durch eine gezielte Ganzkoerper-MRT als Suchmethode wird der letzte Teil des Stagings erfuellt. Die MRT bietet vielfaeltige Moeglichkeiten, zusaetzliche funktionelle, klinisch relevante Informationen innerhalb einer Untersuchung zu erheben. Im onkologischen Kontext sind die Perfusionsbildgebung der Lunge und die Bewegungsabschaetzung der Tumoren am bedeutendsten. Die funktionelle MRT der

  10. Application of ThinPrep Bronchial Brushing Cytology in the Early Diagnosis of Lung Cancer: A Retrospective Study

    Science.gov (United States)

    Liu, Chaoying; Wen, Zhongmei; Li, Yang; Peng, Liping

    2014-01-01

    The majority of lung cancer patients are diagnosed at advanced stages of disease. This study evaluated the diagnostic value of ThinPrep (TP) bronchial brushing cytology in lung cancer. A total of 595 patients with suspicious lung cancer were enrolled in this study. The bronchial brushing samples were prepared by TP. The data were then compared to histology of lung tissue samples. Histologically, 479 of these 595 patients were diagnosed with lung cancer, including 223 cases of lung squamous cell carcinoma (SCC), 77 cases of lung adenocarcinoma (ADC), and 152 cases of small cell lung carcinoma (SCLC). The TP cytology revealed a total of 460 cases of lung cancer (including 232 SCCs, 91 ADCs, and 108 SCLCs). The TP cytological technique had 87.06% sensitivity and 62.93% specificity in the diagnosis of lung cancer. Specifically, TP cytology confirmed 195 of 223 SCCs, 47 of 77 ADCs, and 94 of 152 SCLCs. The TP cytology showed 87.44% sensitivity and 90.05% specificity for the diagnosis of SCC, with a Matthew's correlation coefficient (MCC) of 0.820; while the sensitivity was reduced to 61.04% and the specificity was 90.93% for the diagnosis of ADC, with a MCC of 0.464. For the diagnosis of SCLC, the sensitivity was 61.84% and the specificity was 96.84%, with a MCC of 0.648. Thus, this study demonstrated the usefulness of TP bronchial brushing cytology in the early diagnosis of lung cancer, especially the early stage of lung SCC. A prospective clinical trial will verify these data before being translated into the clinic. PMID:24759600

  11. [Comparison between clinical and surgical-pathological TNM staging in patients with lung cancer].

    Science.gov (United States)

    Wei, Bo; Wang, Tianyou; Gong, Min; Lv, Kejie; Tian, Feng; Wang, Zhicheng

    2005-02-20

    The accuracy of clinical TNM staging correlates with appropriate treatment in patients with lung cancer. The aim of this study is to evaluate the agreement between clinical and surgical-pathological staging in patients with lung cancer and analyze its cause in detail. One hundred and fifty patients with lung cancer treated surgically from 2000 were enrolled randomly. Clinical and surgical-pathological staging of them were made respectively according to the International System for Staging Lung Cancer newly revised by UICC. Then concordance was determined between the two staging results with Kappa value, and difference in coincident rate was analyzed among subgroups of T staging. For T staging, the agreement was excellent (Kappa value=0.729), however, the coincident rate of T3 or T4 was significantly lower than that in T1 or T2 group (P conformity of TNM staging (Kappa value=0.287). Clinical T staging based on CT can indicate the location and size of primary tumor precisely. But the borderline may be difficult to estimate when tumor site is near chest wall or mediastinum, so some patients with clinical T4 still have chances to receive complete resection. The conformity of N staging is rather poor. The key point to improve the accuracy of clinical TNM staging should be to seek more reliable techniques for evaluating N status.

  12. The influence of TP53 mutations on the prognosis of patients with early stage non-small cell lung cancer may depend on the intratumor heterogeneity of the mutations.

    Science.gov (United States)

    Lee, Shin Yup; Jeon, Hyo-Sung; Hwangbo, Yup; Jeong, Ji Yun; Park, Ji Young; Lee, Eun Jin; Jin, Guang; Shin, Kyung Min; Yoo, Seung Soo; Lee, Jaehee; Lee, Eung Bae; Cha, Seung Ick; Kim, Chang Ho; Park, Jae Yong

    2015-02-01

    A large number of studies have evaluated the impact of TP53 mutations on the prognosis of patients with non-small cell lung cancer (NSCLC); however, the results of these studies are still controversial. Recently, considerable intratumor heterogeneity for genetic alterations has been demonstrated in various human cancers, including lung cancer. In the present study, we evaluated TP53 mutations in NSCLCs by direct sequencing and observed remarkable variation in the values of relative intensity (RI, the height of the peak of mutated allele/the height of the peak of non-mutated allele) of the mutations. We also examined whether the RI values were associated with intratumor heterogeneity of TP53 mutations. In addition, we evaluated the relationship between TP53 mutations and survival outcome. The patients with a TP53 mutation did not have significantly worse survival compared to those without the mutation. However, when tumors with a TP53 mutation were categorized into two groups, those with a low and those with a high RI, the latter group had significantly worse survival compared to those with wild-type TP53 (adjusted hazard ratio = 2.58, 95% confidence interval = 1.21-5.48, P = 0.01), whereas the former group did not. These results suggest that intratumor genetic heterogeneity may be an important factor in determining the role of TP53 mutations on the prognosis of NSCLC patients.

  13. Epithelial-Derived Inflammation Disrupts Elastin Assembly and Alters Saccular Stage Lung Development.

    Science.gov (United States)

    Benjamin, John T; van der Meer, Riet; Im, Amanda M; Plosa, Erin J; Zaynagetdinov, Rinat; Burman, Ankita; Havrilla, Madeline E; Gleaves, Linda A; Polosukhin, Vasiliy V; Deutsch, Gail H; Yanagisawa, Hiromi; Davidson, Jeffrey M; Prince, Lawrence S; Young, Lisa R; Blackwell, Timothy S

    2016-07-01

    The highly orchestrated interactions between the epithelium and mesenchyme required for normal lung development can be disrupted by perinatal inflammation in preterm infants, although the mechanisms are incompletely understood. We used transgenic (inhibitory κB kinase β transactivated) mice that conditionally express an activator of the NF-κB pathway in airway epithelium to investigate the impact of epithelial-derived inflammation during lung development. Epithelial NF-κB activation selectively impaired saccular stage lung development, with a phenotype comprising rapidly progressive distal airspace dilation, impaired gas exchange, and perinatal lethality. Epithelial-derived inflammation resulted in disrupted elastic fiber organization and down-regulation of elastin assembly components, including fibulins 4 and 5, lysyl oxidase like-1, and fibrillin-1. Fibulin-5 expression by saccular stage lung fibroblasts was consistently inhibited by treatment with bronchoalveolar lavage fluid from inhibitory κB kinase β transactivated mice, Escherichia coli lipopolysaccharide, or tracheal aspirates from preterm infants exposed to chorioamnionitis. Expression of a dominant NF-κB inhibitor in fibroblasts restored fibulin-5 expression after lipopolysaccharide treatment, whereas reconstitution of fibulin-5 rescued extracellular elastin assembly by saccular stage lung fibroblasts. Elastin organization was disrupted in saccular stage lungs of preterm infants exposed to systemic inflammation. Our study reveals a critical window for elastin assembly during the saccular stage that is disrupted by inflammatory signaling and could be amenable to interventions that restore elastic fiber assembly in the developing lung.

  14. Fifty years of tobacco carcinogenesis research: from mechanisms to early detection and prevention of lung cancer.

    Science.gov (United States)

    Hecht, Stephen S; Szabo, Eva

    2014-01-01

    The recognition of the link between cigarette smoking and lung cancer in the 1964 Surgeon General's Report initiated definitive and comprehensive research on the identification of carcinogens in tobacco products and the relevant mechanisms of carcinogenesis. The resultant comprehensive data clearly illustrate established pathways of cancer induction involving carcinogen exposure, metabolic activation, DNA adduct formation, and consequent mutation of critical genes along with the exacerbating influences of inflammation, cocarcinogenesis, and tumor promotion. This mechanistic understanding has provided a framework for the regulation of tobacco products and for the development of relevant tobacco carcinogen and toxicant biomarkers that can be applied in cancer prevention. Simultaneously, the recognition of the link between smoking and lung cancer paved the way for two additional critical approaches to cancer prevention that are discussed here: detection of lung cancer at an early, curable stage, and chemoprevention of lung cancer. Recent successes in more precisely identifying at-risk populations and in decreasing lung cancer mortality with helical computed tomography screening are notable, and progress in chemoprevention continues, although challenges with respect to bringing these approaches to the general population exist. Collectively, research performed since the 1964 Report demonstrates unequivocally that the majority of deaths from lung cancer are preventable.

  15. Combined endobronchial and oesophageal endosonography for the diagnosis and staging of lung cancer

    DEFF Research Database (Denmark)

    Vilmann, Peter; Clementsen, Paul Frost; Colella, Sara

    2015-01-01

    New guidelines for combined endobronchial and oesophageal mediastinal nodal staging of lung cancer. This is an official guideline of the European Society of Gastrointestinal Endoscopy (ESGE), produced in cooperation with the European Respiratory Society (ERS) and the European Society of Thoracic...... Surgeons (ESTS). It addresses the benefit and burden associated with combined endobronchial and oesophageal mediastinal nodal staging of lung cancer. The Scottish Intercollegiate Guidelines Network (SIGN) approach was adopted to define the strength of recommendations and the quality of evidence....

  16. Diagnosis and minimally invasive treatment of early stage breast carcinoma

    NARCIS (Netherlands)

    van Esser, S.

    1979-01-01

    In this thesis the diagnostic work up and minimally invasive surgical treatment of early stage breast carcinoma is studied. Although the surgical treatment of breast carcinoma has improved significantly over the past decades, there is still room for improvement. On the one hand the focus is on early

  17. In Vivo Tagging of Lung Epithelial Cells To Define the Early Steps of Tumor Cell Dissemination

    Science.gov (United States)

    2015-12-01

    determine the tumor cell of origin [KrasG12D L/-/ /Sftpc- creER or KrasG12D L/-/ / p53 L/L /Sftpc-creER], or the contribution of alveolar type II cells in...cancer have advanced disease at the time of presentation, a finding that may be consistent with early spread. Even when lung cancer is diagnosed and...identify early stage patients at high risk of recurrence or metastatic disease as well as to develop more effective therapies for NSCLC. 7 The studies

  18. Collaboration with Pharma Will Introduce Nanotechnologies in Early Stage Drug Development | FNLCR Staging

    Science.gov (United States)

    The Frederick National Lab has begun to assist several major pharmaceutical companies in adopting nanotechnologies in early stage drug development, when the approach is most efficient and cost-effective. For some time, the national lab’s Nanotechno

  19. [Cognitive rehabilitation in early stage Alzheimer's disease].

    Science.gov (United States)

    Kasper, E; Thöne-Otto, A; Bürger, K; Schröder, S G; Hoffmann, W; Schneider, W; Teipel, S

    2016-07-01

    Dementia impairs the coping with routine daily tasks and social relationships due to an increasing degeneration of cognitive abilities. An appropriate treatment must adequately consider the effects of declined cognitive abilities on patients and their environment. Therefore, in recent times, integrative procedures for cognitive rehabilitation (CR) have become increasingly important for the therapy of patients with mild cognitive impairment (MCI) and mild dementia (MD). CR approaches provide compensatory possibilities for clearly defined routine challenges and the individual needs of those affected. This overview article in the form of a selective review elaborates factors for the effectiveness of CR on the basis of the currently available literature: 1) individuality - consideration of personal needs and targets, 2) compensation - mediation of skills and strategies to compensate for cognitive impairments, 3) interaction - inclusion of relatives and environmental conditions and 4) integration - integration of various therapeutic disciplines and methods. On the basis of this assessment with regards to the content, a critical analysis of the methods of short and long-term therapeutic effects on MCD and MD was carried out. Although the resulting factors were of high long-term relevance for the improvement of depression and quality of life, effects on cognition were more pronounced for MCI than for MD, which emphasizes the importance of beginning therapy as early as possible. The results show that future studies on effectiveness must employ endpoints relevant for routine daily life, and that the possibility of an implementation of therapeutic concepts in a healthcare system should be considered as an essential criterion.

  20. 骨髓间充质干细胞对脂多糖诱导的急性肺损伤小鼠的早期治疗作用%Therapeutic effect of intravenous bone marrow-derived mesenchymal stem cell transplantation on early-stage LPS-induced acute lung injury in mice

    Institute of Scientific and Technical Information of China (English)

    邰文琳; 董昭兴; 张丹丹; 王殿华

    2012-01-01

    administered via the tail vein.The histological findings,lung wet/dry(W/D)weight ratio,neutrophil count and protein and cytokine contents in the bronchoalveolar lavage fluid(BALF),and myeloperoxidase (MPO)level in the lung tissue were analyzed at 24 h after MSC administration.Engraftment of MSCs in the recipient lung was determined by fluorescent PKH26 staining and flow cytometry.Results Compared with the control group,PBS-treated ALI group showed significantly higher protein levels,tumor necrosis factor-α(TNF-α),interleukin-6(IL-6)and neutrophil count in the BALF and MPO content in the lung tissue,with also severe damage of lung histology.MSCs administration significantly reduced the lung W/D weight ratio,the levels of protein,TNF-α,IL-6 and neutrophil count in the BALF and MPO content in the lung tissue,and obviously lessened the lung injury 24 h after the transplantation.MSC administration also significantly increased the level of IL-10 in the BALE Conclusion Intravenous MSC transplantation can effectively improve the lung histology,attenuate the inflammatory response,reduce pulmonary edema in the early stage of LPS-induced ALI in mice,and such effects are independent of MSC engraftment in the lungs.

  1. Lung Adenocarcinoma Staged as an Unknown Primary Presenting with Symptomatic Colon Metastases: Staging by 18F FDG PET/CT

    Energy Technology Data Exchange (ETDEWEB)

    Makis, William [Brandon Regional Health Centre, Brandon (Canada); Ciarallo, Anthony [Royal Victoria Hospital, Montreal (Canada)

    2011-12-15

    A 66 year old man, who presented with bright red blood per rectum, was referred for an {sup 18F} FDG PET/CT after colonoscopy showed two suspicious colon masses, which were biopsied to reveal an adenocarcinoma of unknown origin. PET/CT showed two intensely FDG avid colon massed as well as an unsuspected FDG avid lung mass, which was biopsied to reveal a primary lung adenocarcinoma. Immunohistochemistry confirmed the two colon metastases were of pulmonary origin. It is extremely rare for lung carcinoma to present with symptomatic colon metastases, with only 11 cases described in the literature. We report the first case of the utility of {sup 18F} FDG PET/CT in staging a patient who presented with symptomatic colon metastases of an unknown primary lung malignancy.

  2. The science behind the 7th edition Tumour, Node, Metastasis staging system for lung cancer.

    Science.gov (United States)

    Marshall, Henry M; Leong, Steven C; Bowman, Rayleen V; Yang, Ian A; Fong, Kwun M

    2012-02-01

    The Tumour, Node, Metastasis (TNM) system for classifying lung cancer is the cornerstone of modern lung cancer treatment and underpins comparative research; yet is continuously evolving through updated revisions. The recently published Union for International Cancer Control 7th Edition TNM Classification for lung cancer addresses many of its predecessor's shortcomings and has been subject to rigorous evidence-based methodology. It is based on a retrospective analysis of over 80 000 lung cancer patients treated between 1990 and 2000 carried out by the International Association for the Study of Lung Cancer. The dataset was truly international and included patients treated by all modalities. Extensive internal and external validation of the findings has ensured that the recommendations are robust and generalizable. For the first time, a single classification system has been shown to be applicable not only to non-small cell lung cancer, but also to be of prognostic significance in small cell lung cancer and bronchopulmonary carcinoid tumours. We review the history of the Union for International Cancer Control TNM staging system, the changes in the most recent 7th edition and the strength of the scientific basis motivating these changes. Limitations of the current staging edition are explored, post-publication independent validation studies are reviewed, and the future of TNM staging for lung cancer is discussed.

  3. 扣除杂交法筛选与非小细胞性肺癌转移相关的基因%Identification of Metastasis-associated Genes in Early Stage Non-small Cell Lung Cancer by Subtractive Hybridization

    Institute of Scientific and Technical Information of China (English)

    王文兵; B(..O)ING Sebastian; 周小琴; 季平; 董英; 姚勤; M(..U)LLER-TIDOW Carsten

    2002-01-01

    Nons-mall cell lung cancer (NSCLC) is a leading cause of death and asubstantial fraction of patients with surgically resected disease ultimately dies due to distant metastasis. To identify gene expression differences in early stage adenocarcinoma that either did or did not metastasize within a 5year period, we employed a subtractive hybridization strategy of pooled RNA from primary adenocarcinomas (stage I) of the lung. Individual clones (n=225) of the subtracted Cdna library were sequenced. Further analyses of Mrna expression levels in a cohort of 70 NSCLC patients (stage I to IIIA) showed that the metastasis association of the identified genes was stage and histology specific. Cox regression analyses identified two genes (EIF4A1, MALA1) to be independent prognostic parameters for patients' survival in stage I and II disease. These findings could help to identify early-stage NSCLC patients at high risk for the development of distant metastasis.%非小细胞性肺癌病人的术后死亡率很高, 其原因是该病易发生转移. 收集了肺癌早期患者的样品, 并根据患者资料分成转移型(n=4)和非转移型(n=5), 采用扣除杂交法筛选与非小细胞性肺癌转移相关的基因. 扣除后的cDNA文库中得到了225个有效克隆. 对这些克隆进行了测序, 在基因文库中比较了核苷酸同源性, 初步确定了这些克隆对应的基因, 并根据基因可能涉及的功能加以分类. 通过实时(real time) RT-PCR鉴定, 发现10种基因在用于扣除试验的转移病人样品中的平均表达量比非转移病人高. 进一步对 70位患非小细胞性肺癌病人(I至IIIA期)的样品进行了检测. 根据统计分析, 在I和II期病人中, 2种基因MALA1和EIF4A1在发生转移的病人样品中的表达与在非转移的病人中有显著差异性. 这些结果将有助于分析非小细胞性肺癌病变发生转移的可能性.

  4. Clinical outcome of fiducial-less CyberKnife radiosurgery for stage I non-small cell lung cancer

    Energy Technology Data Exchange (ETDEWEB)

    Jung, In Hye; Song, Si Yeol; Cho, Byung Chul; Kwak, Jung Won; Jung, Nuri Hyun; Kim, Su Ssan; Choi, Eun Kyung [Dept. of Radiation Oncology, Asan Medical Center, University of Ulsan College of Medicine, Seoul (Korea, Republic of); Jung, Jin Hong [Dept. of Radiation Oncology, Kyung Hee University Medical Center, Kyung Hee University School of Medicine, Seoul (Korea, Republic of); Je, Hyoung Uk [Dept. of Radiation Oncology, Ulsan University Hospital, University of Ulsan College of Medicine, Ulsan (Korea, Republic of); Choi, Won Sik [Dept. of Radiation Oncology, Gangneung Asan Hospital, Uiversity of Ulsan College of Medicine, Gangneung (Korea, Republic of)

    2015-06-15

    To evaluate the treatment results in early stage non-small cell lung cancer patients who have undergone fiducial-less CyberKnife radiosurgery (CKRS). From June 2011 to November 2013, 58 patients underwent CKRS at Asan Medical Center for stage I lung cancer. After excluding 14 patients, we retrospectively reviewed the records of the remaining 44 patients. All analyses were performed using SPSS ver. 21. The median age at diagnosis was 75 years. Most patients had inoperable primary lung cancer with a poor pulmonary function test with comorbidity or old age. The clinical stage was IA in 30 patients (68.2%), IB in 14 (31.8%). The mean tumor size was 2.6 cm (range, 1.2 to 4.8 cm), and the tumor was smaller than 2 cm in 12 patients (27.3%). The radiation dose given was 48-60 Gy in 3-4 fractions. In a median follow-up of 23.1 months, local recurrence occurred in three patients (2-year local recurrence-free survival rate, 90.4%) and distant metastasis occurred in 13 patients. All patients tolerated the radiosurgery well, only two patients developing grade 3 dyspnea. The most common complications were radiation-induced fibrosis and pneumonitis. Eight patients died due to cancer progression. The results showed that fiducial-less CKRS shows comparable local tumor control and survival rates to those of LINAC-based SABR or CKRS with a fiducial marker. Thus, fiducial-less CKRS using Xsight lung tracking system can be effectively and safely performed for patients with medically inoperable stage I non-small cell lung cancer without any risk of procedure-related complication.

  5. Pretreatment [{sup 18}F]-fluoro-2-deoxy-glucose Positron Emission Tomography Maximum Standardized Uptake Value as Predictor of Distant Metastasis in Early-Stage Non-Small Cell Lung Cancer Treated With Definitive Radiation Therapy: Rethinking the Role of Positron Emission Tomography in Personalizing Treatment Based on Risk Status

    Energy Technology Data Exchange (ETDEWEB)

    Nair, Vimoj J.; MacRae, Robert [Division of Radiation Oncology, University of Ottawa, Ottawa, Ontario (Canada); Ottawa Hospital Research Institute, Ottawa, Ontario (Canada); Sirisegaram, Abby [Ottawa Hospital Research Institute, Ottawa, Ontario (Canada); Pantarotto, Jason R., E-mail: jpantarotto@toh.on.ca [Division of Radiation Oncology, University of Ottawa, Ottawa, Ontario (Canada); Ottawa Hospital Research Institute, Ottawa, Ontario (Canada)

    2014-02-01

    Purpose: The aim of this study was to determine whether the preradiation maximum standardized uptake value (SUV{sub max}) of the primary tumor for [{sup 18}F]-fluoro-2-deoxy-glucose positron emission tomography (FDG-PET) has a prognostic significance in patients with Stage T1 or T2N0 non-small cell lung cancer (NSCLC) treated with curative radiation therapy, whether conventional or stereotactic body radiation therapy (SBRT). Methods and Materials: Between January 2007 and December 2011, a total of 163 patients (180 tumors) with medically inoperable histologically proven Stage T1 or T2N0 NSCLC and treated with radiation therapy (both conventional and SBRT) were entered in a research ethics board approved database. All patients received pretreatment FDG-PET / computed tomography (CT) at 1 institution with consistent acquisition technique. The medical records and radiologic images of these patients were analyzed. Results: The overall survival at 2 years and 3 years for the whole group was 76% and 67%, respectively. The mean and median SUV{sub max} were 8.1 and 7, respectively. Progression-free survival at 2 years with SUV{sub max} <7 was better than that of the patients with tumor SUV{sub max} ≥7 (67% vs 51%; P=.0096). Tumors with SUV{sub max} ≥7 were associated with a worse regional recurrence-free survival and distant metastasis-free survival. In the multivariate analysis, SUV{sub max} ≥7 was an independent prognostic factor for distant metastasis-free survival. Conclusion: In early-stage NSCLC managed with radiation alone, patients with SUV{sub max} ≥7 on FDG-PET / CT scan have poorer outcomes and high risk of progression, possibly because of aggressive biology. There is a potential role for adjuvant therapies for these high-risk patients with intent to improve outcomes.

  6. Circulating Tumor DNA in Predicting Outcomes in Patients With Stage IV Head and Neck Cancer or Stage III-IV Non-small Cell Lung Cancer

    Science.gov (United States)

    2017-08-18

    Metastatic Squamous Neck Cancer With Occult Primary Squamous Cell Carcinoma; Salivary Gland Squamous Cell Carcinoma; Stage IIIA Non-small Cell Lung Cancer; Stage IIIB Non-small Cell Lung Cancer; Stage IV Non-small Cell Lung Cancer; Stage IV Squamous Cell Carcinoma of the Hypopharynx; Stage IV Squamous Cell Carcinoma of the Nasopharynx; Stage IVA Salivary Gland Cancer; Stage IVA Squamous Cell Carcinoma of the Larynx; Stage IVA Squamous Cell Carcinoma of the Lip and Oral Cavity; Stage IVA Squamous Cell Carcinoma of the Oropharynx; Stage IVA Squamous Cell Carcinoma of the Paranasal Sinus and Nasal Cavity; Stage IVA Verrucous Carcinoma of the Larynx; Stage IVA Verrucous Carcinoma of the Oral Cavity; Stage IVB Salivary Gland Cancer; Stage IVB Squamous Cell Carcinoma of the Larynx; Stage IVB Squamous Cell Carcinoma of the Lip and Oral Cavity; Stage IVB Squamous Cell Carcinoma of the Oropharynx; Stage IVB Squamous Cell Carcinoma of the Paranasal Sinus and Nasal Cavity; Stage IVB Verrucous Carcinoma of the Larynx; Stage IVB Verrucous Carcinoma of the Oral Cavity; Stage IVC Salivary Gland Cancer; Stage IVC Squamous Cell Carcinoma of the Larynx; Stage IVC Squamous Cell Carcinoma of the Lip and Oral Cavity; Stage IVC Squamous Cell Carcinoma of the Oropharynx; Stage IVC Squamous Cell Carcinoma of the Paranasal Sinus and Nasal Cavity; Stage IVC Verrucous Carcinoma of the Larynx; Stage IVC Verrucous Carcinoma of the Oral Cavity; Tongue Cancer; Untreated Metastatic Squamous Neck Cancer With Occult Primary

  7. Functioning in early and late stages of schizophrenia

    Directory of Open Access Journals (Sweden)

    Leonardo Gazzi Costa

    2014-12-01

    Full Text Available INTRODUCTION: Schizophrenia is frequently associated with a debilitating course and prominent impairment in social and occupational functioning. Although the criteria for classification into stages have not been defined in the literature, illness duration and functioning seem to be good candidates.OBJECTIVE:To compare functioning of patients with schizophrenia at different stages of the disease (early vs. late and healthy sex- and age-matched controls.METHODS: This double-blinded, case-controlled study included 79 individuals: 23 patients with schizophrenia diagnosed up to 5 years earlier; 19 patients with schizophrenia diagnosed at least 20 years earlier; and healthy matched controls. Diagnoses were established using the Structured Clinical Interview for Diagnostic and Statistical Manual of Mental Disorders, 4th edition (DSM-IV Axis I Disorder. Functioning was assessed using the Functioning Assessment Short Test (FAST.RESULTS: Patients in the early stage had significantly higher scores than healthy controls in total FAST and in autonomy, occupational functioning, cognitive functioning and interpersonal relationships. Individuals in the late stage had significantly poorer functioning than controls in all domains. The comparison of functioning between the two groups of patients revealed no significant differences, except in occupational functioning, in which late stage patients had a poorer performance.CONCLUSION: Functioning impairment in schizophrenia tends to remain stable despite illness duration. Therefore, functioning should be effectively assessed at an early stage, as illness duration alone may not be the most reliable criterion to stage patients with schizophrenia.

  8. Diagnóstico precoce do câncer de pulmão: o grande desafio. Variáveis epidemiológicas e clínicas, estadiamento e tratamento Early diagnosis of lung cancer: the great challenge. Epidemiological variables, clinical variables, staging and treatment

    Directory of Open Access Journals (Sweden)

    João Adriano Barros

    2006-06-01

    Full Text Available OBJETIVO: Avaliar casos confirmados de câncer de pulmão, revisando suas variáveis epidemiológicas, clínicas, estadiamento e tratamento. MÉTODOS: Foram estudados 263 casos provenientes do Hospital de Clínicas da Universidade Federal do Paraná e do Hospital Erasto Gaertner, instituições responsáveis por parcela significativa do atendimento a pacientes na cidade de Curitiba (PR. Realizou-se um estudo retrospectivo através de preenchimento de questionário e os dados obtidos foram analisados de forma descritiva, utilizando-se o software EPI-INFO. RESULTADOS: Houve predomínio de pacientes do sexo masculino (76%, sendo que a maioria dos pacientes era fumante ou ex-fumante por ocasião do diagnóstico (90%. Não havia referência a doença pulmonar prévia em 87% dos casos. Tosse (142 casos e dor torácica (92 casos foram os sintomas iniciais mais freqüentes. O câncer de pulmão tipo não pequenas células foi encontrado em 87% dos pacientes e o tipo histológico mais freqüente foi o carcinoma espinocelular, representando 49% dos casos. O tabagismo foi considerado o fator predisponente mais importante. CONCLUSÃO: As características evolutivas do câncer de pulmão, como a inespecificidade dos sintomas iniciais e o tempo e evolução do tumor, somadas à ausência de programas de rastreamento efetivos, constituem os principais fatores que contribuem para a não detecção da neoplasia pulmonar de forma precoce, o que torna difícil o tratamento e dificulta o aumento da sobrevida.OBJECTIVE: To evaluate confirmed cases of lung cancer, reviewing epidemiological variables, clinical variables, staging and treatment. METHODS: The cases of 263 patients were studied. All of the patients had been treated at the Universidade Federal do Paraná (Federal University of Paraná Hospital de Clínicas or at the Hospital Erasto Gaertner, two institutions that, together, serve a significant portion of the patients seeking treatment in the city of

  9. Extent of Spine Deformity Predicts Lung Growth and Function in Rabbit Model of Early Onset Scoliosis.

    Directory of Open Access Journals (Sweden)

    J Casey Olson

    Full Text Available Early onset deformity of the spine and chest wall (initiated <8 years of age is associated with increased morbidity at adulthood relative to adolescent onset deformity of comparable severity. Presumably, inhibition of thoracic growth during late stage alveolarization leads to an irreversible loss of pulmonary growth and thoracic function; however the natural history of this disease from onset to adulthood has not been well characterized. In this study we establish a rabbit model of early onset scoliosis to establish the extent that thoracic deformity affects structural and functional respiratory development. Using a surgical right unilateral rib-tethering procedure, rib fusion with early onset scoliosis was induced in 10 young New Zealand white rabbits (3 weeks old. Progression of spine deformity, functional residual capacity, total lung capacity, and lung mass was tracked through longitudinal breath-hold computed tomography imaging up to skeletal maturity (28 weeks old. Additionally at maturity forced vital capacity and regional specific volume were calculated as functional measurements and histo-morphometry performed with the radial alveolar count as a measure of acinar complexity. Data from tethered rib rabbits were compared to age matched healthy control rabbits (N = 8. Results show unilateral rib-tethering created a progressive spinal deformity ranging from 30° to 120° curvature, the severity of which was strongly associated with pulmonary growth and functional outcomes. At maturity rabbits with deformity greater than the median (55° had decreased body weight (89%, right (59% and left (86% lung mass, right (74% and left (69% radial alveolar count, right lung volume at total lung capacity (60%, and forced vital capacity (75%. Early treatment of spinal deformity in children may prevent pulmonary complications in adulthood and these results provide a basis for the prediction of pulmonary development from thoracic structure. This model may

  10. Family caregiver burden: the burden of caring for lung cancer patients according to the cancer stage and patient quality of life

    Directory of Open Access Journals (Sweden)

    Eliana Lourenço Borges

    Full Text Available ABSTRACT Objective: Patients with lung cancer experience different feelings and reactions, based on their family, social, cultural, and religious backgrounds, which are a source of great distress, not only for the patients but also for their family caregivers. This study aimed to evaluate the impact that lung cancer stage and quality of life (QoL of lung cancer patients have on caregiver burden. Methods: This was a prospective cross-sectional study. Consecutive patient-caregiver dyads were selected and asked to complete the Hospital Anxiety and Depression Scale and the Medical Outcomes Study 36-item ShortForm Health Survey (SF-36. Family caregivers also completed the Caregiver Burden Scale. Group-based modeling was used in order to identify patients with early- or advanced-stage cancer (IA to IIIA vs. IIIB to IV plus non-impaired or impaired QoL (SF36 total score > 50 vs. ≤ 50. Patient-caregiver dyads were stratified into four groups: early-stage cancer+non-impaired QoL; advanced-stage cancer+non-impaired QoL; early-stage cancer+impaired QoL; and advanced-stage cancer+impaired QoL. Results: We included 91 patient-caregiver dyads. The majority of the patients were male and heavy smokers. Family caregivers were younger and predominantly female. The burden, QoL, level of anxiety, and level of depression of caregivers were more affected by the QoL of the patients than by their lung cancer stage. The family caregivers of the patients with impaired QoL showed a higher median burden than did those of the patients with non-impaired QoL, regardless of disease stage. Conclusions: Caregiver burden is more affected by patient QoL than by lung cancer stage.

  11. Outcome of combination chemotherapy in extensive stage small-cell lung cancer

    DEFF Research Database (Denmark)

    Lassen, U N; Hirsch, F R; Osterlind, K

    1998-01-01

    During the past two decades many different treatment regimens of combination chemotherapy have been applied in extensive stage small-cell lung cancer (SCLC). This study was carried out to identify whether these modifications have resulted in an improved overall survival for extensive stage during...

  12. Clinical applicability of staging small cell lung cancer according to the seventh edition of the TNM staging system.

    Science.gov (United States)

    Jhun, Byung Woo; Lee, Kyung-Jong; Jeon, Kyeongman; Suh, Gee Young; Chung, Man Pyo; Kim, Hojoong; Kwon, O Jung; Sun, Jong-Mu; Ahn, Jin Seok; Ahn, Myung-Ju; Park, Keunchil; Choi, Joon Young; Lee, Kyung Soo; Han, Joungho; Um, Sang-Won

    2013-07-01

    The two-stage system of limited and extensive disease has been widely employed for small cell lung cancer (SCLC). However, the International Association for the Study of Lung Cancer has proposed that the TNM classification should be incorporated into clinical practice. The purpose of this study was to evaluate the applicability of the Union for International Cancer Control (UICC) 7th TNM staging system to SCLC. We retrospectively reviewed the medical records of consecutive patients with newly diagnosed histologically proven SCLC between March 2005 and January 2010. Patients who had other concurrent malignancies or had combined-type SCLC were excluded. We assessed overall survival (OS) according to the T descriptor, N descriptor, M descriptor, and TNM stage grouping. In total, 320 SCLC patients were included. Median age was 65 years and 286 patients (89.4%) were male. Median OS was 12.7 months. There were no significant differences in OS according to the T descriptor (P = 0.880). However, there were significant differences in OS according to the N (P TNM stage grouping (P TNM stage grouping, but not according to the T descriptors. The UICC 7th TNM staging system may contribute to a more precise prognosis in SCLC patients. Further studies are required to evaluate the applicability of the TNM staging system to SCLC. Copyright © 2013 Elsevier Ireland Ltd. All rights reserved.

  13. Early Stage Software Reliability Estimation with Stochastic Reward Nets

    Institute of Scientific and Technical Information of China (English)

    ZHAO Jing; LIU Hong-wei; CUI Gang; YANG Xiao-zong

    2005-01-01

    This paper presents software reliability modeling issues at the early stage of a software development for fault tolerant software management system. Based on Stochastic Reward Nets, an effective model of hierarchical view for a fault tolerant software management system is put forward, and an approach that consists of system transient performance analysis is adopted. A quantitative approach for software reliability analysis is given. The results show its usefulness for the design and evaluation of the early-stage software reliability modeling when failure data is not available.

  14. Detected troponin elevation is associated with high early mortality after lung resection for cancer

    Directory of Open Access Journals (Sweden)

    Van Tornout Fillip

    2006-10-01

    Full Text Available Abstract Background Myocardial infarction can be difficult to diagnose after lung surgery. As recent diagnostic criteria emphasize serum cardiac markers (in particular serum troponin we set out to evaluate its clinical utility and to establish the long term prognostic impact of detected abnormal postoperative troponin levels after lung resection. Methods We studied a historic cohort of patients with primary lung cancer who underwent intended surgical resection. Patients were grouped according to known postoperative troponin status and survival calculated by Kaplan Meier method and compared using log rank. Parametric survival analysis was used to ascertain independent predictors of mortality. Results From 2001 to 2004, a total of 207 patients underwent lung resection for primary lung cancer of which 14 (7% were identified with elevated serum troponin levels within 30 days of surgery, with 9 (64% having classical features of myocardial infarction. The median time to follow up (interquartile range was 22 (1 to 52 months, and the one and five year survival probabilities (95% CI for patients without and with postoperative troponin elevation were 92% (85 to 96 versus 60% (31 to 80 and 61% (51 to 71 versus 18% (3 to 43 respectively (p T stage and postoperative troponin elevation remained independent predictors of mortality in the final multivariable model. The acceleration factor for death of elevated serum troponin after adjusting for tumour stage was 9.19 (95% CI 3.75 to 22.54. Conclusion Patients with detected serum troponin elevation are at high risk of early mortality with or without symptoms of myocardial infarction after lung resection.

  15. The role of bronchoscopy in the diagnosis of early lung cancer: a review.

    Science.gov (United States)

    Andolfi, Marco; Potenza, Rossella; Capozzi, Rosanna; Liparulo, Valeria; Puma, Francesco; Yasufuku, Kazuhiro

    2016-11-01

    Lung cancer is the leading cause of cancer-related deaths worldwide with an overall 5-year survival rate of 17% after diagnoses. Indeed many patients tend to have a very poor prognosis, due to being diagnosed at an advanced stage. Conversely patients who are diagnosed at an early stage have a 5-year survival >70%, indicating that early detection of lung cancer is crucial to improve survival. Although flexible bronchoscopy is a relatively non-invasive procedure for patients suspected of having lung cancer, only 29% of carcinoma in situ (CIS) and 69% of microinvasive tumors were detectable using white light bronchoscopy (WLB) alone. As a result, in the past two decades, new bronchoscopic techniques have been developed to increase the yield and diagnostic accuracy, such as autofluorescence bronchoscopy (AFB), narrow band imaging (NBI) and high magnification bronchovideoscopy (HMB). However, due to the low specificity and the limitation to detect only proximal bronchial tree, new probe-based technologies have been introduced: radial endobronchial ultrasound (R-EBUS), optical coherence tomography (OCT), confocal laser endomicroscopy (CLE) and laser Raman spectroscopy (LRS). To date, although tissue biopsy remains the gold standard for diagnosing malignant/premalignant airway disease and some techniques are still investigational, bronchoscopic technologies can be considered the safest and most accurate tools to evaluate both central and distal airway mucosa.

  16. Conditional deletion of epithelial IKKβ impairs alveolar formation through apoptosis and decreased VEGF expression during early mouse lung morphogenesis

    Directory of Open Access Journals (Sweden)

    Li Changgong

    2011-10-01

    Full Text Available Abstract Background Alveolar septation marks the beginning of the transition from the saccular to alveolar stage of lung development. Inflammation can disrupt this process and permanently impair alveolar formation resulting in alveolar hypoplasia as seen in bronchopulmonary dysplasia in preterm newborns. NF-κB is a transcription factor central to multiple inflammatory and developmental pathways including dorsal-ventral patterning in fruit flies; limb, mammary and submandibular gland development in mice; and branching morphogenesis in chick lungs. We have previously shown that epithelial overexpression of NF-κB accelerates lung maturity using transgenic mice. The purpose of this study was to test our hypothesis that targeted deletion of NF-κB signaling in lung epithelium would impair alveolar formation. Methods We generated double transgenic mice with lung epithelium-specific deletion of IKKβ, a known activating kinase upstream of NF-κB, using a cre-loxP transgenic recombination strategy. Lungs of resulting progeny were analyzed at embryonic and early postnatal stages to determine specific effects on lung histology, and mRNA and protein expression of relevant lung morphoreulatory genes. Lastly, results measuring expression of the angiogenic factor, VEGF, were confirmed in vitro using a siRNA-knockdown strategy in cultured mouse lung epithelial cells. Results Our results showed that IKKβ deletion in the lung epithelium transiently decreased alveolar type I and type II cells and myofibroblasts and delayed alveolar formation. These effects were mediated through increased alveolar type II cell apoptosis and decreased epithelial VEGF expression. Conclusions These results suggest that epithelial NF-κB plays a critical role in early alveolar development possibly through regulation of VEGF.

  17. Cell- and developmental stage-specific Dicer1 ablation in the lung epithelium models cystic pleuropulmonary blastoma.

    Science.gov (United States)

    Wagh, Purnima K; Gardner, Margaret A; Ma, Xiaolan; Callahan, Melissa; Shannon, John M; Wert, Susan E; Messinger, Yoav H; Dehner, Louis P; Hill, D Ashley; Wikenheiser-Brokamp, Kathryn A

    2015-05-01

    Inherited syndromes provide unique opportunities to identify key regulatory mechanisms governing human disease. We previously identified germline loss-of-function DICER1 mutations in a human syndrome defined by the childhood lung neoplasm pleuropulmonary blastoma (PPB), which arises during lung development. DICER1 regulates many biological processes critical in development and disease pathogenesis. Significant challenges in defining the role of DICER1 in human disease are identifying cause-effect relationships and generating manipulatable systems that model the complexity of organ development and disease pathogenesis. Here we report the generation of a murine model for PPB and demonstrate that precise temporal and cell type-specific Dicer1 ablation is necessary and sufficient for the development of cystic lungs that histologically and phenotypically model PPB. Dicer1 ablation in the distal airway epithelium during early stages of lung development resulted in a cystic lung phenotype indistinguishable from PPB, whereas DICER1 function was not required for development of the proximal airway epithelium or during later stages of organogenesis. Mechanistic studies demonstrate that Dicer1 loss results in epithelial cell death, followed by cystic airway dilatation accompanied by epithelial and mesenchymal proliferation. These studies define precise temporal and epithelial cell type-specific DICER1 functions in the developing lung and demonstrate that loss of these DICER1 functions is sufficient for the development of cystic PPB. These results also provide evidence that PPB arise through a novel mechanism of non-cell-autonomous tumour initiation, in which the genetic abnormality initiating the neoplasm does not occur in the cells that ultimately transform, but rather occurs in a benign-appearing epithelial cell component that predisposes underlying mesenchymal cells to malignant transformation.

  18. Thoracic radiation therapy for limited-stage small-cell lung cancer: unanswered questions.

    Science.gov (United States)

    Faivre-Finn, Corinne; Lorigan, Paul; West, Catharine; Thatcher, Nick

    2005-07-01

    The role of thoracic radiation therapy (RT; TRT) is now established in the management of limited-stage small-cell lung cancer (SCLC). There is increasing evidence in the literature in favor of early concurrent chemoradiation therapy, and a gold standard of care for patients with a good performance status is twice-daily TRT (45 Gy in 3 weeks) with concurrent cisplatin/etoposide. Five-year survival rates > 20% can be expected with this combined-modality approach. Although current clinical trials are exploring the efficacy of new chemotherapeutic strategies for the disease, essential questions related to the optimization of TRT remain unanswered. In particular, the optimal RT dose, fractionation, and treatment volume have not been defined. This review highlights the need for well-designed multinational trials aimed at the optimization and standardization of RT for limited-stage SCLC. These trials should integrate translational research studies to investigate the molecular basis of RT resistance and to develop biomarker profiles of prognosis.

  19. Unlocking biomarker discovery: large scale application of aptamer proteomic technology for early detection of lung cancer.

    Directory of Open Access Journals (Sweden)

    Rachel M Ostroff

    Full Text Available BACKGROUND: Lung cancer is the leading cause of cancer deaths worldwide. New diagnostics are needed to detect early stage lung cancer because it may be cured with surgery. However, most cases are diagnosed too late for curative surgery. Here we present a comprehensive clinical biomarker study of lung cancer and the first large-scale clinical application of a new aptamer-based proteomic technology to discover blood protein biomarkers in disease. METHODOLOGY/PRINCIPAL FINDINGS: We conducted a multi-center case-control study in archived serum samples from 1,326 subjects from four independent studies of non-small cell lung cancer (NSCLC in long-term tobacco-exposed populations. Sera were collected and processed under uniform protocols. Case sera were collected from 291 patients within 8 weeks of the first biopsy-proven lung cancer and prior to tumor removal by surgery. Control sera were collected from 1,035 asymptomatic study participants with ≥ 10 pack-years of cigarette smoking. We measured 813 proteins in each sample with a new aptamer-based proteomic technology, identified 44 candidate biomarkers, and developed a 12-protein panel (cadherin-1, CD30 ligand, endostatin, HSP90α, LRIG3, MIP-4, pleiotrophin, PRKCI, RGM-C, SCF-sR, sL-selectin, and YES that discriminates NSCLC from controls with 91% sensitivity and 84% specificity in cross-validated training and 89% sensitivity and 83% specificity in a separate verification set, with similar performance for early and late stage NSCLC. CONCLUSIONS/SIGNIFICANCE: This study is a significant advance in clinical proteomics in an area of high unmet clinical need. Our analysis exceeds the breadth and dynamic range of proteome interrogated of previously published clinical studies of broad serum proteome profiling platforms including mass spectrometry, antibody arrays, and autoantibody arrays. The sensitivity and specificity of our 12-biomarker panel improves upon published protein and gene expression panels

  20. Application of sub-pulmonary lobectomy under thoracoscope and mediation lymph node sampling in treat-ment of non-small cell lung cancer at early stage%胸腔镜下亚肺叶切除及纵隔淋巴结采样治疗早期非小细胞肺癌临床疗效探讨

    Institute of Scientific and Technical Information of China (English)

    王杰

    2016-01-01

    目的:探讨胸腔镜下亚肺叶切除以及纵隔淋巴结采样在早期非小细胞肺癌患者中的临床治疗效果。方法选取2013年4月至2014年4月我院收治的80例早期非小细胞肺癌患者资料进行分析,根据不同治疗方案将患者分为对照组和实验组,对照组采用开胸肺叶切除手术治疗,实验组采用胸腔镜下亚肺叶切除以及纵隔淋巴结采样治疗,比较两组疗效。结果实验组手术时间、术中出血量、术后疼痛评分、术后胸腔引流管时间、住院时间等指标显著少于对照组( P<0.05);实验组并发症发生率为7.5%,显著低于对照组(并发症发生率为22.5%)(P<0.05);实验组经过病理诊断6例浸润性鳞癌,20例浸润性腺癌,8例微浸润性腺癌,6例浸润前病变。2例确诊纵隔淋巴结转移,给予放疗和化疗治疗。结论早期非小细胞肺癌患者采用胸腔镜下亚肺叶切除以及纵隔淋巴结采样治疗效果理想,值得推广使用。%Objective To investigate the clinical effect of sub-pulmonary lobectomy under thoracoscope and mediation lymph node sampling in treatment of non-small cell lung cancer at early stage. Methods 72 NSCLC pa-tients at early stage from April 2013 to April 2014 in our hospital were randomly divided into the control group and the experimental group. The control group was given thorazine lobotomy treatment, and the experimental group was given sub-pulmonary lobectomy under thoracoscope and mediation lymph node sampling. The clinical effect of the two groups were compared. Results The operation time, blood loss, postoperative pain scores, postoperative chest tube time, and duration of hospital stay were significantly better in the experimental group than in the control group ( P<0. 05). The complication rate was 7. 5% in the experimental group, which was significantly lower than that in the control group (2. 5%, P<0. 05). There were 6 cases of invasive squamous cell carcinoma, 20 cases

  1. A staged approach for a lung-liver transplant patient using ex vivo reconditioned lungs first followed by an urgent liver transplantation

    NARCIS (Netherlands)

    Van De Wauwer, Caroline; Verschuuren, Erik A. M.; Nossent, George D.; van der Bij, Wim; den Hamer, Inez J.; Klinkenberg, Theo J.; van den Berg, Aad P.; de Boer, Marieke T.; Mariani, Massimo A.; Erasmus, Michiel E.

    Combined lung-liver transplantation is a logistically challenging procedure hampered by shortage of organ donors. We describe the case of a young patient with end-stage lung disease due to of cystic fibrosis and liver cirrhosis who needed combined lung-liver transplantation. The long waiting for

  2. SU-E-J-266: Cone Beam Computed Tomography (CBCT) Inter-Scan and Inter-Observer Tumor Volume Variability Assessment in Patients Treated with Stereotactic Body Radiation Therapy (SBRT) for Early Stage Non-Small Cell Lung Cancer (NSCLC)

    Energy Technology Data Exchange (ETDEWEB)

    Hou, Y; Aileen, C; Kozono, D; Killoran, J; Wagar, M; Lee, S; Hacker, F; Aerts, H; Lewis, J; Mak, R [Brigham and Women’s Hospital, Boston, MA (United States)

    2015-06-15

    Purpose: Quantification of volume changes on CBCT during SBRT for NSCLC may provide a useful radiological marker for radiation response and adaptive treatment planning, but the reproducibility of CBCT volume delineation is a concern. This study is to quantify inter-scan/inter-observer variability in tumor volume delineation on CBCT. Methods: Twenty earlystage (stage I and II) NSCLC patients were included in this analysis. All patients were treated with SBRT with a median dose of 54 Gy in 3 to 5 fractions. Two physicians independently manually contoured the primary gross tumor volume on CBCTs taken immediately before SBRT treatment (Pre) and after the same SBRT treatment (Post). Absolute volume differences (AVD) were calculated between the Pre and Post CBCTs for a given treatment to quantify inter-scan variability, and then between the two observers for a given CBCT to quantify inter-observer variability. AVD was also normalized with respect to average volume to obtain relative volume differences (RVD). Bland-Altman approach was used to evaluate variability. All statistics were calculated with SAS version 9.4. Results: The 95% limit of agreement (mean ± 2SD) on AVD and RVD measurements between Pre and Post scans were −0.32cc to 0.32cc and −0.5% to 0.5% versus −1.9 cc to 1.8 cc and −15.9% to 15.3% for the two observers respectively. The 95% limit of agreement of AVD and RVD between the two observers were −3.3 cc to 2.3 cc and −42.4% to 28.2% respectively. The greatest variability in inter-scan RVD was observed with very small tumors (< 5 cc). Conclusion: Inter-scan variability in RVD is greatest with small tumors. Inter-observer variability was larger than inter-scan variability. The 95% limit of agreement for inter-observer and inter-scan variability (∼15–30%) helps define a threshold for clinically meaningful change in tumor volume to assess SBRT response, with larger thresholds needed for very small tumors. Part of the work was funded by a Kaye

  3. Presentation and management of a stage Ia lung cancer patient with a paraneoplastic factor VIII inhibitor.

    Science.gov (United States)

    Laselle, Brooks T; Boggio, Lisa N; Blum, Matthew G

    2006-01-01

    Acquired inhibitors to clotting factors most commonly involve factor VIII and are associated with autoimmune disease. Factor VIII inhibitors can cause severe spontaneous and iatrogenic bleeding that is difficult to manage. Factor VIII inhibitors are rarely associated with solid tumors and only three cases of adenocarcinoma of the lung have been reported. This report describes the multidisciplinary management of a factor VIII inhibitor-producing stage Ia lung adenocarcinoma that ultimately resulted in complete resectability.

  4. Radiation therapy planning for early-stage Hodgkin lymphoma

    DEFF Research Database (Denmark)

    Maraldo, Maja V; Dabaja, Bouthaina S; Filippi, Andrea R

    2015-01-01

    PURPOSE: Early-stage Hodgkin lymphoma (HL) is a rare disease, and the location of lymphoma varies considerably between patients. Here, we evaluate the variability of radiation therapy (RT) plans among 5 International Lymphoma Radiation Oncology Group (ILROG) centers with regard to beam arrangements...

  5. Early Stages of the Evolution of Life: a Cybernetic Approach

    Science.gov (United States)

    Melkikh, Alexey V.; Seleznev, Vladimir D.

    2008-08-01

    Early stages of the evolution of life are considered in terms of control theory. A model is proposed for the transport of substances in a protocell possessing the property of robustness with regard to changes in the environmental concentration of a substance.

  6. Radiation Plus Chemotherapy in Early-Stage Hodgkin Lymphoma

    Science.gov (United States)

    Adding radiation therapy to chemotherapy may improve outcomes in patients with early-stage Hodgkin lymphoma, according to a paper published in the Cochrane Database of Systematic Reviews in February 2011, but the long-term effects of this regimen are not

  7. [Surgical treatment of breast neoplasms in early stages].

    Science.gov (United States)

    Cheshuk, Ie V; Drozdov, V M; Neĭman, A M; Zotov, O S; Zakhartseva, L M; Anikus'ko, M F; Zaĭchuk, V V; Sydorchuk, O I

    2002-01-01

    Analysis of literary data and own investigation results for the modern surgical methods of treatment of mammary gland cancer in early stages was performed. Indexes of patients survival after surgical removal of mammary gland (MG) and quadranthectomy did not differ. Preservation of MG constitutes great social and psycho-emotional significance for women-patients.

  8. Lung Cancer: Early Detection is the Key | NIH MedlinePlus the Magazine

    Science.gov (United States)

    ... of this page please turn Javascript on. Feature: Lung Cancer Early Detection is the Key Past Issues / Winter 2013 Table of Contents Lung cancer survivor Dusty Donaldson helps to spread the word ...

  9. Low cognitive ability in early adulthood is associated with reduced lung function in middle age

    DEFF Research Database (Denmark)

    Carroll, Douglas; Batty, G David; Mortensen, Laust Hvas;

    2011-01-01

    Reduced lung function has been linked to poorer cognitive ability later in life. In the present study, the authors examined the converse: whether there was a prospective association between cognitive ability in early adulthood and lung function in middle age....

  10. Endoscopic ultrasound guided biopsy performed routinely in lung cancer staging spares futile thoracotomies

    DEFF Research Database (Denmark)

    Larsen, Soeren S; Vilmann, Peter; Krasnik, Mark;

    2005-01-01

    BACKGROUND: Up to 45% of operations with curative intent for non-small-cell lung cancer (NSCLC) can be regarded as futile, apparently because the stage of the disease is more advanced than expected preoperatively. During the past decade several studies have evaluated the usefulness of endoscopic...... ultrasound guided fine needle aspiration biopsy (EUS-FNA) in lung cancer staging with promising results. However, no randomised trials have been performed, in which a staging strategy with EUS-FNA performed in all patients is compared with a conventional workup. METHODS: Before surgery (i.e. mediastinoscopy.......3 years (range 0.2-2.4 years). Thoracotomy was regarded as futile if the patient had an explorative thoracotomy without tumour resection or if a resected patient had recurrent disease or died from lung cancer during follow-up. Analysis was by intention to treat. RESULTS: Fifty-three patients were randomly...

  11. Management of Early-stage Hodgkin Lymphoma: A Practice Guideline.

    Science.gov (United States)

    Herst, J; Crump, M; Baldassarre, F G; MacEachern, J; Sussman, J; Hodgson, D; Cheung, M C

    2017-01-01

    In the past, treatment for patients with early-stage Hodgkin lymphoma consisted mainly of radiotherapy. Now, chemotherapy alone and chemoradiotherapy are treatment options. These guidelines aim to provide recommendations on the optimal management of early-stage Hodgkin lymphoma. We conducted a systematic review searching MEDLINE, EMBASE, the Cochrane Library and other literature sources from 2003 to 2015, and applied the Grading of Recommendations Assessment, Development and Evaluation (GRADE). Two authors independently reviewed and selected studies, and appraised the evidence quality. The document underwent internal and external review by content, methodology experts, a patient representative and clinicians in Ontario. We have issued recommendations for patients with classical Hodgkin lymphoma and with nodular lymphocyte predominant Hodgkin lymphoma; with favourable and unfavourable prognosis; and for the use of positron emission tomography to direct treatment. We have provided our interpretation of the evidence and considerations for implementation. Examples of recommendations are: 'Patients with early-stage classical Hodgkin lymphoma should not be treated with radiotherapy alone'; 'chemotherapy plus radiotherapy or chemotherapy alone are recommended treatment options for patients with early-stage non-bulky Hodgkin lymphoma'; 'The Working Group does not recommend the use of a negative interim positron emission tomography scan alone to identify patients with early-stage Hodgkin lymphoma for whom radiotherapy can be omitted without a reduction in progression-free survival'. Through the use of GRADE, recommendations were geared towards patient important outcomes and their strength reflected the available evidence and its interpretation from the patients' point of view. Copyright © 2016 The Royal College of Radiologists. Published by Elsevier Ltd. All rights reserved.

  12. Early Detection of Lung Cancer : “A Role for Serum Biomarkers?”

    OpenAIRE

    Broodman, Ingrid

    2016-01-01

    markdownabstractLung cancer has the highest mortality rate among cancer patients in the world, in particular because most patients are only diagnosed at an advanced and non-curable stage. Computed tomography (CT) screening on high-risk individuals has shown that early detection could reduce the mortality rate. However, the still high false-positive rate of CT may harm healthy individuals because of unnecessary follow-up scans and invasive follow-up procedures. On the other hand, false-negativ...

  13. Understanding quality-of-life while living with late-stage lung cancer: an exploratory study.

    Science.gov (United States)

    Adorno, Gail; Brownell, Gracie

    2014-01-01

    U.S. Veterans have a higher prevalence of advanced lung cancer and poorer survival outcomes compared to the general population; yet, no studies exist which specifically explore the psychosocial and existential quality-of-life (QOL) of late-stage lung cancer among this population. This article presents the perspectives of older veterans (N = 12) living with late-stage lung cancer who were receiving chemotherapy, routine hospice care, or both concurrently. Based on individual interviews, themes associated with loss of functionality, close relationships, and communicative acts contributed to veterans' perceptions of diminished or enhanced QOL while living with advanced disease. An overarching theme, loss of the person I know myself to be, suggests that personhood is an important concept to consider in QOL assessment. While findings suggest that the experiences of older Veterans with late-stage lung cancer are similar to other populations of lung cancer patients, and persons with incurable cancer in general, further research regarding the influence of veteran identity at end-of-life is warranted. Further research is needed which explores the influence of a whole person approach to QOL during life-limiting illness and end-of-life decision-making, particularly while receiving late-stage cancer-directed therapy.

  14. The International Association for the Study of Lung Cancer Lung Cancer Staging Project: Proposals for the Revision of the Clinical and Pathologic Staging of Small Cell Lung Cancer in the Forthcoming Eighth Edition of the TNM Classification for Lung Cancer.

    Science.gov (United States)

    Nicholson, Andrew G; Chansky, Kari; Crowley, John; Beyruti, Ricardo; Kubota, Kaoru; Turrisi, Andrew; Eberhardt, Wilfried E E; van Meerbeeck, Jan; Rami-Porta, Ramón

    2016-03-01

    Small cell lung cancer (SCLC) is commonly classified as either limited or extensive, but the Union for International Cancer Control TNM Classification of Malignant Tumours seventh edition (2009) recommended tumor, node, and metastasis (TNM) staging based on analysis of the International Association for the Study of Lung Cancer (IASLC) database. Survival analyses were performed for clinically and pathologically staged patients presenting with SCLC from 1999 through 2010. Prognosis was compared in relation to the TNM seventh edition staging to serve as validation and analyzed in relation to proposed changes to the T descriptors found in the eighth edition. There were 5002 patients: 4848 patients with clinical and 582 with pathological stages. Among these, 428 had both. Survival differences were confirmed for T and N categories and maintained in relation to proposed revisions to T descriptors for seventh edition TNM categories and proposed changes in the eighth edition. There were also survival differences, notably at 12 months, in patients with brain-only single-site metastasis (SSM) compared to SSM at other sites, and SSM without a pleural effusion showed a better prognosis than other patients in the M1b category. We confirm the prognostic value of clinical and pathological TNM staging in patients with SCLC, and recommend continued usage for SCLC in relation to proposed changes to T, N, and M descriptors for NSCLC in the eighth edition. However, for M descriptors, it remains uncertain whether survival differences in patients with SSM in the brain simply reflect better treatment options rather than better survival based on anatomic extent of disease. Copyright © 2015 International Association for the Study of Lung Cancer. Published by Elsevier Inc. All rights reserved.

  15. 染矽尘小鼠早期肺组织bFGF与FGFR-1的表达及意义%Expression and Significance of Basic Fibroblast Growth Factor and Fibroblast Growth Factor Receptor-1 in Early Stage Lung Tissues of Silica Exposed Mice

    Institute of Scientific and Technical Information of China (English)

    李丹; 向军俭; 王宏; 陶俊; 邓宁; 钟雪云

    2011-01-01

    Objective To investigate the expression of basic fibroblast growth factor (bFGF) and fibroblast growth factor receptor-1 (FGPR-1) in early stage lung tissues of silica exposed mice and to probe into the significance of bFGF in occurrence of silicosis. Methods The mice were instilled with silicon dioxide through trachea to establish modeling (0.2 g/kg). Samples of lung tissue were collected at the 7 th, 14 th, 21 st and 28 th day after injection.RT-PCR was used to detect the gene transcription of bFGF. Immunohistochemistry was used to analyze the expression of bFGF and FGFR-1 in lung tissue from silicotic and control mice. Results The results of RT-PCR showed that the gray scales of bFGF gene transcription in the silicotic group were 32.08% ± 0.05 % ~ 49.07 % ±14.37%, and in the control group were 34.79% ± 15.50%. The immunohistochemistry result showed the protein expression of bFGF was mainly in vascular smooth muscle cell, macrophage and bronchial epithelial cells and the expression had no difference between the silicotic group and the control group at the 7th, 14th and 21st day after injection of silicon dioxide (P>0.05). Nodular lesions in the lungs began to express small mount of bFGF at the 28th day after injection. The expression of FGFR-1 was significantly elevated from the 7th day to 28th day (IOD:16157.63 ± 359.13 vs. 45 873. 24±359. 13~145 030.70±577.49,P<0.05). And it was expressed by vascular smooth muscle cell, macrophage and mesenchymal cell. Conclusions No increase in the expression of bFGF is seen at the early stage of silicosis in mice, but FGFR-1 is highly expressed in a variety of lung cells. The results show that bFGF might play a role in early infection of silicosis through highly expressed FGFR-1, or play no role in silicosis.%目的 观察染矽尘小鼠早期肺组织碱性成纤维细胞生长因子(basic fibroblast growth factor,bFGF)及成纤维细胞生长因子受体-1(fibroblast growth factor receptor-1,FGFR-1

  16. M2型丙酮酸激酶同工酶在人体早期非小细胞肺癌中的表达及临床意义%The expression of PKM2 in early stage human non-small cell lung cancer and its clinical significance

    Institute of Scientific and Technical Information of China (English)

    袁素娟; 乔田奎; 陈伟; 庄喜兵

    2015-01-01

    目的:研究 M2型丙酮酸激酶同工酶(PKM2)在人体早期非小细胞肺癌(NSCLC)、癌旁正常肺组织及肺炎组织中的表达及临床意义。方法收集外科手术切除并经病理确诊的非小细胞肺癌及癌旁正常组织标本以及纤维支气管镜肺活检病理检查确诊为肺炎的肺组织标本各99例,采用免疫组织化学法检测其 PKM2的表达水平,并分析其表达与临床病理的关系。结果PKM2在 NSCLC 组织、癌旁正常肺组织和肺炎组织中的阳性率分别为69.70%、0%和9.09%。鳞状细胞癌明显高于腺癌(P <0.01)、腺鳞癌(P <0.05)和其他少见病理类型(P <0.01)。肿瘤直径>3 cm 的 PKM2表达率为76.92%,肿瘤直径≤3 cm 的阳性表达率为42.86%,两组比较差异有统计学意义(P <0.01)。有淋巴结转移患者的 PKM2表达率为87.18%,无淋巴结转移者为58.33%,两组比较差异有统计学意义(P <0.01)。Ⅰ期和Ⅱ期患者的 PKM2阳性表达率分别为58.62%和85.36%,两组比较差异有统计学意义(P <0.01)。结论PKM2在早期 NSCLC 中的表达率升高,对临床早期诊断 NSCLC 有一定的价值。%Objective To explore the expression of M2 isoform of pyruvate kinase(PKM2)in early non-small cell lung cancer(NSCLC),normal lung tissue adjacent to carcinoma and pneumonia and related clinical significance.Methods Immunohistochemistry was used to detect the expression of PKM2 in NSCLC and normal lung tissue adjacent to carcinoma in 99 cases taken by surgical operation and pneu-monia in 99 cases taken by fiberoptic bronchoscopy lung biopsy,and analyzed the relationship between PKM2 and the clinical characteristics.Results The positive rate of PKM2 expression was 69.70%,0%and 9.09% respectively in NSCLC,normal lung tissue adjacent to carcinoma and pneumonia.The positive rate of PKM2 was the biggest in squamous carcinoma group

  17. Primary treatment options for high risk/medically inoperable early stage NSCLC patients

    Science.gov (United States)

    Jones, Guy C.; Kehrer, Jason D.; Kahn, Jenna; Koneru, Bobby N.; Narayan, Ram; Thomas, Tarita O.; Camphausen, Kevin; Mehta, Minesh P; Kaushal, Aradhana

    2015-01-01

    Lung cancer is among the most common cancers worldwide, and the leading cause of cancer death in both men and women. For patients with early stage (AJCC T1-2, N0) non-small cell lung cancer the current standard of care is lobectomy with systematic lymph node evaluation. Unfortunately, medical comorbities often present in patients with lung cancer, may preclude the option of surgical resection . In such cases, a number of minimal to non-invasive treatment options have gained popularity in the treatment of these high-risk patients. These modalities provide significant advantages including patient convenience, treatment in an outpatient setting, and acceptable toxicities including reduced impact on lung function and a modest risk of post-procedure chest wall pain. This manuscript seeks to provide a comprehensive review of the literature including reported outcomes, complications and limitations of sublobar resection with or without intraoperative brachytherapy, radiofrequency ablation, microwave ablation, percutaneous cryoablation, photodynamic therapy and stereotactic body radiation therapy. PMID:26027433

  18. Treatment Burden of Medicare Beneficiaries With Stage I Non-Small-Cell Lung Cancer.

    Science.gov (United States)

    Presley, Carolyn J; Soulos, Pamela R; Tinetti, Mary; Montori, Victor M; Yu, James B; Gross, Cary P

    2016-12-20

    To quantify the burden and complexity associated with treatment of Medicare beneficiaries with stage I non-small-cell lung cancer (NSCLC). Using the SEER-Medicare database, we conducted a retrospective cohort study of Medicare beneficiaries who were diagnosed with stage I NSCLC from 2007 to 2011 and who were treated with surgery, stereotactic body radiation therapy, or external beam radiation therapy. Main outcome measures were the number of days a patient was in contact with the health care system (encounter days), the number of physicians involved in a patient's care, and the number of medications prescribed. Logistic regression modeled the association between patient characteristics, treatment type, and high treatment burden (defined as ≥ 66 encounter days). On average, 7,955 patients spent 1 in 3 days interacting with the health care system during the initial 60 days of treatment. Patients experienced a median of 44 encounter days with high variability (interquartile range [IQR], 29 to 66) in the 12 months after treatment initiation. The median number of physicians involved was 20 (IQR, 14 to 28), and the median number of medications prescribed was 12 (IQR, 8 to 17). Patients who were treated with surgery had high treatment burden (predicted probability, 21.6%; 95% CI, 20.2 to 23.1) compared with patients who were treated with stereotactic body radiation therapy (predicted probability, 16.1%; 95% CI, 12.9 to 19.3), whereas patients who were treated with external beam radiation therapy had the highest burden (predicted probability, 46.8%; 95% CI, 43.3 to 50.2). The treatment burden imposed on patients with early-stage NSCLC was substantial in terms of the number of encounters, physicians involved, and medications prescribed. Because treatment burden varied markedly across patients and treatment types, future work should identify opportunities to understand and ameliorate this burden.

  19. POST-OPERATIVE STAGING AND SURVIVAL BASED ON THE REVISED TNM STAGING SYSTEM FOR NON-SMALL CELL LUNG CANCER

    Institute of Scientific and Technical Information of China (English)

    2000-01-01

    Objective: To study the factors affecting post-operative staging and survival in non-small cell lung cancer (NSCLC) patients based on the revised TNM staging system adopted by the UICC in 1977. Methods: Data were collected from 1757 consecutively operated NSCLC patients, including those receiving complete tumor excision, tumor debulking and exploratory thoractomy from April 1969 through Dec. 1993. the end point of follow-up was Nov. 30, 1998. Cumulative survival and its influencing factors were analyzed by Kaplan-Meier and Cox model of SPSS software. Results: In this series, 30 patients (1.7%) were lost from follow-up. The 5-year cumulative survival was 88.0% for patients in stage I A, and 53.9% in stage IB, 33.5% in stage II, 14.7% in stage IIIA, 5.5% in stage IIIB and 7.0% in stage IV. The overall 5-year survival rate was 28.2%. The 5-year survivals were 39.8%, 14.4% and 4.2% in patients treated with completely tumor resection, tumor debulking and explorative thoractomy, respectively. The 10-year survival rate was 31.4%, 9.5% and 0, respectively. Factors affecting long-term cumulative survival, in the order of decreasing significance, were the type of operation, lymph node status, staging, size and pathological type of the primary tumor. Conclusion: the revised staging system for NSCLC is superior to that used since 1986 as far as the end results of treatment in patients in different stage and the staging specificity are concerned. The T3N1M0 classification and the definition of M1 need to be further studied.

  20. Fibronectin Matrix Remodeling in the Regulation of the Inflammatory Response within the Lung: An Early Step in Lung Cancer Progression

    Science.gov (United States)

    2011-09-01

    the Inflammatory Response within the Lung: An Early Step in Lung Cancer Progression PRINCIPAL INVESTIGATOR: Paula J. McKeown-Longo, Ph.D...2011 4. TITLE AND SUBTITLE Fibronectin Matrix Remodeling in the Regulation of the 5a. CONTRACT NUMBER W81XWH-10-1-0755 Inflammatory Response within...hypothesis that force dependent unfolding of fibronectin in the tumor stroma drives an inflammatory response within the lung tumor microenvironment

  1. CT perfusion at early stage of hepatic diffuse disease

    Institute of Scientific and Technical Information of China (English)

    Sheng Guan; Wei-Dong Zhao; Kang-Rong Zhou; Wei-Jun Peng; Jian Mao; Feng Tang

    2005-01-01

    AIM: To determine the validity of the non-invasive method of CT perfusion (CTP) in rat model of hepatic diffuse disease. METHODS: Twenty-eight Wistar rats were divided into two groups. Liver diffuse lesions were induced by dietthylnitrosamine in 14 rats of test group. Rats in control groupwere bred with pure water. From the 1st to 12th wk after the test group was intervened, both groups were studied every week with CTP. CTP parameters of liver parenchymain different periods and pathologic changes in two groups were compared and analyzed.RESULTS: The process of hepatic diffuse lesions in test groups was dassified into three stages or periods according to the pathologic alterations, namely hepattitis, hepatic fibrosis, and cirrhosis. During this period, hepatic artery flow (HAF)of control group declined slightly, mean transit time (MTT),blood flow (BF) and volume (BV) increased, but there wereno significant differences between different periods. Tntest group, HAF tended to increase gradually, MTT prolonged obviously, BV and BF decreased at the same time. The results of statistical analysis revealed that the difference in the HAF ratio of test group to control group was significant.The ratio of BV and BF in test group to control group in stageof hepatitis and hepatic cirrhosis, hepatic fibrosis and early stage of hepatic cirrhosis was significantly different, but there was no significant difference between hepatitis and hepatic fibrosis. The main pathological changes in stage of hepatitis were swelling of hepatic cells, while sinusoid capillarization and deposition of collagen aggravated gradually in the extravascular Disse's spaces in stage of fibrosis and early stage of cirrhosis.CONCLUSION: The technique could reflect some early changes of hepatic blood perfusion in rat with liver diffuse disease and is valuable for their early diagnosis.

  2. Lung surfactant metabolism: early in life, early in disease and target in cell therapy.

    Science.gov (United States)

    Lopez-Rodriguez, Elena; Gay-Jordi, Gemma; Mucci, Adele; Lachmann, Nico; Serrano-Mollar, Anna

    2017-03-01

    Lung surfactant is a complex mixture of lipids and proteins lining the alveolar epithelium. At the air-liquid interface, surfactant lowers surface tension, avoiding alveolar collapse and reducing the work of breathing. The essential role of lung surfactant in breathing and therefore in life, is highlighted by surfactant deficiency in premature neonates, which causes neonatal respiratory distress syndrome and results in early death after birth. In addition, defects in surfactant metabolism alter lung homeostasis and lead to disease. Special attention should be paid to two important key cells responsible for surfactant metabolism: alveolar epithelial type II cells (AE2C) and alveolar macrophages (AM). On the one hand, surfactant deficiency coming from abnormal AE2C function results in high surface tension, promoting alveolar collapse and mechanical stress in the epithelium. This epithelial injury contributes to tissue remodeling and lung fibrosis. On the other hand, impaired surfactant catabolism by AM leads to accumulation of surfactant in air spaces and the associated altered lung function in pulmonary alveolar proteinosis (PAP). We review here two recent cell therapies that aim to recover the activity of AE2C or AM, respectively, therefore targeting the restoring of surfactant metabolism and lung homeostasis. Applied therapies successfully show either transplantation of healthy AE2C in fibrotic lungs, to replace injured AE2C cells and surfactant, or transplantation of bone marrow-derived macrophages to counteract accumulation of surfactant lipid and proteinaceous material in the alveolar spaces leading to PAP. These therapies introduce an alternative treatment with great potential for patients suffering from lung diseases.

  3. Alveolar flows of the developing lungs:from embryonic to early childhood airways

    Science.gov (United States)

    Tenenbaum-Katan, Janna; Hofemeier, Philipp; Fishler, Rami; Rothen-Rutishauser, Barbara; Sznitman, Josue

    2014-11-01

    At the onset of life in utero the respiratory system is simply a liquid-filled duct. With our first breath, alveoli are filled with air and become a significant port of entry for airborne particles. As such, alveolar lining is nearly fully functional at birth, though lung development continues during childhood as structural changes increase alveolar surface area to optimize ventilation. We hypothesize that such fluid dynamical changes potentially affect two phenomena occurring within alveoli: (i) flow patterns in airspaces at distinct stages of both in- and ex-utero life and (ii) fate of inhaled particles ex-utero. To investigate these phenomena, we combine experimental and numerical approaches where (i) microfluidic in vitro devices mimic liquid flows across the epithelium of fetal airspaces, and (ii) computational simulations are employed to examine particle transport and deposition in the deep alveolated regions of infants' lungs. Our approaches capture anatomically-inspired geometries based on morphometrical data, as well as physiological flows, including the convective-diffusive nature of submicron particle transport in alveolar regions.Overall, we investigate respiratory flows in alveolar regions of developing lungs, from early embryonic stages to late childhood

  4. An Analysis of Immunoreactive Signatures in Early Stage Hepatocellular Carcinoma

    Science.gov (United States)

    Hong, Yu; Long, Jiang; Li, Hai; Chen, Shuhong; Liu, Qiqi; Zhang, Bei; He, Xiaomin; Wang, Yan; Li, Hongyi; Li, Yimei; Zhang, Tao; Lu, Chenzhen; Yan, Hao; Zhang, Minli; Li, Qing; Cao, Bangwei; Bai, Zhigang; Wang, Jin; Zhang, Zhongtao; Zhu, Shengtao; Zheng, Jiasheng; Ou, Xiaojuan; Ma, Hong; Jia, Jidong; You, Hong; Wang, Shengqi; Huang, Jian

    2015-01-01

    Background Hepatocellular carcinoma (HCC) is prevalent worldwide and early diagnosis of HCC is critical for effective treatment and optimal prognosis. Methods Serum was screened first by immunoproteomic analysis for HCC-related tumor associated antigens (TAAs). Selected TAAs were clinically evaluated retrospectively in patients with HCC, liver cirrhosis, chronic hepatitis and healthy controls. Levels of autoantibody to the selected TAAs were measured by protein microarrays containing protein antigens of the candidate TAAs. Analyses were done by using receiver operating characteristics (ROC) to calculate diagnostic accuracy. Findings Twenty-two candidate TAAs were assessed by protein microarray analysis in 914 participants with serum α-fetoprotein (AFP) available. Twelve candidate TAAs were statistically different in signal intensity between HCC and controls. Among them, CENPF, HSP60 and IMP-2 showed AUC (area under the curve) values of 0.826, 0.764 and 0.796 respectively for early HCC. The highest prevalence of autoantibody positivity was observed in HCC cases with BCLC tumor stage A, well-differentiated histology and Child-Pugh grade C. Specifically, 73.6% or 79.3% cases of early HCC with negative AFP were positive for autoantibody to CENPF or HSP60. Interpretation Tumor-associated autoimmune reactions may be triggered by early stage HCCs. Measurement of serum autoantibody to TAAs may be complementary to AFP measurements and improve diagnosis of early HCC. PMID:26137588

  5. 放射性肺损伤初期Ⅲ、Ⅳ型胶原的变化及氨溴索的影响%The change of Ⅲ, Ⅳ collagen fibers in early stage of radiation-induced lung injury in rats and effect of ambroxol to its

    Institute of Scientific and Technical Information of China (English)

    叶江枫; 袁名辉; 蒙育林

    2011-01-01

    Objective To explore change of Ⅲ, Ⅳ collagen fibers in early stage of radiation-induced lung injury in rats and the efficacy of ambroxol to its.Methods 46 SD female rats were randomly divided into control( C group), radiational injury group( R group)and treatment group after radiational injury (M group).Ambroxol was given to rats in treatment groups at a dose of 20 mg/kg-per day by injection into belly from seven days before radiation until the end of the experiment, The rats in other groups were injection into belly with the same amount of saline.Rats in R group and M group were exposed to thoracic radiation at a dose of 20 Gy by linear accelerator.Collagen Ⅲ ,collagen Ⅳ in rat blood serum and in alveolar lavage were measured by radioimmunoassay in the day of 1,2,3,4 after radiation.The data were analyzed by student's t teat.Results The amount of collagen Ⅲ fibers in blood serum from rots of R group increased significantly compared to C group on day 2,3,4( P <0.01 ).The change was obviously in M group compared to R group ( P <0.01 ).Collagen Ⅲ and Ⅳ fibers in alveolar lavage was no difference among three groups.Conclusions Collagen Ⅲ fibers in blood serum increased in the early stage after the lung was radiated.Ambroxol can influence the change of collagen Ⅲ fibers in blood serum.%目的 探讨放射性肺损伤初期Ⅲ、Ⅳ型胶原的变化及氨溴索对放射性肺损伤的治疗作用.方法 雌性SD大鼠46只随机分为正常对照组C,照射组R和治疗组M.照射组和治疗组给予直线加速器照射,照射剂量单次20 Gy/min,照射组于照射后当天给予生理盐水腹腔内注射,治疗组于照射后当天给予氨溴索20 mg/kg/d,直至实验结束.于照射后1、2、3、4 d取大鼠血清及肺灌洗液放免法测定Ⅲ、Ⅳ型胶原,数据用组间t检验.结果 照射后R组2、3、4 d血清Ⅲ型胶原较C组显著升高(P<0.01).M组较同期R组变化显著(P<0.01).肺灌洗液中Ⅲ/Ⅳ型胶原三组

  6. Socioeconomic position, stage of lung cancer and time between referral and diagnosis in Denmark, 2001-2008

    DEFF Research Database (Denmark)

    Dalton, Susanne Oksbjerg; Frederiksen, Flemming B.; Jacobsen, E;

    2011-01-01

    INTRODUCTION: We investigated the association between socioeconomic position, stage at diagnosis, and length of period between referral and diagnosis in a nationwide cohort of lung cancer patients. METHODS: Through the Danish Lung Cancer Register, we identified 18,103 persons diagnosed with lung...

  7. Early morbidity after simultaneous and staged bilateral total knee arthroplasty

    DEFF Research Database (Denmark)

    Lindberg-Larsen, Martin; Jørgensen, Christoffer Calov; Husted, Henrik;

    2015-01-01

    PURPOSE: The aim of this nationwide study was to investigate the early morbidity after bilateral simultaneous and staged total knee arthroplasty (TKA) in order to clarify potential benefits of a well-established fast-track regime. METHODS: The Danish National Patient Registry was searched for all...... bilateral simultaneous and staged TKA procedures from 2010 to 2011. The staged procedures were defined as two separate procedures done within 0-6 months or within 7-18 months. RESULTS: A total of 157 patients had bilateral simultaneous TKA, 346 patients had bilateral staged TKA within 0-6 months and 292...... simultaneous TKA versus three deaths (0.9 and 1.0 %) in each of the bilateral staged groups within 90 days of surgery (n.s.). The total readmission rate within 30 days of surgery was lower after bilateral simultaneous TKA (7 %, CI 4.0-12.0) and bilateral staged TKA within 0-6 months (9 %, CI 6.4-12.4) compared...

  8. The early stages in the oxidation of Na

    Energy Technology Data Exchange (ETDEWEB)

    Shek, M.L. (25 Old Saddle Road, Ridge, New York 11961 (USA)); Hrbek, J. (Chemistry Department, Brookhaven National Laboratory, Upton, New York 11973 (USA)); Sham, T.K. (Department of Chemistry, University of Western Ontario, Ontario, NA6 5B7, Canada (CA)); Xu, G. (Chemistry Department, Brookhaven National Laboratory, Upton, New York 11973 (USA))

    1991-05-01

    We report soft x-ray photoemission results on the early stages of the oxidation of Na at {similar to}80 K. The first stage (up to {approx gt}0.5 L exposure) is characterized by a narrow O 2{ital p} level and a Na 2{ital p} surface core level shifted by {minus}0.55 eV with respect to the bulk core level. The Na 2{ital p} surface plasmon loss intensity shifts toward smaller energies, consistent with a decrease in surface conduction electron density. The second stage (starting from {similar to}1 L) is characterized by the emergence of di-oxygen'' valence levels and a Na 2{ital p} component shifted by {similar to}0.8 eV with respect to the bulk binding energy. The oxidation is strongly nonuniform, as suggested by the small oxygen doses needed for the onset of the second oxidation stage, and the continued presence of the bulk plasmon loss from metallic Na. The two new Na 2{ital p} binding energies are tentatively attributed to different final-state screening of metallic Na adjacent to dispersed oxygen atoms in the first stage, and of the Na atoms with mostly oxygen nearest neighbors in the second stage. Observations regarding large negative core level shifts upon large oxygen exposures are also summarized.

  9. Information processing theory in the early design stages

    DEFF Research Database (Denmark)

    Cash, Philip; Kreye, Melanie

    2014-01-01

    suggestions for improvements and support. One theory that may be particularly applicable to the early design stages is Information Processing Theory (IPT) as it is linked to the design process with regard to the key concepts considered. IPT states that designers search for information if they perceive......, the new knowledge is shared between the design team to reduce ambiguity with regards to its meaning and to build a shared understanding – reducing perceived uncertainty. Thus, we propose that Information-Processing Theory is suitable to describe designer activity in the early design stages......Developing appropriate theory is one of the main challenges facing engineering design (Cross, 2007). Theory helps to both explain design activity but also support greater research impact in the domain. It is useful for gaining a more comprehensive understanding of design activity and developing...

  10. Information processing theory in the early design stages

    DEFF Research Database (Denmark)

    Cash, Philip; Kreye, Melanie

    2014-01-01

    Developing appropriate theory is one of the main challenges facing engineering design (Cross, 2007). Theory helps to both explain design activity but also support greater research impact in the domain. It is useful for gaining a more comprehensive understanding of design activity and developing...... suggestions for improvements and support. One theory that may be particularly applicable to the early design stages is Information Processing Theory (IPT) as it is linked to the design process with regard to the key concepts considered. IPT states that designers search for information if they perceive...... uncertainty with regard to the knowledge necessary to solve a design challenge. They then process this information and compare if the new knowledge they have gained covers the previous knowledge gap. In engineering design, uncertainty plays a key role, particularly in the early design stages which has been...

  11. Adjuvant chemotherapy for early-stage cervical cancer.

    Science.gov (United States)

    Asano, Hiroshi; Todo, Yukiharu; Watari, Hidemichi

    2016-04-01

    The aim of this review is to address the current status of adjuvant chemotherapy alone in early-stage cervical cancer treatments in the literature. At present, the therapeutic effect of adjuvant chemotherapy alone after radical surgery (RS) has not yet been established, and radiation therapy (RT) or concurrent chemoradiotherapy (CCRT) is recommended as the standard adjuvant therapy after RS for early-stage cervical cancer in various guidelines. The main purpose of adjuvant therapy after RS, however, should be to reduce extrapelvic recurrence rather than local recurrence, although adjuvant RT or CCRT has survival benefits for patients with intermediate- or high-risk factors for recurrence. Moreover, several studies reported that adjuvant therapies including RT were associated with a higher incidence of complications, such as lymphedema, bowel obstruction and urinary disturbance, and a lower grade of long-term quality of life (QOL) or sexual functioning than adjuvant chemotherapy alone. The effect of adjuvant chemotherapy alone for early-stage cervical cancer with intermediate- or high-risk factors for recurrence were not fully investigated in prospective studies, but several retrospective studies suggest that the adjuvant effects of chemotherapy alone are at least similar to that of RT or CCRT in terms of recurrence rate, disease-free survival, or overall survival (OS) with lower incidence of complications. Whereas cisplatin based combination regimens were used in these studies, paclitaxel/cisplatin (TP) regimen, which is currently recognized as a standard chemotherapy regimen for patients with metastatic, recurrent or persistent cervical cancer by Gynecologic Oncology Group (GOG), had also survival benefit as an adjuvant therapy. Therefore, it may be worth considering a prospective randomized controlled trial (RCT) of adjuvant chemotherapy alone using TP regimen versus adjuvant RT as an alternative adjuvant therapy. Because early-stage cervical cancer is a curable

  12. Effects of genistein on early-stage cutaneous wound healing

    Energy Technology Data Exchange (ETDEWEB)

    Park, Eunkyo [Department of Home Economics Education, Chung-Ang University, Seoul 156-756 (Korea, Republic of); Lee, Seung Min [Research Institute of Health Sciences, Korea University, Seoul 136-701 (Korea, Republic of); Jung, In-Kyung [Department of Home Economics Education, Chung-Ang University, Seoul 156-756 (Korea, Republic of); Lim, Yunsook [Department of Foods and Nutrition, Kyung Hee University, Seoul 130-701 (Korea, Republic of); Kim, Jung-Hyun, E-mail: jjhkim@cau.ac.kr [Department of Home Economics Education, Chung-Ang University, Seoul 156-756 (Korea, Republic of)

    2011-07-08

    Highlights: {yields} We examine the effect of genistein on cutaneous wound healing. {yields} Genistein enhanced wound closure during the early stage of wound healing. {yields} These genistein effects on wound closure were induced by reduction of oxidative stress through increasing antioxidant capacity and modulation of pro-inflammatory cytokine expression. -- Abstract: Wound healing occurs in three sequential phases: hemostasis and inflammation, proliferation, and remodeling. Inflammation, the earliest phase, is considered a critical period for wound healing because immune cells remove damaged tissues, foreign debris, and remaining dead tissue. Wound healing would be delayed without inflammation, and this phase is affected by antioxidation capacity. Therefore, we hypothesized that genistein, which has an antioxidant effect, might modulate the wound healing process by altering the inflammatory response. After three days of acclimation, mice were divided into three groups: control, 0.025% genistein, and 0.1% genistein. After two weeks of an experimental diet, skin wounds were induced. Wounded skin areas were imaged, and the healing rate calculated. To measure lipid peroxidation, antioxidant enzyme expression and activity, and pro-inflammatory cytokine expression, skin and liver tissues were harvested at 12, 24, 48, and 72 h. Genistein did not affect body weight. The rate of wound closure in mice fed genistein was significantly faster than in the control group during the early stage of wound healing, especially in first three days. Cu, Zn-SOD and Mn-SOD expression in wound skin tissue in the 0.1% genistein group was lower than in the control group. However, CAT expression did not differ among groups. We also found that genistein modulated NF-{kappa}B and TNF-{alpha} expression during the early stage of wound healing. The genistein group had significantly lower hepatic lipid peroxidation and higher SOD, CAT, and GPx activities than the control group. These results

  13. Awareness of memory deficits in early stage Huntington's disease.

    Directory of Open Access Journals (Sweden)

    Laurent Cleret de Langavant

    Full Text Available Patients with Huntington's disease (HD are often described as unaware of their motor symptoms, their behavioral disorders or their cognitive deficits, including memory. Nevertheless, because patients with Parkinson's disease (PD remain aware of their memory deficits despite striatal dysfunction, we hypothesize that early stage HD patients in whom degeneration predominates in the striatum can accurately judge their own memory disorders whereas more advanced patients cannot. In order to test our hypothesis, we compared subjective questionnaires of memory deficits (in HD patients and in their proxies and objective measures of memory dysfunction in patients. Forty-six patients with manifest HD attending the out-patient department of the French National Reference Center for HD and thirty-three proxies were enrolled. We found that HD patients at an early stage of the disease (Stage 1 were more accurate than their proxies at evaluating their own memory deficits, independently from their depression level. The proxies were more influenced by patients' functional decline rather than by patients' memory deficits. Patients with moderate disease (Stage 2 misestimated their memory deficits compared to their proxies, whose judgment was nonetheless influenced by the severity of both functional decline and depression. Contrasting subjective memory ratings from the patients and their objective memory performance, we demonstrate that although HD patients are often reported to be unaware of their neurological, cognitive and behavioral symptoms, it is not the case for memory deficits at an early stage. Loss of awareness of memory deficits in HD is associated with the severity of the disease in terms of CAG repeats, functional decline, motor dysfunction and cognitive impairment, including memory deficits and executive dysfunction.

  14. Early Contact Stage of Apoptosis: Its Morphological Features and Function

    Directory of Open Access Journals (Sweden)

    Etheri Mikadze

    2006-01-01

    Full Text Available Apoptosis has been a biological phenomenon of intense interest for 20 years, but the earlier morphological features of apoptosis have not been determined hitherto. Using the methods of semi- and ultrathin sections, the livers of intact embryos and young rats have been studied under the effect of cycloheximide to determine morphological features of an early stage of apoptosis. It is discovered that both in hepatoblasts and hepatocytes, apoptosis, besides the well-known stages, also includes an early contact stage, distinguishing features of which are agglutination of bound ribosomes (breaking of translation, elimination of the nucleolus, reduction of free polysomes (and in hepatocytes, reduction of cisterns of rough endoplasmic reticulum, formation of cytoplasmic excrescences, and cell shape changes. The early stage of apoptosis is characterized by close contact with neighboring cells. At a certain phase of the contact stage of apoptosis, the nucleolus reappears in the nucleus and the number of free polysomes in the cytoplasm increases, which suggests the renewal of synthesis of new RNA and proteins. Close contact of differentiating and mitotic hepatoblasts with apoptotic cells indicates a certain functional relationship between these cells that is realized not only by micropinocytosis, but through gap junctions as well. We assume that the apoptotic cell, besides proteolytic products, can contain newly synthesized, low-molecular substances, the relocation of which from apoptotic to neighboring cells may contribute to both functional activity and proliferation of adjacent hepatoblasts and, therefore, the function of apoptosis may not be limited only to the elimination of harmful, damaged, and unwanted cells.

  15. Technical description of endoscopic ultrasonography with fine-needle aspiration for the staging of lung cancer

    NARCIS (Netherlands)

    Kramer, H; van Putten, JWG; Douma, WR; Smidt, AA; van Dullemen, HM; Groen, HJM

    2005-01-01

    Background: Encloscopic ultrasonography (EUS) is a novel method for staging of the mediastinum in lung cancer patients. The recent development of linear scanners enables safe and accurate fine-needle aspiration (FNA) of mediastinal and upper abdominal structures under real-time ultrasound guidance.

  16. Validity of the stage of lung cancer in records of the Maastricht Cancer Registry, the Netherlands

    NARCIS (Netherlands)

    Schouten, LJ; Langendijk, JA; Jager, JJ; vandenBrandt, PA

    1997-01-01

    Information collected in a clinical study on a random sample of 99 patients with inoperable lung cancer, treated with radiotherapy, was compared to the staging information in the Maastricht cancer registry. Validity of sex (0% disagreements), date of birth (0%), histology (1% major disagreements) an

  17. Validity of the stage of lung cancer in records of the Maastricht Cancer Registry, the Netherlands

    NARCIS (Netherlands)

    Schouten, Leo J.; Langendijk, JA; Jager, JJ; vandenBrandt, PA

    Information collected in a clinical study on a random sample of 99 patients with inoperable lung cancer, treated with radiotherapy, was compared to the staging information in the Maastricht cancer registry. Validity of sex (0% disagreements), date of birth (0%), histology (1% major disagreements)

  18. Technical description of endoscopic ultrasonography with fine-needle aspiration for the staging of lung cancer

    NARCIS (Netherlands)

    Kramer, H; van Putten, JWG; Douma, WR; Smidt, AA; van Dullemen, HM; Groen, HJM

    2005-01-01

    Background: Encloscopic ultrasonography (EUS) is a novel method for staging of the mediastinum in lung cancer patients. The recent development of linear scanners enables safe and accurate fine-needle aspiration (FNA) of mediastinal and upper abdominal structures under real-time ultrasound guidance.

  19. Phyllotactic pattern formation in early stages of cactus ontogeny

    Directory of Open Access Journals (Sweden)

    Edyta M. Gola

    2011-01-01

    Full Text Available Representatives of the family Cactaceae are characterized by a wide range of phyllotaxis. To assess the origin of this diversity, early stages of phyllotactic pattern formation were examined in seedlings. The analysis of the sequence of areole initiation revealed intertribal differences. In seedlings from the Trichocereeae (Gymnocalycium, Rebutia and Notocacteae (Parodia tribes, two opposite cotyledonal areoles developed as the first elements of a pattern. Usually, next pair of areoles was initiated perpendicularly to cotyledonal areoles, starting the decussate pattern. This pattern was subsequently transformed into bijugate or into simple spiral phyllotaxis. In seedlings from the Cacteae tribe (Mammillaria and Thelocactus, cotyledonal areoles were never observed and the first areoles always appeared in the space between cotyledons. It was either areole pair (mainly in Mammillaria, starting a decussate pattern, or a single areole (mainly in Thelocactus quickly followed by areoles spirally arranged, usually in accordance with the main Fibonacci phyllotaxis. Differences in the initial stages of pattern formation do not fully explain the phyllotaxis diversity in mature cacti. Only two, the most common phyllotactic patterns occurred in the early development of studied seedlings, i.e. the main Fibonacci and the decussate pattern. Discrepancy in the range of phyllotactic spectra in seedlings and in mature plants suggests that phyllotaxis diversity emerges during further plant growth. Initial phyllotactic transformations, occurring already in the very early stages, indicate great plasticity of cactus growth and seem to support the hypothesis of the ontogenetic increase of phyllotaxis diversity due to transformations.

  20. 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone Induces Circulating MicroRNA Deregulation in Early Lung Carcinogenesis

    Institute of Scientific and Technical Information of China (English)

    WU Jian Jun; YANG Ti; LI Xun; XIA Yuan; ZHAO Yao; ZOU Fei; JIANG Yi Guo

    2014-01-01

    Objective To study the alteration of circulating microRNAs in 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone (NNK)-induced early stage lung carcinogenesis. Methods A lung cancer model of male F344 rats was induced with systemic NNK and levels of 8 lung cancer-associated miRNAs in whole blood and serum of rats were measured by quantitative RT-PCR of each at weeks 1, 5, 10, and 20 following NNK treatment. Results No lung cancer was detected in control group and NNK treatment group at week 20 following NNK treatment. The levels of some circulating miRNAs were significantly higher in NNK treatment group than in control group. The miR-210 was down-regulated and the miR-206 was up-regulated in NNK treatment group. The expression level of circulating miRNAs changed from week 1 to week 20 following NNK treatment. Conclusion The expression level of circulating miRNAs is related to NNK-induced early stage lung carcinogenesis in rats and can therefore serve as its potential indicator.

  1. Requirement Defect Mitigation Technique: An Early Stage Implementation

    Directory of Open Access Journals (Sweden)

    Md. Rizwan Beg

    2012-09-01

    Full Text Available Requirement defect identification and mitigation at early stage of Software Development Life Cycle (SDLC is very cost effective than to later stages. The requirements analysis in requirement engineering process is critical and major foundation of requirement defect identification. A poor requirement analysis process may lead to software requirement specification (SRS full of defects akin to misplaced, ambiguous, incompatible, misinterpreted, and incomplete requirements. In this paper, requirement defects are being identified and properly mitigated as per its severity in the requirement phase to get rid of major rework by spending extra cost and effort at the later stages. Here, a Defect Mitigation Technique (DMT is proposed for mitigating the identified requirement defect and also the reliability of requirement is being assessed to deliver Reliable Requirement. The proposed algorithm is helping the DMT for its proper processing, defect mitigation and reliability assessment. The prime motive of this study is an effort to put off requirements stage defects from entering into later stages of SDLC.

  2. Stage-specific proteome signatures in early bovine embryo development.

    Science.gov (United States)

    Deutsch, Daniela R; Fröhlich, Thomas; Otte, Kathrin A; Beck, Andrea; Habermann, Felix A; Wolf, Eckhard; Arnold, Georg J

    2014-10-03

    Development of early embryonic stages before activation of the embryonic genome depends on sufficiently stored products of the maternal genome, adequate recruitment and degradation of mRNAs, as well as activation, deactivation, and relocation of proteins. By application of an isobaric tagging for relative and absolute quantification (iTRAQ)-based approach, the proteomes of bovine embryos at the zygote and 2-cell and 4-cell stage with MII oocytes as a reference were quantitatively analyzed. Of 1072 quantified proteins, 87 differed significantly in abundance between the four stages. The proteomes of 2-cell and 4-cell embryos differed most from the reference MII oocyte, and a considerable fraction of proteins continuously increased in abundance during the stages analyzed, despite a strongly attenuated rate of translation reported for this period. Bioinformatic analysis revealed particularly interesting proteins involved in the p53 pathway, lipid metabolism, and mitosis. Verification of iTRAQ results by targeted SRM (selected reaction monitoring) analysis revealed excellent agreement for all five proteins analyzed. By principal component analysis, SRM quantifications comprising a panel of only five proteins were shown to discriminate between all four developmental stages analyzed here. For future experiments, an expanded SRM protein panel will provide the potential to detect developmental disturbances with high sensitivity and enable first insights into the underlying molecular pathways.

  3. Subthalamic nucleus deep brain stimulation in early stage Parkinson's disease.

    Science.gov (United States)

    Charles, David; Konrad, Peter E; Neimat, Joseph S; Molinari, Anna L; Tramontana, Michael G; Finder, Stuart G; Gill, Chandler E; Bliton, Mark J; Kao, Chris; Phibbs, Fenna T; Hedera, Peter; Salomon, Ronald M; Cannard, Kevin R; Wang, Lily; Song, Yanna; Davis, Thomas L

    2014-07-01

    Deep brain stimulation (DBS) is an effective and approved therapy for advanced Parkinson's disease (PD), and a recent study suggests efficacy in mid-stage disease. This manuscript reports the results of a pilot trial investigating preliminary safety and tolerability of DBS in early PD. Thirty subjects with idiopathic PD (Hoehn & Yahr Stage II off medication), age 50-75, on medication ≥6 months but ≤4 years, and without motor fluctuations or dyskinesias were randomized to optimal drug therapy (ODT) (n = 15) or DBS + ODT (n = 15). Co-primary endpoints were the time to reach a 4-point worsening from baseline in the UPDRS-III off therapy and the change in levodopa equivalent daily dose from baseline to 24 months. As hypothesized, the mean UPDRS total and part III scores were not significantly different on or off therapy at 24 months. Medication requirements in the DBS + ODT group were lower at all time points with a maximal difference at 18 months. With a few exceptions, differences in neuropsychological functioning were not significant. Two subjects in the DBS + ODT group suffered serious adverse events; remaining adverse events were mild or transient. This study demonstrates that subjects with early stage PD will enroll in and complete trials testing invasive therapies and provides preliminary evidence that DBS is well tolerated in early PD. The results of this trial provide the data necessary to design a large, phase III, double-blind, multicenter trial investigating the safety and efficacy of DBS in early PD. Copyright © 2014 Elsevier Ltd. All rights reserved.

  4. Lung cancer: Morphological and functional approach to screening, staging and treatment planning.

    Science.gov (United States)

    Coche, Emmanuel; Lonneux, Max; Geets, Xavier

    2010-03-01

    Lung cancer is a major problem in public health and constitutes the leading cause of cancer-related mortality in the world. Lung cancer screening with low-dose computed tomography is promising but needs to overcome many difficulties, such as the large number of incidentally discovered nodules, the radiation dose delivered to the patient during a whole screening program and its cost. The ultimate target point represented by the reduction of lung cancer-related mortality needs to be proved in large, well-designed, randomized, multicenter, prospective trials. Lung cancer staging by morphological tools seems to be limited owing to the presence of metastases in normal-sized lymph nodes. In this context, multidetector computed tomography cannot be used alone but is useful in conjunction with molecular imaging and MRI. Today, flurodeoxglucose PET-CT appears to be the most accurate method for lung cancer staging and may prevent unnecessary thoracotomies. For treatment planning, flurodeoxglucose PET-CT is playing an increasing role in radiotherapy planning at the target selection and definition steps.

  5. Early stages of bipolar disorder: characterization and strategies for early intervention

    Directory of Open Access Journals (Sweden)

    Adiel C. Rios

    2015-12-01

    Full Text Available Objective: To characterize the early stages of bipolar disorder (BD, defined as the clinical prodrome/subsyndromal stage and first-episode phase, and strategies for their respective treatment. Methods: A selective literature search of the PubMed, Embase, PsycINFO, and ISI databases from inception until March 2014 was performed. Included in this review were articles that a characterized prodromal and first-episode stages of BD or b detailed efficacy and safety/tolerability of interventions in patients considered prodromal for BD or those with only one episode of mania/hypomania. Results: As research has only recently focused on characterization of the early phase of BD, there is little evidence for the effectiveness of any treatment option in the early phase of BD. Case management; individual, group, and family therapy; supportive therapy; and group psychoeducation programs have been proposed. Most evidence-based treatment guidelines for BD do not address treatment specifically in the context of the early stages of illness. Evidence for pharmacotherapy is usually presented in relation to illness polarity (i.e., manic/mixed or depressed or treatment phase. Conclusions: Although early recognition and treatment are critical to preventing unfavorable outcomes, there is currently little evidence for interventions in these stages of BD.

  6. Outcomes of patients with unresected stage III and stage IV non-small cell lung cancer: A single institution experience

    Directory of Open Access Journals (Sweden)

    Manpreet Singh Tiwana

    2013-01-01

    Full Text Available Introduction: To report on the demographic profile and survival outcomes of North Indian population affected with stage III and stage IV non-small cell lung cancer (NSCLC. Materials and Methods: From November 2008 to January 2012, 138 consecutively diagnosed NSCLC patients were included in this study. The patient, tumor and treatment related factors were analyzed. Median overall survival (OS, Kaplan-Meier survival plots, t-test, Cox proportional hazards models were generated by multivariate analysis [MVA] and analyzed on SPSS software (version 19.0; SPSS, Inc., Chicago, IL. Results: Median OS of stage III patients was 9.26 ± 1.85 months and 2-year survival rate of 13% while stage IV patients had median OS of 5 ± 1.5 months with a 2-year survival rate of 8%. Cox regression modeling for MVA demonstrated higher biologically equivalent dose (BED ( P = 0.01 in stage III while in stage IV non-squamous histology ( P = 0.01, administration of chemotherapy ( P = 0.02, partial responders to chemotherapy ( P = 0.001, higher BED ( P = 0.02, and those with skeletal metastasis alone ( P = 0.17 showed a better OS. Conclusion: Our data showed that a higher BED is associated with favorable outcomes, indicating a role of dose escalated radiation therapy to the primary lesion in both stage III and essentially in stage IV NSCLC. Additionally, optimal use of chemotherapy relates to better survival. The developing, resource restrained nations need to follow an economically feasible multimodality approach.

  7. Neural changes underlying early stages of L2 vocabulary acquisition.

    Science.gov (United States)

    Pu, He; Holcomb, Phillip J; Midgley, Katherine J

    2016-11-01

    Research has shown neural changes following second language (L2) acquisition after weeks or months of instruction. But are such changes detectable even earlier than previously shown? The present study examines the electrophysiological changes underlying the earliest stages of second language vocabulary acquisition by recording event-related potentials (ERPs) within the first week of learning. Adult native English speakers with no previous Spanish experience completed less than four hours of Spanish vocabulary training, with pre- and post-training ERPs recorded to a backward translation task. Results indicate that beginning L2 learners show rapid neural changes following learning, manifested in changes to the N400 - an ERP component sensitive to lexicosemantic processing and degree of L2 proficiency. Specifically, learners in early stages of L2 acquisition show growth in N400 amplitude to L2 words following learning as well as a backward translation N400 priming effect that was absent pre-training. These results were shown within days of minimal L2 training, suggesting that the neural changes captured during adult second language acquisition are more rapid than previously shown. Such findings are consistent with models of early stages of bilingualism in adult learners of L2 (e.g. Kroll and Stewart's RHM) and reinforce the use of ERP measures to assess L2 learning.

  8. Ipsilateral pleural recurrence after diagnostic transthoracic needle biopsy in pathological stage I lung cancer patients who underwent curative resection.

    Science.gov (United States)

    Moon, Seong Mi; Lee, Dae Geun; Hwang, Na Young; Ahn, Soohyun; Lee, Hyun; Jeong, Byeong-Ho; Choi, Yong Soo; Shim, Young Mog; Kim, Tae Jeong; Lee, Kyung Soo; Kim, Hojoong; Kwon, O Jung; Lee, Kyung Jong

    2017-09-01

    The relationship between transthoracic needle biopsy (TTNB) and pleural recurrence of cancer after curative lung resection remains unclear. We aimed to assess whether TTNB increases the ipsilateral pleural recurrence (IPR) rate and identify other potential risk factors for pleural recurrence after surgery. This retrospective study included 392 patients with p-stage I non-small cell lung cancer with solid or part-solid nodules after curative lung resection in 2009-2010. Imbalances among the characteristics were adjusted using an inverse probability-weighted method based on propensity scoring. Multivariate Cox's regression analysis and the Kaplan-Meier method were used to determine independent risk factors for IPR. A total of 243 (62%) patients received TTNB, while 149 (38%) underwent an alternate, or no, diagnostic technique. IPR was significantly more frequent in the TTNB group (p=0.004), while total recurrence was similar between the groups (p=0.098). After applying the weighted model, diagnostic TTNB (hazard ratio [HR], 5.27; 95% confidence interval [CI], 1.49-18.69; p=0.010), microscopic visceral pleural invasion (HR, 2.76; 95% CI, 1.08-7.01; p=0.033) and microscopic lymphatic invasion (HR, 3.25; 95% CI, 1.30-8.10; p=0.012) were associated with an increased frequency of IPR. Among patients who received TTNB, microscopic lymphatic invasion was a risk factor for IPR (HR, 2.74; 95% CI, 1.10-6.79; p=0.030). The diagnostic TTNB procedure is associated with pleural recurrence but may be unrelated to overall recurrence-free survival in early lung cancer. Moreover, microscopic lymphatic invasion could be a risk factor for pleural recurrence. TTNB should be carefully considered before lung resection and close follow-up to detect if pleural recurrence is needed. Copyright © 2017 Elsevier B.V. All rights reserved.

  9. Lung findings on high resolution CT in early ankylosing spondylitis

    Energy Technology Data Exchange (ETDEWEB)

    Kiris, Adem E-mail: ademkiris@hotmail.com; Ozgocmen, Salih; Kocakoc, Ercan; Ardicoglu, Ozge; Ogur, Erkin

    2003-07-01

    Objective: Ankylosing spondylitis (AS) is a chronic inflammatory disease mainly affecting the axial skeleton and pulmonary involvement is a well known feature of the disease. The aim of this study was to investigate the pulmonary high resolution computed tomography (HRCT) findings of patients with early AS. The relationship between pulmonary function tests (PFT) and HRCT findings was also determined. Subjects and methods: Twenty-eight patients with AS (mean age 30.8{+-}7.4 and disease duration 7.0{+-}2.6) were included in the study. Patients with a disease duration of >10 years or had other pulmonary diseases were excluded. All patients underwent plain chest radiography (posteroanterior and lateral views), thoracic HRCT and PFT. Results: All chest radiographs were normal and HRCT revealed abnormalities in 18 patients. The most common abnormalities seen on HRCT were mosaic pattern (ten of 28), subpleural nodule (seven of 28) and parenchymal bands (five of 28). Seven of ten patients with mosaic pattern revealed air trapping areas on end expiratory scans. Twelve patients had abnormal PFT and all had restrictive type of involvement. Ten of these 12 patients had abnormal HRCT and the remaining two patients had normal HRCT. On the other hand, eight patients with normal PFT had abnormalities on HRCT. Conclusion: Patients with early AS frequently have abnormalities on HRCT, even though they have normal PFT and chest X-ray. Small airway involvement was found as frequent as interstitial lung disease in early AS.

  10. Stereotactic body radiotherapy for stage I lung cancer and small lung metastasis: evaluation of an immobilization system for suppression of respiratory tumor movement and preliminary results

    OpenAIRE

    Ayakawa Shiho; Oda Kyota; Ikeya-Hashizume Chisa; Tomita Natsuo; Shibamoto Yuta; Baba Fumiya; Ogino Hiroyuki; Sugie Chikao

    2009-01-01

    Abstract Background In stereotactic body radiotherapy (SBRT) for lung tumors, reducing tumor movement is necessary. In this study, we evaluated changes in tumor movement and percutaneous oxygen saturation (SpO2) levels, and preliminary clinical results of SBRT using the BodyFIX immobilization system. Methods Between 2004 and 2006, 53 consecutive patients were treated for 55 lesions; 42 were stage I non-small cell lung cancer (NSCLC), 10 were metastatic lung cancers, and 3 were local recurrenc...

  11. Cell cycle progression score is a marker for five-year lung cancer-specific mortality risk in patients with resected stage I lung adenocarcinoma

    Science.gov (United States)

    Eguchi, Takashi; Kadota, Kyuichi; Chaft, Jamie; Evans, Brent; Kidd, John; Tan, Kay See; Dycoco, Joe; Kolquist, Kathryn; Davis, Thaylon; Hamilton, Stephanie A.; Yager, Kraig; Jones, Joshua T.; Travis, William D.; Jones, David R.; Hartman, Anne-Renee; Adusumilli, Prasad S.

    2016-01-01

    Purpose The goals of our study were (a) to validate a molecular expression signature (cell cycle progression [CCP] score and molecular prognostic score [mPS; combination of CCP and pathological stage {IA or IB}]) that identifies stage I lung adenocarcinoma (ADC) patients with a higher risk of cancer-specific death following curative-intent surgical resection, and (b) to determine whether mPS stratifies prognosis within stage I lung ADC histological subtypes. Methods Formalin-fixed, paraffin-embedded stage I lung ADC tumor samples from 1200 patients were analyzed for 31 proliferation genes by quantitative RT-PCR. Prognostic discrimination of CCP score and mPS was assessed by Cox proportional hazards regression, using 5-year lung cancer–specific mortality as the primary outcome. Results In multivariable analysis, CCP score was a prognostic marker for 5-year lung cancer–specific mortality (HR=1.6 per interquartile range; 95% CI, 1.14–2.24; P=0.006). In a multivariable model that included mPS instead of CCP, mPS was a significant prognostic marker for 5-year lung cancer–specific mortality (HR=1.77; 95% CI, 1.18–2.66; P=0.006). Five-year lung cancer–specific survival differed between low-risk and high-risk mPS groups (96% vs 81%; P<0.001). In patients with intermediate-grade lung ADC of acinar and papillary subtypes, high mPS was associated with worse 5-year lung cancer–specific survival (P<0.001 and 0.015, respectively), compared with low mPS. Conclusion This study validates CCP score and mPS as independent prognostic markers for lung cancer–specific mortality and provides quantitative risk assessment, independent of known high-risk features, for stage I lung ADC patients treated with surgery alone. PMID:27153551

  12. Early stages of irradiation induced dislocations in urania

    Science.gov (United States)

    Chartier, A.; Onofri, C.; Van Brutzel, L.; Sabathier, C.; Dorosh, O.; Jagielski, J.

    2016-10-01

    The early stages of nucleation and growth of dislocations by irradiation in urania is clarified based on the combination of experiments and atomistic calculations. It is established that irradiation induced dislocations follow a five stage process: (i) point defects are first created by irradiation, (ii) they aggregate into clusters, (iii) from which nucleate Frank loops, (iv) which transform into unfaulted loops via Shockley that in turn grow, and (v) finally reorganize into forest dislocations. Stages (i)-(iii) participate in the lattice expansion while the onset of lattice contraction starts with stage (iv), i.e., when unfaulted loops nucleate. Irradiation induced dislocations operate in the spontaneous recombination regime, to be opposed to the thermal diffusion regime. Body of arguments collaborates to this statement, the main one is the comparison between characteristic distances estimated from the dose rate (Vat/(K0×τ ) ) 1/3 and from the diffusion coefficient (D×τ ) 1/2 . Such a comparison identifies materials under irradiation as belonging either into the recombination regime or not.

  13. Early stage design and analysis of biorefinery networks

    DEFF Research Database (Denmark)

    Sin, Gürkan

    2013-01-01

    Recent work regarding biorefineries resulted in many competing concepts and technologies for conversion of renewable bio-based feedstock into many promising products including fuels, chemicals, materials, etc. The design of a biorefinery process requires, at its earlier stages, the selection...... biorefinery concept for a lignocellulosic biorefinery. More specifically we highlight the required information management (management of various sources of data), the superstructure which is needed to represent the design space, generic but simple models covering all the processing steps of biorefineries...... of the process configuration which exhibits the best performances, for a given set of economical, technical and environmental criteria. To this end, we formulate a computer-aided framework as an enabling technology for early stage design and analysis of biorefineries. The tool represents different raw materials...

  14. [Ophthalmologic manifestations in early and late stages of AIDS].

    Science.gov (United States)

    Schnaudigel, O E; Gümbel, H; Richter, R; Subklew, R; Garweg, T

    1994-10-01

    In a prospective study of 101 patients with HIV infection and a medium CD4 lymphocyte cell count of 350 x 10(6)/l and a retrospective study of the records of 79 AIDS patients, we compared the first ocular symptoms in HIV-infected patients to the CD4 count. In Walter-Reed stages 2-4 (n = 101) we found sicca syndrome in 9.2%, in 52% lens opacities in the cortex and only in less than 1% HIV-related angiopathy of the retina. In Walter Reed stages 5-6 (n = 79), 26% of the AIDS patients developed CMV retinitis, 33% HIV angiopathy of the retina and only 1% retinal toxoplasmosis. The average CD4 lymphocyte cell count was never better than 100 x 10(6). Lens opacities in HIV-infected patients could be an early ophthalmological symptom of HIV infection.

  15. Sarcopenia is a novel poor prognostic factor in male patients with pathological Stage I non-small cell lung cancer.

    Science.gov (United States)

    Tsukioka, Takuma; Nishiyama, Noritoshi; Izumi, Nobuhiro; Mizuguchi, Shinjiro; Komatsu, Hiroaki; Okada, Satoshi; Toda, Michihito; Hara, Kantaro; Ito, Ryuichi; Shibata, Toshihiko

    2017-04-01

    Sarcopenia is the progressive loss of muscle mass and strength, and has a risk of adverse outcomes such as disability, poor quality of life and death. As prognosis depends not only on disease aggressiveness, but also on a patient's physical condition, sarcopenia can predict survival in patients with various cancer types. However, its effects on postoperative prognosis in patients with localized non-small cell lung cancers (NSCLC) have never been reported. We retrospectively investigated 215 male patients with pathological Stage I NSCLC. L3 muscle index is defined as the cross-section area of muscle at the third lumbar vertebra level, normalized for height, and is a clinical measurement of sarcopenia. We then investigated the effect of preoperative sarcopenia on their postoperative prognosis. Our 215 subjects included 30 patients with sarcopenia. Sarcopenia was significantly associated with body mass index, nutritional condition, serum CYFRA 21-1 level and pathological stage, but not with preoperative respiratory function or performance status. Frequency of postoperative complications, length of postoperative hospital stay, thoracic drainage period or causes of death were not correlated with the presence of sarcopenia. The sarcopenia group had a significantly shorter median overall survival (32 months) than the no-sarcopenia group. Sarcopenia might not affect short-term outcomes in patients with early-stage lung cancer. Sarcopenia was a predictor of poor prognosis in male patients with Stage I NSCLC. As sarcopenic patients with NSCLC patients are at risk for significantly worse outcomes, their treatments require careful planning, even for those with Stage I disease.

  16. Effects of genistein on early-stage cutaneous wound healing.

    Science.gov (United States)

    Park, Eunkyo; Lee, Seung Min; Jung, In-Kyung; Lim, Yunsook; Kim, Jung-Hyun

    2011-07-08

    Wound healing occurs in three sequential phases: hemostasis and inflammation, proliferation, and remodeling. Inflammation, the earliest phase, is considered a critical period for wound healing because immune cells remove damaged tissues, foreign debris, and remaining dead tissue. Wound healing would be delayed without inflammation, and this phase is affected by antioxidation capacity. Therefore, we hypothesized that genistein, which has an antioxidant effect, might modulate the wound healing process by altering the inflammatory response. After three days of acclimation, mice were divided into three groups: control, 0.025% genistein, and 0.1% genistein. After two weeks of an experimental diet, skin wounds were induced. Wounded skin areas were imaged, and the healing rate calculated. To measure lipid peroxidation, antioxidant enzyme expression and activity, and pro-inflammatory cytokine expression, skin and liver tissues were harvested at 12, 24, 48, and 72 h. Genistein did not affect body weight. The rate of wound closure in mice fed genistein was significantly faster than in the control group during the early stage of wound healing, especially in first three days. Cu, Zn-SOD and Mn-SOD expression in wound skin tissue in the 0.1% genistein group was lower than in the control group. However, CAT expression did not differ among groups. We also found that genistein modulated NF-κB and TNF-α expression during the early stage of wound healing. The genistein group had significantly lower hepatic lipid peroxidation and higher SOD, CAT, and GPx activities than the control group. These results suggest that genistein supplementation reduces oxidative stress by increasing antioxidant capacity and modulating proinflammatory cytokine expression during the early stage of wound healing.

  17. FGFR4 Gly388Arg polymorphism may affect the clinical stage of patients with lung cancer by modulating the transcriptional profile of normal lung.

    Science.gov (United States)

    Falvella, Felicia S; Frullanti, Elisa; Galvan, Antonella; Spinola, Monica; Noci, Sara; De Cecco, Loris; Nosotti, Mario; Santambrogio, Luigi; Incarbone, Matteo; Alloisio, Marco; Calabrò, Elisa; Pastorino, Ugo; Skaug, Vidar; Haugen, Aage; Taioli, Emanuela; Dragani, Tommaso A

    2009-06-15

    The association of the fibroblast growth factor receptor 4 (FGFR4) Gly388Arg polymorphism with clinical stage and overall survival in a series of 541 Italian lung adenocarcinoma (ADCA) patients indicated a significantly decreased survival in patients carrying the rare Arg388 allele as compared to that in Gly/Gly homozygous patients [hazard ratio (HR) = 1.5; 95% confidence interval (CI) 1.1-1.9], with the decrease related to the association of the same polymorphism with clinical stage (HR = 1.8, 95% CI 1.3-2.6). By contrast, no significant association was detected in small series of either Norwegian lung ADCA patients or Italian lung squamous cell carcinoma (SQCC) patients. Single nucleotide polymorphisms of known FGFR4 ligands expressed in lung (FGF9, FGF18 and FGF19) were not associated with clinical stage or survival and showed no interaction with FGFR4. Analysis of gene expression profile in normal lungs according to FGFR4 genotype indicated a specific transcript pattern associated with the allele carrier status, suggesting a functional role for the FGFR4 polymorphism already detectable in normal lung. These findings confirm the significant association of the FGFR4 Gly388Arg polymorphism with clinical stage and overall survival in an Italian lung ADCA population and demonstrate a FGFR4 genotype-dependent transcriptional profile present in normal lung tissue.

  18. Controversies in the management of stage IIIA non-small-cell lung cancer.

    Science.gov (United States)

    Santos, Edgardo S; Castrellon, Aurelio; Blaya, Marcelo; Raez, Luis E

    2008-12-01

    New developments in the management of non-small-cell lung cancer, as well as recent proposals for changing the current lung cancer staging system, are posing a challenge in the therapeutic decision making regarding this disease. For the last two decades, the management of stage IIIA (N2) disease has been controversial and the target for clinical trials has been to determine the best therapeutic approach that may result in better survival outcomes without increasing toxicity. For many years, combined modality treatment (systemic chemotherapy plus radiation therapy) became the standard of care in this setting. However, the poor outcomes seen with combined modality for N2 has obligated us to explore other possibilities. In this sense, recent clinical trials in the neoadjuvant setting using chemotherapy alone or combined modality are providing fruitful results and shifting the paradigm on this stage. A recent, large randomized multicenter trial argues against what has slowly become a current practice in some centers - the use of preoperative modality for N2 disease. Another controversy that we will discuss here is the acceptance of adjuvant therapy for resected stage IB-IIIA non-small-cell lung cancer. It was not long ago that adjuvant radiation therapy was still the standard of care for patients who have pathological nodal disease. We will present the current data on these debatable issues and how to implement this new knowledge into clinical practice.

  19. USANS investigation of early stages of metal foam formation

    CERN Document Server

    Bellmann, D; Banhart, J

    2002-01-01

    Metallic foams are on the verge of being used in industrial applications. However, the mechanism of foam creation, especially the early stages, are still unexplored. Ultra small-angle neutron scattering (USANS), performed with the double-crystal diffractometer (DCD) at the Geesthacht Neutron Facility (GeNF), is a promising method for obtaining a three-dimensional average of a pore size distribution in a wide size range from about 100 nm to about 20 mu m. Analysis of the neutron scattering curves yielded pore size distributions which conformed with the results obtained by microscopy. (orig.)

  20. Histopathological diagnosis of acral lentiginous melanoma in early stages.

    Science.gov (United States)

    Fernandez-Flores, Angel; Cassarino, David S

    2017-02-01

    Acral lentiginous melanoma is a rare variant of melanoma that is associated with a relatively low survival rate. The latter is partly due to the advanced stage in which the tumor is usually diagnosed. The diagnostic delay is mainly due to difficulties in identifying the very early histopathological signs of acral melanoma. The current article is a review of diagnostic clues, concepts, and definitions from the literature, as well as illustrating examples from our own archives. We have sought to provide an article that can be easily consulted in difficult cases of acral lentiginous melanoma.

  1. In vivo research using early life stage models.

    Science.gov (United States)

    Seabra, Rita; Bhogal, Nirmala

    2010-01-01

    Scientists, for a variety of reasons, need to carry out in vivo research. Since experiments that require the use of adult animals pose various logistical, economical and ethical issues, the use of embryonic and larval forms of some organisms are potentially attractive alternatives. Early life stages are appealing because, in general, large numbers of individuals can be maintained in relatively simple housing, minimising costs, and their use involves fewer legal formalities. With this succinct review, we aim to provide an overview of different biological issues that have been successfully explored with the help of eggs, embryos and larvae from the frog, zebrafish and chicken.

  2. The studies of nodular graphite cast iron early stages austempering

    OpenAIRE

    A. Krzyńska; M. Kaczorowski

    2008-01-01

    The results of early stage of ductile cast iron austempering are presented. The aim of the investigations was to look closer into the structure – mechanical properties relationships of this very attractive cast material. The experiment was carried out with enriched with Cu EN-GJS-500-7 grade ductile iron. The specimens were first solution heat treated 1 hour in 910oC and then isothermally quenched for different time in molten tin at the temperature 275oC. The mechanical properties of as cast ...

  3. Nontrivial dynamics in the early stages of inflation

    CERN Document Server

    Calzetta, E A

    1995-01-01

    Abstract: Inflationary cosmologies, regarded as dynamical systems, have rather simple asymptotic behavior, insofar as the cosmic baldness principle holds. Nevertheless, in the early stages of an inflationary process, the dynamical behavior may be very complex. In this paper, we show how even a simple inflationary scenario, based on Linde's ``chaotic inflation'' proposal, manifests nontrivial dynamical effects such as the breakup of invariant tori, formation of cantori and Arnol'd's diffusion. The relevance of such effects is highlighted by the fact that even the occurrence or not of inflation in a given Universe is dependent upon them.

  4. Emerging Literature on Cognitive Intervention Techniques for Early Stage Dementia

    Directory of Open Access Journals (Sweden)

    John W Den Boer

    2016-10-01

    Full Text Available Dementia is a growing world-wide phenomenon, impacting more than six million people in the United States. Despite its high projected prevalence, it is a significantly under-represented phenomena, with (underestimate ranging from 15-25% of the general population. The effect of the aging of the population and significant increase in life expectancy has combined to catapult dementia into the range of one of most alarming healthcare problems. Diverse and emerging literature in the area of cognitive prevention/intervention for mild cognitive impairment (MCI/early stage dementia will be reviewed. Additionally, future research and clinical directions will be explored.

  5. Reproductive and early life stages pathology - Histopathology workshop report

    Science.gov (United States)

    Bruno, D.W.; Nowak, B.; Elliott, D.G.

    2006-01-01

    Pathology occurring during reproduction and larval development represents an important part of the life cycle of fish, and the diseases that affect eggs and larvae often result in significant losses. However, mortality during this period is frequently ignored or poorly researched as the temptation is to replace the losses rather than investigate the causes. A histopathology workshop organised at the newly refurnished laboratory within the Danish Veterinary School was an opportunity to discuss the pathology of selected diseases associated with Reproductive and Early Life Stages Pathology. Several people also kindly provided reference slides.

  6. Inhaled cisplatin deposition and distribution in lymph nodes in stage II lung cancer patients.

    Science.gov (United States)

    Zarogoulidis, Paul; Darwiche, Kaid; Krauss, Leslie; Huang, Haidong; Zachariadis, George A; Katsavou, Anna; Hohenforst-Schmidt, Wolfgang; Papaiwannou, Antonis; Vogl, Thomas J; Freitag, Lutz; Stamatis, George; Zarogoulidis, Konstantinos

    2013-09-01

    Lung cancer therapies during the last decade have focused on targeting the genome of cancer cells, and novel routes for administering lung cancer therapies have been investigated for decades. Aerosol therapies for several systematic diseases and systemic infections were introduced into the market a decade ago. One of the main issues of aerosol therapies has been the ability to investigate the deposition of a drug compound throughout the systematic circulation and lymph node circulation. Until now, none of the published studies have efficiently shown the deposition of a chemotherapy pharmaceutical within the lymph node tissue. In our current work we present, for the first time, with the novel CytoViva(®) (AL, USA) technique, the deposition of cisplatin aerosol therapy in surgically resected stage II lymph nodes from lung cancer patients. Finally, we present the distribution of cisplatin in correlation with the cisplatin concentration in different lymph stations and comment on the possible mechanisms of distribution.

  7. Dosimetric comparison of 3DCRT versus IMRT in whole breast irradiation of early stage breast cancer

    Directory of Open Access Journals (Sweden)

    Mudasir Ashraf

    2014-08-01

    Full Text Available Purpose: The counseling regarding the treatment option is an important objective in the management of early stages breast cancer. In this study, we attempt to compare and analyze the dosimetric aspects of 3DRT over IMRT in the whole breast radiotherapy.Methods and Materials:  Both right and left sided computed tomography simulations of 14 women with early stage breast cancer were used for our retrospective study to compare the 3DCRT and IMRT. The dose prescribed was 50 Gy in 25 fractions to the whole breast PTV. The PTV was defined by adding unequal margins to the directional safety margin status of each lumpectomy cavity (i.e., medial, lateral, superior, inferior and deep margins measured from the tumor front after the examination of the surgical specimen: 2, 1.5, and 1 cm for resection margins < 1 cm, 1-2 cm, and > 2cm, respectively. And than modified so that it was no longer closer than 3mm to the skin surface and was no deep than the lung –chest interface. The prescribed dose delivered in 5 fractions per week schedule. Treatment plans were compared for target minimum dose, maximum dose, mean dose, conformity index, heterogeneity index and doses to organs at risk were compared and analysed.Results: The target coverage was achieved with 90% prescription to the 95% of the PTV. Conformity to the PTV was significantly higher with 3DCRT technique than IMRT. 3DCRT technique seems better in sparing critical organs parameters like lung V20 and Mean, heart, V25, Maximum, both lungs V20, Mean and Dose to the Normal Healthy tissue.Conclusion: We conclude from our study that treatment technique selection for whole Breast irradiation is an important factor in sparing the adjacent normal structures and in determining the associated risk. 3DCRT produces better conformity and heterogeneity indices of the target volume, also reduces dose to OARs the 3DCRT reduces the risk of radiation induced heart diseases

  8. CT screening for lung cancer brings forward early disease. The Randomised Danish Lung Cancer Screening Trial (DLCST)

    DEFF Research Database (Denmark)

    Saghir, Zaigham; Dirksen, Asger; Ashraf, Haseem

    2012-01-01

    BackgroundThe effects of low-dose CT screening on disease stage shift, mortality and overdiagnosis are unclear. Lung cancer findings and mortality rates are reported at the end of screening in the Danish Lung Cancer Screening Trial.Methods4104 men and women, healthy heavy smokers/former smokers...... increase and/or volume doubling time15 mm were referred for diagnostic workup. In the control group, lung cancers were diagnosed and treated outside the study by the usual clinical practice.ResultsParticipation rates were high in both groups (screening: 95.5%; control: 93.0%; p...

  9. An ex vivo model to induce early fibrosis-like changes in human precision-cut lung slices.

    Science.gov (United States)

    Alsafadi, Hani N; Staab-Weijnitz, Claudia A; Lehmann, Mareike; Lindner, Michael; Peschel, Britta; Königshoff, Melanie; Wagner, Darcy E

    2017-06-01

    Idiopathic pulmonary fibrosis (IPF) is a devastating chronic interstitial lung disease (ILD) characterized by lung tissue scarring and high morbidity. Lung epithelial injury, myofibroblast activation, and deranged repair are believed to be key processes involved in disease onset and progression, but the exact molecular mechanisms behind IPF remain unclear. Several drugs have been shown to slow disease progression, but treatments that halt or reverse IPF progression have not been identified. Ex vivo models of human lung have been proposed for drug discovery, one of which is precision-cut lung slices (PCLS). Although PCLS production from IPF explants is possible, IPF explants are rare and typically represent end-stage disease. Here we present a novel model of early fibrosis-like changes in human PCLS derived from patients without ILD/IPF using a combination of profibrotic growth factors and signaling molecules (transforming growth factor-β, tumor necrosis factor-α, platelet-derived growth factor-AB, and lysophosphatidic acid). Fibrotic-like changes of PCLS were qualitatively analyzed by histology and immunofluorescence and quantitatively by water-soluble tetrazolium-1, RT-qPCR, Western blot analysis, and ELISA. PCLS remained viable after 5 days of treatment, and fibrotic gene expression (FN1, SERPINE1, COL1A1, CTGF, MMP7, and ACTA2) increased as early as 24 h of treatment, with increases in protein levels at 48 h and increased deposition of extracellular matrix. Alveolar epithelium reprogramming was evident by decreases in surfactant protein C and loss of HOPX In summary, using human-derived PCLS, we established a novel ex vivo model that displays characteristics of early fibrosis and could be used to evaluate novel therapies and study early-stage IPF pathomechanisms. Copyright © 2017 the American Physiological Society.

  10. Early Life Origins of Lung Ageing: Early Life Exposures and Lung Function Decline in Adulthood in Two European Cohorts Aged 28-73 Years.

    Directory of Open Access Journals (Sweden)

    Julia Dratva

    Full Text Available Early life environment is essential for lung growth and maximally attained lung function. Whether early life exposures impact on lung function decline in adulthood, an indicator of lung ageing, has scarcely been studied.Spirometry data from two time points (follow-up time 9-11 years and information on early life exposures, health and life-style were available from 12862 persons aged 28-73 years participating in the European population-based cohorts SAPALDIA (n = 5705 and ECRHS (n = 7157. The associations of early life exposures with lung function (FEV1 decline were analysed using mixed-effects linear regression.Early life exposures were significantly associated with FEV1 decline, with estimates almost as large as personal smoking. FEV1 declined more rapidly among subjects born during the winter season (adjusted difference in FEV1/year of follow-up [95%CI] -2.04ml [-3.29;-0.80], of older mothers, (-1.82 ml [-3.14;-0.49] of smoking mothers (-1.82ml [-3.30;-0.34] or with younger siblings (-2.61ml [-3.85;-1.38]. Less rapid FEV1-decline was found in subjects who had attended daycare (3.98ml [2.78;5.18], and indicated in subjects with pets in childhood (0.97ml [-0.16;2.09]. High maternal age and maternal smoking appeared to potentiate effects of personal smoking. The effects were independent of asthma at any age.Early life factors predicted lung function decline decades later, suggesting that some mechanisms related lung ageing may be established early in life. Early life programming of susceptibility to adult insults could be a possible pathway that should be explored further.

  11. AUTOFLUORESCENCE BRONCHOSCOPY AS A MODALITY FOR EARLY DIAGNOSIS OF LUNG CANCER

    Directory of Open Access Journals (Sweden)

    KAW Nugraha

    2013-03-01

    Full Text Available Lung cancer has become a complicated health problem in the world. In 2005, approximately 172,500 people diagnosed with lung cancer in the United States. In Indonesia, lung cancer ranks fourth highest. Lung cancer is also the most common cause of death from cancer, so we need appropriate early detection modality to reduce the number of deaths from lung cancer. Compared with other modalities that currently available, Autofluorescence Bronchoscopy (AFB seems to have better accuracy in early diagnosis of lung cancer. AFB can be used to evaluate patients with high-grade sputum atypia, evaluating patients with suspected or had suffered from lung cancer, and have a role in follow-up of bronchial high-grade intraepithelial neoplasia.

  12. Upregulation of APE/ref-1 in recurrence stage I, non small cell lung cancer.

    Science.gov (United States)

    Kang, Min-Woong; Kang, Shin Kwang; Choi, Songyi; Lee, Choong Sik; Jeon, Byeong Hwa; Lim, Seung Pyung

    2012-02-01

    Lung cancer, the leading cause of cancer-related death, still lacks reliable biomarkers. Apurinic/apyrimidinic endonuclease 1/Ref-1 is a multifunctional protein involved in the base excision repair of DNA damaged by oxidative stress or alkylating compounds, as well as in the regulation of multiple transcription factors. To validate apurinic/apyrimidinic endonuclease 1/Ref-1 as a biomarker for prediction of lung cancer recurrence, we studied 42 patients who received curative resection and mediastinal lymph node dissection for stage I non-small-cell lung cancer. They were divided into 2 groups based on recurrence, and compared by immunohistochemistry staining of paraffin-embedded tissues and Western blot analysis. Immunohistochemical staining showed a significant difference between the cytoplasm and nucleus in patients who had a recurrence compared to those with nonrecurrent adenocarcinoma. In Western blot analysis, the recurrent adenocarcinoma group showed increased expression of apurinic/apyrimidinic endonuclease 1/Ref-1 in cytoplasm, nucleus, and in total. This indicates that apurinic/apyrimidinic endonuclease 1/Ref-1 is unregulated in recurrent stage I adenocarcinoma. For clinical application as a prognostic marker for non-small-cell lung cancer, further investigation into the role of apurinic/apyrimidinic endonuclease 1/Ref-1 in carcinogenesis is needed in an expanded prospective study.

  13. A patient with medulloblastoma in its early developmental stage.

    Science.gov (United States)

    Shinojima, Naoki; Nakamura, Hideo; Tasaki, Masayoshi; Kameno, Kouki; Anai, Shigeo; Iyama, Ken-ichi; Ando, Yukio; Seto, Hiroshi; Kuratsu, Jun-Ichi

    2014-12-01

    Medulloblastoma is the most frequent malignant brain tumor of the posterior fossa in children and is considered an embryonal tumor. It has been suggested that medulloblastomas be categorized into 4 distinct molecular subgroups- WNT (DKK1), SHH (SFRP1), Group 3 (NPR3), or Group 4 (KCNA1)-since each subgroup is distinct and there is no overlap. The authors report on a 13-year-old boy with medulloblastoma. He presented with sudden-onset nausea and vomiting due to intratumoral hemorrhage. The medulloblastoma was thought to be in an early developmental stage because the tumor volume was extremely small. Immunohistochemical analysis showed that the tumor was mainly composed of DKK1- and NPR3-positive areas. The individual areas of the tumor stained only for DKK1 or NPR3, with no overlap-that is, DKK1 and NPR3 expression were mutually exclusive. Samples obtained by laser microdissection of individual areas and subjected to mass spectrometry confirmed that the expression patterns of proteins were different. Fluorescence in situ hybridization for chromosome 6 showed there were 2 distinct types of cells that exhibited monosomy or disomy of chromosome 6. These results demonstrated that distinct subtypes of medulloblastoma may be present within a single tumor, an observation that has not been previously reported. Our findings in this case indicate that early-stage medulloblastoma may include more than 1 distinct subtype and hint at factors involved in the origin and development of medulloblastomas.

  14. Prospective study on stereotactic radiotherapy of limited-stage non-small-cell lung cancer

    DEFF Research Database (Denmark)

    Høyer, Morten; Roed, Henrik; Hansen, Anders Traberg

    2006-01-01

    Purpose: To test the effect of stereotactic body radiotherapy (SBRT) in       the treatment of medically inoperable patients with limited-stage       non-small-cell lung cancer (NSCLC) in a Phase II trial. Methods and       Materials: Forty patients with Stage I NSCLC were treated with SBRT...... resulted in a high       probability of local control and a promising survival rate. The toxicity       after SBRT of lung tumors was moderate. However, deterioration in       performance status, respiratory insufficiency, and other side effects were       observed...

  15. On Branching Processes and the Early Stages of the Spread of an Epidemic

    Institute of Scientific and Technical Information of China (English)

    Ahmed E; Yassen M T

    1998-01-01

    Branching process (BP) is used to model the early stages of the spread of a sexually transmitted disease. The early stages of AIDS spread which is transmitted both homosexually and heterosexually are studied as a BP.

  16. The effects of blocking angiotensin receptors on early stages of diabetic nephropathy

    Directory of Open Access Journals (Sweden)

    Alaleh Gheissari

    2012-01-01

    Conclusion: Angiotensin receptor blockers may reduce VCAM-1 and microalbuminuria and may increase NO levels in early stages of DN. Thus administration of ARBs might be considered even in early stages of DN.

  17. The surgical management of early-stage cervical cancer.

    Science.gov (United States)

    Salicrú, Sabina R; de la Torre, Javier F V; Gil-Moreno, Antonio

    2013-08-01

    The main objective is to update the literature data in the last year which may support a surgical approach to early cervical cancer [ECC; Stage International Federation of Gynecology and Obstetrics (FIGO) IA-IB1-IIA1]. Radical hysterectomy remains the gold standard by most international guidelines because surgical treatment has hardly changed in recent decades, except for stage IA1. Trends in clinical research in the past 12-18 months involve minimal invasive surgery (with laparoscopic surgery or robotic-assisted surgery), fertility preservation (in the initial stages and in the absence of bad prognostic factors), nerve-sparing and sentinel node techniques. Some institutions have published studies in specific groups such as older, obese or pregnant women. There is a growing trend to practice less aggressive surgery in order to preserve fertility in young women and avoid an excess of treatment in some selected patients. Therefore, nerve-sparing techniques can help to improve the quality of life. More studies are needed to demonstrate oncologic results of the sentinel node technique. Laparoscopic and robotic-assisted surgery can substitute open surgical treatment.

  18. Genetic Circuit for the Early Warning of Lung Cancer using iBioSim

    Directory of Open Access Journals (Sweden)

    Wang Xiang

    2016-01-01

    Full Text Available With the development of molecular biology and gene-engineering technology, gene diagnosis has been an emerging approach for modern life sciences. Biological marker, recognized as the hot topic in the molecular and gene fields, has important values in early diagnosis, malignant tumour stage, treatment and therapeutic efficacy evaluation. The design of markers detection genetic circuit system for lung cancer is presented as a new method to provide basis for early warning and therapy. The system consists of three single-marker detection circuits and an integration circuit. The single-marker detection circuit provides an instantaneous low level when target marker’s concentration reaches the threshold. The integration circuit uses gene and gate to complete the output data fusion from single-marker detection circuit through logic operations to finish the combined detection. All the structure is modelled and analyzed by iBioSim through the biochemical reactions of different gene circuits. The experimental result indicates that the whole lung cancer detection system can realize joint detection of tumor markers with good stability and sensitivity.

  19. Conservative surgery and radiation for early-stage breast cancer.

    Science.gov (United States)

    Fowble, B L; Orel, S G; Jardines, L

    1993-07-01

    In selected patients with early-stage breast cancer, conservative surgery and radiation represent an alternative equal to mastectomy in terms of local recurrence, distant metastasis, survival, and long-term complications. Patients with early-stage breast cancer who are candidates for conservative surgery and radiation include those whose primary tumor is less than 4 to 5 cm in size without evidence of gross multicentricity or diffuse microcalcifications. Patients with an extensive intraductal component may be appropriate candidates provided that margins of resection are negative. Young age is not a contraindication to the conservative treatment. A preexisting history of collagen vascular disease or prior mantle irradiation for Hodgkin's or non-Hodgkin's lymphoma represents a contraindication to conservative surgery and radiation because of the potential for severe complications. An additional contraindication is the pregnant woman in whom delivery cannot be accomplished before the initiation of radiation. Mammography is essential in the pretreatment evaluation and posttreatment follow-up of the conservatively treated patient. The goal of the pretreatment mammogram is to assess the extent of disease in the ipsilateral breast as well as to evaluate the contralateral breast. In patients who present with microcalcifications, a postbiopsy mammogram before radiation is essential to document complete removal of all malignant-appearing microcalcifications. Mammography is an essential part of the follow-up program in order to detect a recurrence in the treated breast as well as a cancer in the contralateral breast cancer. The optimal interval for follow-up mammography has not been determined, although programs employing mammography on a yearly basis after treatment have been associated with the detection of early recurrences and excellent survival after salvage mastectomy for these recurrences.

  20. 30 Gy or 34 Gy? Comparing 2 Single-Fraction SBRT Dose Schedules for Stage I Medically Inoperable Non-Small Cell Lung Cancer

    Energy Technology Data Exchange (ETDEWEB)

    Videtic, Gregory M.M., E-mail: videtig@ccf.org; Stephans, Kevin L.; Woody, Neil M.; Reddy, Chandana A.; Zhuang, Tingliang; Magnelli, Anthony; Djemil, Toufik

    2014-09-01

    Purpose: To review outcomes of 2 single-fraction lung stereotactic body radiation therapy (SBRT) schedules used for medically inoperable early stage lung cancer. Methods and Materials: Patients in our institution have been treated on and off protocols using single-fraction SBRT (30 Gy and 34 Gy, respectively). All patients had node-negative lung cancer measuring ≤5 cm and lying ≥2 cm beyond the trachea-bronchial tree and were treated on a Novalis/BrainLAB system with the ExactTrac positioning system for daily image guidance. Results: For the interval from 2009 to 2012, 80 patients with 82 lesions were treated with single-fraction lung SBRT. Fifty-five patients (69%) and 25 patients (31%) received 30 Gy and 34 Gy, respectively. In a comparison of 30 Gy and 34 Gy cohorts, patient and tumor characteristics were balanced and median follow-up in months was 18.7 and 17.8, respectively. The average heterogeneity-corrected mean doses to the target were 33.75 Gy and 37.94 Gy for the 30-Gy and 34-Gy prescriptions, respectively. Comparing 30-Gy and 34-Gy cohorts, 92.7% and 84.0% of patients, respectively, experienced no toxicity (P was not significant), and had neither grade 3 nor higher toxicities. For the 30-Gy and 34-Gy patients, rates of 1-year local failure, overall survival, and lung cancer-specific mortality were 2.0% versus 13.8%, 75.0% versus 64.0%, and 2. 1% versus 16.0%, respectively (P values for differences were not significant). Conclusions: This is the largest single-fraction lung SBRT series yet reported. and it confirms the safety, efficacy, and minimal toxicity of this schedule for inoperable early stage lung cancer.

  1. Survival after Pneumonectomy for Stage III Non-small Cell Lung Cancer

    Directory of Open Access Journals (Sweden)

    Sibu P. Saha

    2014-01-01

    Full Text Available Objectives: Stage III non-small cell lung cancer (NSCLC has a poor prognosis. Reports suggest that five-year survival after current treatment is between 14 to 24 percent. The purpose of this retrospective study was to investigate the morbidity and mortality of patients diagnosed with stage III NSCLC and treated with pneumonectomy at the University of Kentucky Medical Center in Lexington, KY. Methods: We reviewed the medical record and tumor registry follow-up data on 100 consecutive patients who underwent pneumonectomy for lung cancer at the University of Kentucky. Results: We identified thirty-six patients in stage III who underwent pneumonectomy. Ten patients had surgery only, eight patients received adjuvant chemotherapy, and eighteen patients received neoadjuvant therapy. There was one surgical death in this series. Mean follow-up was 2.9 years. One-, three-, and five-year survival was 66%, 38%, and 38%, respectively. Five-year survival for the group with adjuvant therapy was 60%. Conclusion: Most lung cancer patients present with advanced disease and the prognosis remains poor. Our experience indicates resection offers an above average chance of long-term survival when supplemented with neoadjuvant and/or adjuvant therapy.

  2. The reticular network contributes to the staging of idiopathic lung fibrosis

    Directory of Open Access Journals (Sweden)

    Djeska Irina Stoia

    2013-01-01

    Full Text Available The aspect of reticular fibers is not considered in the current classifications of lung fibrosis. The aim of our study was to evaluate the distribution and the architecture of the reticular fibers for potential use as a tissue marker of fibrosis severity. We included in our study 25 pulmonary samples obtained by video-assisted thoracoscopy surgery (VATS from a number of 20 cases. The cases were subdivided according to four criteria into: degree II, III and IV. We noticed no significant changes in the reticular network from interalveolar septa to the cases scored with 0, an accumulation of reticular fibers in the interalveolar septa (stage II, the condensation and thick bundles with network disorganization in all areas affected by fibrosis (stage III, partial to full depletion of reticular fibers (stage IV. Depletion of reticular fibers was constantly associated with advanced fibrosis stages.

  3. Early stage health technology assessment (HTA) of biomedical devices: the MATCH experience

    OpenAIRE

    Pecchia, Leandro; Craven, Michael P

    2013-01-01

    Early stage Health Technology Assessment (HTA) of biomedical devices requires different methods than those usually employed for pharmaceuticals. This paper reviews widely used methods for HTA, discusses their limits for early stage evaluation of biomedical devices and presents two methods for early stage HTA being developed in the Multidisciplinary Assessment of Technology Centre for Healthcare (MATCH) project: Analytic Hierarchy Process (AHP) to elicit user needs; and early stage economic ev...

  4. Early stage health technology assessment (HTA) of biomedical devices: the MATCH experience

    OpenAIRE

    Pecchia, Leandro; Craven, Michael P

    2013-01-01

    Early stage Health Technology Assessment (HTA) of biomedical devices requires different methods than those usually employed for pharmaceuticals. This paper reviews widely used methods for HTA, discusses their limits for early stage evaluation of biomedical devices and presents two methods for early stage HTA being developed in the Multidisciplinary Assessment of Technology Centre for Healthcare (MATCH) project: Analytic Hierarchy Process (AHP) to elicit user needs; and early stage economic e...

  5. Video-assisted thoracoscopic lobectomy is associated with greater recurrence-free survival than stereotactic body radiotherapy for clinical stage I lung cancer.

    Science.gov (United States)

    Cornwell, Lorraine D; Echeverria, Alfredo E; Samuelian, Jason; Mayor, Jessica; Casal, Roberto F; Bakaeen, Faisal G; Omer, Shuab; Preventza, Ourania; Mai, Weiyuan; Chen, George; Simpson, Katherine H; Moghanaki, Drew; Zhu, Angela W

    2017-08-16

    Stereotactic body radiotherapy is the standard treatment for medically inoperable early-stage non-small cell lung cancer. Recent data suggest that in operable patients, stereotactic body radiotherapy produces outcomes comparable to those of surgical resection. In veterans with early non-small cell lung cancer, we compared the outcomes of stereotactic body radiotherapy and video-assisted thoracoscopic lobectomy. We retrospectively reviewed data from 183 patients (94.0% male) with clinical stage I non-small cell lung cancer who underwent stereotactic body radiotherapy (n = 56) or video-assisted thoracoscopic lobectomy (n = 127) from 2009 to 2014. Propensity matching was used to produce more comparable groups. Primary end points were tumor control and overall, recurrence-free, and lung-cancer-specific survival, as estimated by Kaplan-Meier actuarial analysis. Multivariable analysis was used to identify independent predictors. In the overall cohort, the patients who received stereotactic body radiotherapy were older than the patients who received video-assisted thoracoscopic lobectomy (median age, 79.5 vs 64 years) and had more comorbidities. In the 37 propensity-matched pairs, the 3-year actuarial tumor control rate was 54.3% after stereotactic body radiotherapy and 90.6% after video-assisted thoracoscopic lobectomy (P = .0038). Actuarial lung cancer-specific 3-year survival was 78.1% (stereotactic body radiotherapy) versus 93.6% (video-assisted thoracoscopic lobectomy) (P = .055). One-year overall, 3-year overall, and 3-year recurrence-free survivals were 89.2%, 52.9%, and 38.5% after stereotactic body radiotherapy and 94.6%, 85.7%, and 82.8% after video-assisted thoracoscopic lobectomy (P recurrence and poorer survival. In veteran patients with early-stage non-small cell lung cancer, video-assisted thoracoscopic lobectomy resulted in better disease control and survival than stereotactic body radiotherapy. Although prior reports suggest that stereotactic

  6. The IASLC Lung Cancer Staging Project: External Validation of the Revision of the TNM Stage Groupings in the Eighth Edition of the TNM Classification of Lung Cancer.

    Science.gov (United States)

    Chansky, Kari; Detterbeck, Frank C; Nicholson, Andrew G; Rusch, Valerie W; Vallières, Eric; Groome, Patti; Kennedy, Catherine; Krasnik, Mark; Peake, Michael; Shemanski, Lynn; Bolejack, Vanessa; Crowley, John J; Asamura, Hisao; Rami-Porta, Ramón

    2017-07-01

    Revisions to the TNM stage classifications for lung cancer, informed by the international database (N = 94,708) of the International Association for the Study of Lung Cancer (IASLC) Staging and Prognostic Factors Committee, need external validation. The objective was to externally validate the revisions by using the National Cancer Data Base (NCDB) of the American College of Surgeons. Cases presenting from 2000 through 2012 were drawn from the NCDB and reclassified according to the eighth edition stage classification. Clinically and pathologically staged subsets of NSCLC were analyzed separately. The T, N, and overall TNM classifications were evaluated according to clinical, pathologic, and "best" stage (N = 780,294). Multivariate analyses were carried out to adjust for various confounding factors. A combined analysis of the NSCLC cases from both databases was performed to explore differences in overall survival prognosis between the two databases. The databases differed in terms of key factors related to data source. Survival was greater in the IASLC database for all stage categories. However, the eighth edition TNM stage classification system demonstrated consistent ability to discriminate TNM categories and stage groups for clinical and pathologic stage. The IASLC revisions made for the eighth edition of lung cancer staging are validated by this analysis of the NCDB database by the ordering, statistical differences, and homogeneity within stage groups and by the consistency within analyses of specific cohorts. Copyright © 2017 International Association for the Study of Lung Cancer. Published by Elsevier Inc. All rights reserved.

  7. Single-port video-assisted thoracic surgery for early lung cancer: initial experience in Japan

    Science.gov (United States)

    Takeuchi, Shingo; Usuda, Jitsuo

    2016-01-01

    Background Single-port video-assisted thoracic surgery (SPVATS) emerged several years ago as a new, minimally invasive surgery for diseases in the field of respiratory surgery, and is increasingly becoming a subject of interest for some thoracic surgeons in Europe and Asia. However, the adoption rate of this procedure in the United States and Japan remains low. We herein reviewed our experience of SPVATS for early lung cancer in our center, and evaluated the safety and minimal invasiveness of this technique. Methods We retrospectively analyzed patients who had undergone SPVATS for pathological stage I lung cancer in Nippon Medical School Chiba Hokusoh Hospital between September 2012 and October 2015. In SPVATS, an approximately 4-cm incision was made at the 4th or 5th intercostal space between the anterior and posterior axillary lines. A rib spreader was not used at the incision site, and surgical manipulation was performed very carefully in order to avoid contact between surgical instruments and the intercostal nerves. The same surgeon performed surgery on all patients, and analyzed laboratory data before and after surgery. Results Eighty-four patients underwent anatomical lung resection for postoperative pathological stage I lung cancer. The mean wound length was 4.2 cm. Eighty-four patients underwent lobectomy and segmentectomy, respectively. The mean preoperative forced expiratory volume in 1 second (FEV1%) was 1.85%±0.36%. Our patients consisted of 49 men (58.3%) and 35 women (41.7%), with 64, 18, 1, and 1 having adenocarcinoma, squamous cell carcinoma, adenosquamous carcinoma, and small-cell lung cancer, respectively. The mean operative time was 175±21 min, operative blood loss 92±18 mL, and duration of drain placement 1.9±0.6 days. The duration of the postoperative hospital stay was 7.1±1.7 days, numeric rating scale (NRS) 1 week after surgery 2.8±0.6, and occurrence rate of allodynia 1 month after surgery 10.7%. No patient developed serious

  8. A prospective cohort study among new Chinese coal miners: the early pattern of lung function change

    Energy Technology Data Exchange (ETDEWEB)

    Wang, M.L.; Wu, Z.E.; Du, Q.G.; Petsonk, E.L.; Peng, K.L.; Li, Y.D.; Li, S.K.; Han, G.H.; Atffield, M.D. [NIOSH, Morgantown, WV (United States)

    2005-11-01

    The early pattern of lung function changes in 317 newly hired Chinese underground coal miners was compared to 132 referents. This three year prospective cohort study involved a pre-employment and 15 follow up health surveys, including a questionnaire and spirometry tests. Twice a month, total and respirable dust area sampling was done. The authors used a two stage analysis and a linear mixed effects model approach to analyse the longitudinal spirometry data, and to investigate the changes in forced expiratory volume in 1 second (FEV1) over time, controlling for age, height, pack years of smoking, mean respirable dust concentration, the room temperature during testing, and the group x time interaction terms. Results: FEV1 change over time in new miners is non-linear. New miners experience initial rapid FEV1 declines, primarily during the first year of mining, little change during the second year, and partial recovery during the third year. Both linear and quadratic time trends in FEV1 change are highly significant. Smoking miners lost more FEV1 than non-smokers. Referents, all age less than 20 years, showed continued lung growth, whereas the miners who were under age 20 exhibited a decline in FEV1. Conclusion: Dust and smoking affect lung function in young, newly hired Chinese coal miners. FEV1 change over the first three years of employment is non-linear. The findings have implications for both methods and interpretation of medical screening in coal mining and other dusty work: during the first several years of employment more frequent testing may be desirable, and caution is required in interpreting early FEV1 declines.

  9. Effect of Shengmai injection on extravascular lung water and related factors at early fluid resuscitation stage of septic shock%生脉注射液对脓毒性休克早期液体复苏血管外肺水及相关因素的影响

    Institute of Scientific and Technical Information of China (English)

    赵滋苗; 陆军; 丁月平; 马丹女

    2013-01-01

    Objective To investigate the effect of Shengmai injection on extravacular lung water and related factors at the early fluid resuscitation stage of septic shock. Methods Thirty-eight patients with septic shock were randomly assigned to the treatment group(n=20) and the control group(n=18). Patients received basic treatment combined with fluid resuscitation until the central venous pressure (CVP) reached ≥8mmHg. Patients in treatment group additional y received Shengmai injection. The hemodynamic indices, including extra-vascular lung water index(EVLWI), CVP, cardiac index(CI), systemic vascular resistance index (SVRI), global end-diastolic volume index (GEDVI), intrathoracic blood volume index (ITBVI) and oxygenation index (PaO2/FiO2) were monitored at baseline(T0), 6(T6), 12(T12) and 24h(T24) after ending fluid resuscitation, and the 28d mortality was also observed. Results Compared with the control group, CI, GEDVI and PaO2/FiO2 increased significantly at T6,T12 and T24, while EVLWI and 28d mortality was decreased in the treatment group ( P0.05). Conclusion On the basis of the fluid resuscitation and basic treatment Shengmai injection can further improve CI, GEDVI, ITBVI and PaO2/FiO2, decrease EVLWI and 28-d mortality, but showed no effect on CVP or SVRI at the early fluid resuscitation stage of septic shock.%  目的探讨生脉注射液对脓毒性休克早期液体复苏患者血管外肺水及相关因素的影响。方法选取38例感染性休克患者(生脉组20例,对照组18例),两组患者均以液体复苏至患者中心静脉压(CVP)≥8mmHg作为复苏终点,并施以内科基础治疗。生脉组同时加用生脉注射液80ml,用5%葡萄糖注射液250ml稀释,1次/d。通过脉搏轮廓曲线连续心排血量监测技术监测两组患者液体复苏结束后即刻(T0)、6h(T6)、12h(T12)、24h(T24)的血管外肺水指数(EVLWI)、CVP、心排血指数(CI)、外周血管阻力指数(SVRI)、

  10. [Guidelines for the early diagnosis of lung cancer for primary care physicians].

    Science.gov (United States)

    2016-01-01

    Lung cancer is a serious/medical and social problem. It belongs to the most common cancers. In the past decades, lung cancer has steadily held a leading place in the structure of cancer morbidity and mortality in our country and in the majority of European countries. Cigarette smoking remains to be the major if not only risk factor for lung cancer. Many attempts were previously made to set up systems for the early (timely) lung cancerdetection in risk groups through cytological and radiological examinations. Prophylactic fluorography and X-ray study have long been an important screening procedure in Russia and foreign countries. Recently this procedure has transformed into digital lung radiography. However, there have been no conclusive proofs for its efficiency in the early detection of lung cancer for a few decades. In the past decade, large-scale prospective randomized trials of low-dose computed tomography (CT) have been performed to screen lung cancer. These have shown that this technology can potentially reduce mortality from this disease. This encouraging result has caused a substantial change in the tactics of examining people at high risk for lung cancer. CT has fully replaced linear tomography and all others special X-ray procedures in the verified diagnosis of lung cancer. The indications for pre-examination CT have been considerably expanded in patients with X-ray detected pathology. The tactics for estimating the small lung tissue foci found at CT has been changed. Availability of CT, clear clinical indications for the study, and observance of the standard procedure have become important elements of the entire system for the early identification of lung cancer. These clinical recommendations largely deal just with organizational and methodological issues. The authors hope that the recommendations will serve as a guide for primary care physicians (therapists, pulmonologists,and radiologists) in the early diagnosis of lung cancer and in the optimization

  11. Circulating MicroRNAs as Non-Invasive Biomarkers for Early Detection of Non-Small-Cell Lung Cancer.

    Directory of Open Access Journals (Sweden)

    Magdalena B Wozniak

    Full Text Available Detection of lung cancer at an early stage by sensitive screening tests could be an important strategy to improving prognosis. Our objective was to identify a panel of circulating microRNAs in plasma that will contribute to early detection of lung cancer.Plasma samples from 100 early stage (I to IIIA non-small-cell lung cancer (NSCLC patients and 100 non-cancer controls were screened for 754 circulating microRNAs via qRT-PCR, using TaqMan MicroRNA Arrays. Logistic regression with a lasso penalty was used to select a panel of microRNAs that discriminate between cases and controls. Internal validation of model discrimination was conducted by calculating the bootstrap optimism-corrected AUC for the selected model.We identified a panel of 24 microRNAs with optimum classification performance. The combination of these 24 microRNAs alone could discriminate lung cancer cases from non-cancer controls with an AUC of 0.92 (95% CI: 0.87-0.95. This classification improved to an AUC of 0.94 (95% CI: 0.90-0.97 following addition of sex, age and smoking status to the model. Internal validation of the model suggests that the discriminatory power of the panel will be high when applied to independent samples with a corrected AUC of 0.78 for the 24-miRNA panel alone.Our 24-microRNA predictor improves lung cancer prediction beyond that of known risk factors.

  12. Five-Year Survival Among Stage IIIA Lung Cancer Patients Receiving Two Different Treatment Modalities.

    Science.gov (United States)

    Bilfinger, Thomas; Keresztes, Roger; Albano, Denise; Nemesure, Barbara

    2016-07-21

    BACKGROUND Five-year survival rates among stage IIIA lung cancer patients range between 2% and 15%, and there is currently no consensus regarding optimal treatment approaches for these patients. The current investigation evaluated survival outcomes among stage IIIA lung cancer patients receiving 2 different treatment modalities, neoadjuvant chemotherapy followed by resection versus chemoradiation alone. MATERIAL AND METHODS This retrospective study is based on 127 patients attending the Lung Cancer Evaluation Center at Stony Brook Cancer Center between 2002 and 2014. Patients were treated either with neoadjuvant chemotherapy followed by resection or a regimen of chemoradiation alone. Kaplan-Meier curves were used to compare survival outcomes between groups and Cox proportional hazard models were used to evaluate treatment effects on survival, while adjusting for possible confounders. RESULTS Approximately one-fourth (n=33) of patients received neoadjuvant chemotherapy followed by surgery, whereas 94 patients received definitive chemoradiation. Patients in the surgical group were found to be significantly younger than those receiving chemoradiation alone (60.1 vs. 67.9 years, respectively; p=0.001). Five-year survival among patients receiving preoperative chemotherapy followed by resection was significantly higher than that among patients receiving chemoradiation alone (63% vs. 19%, respectively; p<0.001), whereas the hazard ratio (HR) was 3-4 times greater in the latter group (HR=3.77, 95% confidence interval=1.87, 7.61). CONCLUSIONS Findings from this study indicate that preoperative chemotherapy followed by resection can improve survival outcomes for stage IIIA lung cancer patients compared with chemoradiation alone. The results reflect a select surgical group of patients; thus, the data highlight the need to develop new therapies that may result in more patients being viable surgical candidates.

  13. Axillary radiotherapy in conservative surgery for early-stage breast cancer (stage I and II).

    Science.gov (United States)

    García Novoa, Alejandra; Acea Nebril, Benigno; Díaz, Inma; Builes Ramírez, Sergio; Varela, Cristina; Cereijo, Carmen; Mosquera Oses, Joaquín; López Calviño, Beatriz; Seoane Pillado, María Teresa

    2016-01-01

    Several clinical studies analyze axillary treatment in women with early-stage breast cancer because of changes in the indication for axillary lymph node dissection. The aim of the study is to analyze the impact of axillary radiotherapy in disease-free and overall survival in women with early breast cancer treated with lumpectomy. Retrospective study in women with initial stages of breast carcinoma treated by lumpectomy. A comparative analysis of high-risk women with axillary lymph node involvement who received axillary radiotherapy with the group of women with low risk without radiotherapy was performed. Logistic regression was used to determine factors influencing survival and lymphedema onset. A total of 541 women were included in the study: 384 patients (71%) without axillary lymph node involvement and 157 women (29%) with 1-3 axillary lymph node involvement. Patients with axillary radiotherapy had a higher number of metastatic lymph node compared to non-irradiated (1.6±0.7 vs. 1.4±0.6, P=.02). The group of women with axillary lymph node involvement and radiotherapy showed an overall and disease-free survival at 10 years similar to that obtained in patients without irradiation (89.7% and 77.2%, respectively). 3 lymph nodes involved multiplied by more than 7 times the risk of death (HR=7.20; 95% CI: 1.36 to 38.12). The multivariate analysis showed axillary lymph node dissection as the only variable associated with the development of lymphedema. The incidence of axillary relapse on stage I and II breast cancer is rare. In these patients axillary radiotherapy does not improve overall survival, but contributes to regional control in those patients with risk factors. Copyright © 2016 AEC. Publicado por Elsevier España, S.L.U. All rights reserved.

  14. Early Stage Disease Diagnosis System Using Human Nail Image Processing

    Directory of Open Access Journals (Sweden)

    Trupti S. Indi

    2016-07-01

    Full Text Available Human’s hand nail is analyzed to identify many diseases at early stage of diagnosis. Study of person hand nail color helps in identification of particular disease in healthcare domain. The proposed system guides in such scenario to take decision in disease diagnosis. The input to the proposed system is person nail image. The system will process an image of nail and extract features of nail which is used for disease diagnosis. Human nail consist of various features, out of which proposed system uses nail color changes for disease diagnosis. Here, first training set data is prepared using Weka tool from nail images of patients of specific diseases. A feature extracted from input nail image is compared with the training data set to get result. In this experiment we found that using color feature of nail image average 65% results are correctly matched with training set data during three tests conducted.

  15. Socio-economic inequalities in stage at diagnosis, and in time intervals on the lung cancer pathway from first symptom to treatment: systematic review and meta-analysis.

    Science.gov (United States)

    Forrest, Lynne F; Sowden, Sarah; Rubin, Greg; White, Martin; Adams, Jean

    2017-05-01

    Cancer diagnosis at an early stage increases the chance of curative treatment and of survival. It has been suggested that delays on the pathway from first symptom to diagnosis and treatment may be socio-economically patterned, and contribute to socio-economic differences in receipt of treatment and in cancer survival. This review aimed to assess the published evidence for socio-economic inequalities in stage at diagnosis of lung cancer, and in the length of time spent on the lung cancer pathway. MEDLINE, EMBASE and CINAHL databases were searched to locate cohort studies of adults with a primary diagnosis of lung cancer, where the outcome was stage at diagnosis or the length of time spent within an interval on the care pathway, or a suitable proxy measure, analysed according to a measure of socio-economic position. Meta-analysis was undertaken when there were studies available with suitable data. Of the 461 records screened, 39 papers were included in the review (20 from the UK) and seven in a final meta-analysis for stage at diagnosis. There was no evidence of socio-economic inequalities in late stage at diagnosis in the most, compared with the least, deprived group (OR=1.04, 95% CI=0.92 to 1.19). No socio-economic inequalities in the patient interval or in time from diagnosis to treatment were found. Socio-economic inequalities in stage at diagnosis are thought to be an important explanatory factor for survival inequalities in cancer. However, socio-economic inequalities in stage at diagnosis were not found in a meta-analysis for lung cancer. CRD42014007145. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/.

  16. Infrared coagulation versus rubber band ligation in early stage hemorrhoids

    Directory of Open Access Journals (Sweden)

    P.J. Gupta

    2003-10-01

    Full Text Available The ideal therapy for early stages of hemorrhoids is always debated. Some are more effective but are more painful, others are less painful but their efficacy is also lower. Thus, comfort or efficacy is a major concern. In the present randomized study, a comparison is made between infrared coagulation and rubber band ligation in terms of effectiveness and discomfort. One hundred patients with second degree bleeding piles were randomized prospectively to either rubber band ligation (N = 54 or infrared coagulation (N = 46. Parameters measured included postoperative discomfort and pain, time to return to work, relief in incidence of bleeding, and recurrence rate. The mean age was 38 years (range 19-68 years. The mean duration of disease was 17.5 months (range 12 to 34 months. The number of male patients was double that of females. Postoperative pain during the first week was more intense in the band ligation group (2-5 vs 0-3 on a visual analogue scale. Post-defecation pain was more intense with band ligation and so was rectal tenesmus (P = 0.0059. The patients in the infrared coagulation group resumed their duties earlier (2 vs 4 days, P = 0.03, but also had a higher recurrence or failure rate (P = 0.03. Thus, we conclude that band ligation, although more effective in controlling symptoms and obliterating hemorrhoids, is associated with more pain and discomfort to the patient. As infrared coagulation can be conveniently repeated in case of recurrence, it could be considered to be a suitable alternative office procedure for the treatment of early stage hemorrhoids.

  17. Locomotor function in the early stage of Parkinson's disease.

    Science.gov (United States)

    Carpinella, Ilaria; Crenna, Paolo; Calabrese, Elena; Rabuffetti, Marco; Mazzoleni, Paolo; Nemni, Raffaello; Ferrarin, Maurizio

    2007-12-01

    The cardinal motor symptoms of Parkinson's disease (PD) have been widely investigated with particular reference to abnormalities of steady-state walking. The great majority of studies, however are related to severe forms of PD patients (phases > = 3 of Hoehn and Yahr scale), where locomotor abnormalities are clearly manifested. Goal of the present study was to quantitatively describe locomotor symptoms in subjects with mild PD. Accordingly, a multitask protocol involving instrumental analysis of steady-state linear walking, initiation of gait, and turning while walking was applied to a group of patients with idiopathic PD in their early clinical stage (phases 1 and 2 of Hoehn and Yahr scale), as well as in age-matched elderly controls. Kinematic, kinetic, and myoelectric measures were obtained by optoelectronic motion analysis, force platform, and telemetric electromyography. Results in PD patients showed a tendency to bradykinetic gait, with reduction of walking speed and cadence. Impairments of gait initiation consisted in reduction of the backward shift of the center of pressure (CoP) and prolongation of the stepping phase. Alterations of the turning task were more consistent and included delayed reorientation of the head toward the new direction, altered head-upper trunk rotational strategy, and adoption of a greater number of steps to complete the turning. It is concluded that patients in the early stage of PD reveal mild alterations of steady-state linear walking and more significant anomalies in the transitional conditions, especially during changes in the travel direction. Quantitative analysis of nonstationary locomotor tasks might be a potentially useful starting point for further studies on the pathophysiology of PD.

  18. Paranasal Manifestations of Early Stage Chronic Lymphocytic Leukemia

    Directory of Open Access Journals (Sweden)

    Ceren Günel

    2015-04-01

    Full Text Available OBJECTIVE: Chronic lymphocytic leukemia (CLL is the most common adult leukemia. A few studies have been reported about the relationship between CLL and paranasal sinuses. We aimed to investigate the paranasal manifestations of CLL and to determine the expression of nuclear factor-ĸB (NF-kB and tumor necrosis factor (TNF-α in the nasal mucosa in patients with CLL. MATERIALS AND METHODS: This study was a clinical trial that involved 40 patients. Group CLL (n=20 consisted of patients with early-stage CLL who were followed-up at the hematology clinic and who did not receive any treatment. The control group (n=20 consisted of patients who had undergone concha surgery because of nasal obstruction. Paranasal sinus computer tomography scans of all patients were taken, they were scored on the basis of the Lund–Mackay system, and sinusitis findings were recorded. The biopsy material taken from the inferior concha head of all patients was immunohistochemically stained with primary antibodies against NF-kB and TNF-α. RESULTS: There were no statistically significant differences between the two groups with respect to NF-κB (p=0.716 and TNF-α staining scores (p=1.000. The Lund–Mackay scores were significantly higher in the CLL group than in the control group (p=0.004. Fourteen patients had sinusitis at different locations, while the most common diagnosis was maxillary sinusitis (n=8 in the CLL group. CONCLUSION: This study showed that patients with early-stage CLL tend to have rhinosinusitis. However, NF-kB and TNF-α may not have a role in the inflammatory process involving the paranasal sinuses in patients with CLL.

  19. Heart-lung transplantation for end-stage heart disease with Eisenmenger's syndrome: report of two cases

    Institute of Scientific and Technical Information of China (English)

    ZHANG Xi; XIONG Mai; WANG Zhi-ping; YIN Sheng-li; WU Zhong-kai; XU Ying-qi; TANG Bai-yun; YAO Jian-ping; CHEN Guang-xian

    2009-01-01

    @@ From September 2006 to January 2007, 2 patients with end-staged heart and lung disease (congenital disease, Eisenmenger's syndrome, severe pulmonary artery hypertension and heart failure) underwent heart and lung transplantation (HLT) at the First Affiliated Hospital of Sun Yat-sen University, Guangzhou, China.

  20. Longitudinal trajectories of awareness in early-stage dementia.

    Science.gov (United States)

    Clare, Linda; Nelis, Sharon M; Martyr, Anthony; Whitaker, Christopher J; Marková, Ivana S; Roth, Ilona; Woods, Robert T; Morris, Robin G

    2012-01-01

    Although it is often assumed that awareness decreases as dementia severity increases, there is limited evidence regarding changes in awareness over time. We examined awareness in 101 individuals with early-stage dementia (PwD) and their carers; 66 were reassessed after 12 months and 51 were seen again at 20 months. Awareness was assessed in relation to memory, everyday activities, and socio-emotional functioning using discrepancies between PwD and carer ratings on parallel questionnaires. PwD completed neuropsychological tests and measures of mood and quality of life. Carers completed measures of mood and stress. At initial assessment, discrepancies were greatest for activities of daily living, moderate for memory, and least pronounced for socio-emotional functioning. Discrepancy scores did not change over time. PwD self-ratings indicated perceived poorer functioning in everyday activities over time, but no change for memory and socio-emotional functioning. Carer ratings indicated perceived decline in everyday activities and socio-emotional functioning, but no change for memory. PwD declined in neuropsychological functioning, but self-ratings of depression, anxiety, and quality of life remained stable over time. Carer mood and stress levels also remained stable. At least in the earlier stages of dementia, it should not be assumed that awareness will inevitably decrease as dementia progresses.

  1. Chinese consensus on early diagnosis of primary lung cancer (2014 version).

    Science.gov (United States)

    Hu, Jie; Qian, Gui-Sheng; Bai, Chun-Xue

    2015-09-01

    The incidence and mortality of lung cancer in China have rapidly increased. Lung cancer is the leading cause of cancer death in China, possibly because of the inadequate early diagnosis of lung cancer. Reaching a consensus on early diagnostic strategies for lung cancer in China is an unmet needed. Recently, much progress has been made in lung cancer diagnosis, such as screening in high-risk populations, the application of novel imaging technologies, and the use of minimally invasive techniques for diagnosis. However, systemic reviews of disease history, risk assessment, and patients' willingness to undergo invasive diagnostic procedures also need to be considered. A diagnostic strategy for lung cancer should be proposed and developed by a multidisciplinary group. A comprehensive evaluation of patient factors and clinical findings should be completed before treatment.

  2. Phase II proof-of-concept study of pazopanib monotherapy in treatment-naive patients with stage I/II resectable non-small-cell lung cancer.

    Science.gov (United States)

    Altorki, Nasser; Lane, Maureen E; Bauer, Thomas; Lee, Paul C; Guarino, Michael J; Pass, Harvey; Felip, Enriqueta; Peylan-Ramu, Nili; Gurpide, Alfonso; Grannis, Frederic W; Mitchell, John D; Tachdjian, Sabrina; Swann, R Suzanne; Huff, Anne; Roychowdhury, Debasish F; Reeves, Anthony; Ottesen, Lone H; Yankelevitz, David F

    2010-07-01

    Patients with early-stage, resectable, non-small-cell lung cancer (NSCLC) are at risk for recurrent disease, and 5-year survival rates do not exceed 75%. Angiogenesis inhibitors have shown clinical activity in patients with late-stage NSCLC, raising the possibility that targeting the vascular endothelial growth factor pathway in earlier-stage disease may be beneficial. This proof-of-concept study examined safety and efficacy of short-term, preoperative pazopanib monotherapy in patients with operable stage I/II NSCLC. Patients scheduled for resection received oral pazopanib 800 mg/d for 2 to 6 weeks preoperatively. Tumor response was measured by high-resolution computed tomography, permitting estimation of change in tumor volume and diameter. Gene-expression profiling was performed on 77 pre- and post-treatment lung samples from 34 patients. Of 35 patients enrolled, 33 (94%) had clinical stage I NSCLC and two (6%) had clinical stage II NSCLC. Median treatment duration was 16 days (range, 3 to 29 days). Thirty patients (86%) achieved tumor-volume reduction after pazopanib treatment. Two patients achieved tumor-volume reduction > or = 50%, and three patients had partial response according to Response Evaluation Criteria in Solid Tumors. Pazopanib was generally well tolerated. The most common adverse events included grade 2 hypertension, diarrhea, and fatigue. One patient developed pulmonary embolism 11 days after surgery. Several pazopanib target genes and other angiogenic factors were dysregulated post-treatment. Short-duration pazopanib was generally well tolerated and demonstrated single-agent activity in patients with early-stage NSCLC. Several target genes were dysregulated after pazopanib treatment, validating target-specific response and indicating a persistent pazopanib effect on lung cancer tissue. Further clinical evaluation of pazopanib in NSCLC is planned.

  3. Treatment of early-stage Hodgkin lymphoma.

    Science.gov (United States)

    Engert, Andreas; Raemaekers, John

    2016-07-01

    Hodgkin lymphoma (HL) has become one of the best curable malignancies today. This is particularly true for patients with early-stage disease. Today, most patients in this risk group are treated with a combination of chemotherapy followed by small-field radiotherapy. More recent clinical trials such as the German Hodgkin Study Group (GHSG) HD10 study demonstrated, that even two cycles of ABVD followed by 20 Gy involved-field radiation therapy (IF-RT) are sufficient and result in more than 90% of patients being cured. The current treatment for early unfavorable patients is either four cycles of ABVD plus 30 Gy IF-RT or two cycles of BEACOPPbaseline followed by two cycles of ABVD plus IF-RT. Here, the European Organization for Research and Treatment of Cancer (EORTC) demonstrated that in positron emission tomography (PET)-positive patients after two cycles of ABVD, treatment switched to two cycles of BEACOPPbaseline plus radiotherapy results in significantly improved outcomes. Other aspects including attempts to further reduce intensity of treatment will be discussed.

  4. Modelling the cost-effectiveness of public awareness campaigns for the early detection of non-small-cell lung cancer

    Science.gov (United States)

    Hinde, S; McKenna, C; Whyte, S; Peake, M D; Callister, M E J; Rogers, T; Sculpher, M

    2015-01-01

    Background: Survival rates in lung cancer in England are significantly lower than in many similar countries. A range of Be Clear on Cancer (BCOC) campaigns have been conducted targeting lung cancer and found to improve the proportion of diagnoses at the early stage of disease. This paper considers the cost-effectiveness of such campaigns, evaluating the effect of both the regional and national BCOC campaigns on the stage distribution of non-small-cell lung cancer (NSCLC) at diagnosis. Methods: A natural history model of NSCLC was developed using incidence data, data elicited from clinical experts and model calibration techniques. This structure is used to consider the lifetime cost and quality-adjusted survival implications of the early awareness campaigns. Incremental cost-effectiveness ratios (ICERs) in terms of additional costs per quality-adjusted life-years (QALYs) gained are presented. Two scenario analyses were conducted to investigate the role of changes in the ‘worried-well' population and the route of diagnosis that might occur as a result of the campaigns. Results: The base-case theoretical model found the regional and national early awareness campaigns to be associated with QALY gains of 289 and 178 QALYs and ICERs of £13 660 and £18 173 per QALY gained, respectively. The scenarios found that increases in the ‘worried-well' population may impact the cost-effectiveness conclusions. Conclusions: Subject to the available evidence, the analysis suggests that early awareness campaigns in lung cancer have the potential to be cost-effective. However, significant additional research is required to address many of the limitations of this study. In addition, the estimated natural history model presents previously unavailable estimates of the prevalence and rate of disease progression in the undiagnosed population. PMID:26010412

  5. MicroRNA-486 as a Biomarker for Early Diagnosis and Recurrence of Non-Small Cell Lung Cancer.

    Science.gov (United States)

    Li, Wanshuai; Wang, Yong; Zhang, Qi; Tang, Lili; Liu, Xiaoping; Dai, Yunhua; Xiao, Liang; Huang, Shuguang; Chen, Lu; Guo, Zhongmin; Lu, Jim; Yuan, Kai

    2015-01-01

    Non-small cell lung cancer (NSCLC) is a leading cause of cancer death worldwide. Early diagnosis is essential for improvements of prognosis and survival of the patients. Currently, there is no effective biomarker available in clinical settings for early detection of lung cancer. Altered expressions in many cancer types including NSCLC and stable existence in plasma make microRNAs (miRNAs) a group of potentially useful biomarkers for clinical assessments of patients with NSCLC. To evaluate the potential values of miRNAs as blood-based biomarkers for early diagnosis and prognosis in NSCLC patients. Peripheral blood samples from healthy volunteers and early-staged NSCLC patients before and after surgery were collected, and plasma was separated. Expression of ten miRNAs in the plasma and tumor sections of the patients was detected by quantitative real-time polymerase chain reaction. MiRNA (miR)-486 and miR-150 were found to significantly distinguish lung cancer patients from healthy volunteers. Area under curve of miR-486 and miR-150 were 0.926 (sensitivity, 0.909; specificity, 0.818) and 0.752 (sensitivity, 0.818; specificity, 0.818), respectively. In response to therapy, patients with down-regulated miR-486 expression showed prolonged recurrence-free survival than those with un-reduced miR-486 expression (median, unreached vs. 19 months; hazard ratio, 0.1053; 95% confidence interval, 0.01045 to 1.060; P=0.056). The results suggest that miR-486 and miR-150 could be potential blood-based biomarkers for early diagnosis of NSCLC. Monitoring change of miR-486 expression in plasma might be an effective and non-invasive method for recurrence prediction of early-staged NSCLC patients.

  6. Molecular targeted therapy in the treatment of advanced stage non-small cell lung cancer (NSCLC).

    Science.gov (United States)

    Kumarakulasinghe, Nesaretnam Barr; van Zanwijk, Nico; Soo, Ross A

    2015-04-01

    Historically, patients with advanced stage non-small cell lung cancer (NSCLC) were treated with chemotherapy alone, but a therapeutic plateau has been reached. Advances in the understanding of molecular genetics have led to the recognition of multiple molecularly distinct subsets of NSCLC. This in turn has led to the development of rationally directed molecular targeted therapy, leading to improved clinical outcomes. Tumour genotyping for EGFR mutations and ALK rearrangement has meant chemotherapy is no longer given automatically as first-line treatment but reserved for when patients do not have a 'druggable' driver oncogene. In this review, we will address the current status of clinically relevant driver mutations and emerging new molecular subsets in lung adenocarcinoma and squamous cell carcinoma, and the role of targeted therapy and mechanisms of acquired resistance to targeted therapy.

  7. New dilemmas in small-cell lung cancer TNM clinical staging

    Science.gov (United States)

    Zarogoulidis, Konstantinos; Latsios, Dimitrios; Porpodis, Konstantinos; Zarogoulidis, Paul; Darwiche, Kaid; Antoniou, Nick; Hohenforst-Schmidt, Wolfgang; Eleftheriadou, Ellada; Boutsikou, Efimia; Kontakiotis, Theodoros

    2013-01-01

    Background Many patients with limited disease (LD) behave similarly to those with extensive disease (ED) from a prognostic point of view. On the other hand, a proportion of patients with ED small-cell lung cancer (SCLC) behave similarly to those with LD. Patients and methods In this retrospective study analysis, 764 patients with proven SCLC were included and managed with the same therapeutic protocols. Of these patients, 278 (36.4%) had LD, while 486 (63.6%) had ED. Results No statistically significant difference was observed for survival for IA and IB disease stages (P = 0.254) and between IIA and IIB stages (P = 0.256) according to the new tumor, node, metastasis (TNM) staging classification classification. In addition, no statistical significant difference was observed for survival between patients with (IIA + IIB) and IIIA (P = 0.951), (IIA + IIIA, P = 0.658), and (IIB + IIIA, P = 0.573) stages. Statistical significant difference was observed for survival among the LD SCLC patients with (IA + IB), (IIA + IIB + IIIA), and IIIB stages (P TNM staging system is recommended for more detailed prognostic information and treatment evaluation in these patients. PMID:23700372

  8. Validation of the Stage Groupings in the Eighth Edition of the TNM Classification for Lung Cancer.

    Science.gov (United States)

    Sui, Xizhao; Jiang, Wei; Chen, Haiqing; Yang, Fan; Wang, Jun; Wang, Qun

    2017-08-04

    The aim of this study was to validate stage groupings in the eighth edition of the TNM classification in an independent Chinese cohort. We retrospectively analyzed a total of 3599 patients with pathological stage IA to IIIA (seventh edition of the TNM) NSCLC who underwent surgical treatment in two surgical centers in the People's Republic of China between 2005 and 2012. All patients were reclassified according to the eighth edition of the TNM classification. Survival was compared between adjacent stage groupings by using a log-rank test and a Cox regression model. R(2) was calculated to evaluate the discrimination of the two TNM stage classifications. The median follow-up time was 48.7 months. According to the eighth edition of the TNM classification, the overall survival (OS) of adjacent stage groupings showed significant differences except for IA3 vs. IB. The eighth edition of the TNM classification yielded a slightly higher R(2) than the seventh edition (0.172 vs. 0.162). This study provided an external validation of the stage groupings in the eighth edition of the TNM classification for lung cancer among surgically treated Chinese patients with NSCLC. Copyright © 2017. Published by Elsevier Inc.

  9. Interaction between asthma and lung function growth in early life

    DEFF Research Database (Denmark)

    Bisgaard, Hans; Jensen, Signe Marie; Bønnelykke, Klaus

    2012-01-01

    The causal direction between asthma and lung function deficit is unknown, but important for the focus of preventive measures and research into the origins of asthma.......The causal direction between asthma and lung function deficit is unknown, but important for the focus of preventive measures and research into the origins of asthma....

  10. Exome sequencing identifies early gastric carcinoma as an early stage of advanced gastric cancer.

    Science.gov (United States)

    Kang, Guhyun; Hwang, Woo Cheol; Do, In-Gu; Wang, Kai; Kang, So Young; Lee, Jeeyun; Park, Se Hoon; Park, Joon Oh; Kang, Won Ki; Jang, Jiryeon; Choi, Min-Gew; Lee, Jun Ho; Sohn, Tae Sung; Bae, Jae Moon; Kim, Sung; Kim, Min Ji; Kim, Seonwoo; Park, Cheol Keun; Kim, Kyoung-Mee

    2013-01-01

    Gastric carcinoma is one of the major causes of cancer-related mortality worldwide. Early detection and treatment leads to an excellent prognosis in patients with early gastric cancer (EGC), whereas the prognosis of patients with advanced gastric cancer (AGC) remains poor. It is unclear whether EGCs and AGCs are distinct entities or whether EGCs are the beginning stages of AGCs. We performed whole exome sequencing of four samples from patients with EGC and compared the results with those from AGCs. In both EGCs and AGCs, a total of 268 genes were commonly mutated and independent mutations were additionally found in EGCs (516 genes) and AGCs (3104 genes). A higher frequency of C>G transitions was observed in intestinal-type compared to diffuse-type carcinomas (P = 0.010). The DYRK3, GPR116, MCM10, PCDH17, PCDHB1, RDH5 and UNC5C genes are recurrently mutated in EGCs and may be involved in early carcinogenesis.

  11. Can FDG-PET be used to predict growth of stage I lung cancer?

    Energy Technology Data Exchange (ETDEWEB)

    Tann, M. [Department of Radiology, Indiana University School of Medicine, Indianapolis (United States); Sandrasegaran, K. [Department of Radiology, Indiana University School of Medicine, Indianapolis (United States)], E-mail: ksandras@iupui.edu; Winer-Muram, H.T. [Department of Radiology, Richard L. Roudebush Veterans' Association Medical Center, Indianapolis (United States); Jennings, S.G.; Welling, M.E.; Fletcher, J.W. [Department of Radiology, Indiana University School of Medicine, Indianapolis (United States)

    2008-08-15

    Aim: To determine the relationship between the metabolic activity measured by 2-[{sup 18}F]-fluoro-2-deoxy-D-glucose (FDG) positron emission tomography (PET) and computed tomography (CT)-derived tumour growth rates for stage 1 lung cancer. Methods: Stage I lung cancer patients at our institution who underwent FDG PET, and who had at least two pre-treatment chest CT examinations (n = 51), were retrospectively identified. Metabolic activity was defined by maximum lesion standardized uptake value (SUV) and maximum lesion-to-mean background activity (LBR). Growth rates were determined from serial CT volume measurements and the doubling time (DT) was calculated. Tumour growth rates were divided into rapid (DT < 180 days), intermediate (DT = 180-270 days), and slow (DT > 270 days) groups. Results: Rapid, moderate, and slow DT were seen in 22, 19, and 10 patients, respectively. Means (standard deviations) of SUV in the three groups (from rapid to slow growth rate) were 8.2 (4.8), 5.5 (4.5), and 2.2 (1.1), respectively and of LBR were 22.7 (10.1), 15.1 (12.6), and 6 (2.6), respectively. There was a significant relationship between SUV and DT (p < 0.05), as well as between LBR and DT (p < 0.05). Conclusions: For stage I lung tumours, there is a significant relationship between growth rates, as measured by serial CT examinations, and the initial pre-treatment metabolic activities, as measured by FDG uptake. This suggests that in patients in whom it is difficult to decide on the aggressiveness on treatment, FDG-PET may be used as additional prognostic tool for determining management.

  12. Radiation therapy for early stages of Morbus Ledderhose

    Energy Technology Data Exchange (ETDEWEB)

    Heyd, Reinhard [Dept. of Radiotherapy, Klinikum Offenbach (Germany); Dorn, Anne Pia; Mueller-Schimpfle, Marcus [Central Inst. of Radiology, Municipal Hospitals, Frankfurt/Main-Hoechst (Germany); Herkstroeter, Markus [Radiotherapeutic Practice at the Municipal Hospitals, Frankfurt/Main-Hoechst (Germany); Roedel, Claus; Fraunholz, Ingeborg [Dept. of Radiotherapy and Oncology, Univ. Hospital Frankfurt/Main (Germany)

    2010-01-15

    Purpose: To evaluate the efficacy of radiation therapy (RT) in the treatment of early stages of benign plantar fibromatosis (Morbus Ledderhose [ML]). Patients and Methods: From 2003 to 2008, 24 patients (33 sites) with a mean age of 52 years received RT for symptomatic ML. Prior to RT, 19 patients complained of pain and 15 had walking difficulties. 21 patients (28 sites) were irradiated with orthovolt-age X-rays and three (five sites) received electron-beam irradiation. The RT protocol consisted of five weekly fractions of 3.0 Gy (15 Gy), repeated after 6 weeks to a total dose of 30 Gy in 20 patients (28 sites). In four patients (five sites), two single fractions of 4.0 Gy were applied, repeated at intervals of 4 weeks to total doses of 24-32 Gy. Primary study endpoints were the prevention of disease progression and the avoidance of a surgical intervention. Secondary endpoints were pain relief, improvement of gait, and patients' subjective satisfaction measured with a linear analog scale (LAS). Results: After a median follow-up of 22.5 months, none of the patients experienced a progression of number and size of the lesions or the clinical symptoms. In eleven sites (33.3%) complete remission of cords or nodules occurred, in 18 (54.5%) a reduced number or size was noted, and four sites (12.1%) were unchanged. Pain relief was achieved in 13/19 patients (68.4%), and an improvement of gait abnormalities was noted in 11/15 patients (73.3%). The patients' subjective satisfaction measured by means of the LAS revealed a median improvement of 3.5 points in 22/24 patients (91.6%). Skin or soft tissues toxicities RTOG grade > 2 were not noted. Conclusion: RT is effective for treatment of the early stages of ML and may obviate the need for a surgical intervention. Long-term follow-up studies including a larger number of patients are required to define the role of RT in the management of this disorder. (orig.)

  13. Clinical significance of preoperative carcinoembryonic antigen level in patients with clinical stage IA non-small cell lung cancer

    Science.gov (United States)

    Suda, Takashi; Hachimaru, Ayumi; Tochii, Daisuke; Tochii, Sachiko; Takagi, Yasushi

    2017-01-01

    Background The objective of this study was to assess the preoperative serum carcinoembryonic antigen (CEA) level in patients with clinical stage IA non-small cell lung cancer (NSCLC) and to evaluate its clinical significance. Methods Between January 2005 and December 2014, a total of 378 patients with clinical stage IA NSCLC underwent complete resection with systematic node dissection. The survival rate was estimated starting from the date of surgery to the date of either death or the last follow-up by the Kaplan-Meier method. Univariate analyses by log-rank tests were used to determine prognostic factors. Cox proportional hazards ratios were used to identify independent predictors of poor prognosis. Clinicopathological predictors of lymph node metastases were evaluated by logistic regression analyses. Results The 5-year survival rate of patients with an elevated preoperative serum CEA level was significantly lower than that of patients with a normal CEA level (75.5% vs. 87.7%; P=0.02). However, multivariate analysis did not show the preoperative serum CEA level to be an independent predictor of poor prognosis. Postoperative pathological factors, including lymphatic permeation, visceral pleural invasion, and lymph node metastases, tended to be positive in patients with an elevated preoperative serum CEA level. In addition, the CEA level was a statistically significant independent clinical predictor of lymph node metastases. Conclusions The preoperative serum CEA level was not an independent predictor of poor prognosis in patients with pathological stage IA NSCLC but was an important clinical predictor of tumor invasiveness and lymph node metastases in patients with clinical stage IA NSCLC. Therefore, measurement of the preoperative serum CEA level should be considered even for patients with early-stage NSCLC.

  14. Metabotyping Patients’ Journeys Reveals Early Predisposition to Lung Injury after Cardiac Surgery

    DEFF Research Database (Denmark)

    Maltesen, Raluca; Rasmussen, Bodil Steen; Pedersen, Shona

    2017-01-01

    Cardiovascular disease is the leading cause of death worldwide and patients with severe symptoms undergo cardiac surgery. Even after uncomplicated surgeries, some patients experience postoperative complications such as lung injury. We hypothesized that the procedure elicits metabolic activity...... early, during or just after the end of surgery, may have potential impact in hospitals for the early diagnosis of postoperative lung injury, and for the monitoring of therapeutics targeting disease progression....

  15. Native language change during early stages of second language learning.

    Science.gov (United States)

    Bice, Kinsey; Kroll, Judith F

    2015-11-11

    Research on proficient bilinguals has demonstrated that both languages are always active, even when only one is required. The coactivation of the two languages creates both competition and convergence, facilitating the processing of cognate words, but slowing lexical access when there is a requirement to engage control mechanisms to select the target language. Critically, these consequences are evident in the native language (L1) as well as in the second language (L2). The present study questioned whether L1 changes can be detected at early stages of L2 learning and how they are modulated by L2 proficiency. Native English speakers learning Spanish performed an English (L1) lexical decision task that included cognates while event-related potentials were recorded. They also performed verbal fluency, working memory, and inhibitory control tasks. A group of matched monolinguals performed the same tasks in English only. The results revealed that intermediate learners demonstrate a reduced N400 for cognates compared with noncognates in English (L1), and an emerging effect is visually present in beginning learners as well; however, no behavioral cognate effect was present for either group. In addition, slower reaction times in English (L1) are related to a larger cognate N400 magnitude in English (L1) and Spanish (L2), and to better inhibitory control for learners but not for monolinguals. The results suggest that contrary to the claim that L2 affects L1 only when L2 speakers are highly proficient, L2 learning begins to impact L1 early in the development of the L2 skill.

  16. Two-stage induced differentiation of OCT4+/Nanog+ stem-like cells in lung adenocarcinoma.

    Science.gov (United States)

    Li, Rong; Huang, Jinsu; Ma, Meili; Lou, Yuqing; Zhang, Yanwei; Wu, Lixia; Chang, David W; Zhao, Picheng; Dong, Qianggang; Wu, Xifeng; Han, Baohui

    2016-10-18

    Stem-like cells in solid tumors are purported to contribute to cancer development and poor treatment outcome. The abilities to self-renew, differentiate, and resist anticancer therapies are hallmarks of these rare cells, and steering them into lineage commitment may be one strategy to curb cancer development or progression. Vitamin D is a prohormone that can alter cell growth and differentiation and may induce the differentiation cancer stem-like cells. In this study, octamer-binding transcription factor 4 (OCT4)-positive/Nanog homeobox (Nanog)- positive lung adenocarcinoma stem-like cells (LACSCs) were enriched from spheroid cultured SPC-A1 cells and differentiated by a two-stage induction (TSI) method, which involved knockdown of hypoxia-inducible factor 1-alpha (HIF1α) expression (first stage) followed by sequential induction with 1alpha,25-dihydroxyvitamin D3 (1,25(OH)2D3, VD3) and suberoylanilide hydroxamic acid (SAHA) treatment (second stage). The results showed the HIF1α-knockdowned cells displayed diminished cell invasion and clonogenic activities. Moreover, the TSI cells highly expressed tumor suppressor protein p63 (P63) and forkhead box J1 (FOXJ1) and lost stem cell characteristics, including absent expression of OCT4 and Nanog. These cells regained sensitivity to cisplatin in vitro while losing tumorigenic capacity and decreased tumor cell proliferation in vivo. Our results suggest that induced transdifferentiation of LACSCs by vitamin D and SAHA may become novel therapeutic avenue to alter tumor cell phenotypes and improve patient outcome.The development and progression of lung cancer may involve rare population of stem-like cells that have the ability to grow, differentiate, and resist drug treatment. However, current therapeutic strategies have mostly focused on tumor characteristics and neglected the potential source of cells that may contribute to poor clinical outcome. We generated lung adenocarcinoma stem-like cells from spheroid culture and

  17. How to choose PET-CT or CT in the diagnosis and staging of lung cancer. Practical experience in China

    Energy Technology Data Exchange (ETDEWEB)

    Jiang, T.; Tao, X.; Liu, H.; Liu, S. [Dept. of Radiology, ChangZheng Hospital, Second Military Medical Univ., SH (China); Zheng, X. [Dept. of Nutrition, ChangHai Hospital, Second Military Medical Univ., SH (China)

    2010-07-01

    How to use CT and PET-CT rationally to raise diagnosis, staging and prognostic assessment of lung cancer to a higher level at the best cost-effect ratio is a subject that Chinese clinicians and radiologists should face conscientiously. We review the rational application of CT and PET-CT in four aspects of lung cancer, including screening and detection, morphologic evaluation, haemodynamic or metabolic feature evaluation, and follow-up, staging and prognostic evaluation. As PET-CT is only available in class III-A hospitals today, CT is the most popular equipment in China. PET-CT is more valuable only in cases where CT presentation of lung cancer is atypical or difficult to determine, or in cases where the diagnosis of lung cancer has been initially confirmed, for which clinical staging and decision concerning on therapeutic regimens are needed. We also recommend the current strategies of CT and PET-CT managing of SPN in China. (orig.)

  18. Efficiency of teaching patients with early-stage rheumatoid arthritis

    Directory of Open Access Journals (Sweden)

    Evgenia Vladislavovna Orlova

    2014-01-01

    Full Text Available Education programs are an important part of the management of patients with rheumatoid arthritis (RA.Objective: to develop a unified model of an education program for RA patients and to evaluate its efficiency at the early stage of the disease.Material and methods. A group education program was worked out with the support of the All-Russian public organization of the disabled “The Russian rheumatology organization “Nadezhda” (Hope” and encompassed 4 daily classes lasting 90 min. All information was presented by a multidisciplinary team of specialists (rheumatologists, a cardiologist, a psychologist, a physiotherapist, and a physical trainer. The study included 55 patients with early RA (89.1% of women aged 18 to 62 years; the duration of the disease was 2 to 22 months; of them 25 were taught using the education program (a study group; 30 received drug therapy only (a control group. Following 3 and 6 months, the number of tender and swollen joints, erythrocyte sedimentation rate (ESR, C-reactive protein (CRP, and pain were determined applying a 100-ml VAS, DAS28, HAQ, and RAPID3. Adherence to non-drug treatments was assessed employing a special patient questionnaire.Results. Three and six months after being taught, two patient groups showed increases in adherence to joint protection methods by 13 and 10 times (p<0.01, regular physical training by 4 and 3.25 times (p<0.01, uses of orthoses for the wrist joint by 2 times and 75% (p<0.01 and knee orthoses by 33.3 and 50.0% (p<0.01, and orthopedic insoles by 71.4 and 57.1% (p<0.01, respectively. Following 6 months, there were statistically significant differences between the two groups in most parameters (p<0.05, except for ESR, CRP, and DAS28 (p>0.05. Further more, a good response to treatment was significantly more common in these periods, as shown by the EULAR response criteria (DAS28: 56.3% versus 40% in the control group (p<0.05.Conclusion. The education program decreases the intensity

  19. Silicon: The key element in early stages of biocalcification.

    Science.gov (United States)

    Matsko, Nadejda B; Znidaršič, Nada; Letofsky-Papst, Ilse; Dittrich, Maria; Grogger, Werner; Strus, Jasna; Hofer, Ferdinand

    2011-04-01

    Biocalcification is a widespread process of forming hard tissues like bone and teeth in vertebrates. It is also a topic connecting life sciences and earth sciences: calcified skeletons and shells deposited as sediments represent the earth's fossil record and are of paramount interest for biogeochemists trying to get an insight into the past of our planet. This study reports on the role of silicon in the early biocalcification steps, where silicon and calcium were detected on the surface of cyanobacteria (initial stage of lacustrine calcite precipitation) and in crustacean cuticles. By using innovative methodological approaches of correlative microscopy (AFM in combination with analytical TEM: EFTEM, EELS) the chemical form of silicon in biocalcifying matrices and organic-inorganic particles is determined. Previously, silicon was reported to be localized in active growth areas in the young bone of vertebrates. We have found evidence that biocalcification in evolutionarily distant organisms involves very similar initial phases with silicon as a key element at the organic-inorganic interface.

  20. Cytonuclear incompatibility contributes to the early stages of speciation.

    Science.gov (United States)

    Barnard-Kubow, Karen B; So, Nina; Galloway, Laura F

    2016-12-01

    Genetic incompatibility is a hallmark of speciation. Cytonuclear incompatibilities are proposed to be among the first genetic barriers to arise during speciation. Accordingly, reproductive isolation (RI) within species should be heavily influenced by interactions between the organelle and nuclear genomes. However, there are few clear examples of cytonuclear incompatibility within a species. Here, we show substantial postzygotic RI in first-generation hybrids between differentiated populations of an herbaceous plant (up to 92% reduction in fitness). RI was primarily due to germination and survival, with moderate RI for pollen viability. RI for survival was asymmetric and caused by cytonuclear incompatibility, with the strength of incompatibility linearly related to chloroplast genetic distance. This cytonuclear incompatibility may be the result of a rapidly evolving plastid genome. Substantial asymmetric RI was also found for germination, but was not associated with cytonuclear incompatibility, indicating endosperm or maternal-zygote incompatibilities. These results demonstrate that cytonuclear incompatibility contributes to RI within species, suggesting that initial rates of speciation could be influenced by rates of organelle evolution. However, other genetic incompatibilities are equally important, indicating that even at early stages, speciation can be a complex process involving multiple genes and incompatibilities.

  1. Affective motives for smoking among early stage smokers.

    Science.gov (United States)

    Mathew, Amanda R; Wahlquist, Amy E; Garrett-Mayer, Elizabeth; Gray, Kevin M; Saladin, Michael E; Carpenter, Matthew J

    2014-10-01

    As most smokers initiate smoking during adolescence, assessment of smoking motives that underlie trajectories of dependence is critical for both prevention and cessation efforts. In the current study, we expected participants with higher nicotine dependence would smoke (a) less for positive reinforcement (PR) and (b) more for negative reinforcement (NR) motives. We secondarily assessed the relative contribution of PR to NR motives across levels of dependence. Data were drawn from a study on cue-elicited craving among occasional versus daily adolescent smokers aged 16-20 years (N = 111). Smoking motives were assessed in relation to 3 commonly used measures of nicotine dependence: (a) Fagerström Test for Nicotine Dependence (FTND), (b) Autonomy over Smoking Scale (AUTOS), and (c) Nicotine Dependence Syndrome Scale (NDSS). Compared to occasional smokers, daily smokers had significantly higher scores on each dependence measure and endorsed more prominent NR smoking motives. Each measure of nicotine dependence was strongly associated with NR motives for smoking, although measures differed in their association with PR motives. As expected, the FTND, AUTOS, and NDSS each significantly predicted smoking motive difference score (PR - NR), such that higher dependence was associated with more prominent NR motives for smoking. Results are consistent with our understanding of dependence and provide further support for 3 common measures of nicotine dependence among early stage smokers. © The Author 2014. Published by Oxford University Press on behalf of the Society for Research on Nicotine and Tobacco. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

  2. Early stages of diamond BEN-HFCVD on iridium

    Energy Technology Data Exchange (ETDEWEB)

    Arnault, J.C.; Faerber, J. [Groupe Surfaces-Interfaces, Institut de Physique et Chimie de Strasbourg, IPCMS-GSI, UMR 7504, BP 43, 23, rue du Loess, 67034 Strasbourg Cedex 2 (France); Vonau, F. [Laboratoire de Physique et Spectroscopie Electronique, 4, rue des Freres Lumiere, 68093 Mulhouse Cedex (France); Arabski, J.; Schmerber, G. [Groupe des Materiaux Metalliques, IPCMS-GEMM, 91404 Orsay (France); Wyczisk, F.; Legagneux, P. [Thales R and T, Domaine de Corbeville, 91404 Orsay Cedex (France)

    2003-09-01

    This study attempts to better understand the BEN effects on diamond nucleation on iridium buffer layers investigated by in situ electron spectroscopies (XPS, AES). The surface morphology is further characterised by AFM and SEM FEG. Nano-Auger experiments provide information about the chemical nature of the crystals. During the early stages of BEN, nano-Auger observations revealed a significant carbon sp{sup 3} contribution within the bright crystals whereas the surrounding areas are mainly sp{sup 2}. This emphasizes the BEN effect on the diamond nucleation. Moreover, AES experiments reveal the formation of graphite. The equivalent thickness of the graphite layer is estimated from XPS data, it is close to a monolayer. The graphite formation is not a proper effect of BEN because it is also obtained under CVD environment according to our study. Anisotrope crystals arranged along left angle 110 right angle directions have been characterized by HR-SEM and AFM. (copyright 2003 WILEY-VCH Verlag GmbH and Co. KGaA, Weinheim) (orig.)

  3. The studies of nodular graphite cast iron early stages austempering

    Directory of Open Access Journals (Sweden)

    A. Krzyńska

    2008-12-01

    Full Text Available The results of early stage of ductile cast iron austempering are presented. The aim of the investigations was to look closer into the structure – mechanical properties relationships of this very attractive cast material. The experiment was carried out with enriched with Cu EN-GJS-500-7 grade ductile iron. The specimens were first solution heat treated 1 hour in 910oC and then isothermally quenched for different time in molten tin at the temperature 275oC. The mechanical properties of as cast and heat treated specimens were tested to evaluate tensile Rm and yield strength R p, 0.2 and elongation A5. Additionally hardness measurements were carried out using Brinell-Rockwell method. Structure of the specimens both as cast and after austempering was studied using conventional light microscopy. Moreover, scanning electron microscopy (SEM was applied for fracture surface observations. It was concluded that short time low temperature austempering lead to formation martensitic microstructure characterized by very high hardness with almost zero ductility. The lack of ductility make the material very sensitive to any structure defects which work as a stress concentrators which strongly influence the strength of heat treated ductile iron specimens.

  4. Cognitive Stimulation for Apathy in Probable Early-Stage Alzheimer's

    Directory of Open Access Journals (Sweden)

    Linda L. Buettner

    2011-01-01

    Full Text Available We studied changes in apathy among 77 community-dwelling older persons with mild memory loss in a randomized clinical trial comparing two nonpharmacological interventions over four weeks. The study used a pre-post design with randomization by site to avoid contamination and diffusion of effect. Interventions were offered twice weekly after baseline evaluations were completed. The treatment group received classroom style mentally stimulating activities (MSAs while the control group received a structured early-stage social support (SS group. The results showed that the MSA group had significantly lower levels of apathy (P<.001 and significantly lower symptoms of depression (P<.001. While both groups improved on quality of life, the MSA group was significantly better (P=.02 than the SS group. Executive function was not significantly different for the two groups at four weeks, but general cognition improved for the MSA group and declined slightly for the SS group which produced a significant posttest difference (P<.001. Recruitment and retention of SS group members was difficult in this project, especially in senior center locations, while this was not the case for the MSA group. The examination of the data at this four-week time point shows promising results that the MSA intervention may provide a much needed method of reducing apathy and depressive symptoms, while motivating participation and increasing quality of life.

  5. Metformin inhibits early stage diethylnitrosamine‑induced hepatocarcinogenesis in rats.

    Science.gov (United States)

    Jo, Woori; Yu, Eun-Sil; Chang, Minsun; Park, Hyun-Kyu; Choi, Hyun-Ji; Ryu, Jae-Eun; Jang, Sungwoong; Lee, Hyo-Ju; Jang, Ja-June; Son, Woo-Chan

    2016-01-01

    Antitumor effects of metformin have recently emerged despite its original use for type II diabetes. In the present study, the effects of metformin on the development and recurrence of hepatocellular carcinoma (HCC) were investigated using the diethylnitrosamine (DEN)‑induced rat model of HCC. Tumor foci were characterized by gross examination and by histopathological characteristics, including proliferation, hepatic progenitor cell content and the expression of hepatocarcinoma‑specific molecular markers. Potential target molecules of metformin were investigated to determine the molecular mechanism underlying the inhibitory effects of metformin on chemically induced liver tumorigenesis. The antitumor effects of metformin were increased by the reduction of surface nodules and decreased the incidence of altered hepatocellular foci, hepatocellular adenoma and carcinoma. Also, decreased expression levels of glutathione S‑transferase placental form, proliferating cell nuclear antigen and cytokeratin 8 described the inhibitory effects of metformin on HCC. In the present study, Wistar rats receiving treatment with DEN were administered metformin for 16 weeks. In addition, metformin suppressed liver tumorigenesis via an AMPK‑dependent pathway. These results suggested that metformin has promising effects on the early stage of HCC in rats. Therefore, metformin may be used for the prevention of HCC recurrence following primary chemotherapy for HCC and/or for high‑risk patients, including chronic hepatitis and cirrhosis.

  6. Modeling Local Control After Hypofractionated Stereotactic Body Radiation Therapy for Stage I Non-Small Cell Lung Cancer: A Report From the Elekta Collaborative Lung Research Group

    Energy Technology Data Exchange (ETDEWEB)

    Ohri, Nitin, E-mail: ohri.nitin@gmail.com [Department of Radiation Oncology, Jefferson Medical College of Thomas Jefferson University, Philadelphia, Pennsylvania (United States); Werner-Wasik, Maria [Department of Radiation Oncology, Jefferson Medical College of Thomas Jefferson University, Philadelphia, Pennsylvania (United States); Grills, Inga S. [Department of Radiation Oncology, William Beaumont Hospital, Royal Oak, Michigan (United States); Belderbos, Jose [Department of Radiation Oncology, The Netherlands Cancer Institute, Amsterdam (Netherlands); Hope, Andrew [Department of Radiation Oncology, Princess Margaret Hospital and University of Toronto, Toronto, ON (Canada); Yan Di; Kestin, Larry L. [Department of Radiation Oncology, William Beaumont Hospital, Royal Oak, Michigan (United States); Guckenberger, Matthias [Department of Radiation Oncology, University of Wuerzburg, Wuerzburg (Germany); Sonke, Jan-Jakob [Department of Radiation Oncology, The Netherlands Cancer Institute, Amsterdam (Netherlands); Bissonnette, Jean-Pierre [Department of Radiation Oncology, Princess Margaret Hospital and University of Toronto, Toronto, ON (Canada); Xiao, Ying [Department of Radiation Oncology, Jefferson Medical College of Thomas Jefferson University, Philadelphia, Pennsylvania (United States)

    2012-11-01

    Purpose: Hypofractionated stereotactic body radiation therapy (SBRT) has emerged as an effective treatment option for early-stage non-small cell lung cancer (NSCLC). Using data collected by the Elekta Lung Research Group, we generated a tumor control probability (TCP) model that predicts 2-year local control after SBRT as a function of biologically effective dose (BED) and tumor size. Methods and Materials: We formulated our TCP model as follows: TCP = e{sup [BED10-c Asterisk-Operator L-TCD50]/k} Division-Sign (1 + e{sup [BED10-c Asterisk-Operator L-TCD50]/k}), where BED10 is the biologically effective SBRT dose, c is a constant, L is the maximal tumor diameter, and TCD50 and k are parameters that define the shape of the TCP curve. Least-squares optimization with a bootstrap resampling approach was used to identify the values of c, TCD50, and k that provided the best fit with observed actuarial 2-year local control rates. Results: Data from 504 NSCLC tumors treated with a variety of SBRT schedules were available. The mean follow-up time was 18.4 months, and 26 local recurrences were observed. The optimal values for c, TCD50, and k were 10 Gy/cm, 0 Gy, and 31 Gy, respectively. Thus, size-adjusted BED (sBED) may be defined as BED minus 10 times the tumor diameter (in centimeters). Our TCP model indicates that sBED values of 44 Gy, 69 Gy, and 93 Gy provide 80%, 90%, and 95% chances of tumor control at 2 years, respectively. When patients were grouped by sBED, the model accurately characterized the relationship between sBED and actuarial 2-year local control (r=0.847, P=.008). Conclusion: We have developed a TCP model that predicts 2-year local control rate after hypofractionated SBRT for early-stage NSCLC as a function of biologically effective dose and tumor diameter. Further testing of this model with additional datasets is warranted.

  7. Building performance simulation in the early design stage: An introduction to integrated dynamic models

    DEFF Research Database (Denmark)

    Negendahl, Kristoffer

    2015-01-01

    Designing with building performance simulation feedback in the early design stage has existed since the early days of computational modeling. However, as a consequence of a fragmented building industry building performance simulations (BPSs) in the early design stage are closely related to who is...

  8. MRI detection of brain metastases at initial staging of small-cell lung cancer

    Energy Technology Data Exchange (ETDEWEB)

    Pol, M. van de [Dept. of Neurology, Univ. Hospital, Maastricht (Netherlands); Oosterhout, A.G. van [Dept. of Neurology, Univ. Hospital, Maastricht (Netherlands); Wilmink, J.T. [Dept. of Diagnostic Radiology, Univ. Hospital, Maastricht (Netherlands); Velde, G.P.M. ten [Dept. of Pulmonology, Univ. Hospital, Maastricht (Netherlands); Twijnstra, A. [Dept. of Neurology, Univ. Hospital, Maastricht (Netherlands)

    1996-04-01

    We prospectively investigated 40 patients with small-cell carcinoma of the lung (SCLC) for signs of brain metastasis by neurological examination and MRI of the brain, to determine the significance of MRI for staging. MRI could not be completed in one patient, who was excluded from the study. The MRI studies of the remaining patients showed no abnormalities in 12, cerebral infarcts in 2 and brain metastases in 11 patients, of whom 3 no relevant symptoms. Nonenhancing white matter lesions were found in 14 patients. In 3 of the 4 patients with an abnormal neurological examination at diagnosis, nonenhancing white matter lesions later developed into contrast enhancing lesions compatible with breain metastases; in 2, this occurred during the course of the chemotherapy. MRI did not change the clinical staging in patients with asymptomatic brain metastases. (orig.)

  9. Changes of pulmonary intercellular adhesion molecule-1 and CD11b/CD18 in peripheral polymorphonuclear neutrophils and their significance at the early stage of burns

    Institute of Scientific and Technical Information of China (English)

    金榕兵; 朱佩芳; 王正国; 刘大维; 周继红

    2003-01-01

    Objective: To investigate the role of intercellular adhesion molecule-1 (ICAM-1) in the accumulation of polymorphonuclear neutrophils (PMN) in the lungs at the early stage of burns. Methods: Myeloperoxidase content in lung tissues and bronchoalveolar lavage fluid (BALF) were detected. ICAM-1 and its mRNA expression in lung tissues were determined by immunohistochemical method and in situ hybridization. CD11b/CD18 expression on the peripheral PMNs was measured by flowcytometry. Results: The levels of myeloperoxidase in lung tissues and BALF after burn injury were markedly higher than those of control. Expression of ICAM-1 and its mRNA in the lung tissues and CD11b/CD18 on peripheral PMNs surface was significantly increased at 2, 6, 12, 24 h after burns. Conclusions: PMNs accumulation in the lungs is related to increased ICAM-1 expression on pulmonary microvascular endothelial cells and CD11b/CD18 expression on PMN at the early stage of burn injury.

  10. Exercise maintains blood-brain barrier integrity during early stages of brain metastasis formation.

    Science.gov (United States)

    Wolff, Gretchen; Davidson, Sarah J; Wrobel, Jagoda K; Toborek, Michal

    2015-08-07

    Tumor cell extravasation into the brain requires passage through the blood-brain barrier, which is a highly protected microvascular environment fortified with tight junction (TJ) proteins. TJ integrity can be regulated under physiological and pathophysiological conditions. There is evidence that exercise can modulate oxidation status within the brain microvasculature and protect against tumor cell extravasation and metastasis formation. In order to study these events, mature male mice were given access to voluntary exercise on a running wheel (exercise) or access to a locked wheel (sedentary) for five weeks. The average running distance was 9.0 ± 0.2 km/day. Highly metastatic tumor cells (murine Lewis lung carcinoma) were then infused into the brain microvasculature through the internal carotid artery. Analyses were performed at early stage (48 h) and late stage (3 weeks) post tumor cell infusion. Immunohistochemical analysis revealed fewer isolated tumor cells extravasating into the brain at both 48 h and 3 weeks post surgery in exercised mice. Occludin protein levels were reduced in the sedentary tumor group, but maintained in the exercised tumor group at 48 h post tumor cell infusion. These results indicate that voluntary exercise may participate in modulating blood-brain barrier integrity thereby protecting the brain during metastatic progression.

  11. Circumventing Y. pestis Virulence by Early Recruitment of Neutrophils to the Lungs during Pneumonic Plague.

    Directory of Open Access Journals (Sweden)

    Yaron Vagima

    2015-05-01

    Full Text Available Pneumonic plague is a fatal disease caused by Yersinia pestis that is associated with a delayed immune response in the lungs. Because neutrophils are the first immune cells recruited to sites of infection, we investigated the mechanisms responsible for their delayed homing to the lung. During the first 24 hr after pulmonary infection with a fully virulent Y. pestis strain, no significant changes were observed in the lungs in the levels of neutrophils infiltrate, expression of adhesion molecules, or the expression of the major neutrophil chemoattractants keratinocyte cell-derived chemokine (KC, macrophage inflammatory protein 2 (MIP-2 and granulocyte colony stimulating factor (G-CSF. In contrast, early induction of chemokines, rapid neutrophil infiltration and a reduced bacterial burden were observed in the lungs of mice infected with an avirulent Y. pestis strain. In vitro infection of lung-derived cell-lines with a YopJ mutant revealed the involvement of YopJ in the inhibition of chemoattractants expression. However, the recruitment of neutrophils to the lungs of mice infected with the mutant was still delayed and associated with rapid bacterial propagation and mortality. Interestingly, whereas KC, MIP-2 and G-CSF mRNA levels in the lungs were up-regulated early after infection with the mutant, their protein levels remained constant, suggesting that Y. pestis may employ additional mechanisms to suppress early chemoattractants induction in the lung. It therefore seems that prevention of the early influx of neutrophils to the lungs is of major importance for Y. pestis virulence. Indeed, pulmonary instillation of KC and MIP-2 to G-CSF-treated mice infected with Y. pestis led to rapid homing of neutrophils to the lung followed by a reduction in bacterial counts at 24 hr post-infection and improved survival rates. These observations shed new light on the virulence mechanisms of Y. pestis during pneumonic plague, and have implications for the

  12. Clinical outcome and predictors of survival and pneumonitis after stereotactic ablative radiotherapy for stage I non-small cell lung cancer

    Directory of Open Access Journals (Sweden)

    Chang Joe Y

    2012-09-01

    Full Text Available Abstract Background Stereotactic ablative radiotherapy (SABR can achieve excellent local control rates in early-stage non-small cell lung cancer (NSCLC and has emerged as a standard treatment option for patients who cannot undergo surgery or those with isolated recurrences. However, factors that may predict toxicity or survival are largely unknown. We sought here to identify predictors of survival and pneumonitis after SABR for NSCLC in a relatively large single-institution series. Methods Subjects were 130 patients with stage I NSCLC treated with four-dimensional computed tomography (4D CT –planned, on-board volumetric image–guided SABR to 50 Gy in 4 fractions. Disease was staged by positron emission tomography/computed tomography (PET/CT and scans were obtained again at the second follow-up after SABR. Results At a median follow-up time of 26 months, the 2-year local control rate was 98.5%. The median overall survival (OS time was 60 months, and OS rates were 93.0% at 1 year, 78.2% at 2 years, and 65.3% at 3 years. No patient experienced grade 4–5 toxicity; 15 had radiation pneumonitis (12 [9.3%] grade 2 and 3 [2.3%] grade 3. Performance status, standardized uptake value (SUVmax on staging PET/CT, tumor histology, and disease operability were associated with OS on univariate analysis, but only staging SUVmax was independently predictive on multivariate analysis (P = 0.034. Dosimetric factors were associated with radiation pneumonitis on univariate analysis, but only mean ipsilateral lung dose ≥9.14 Gy was significant on multivariate analysis (P = 0.005. Conclusions OS and radiation pneumonitis after SABR for stage I NSCLC can be predicted by staging PET SUVmax and ipsilateral mean lung dose, respectively.

  13. Observer variation in FDG PET-CT for staging of non-small-cell lung carcinoma

    Energy Technology Data Exchange (ETDEWEB)

    Hofman, Michael S. [St Thomas' Hospital, PET Imaging Centre, London (United Kingdom)]|[Southern Health, Nuclear Medicine, Melbourne (Australia); Smeeton, Nigel C. [King' s College London, Division of Health and Social Care Research, London (United Kingdom); Rankin, Sheila C.; Nunan, Tom; O' Doherty, Michael J. [St Thomas' Hospital, PET Imaging Centre, London (United Kingdom)

    2009-02-15

    Error and variation in reporting remains one of the weakest features of clinical imaging despite enormous technological advances in nuclear medicine and radiology. The aim of this study was to evaluate agreement amongst experienced readers in staging non-small-cell lung cancer (NSCLC) with PET-CT. A series of {sup 18}F-FDG PET-CT scans from 100 consecutive patients were reviewed independently by three experienced readers, with two readers reviewing each scan series a second time. Individual mediastinal lymph node stations were assessed as benign/inflammatory, equivocal or malignant, and AJCC N and M stage were also assigned. Kappa ({kappa}) was used to compare ratings from two categories and weighted kappa ({kappa}{sub w}) for three or more categories, and kappa values were interpreted according to the Landis-Koch benchmarks. Both intra- and interobserver agreement for N and M staging were high. For M staging there was almost perfect intra- and interobserver agreement ({kappa} = 0.90-0.93). For N staging, agreement was either almost perfect or substantial (intraobserver {kappa}{sub w} = 0.79, 0.91; interobserver {kappa}{sub w} = 0.75-0.81). Importantly, there was almost perfect agreement for N0/1 vs N2/3 disease ({kappa} = 0.80-0.97). Agreement for inferior and superior mediastinal nodes (stations 1, 2, 3, 7, 8, 9) was either almost perfect or substantial ({kappa}{sub w} = 0.71-0.88), but lower for hilar nodes (10; {kappa}{sub w} = 0.56-0.71). Interreporter variability was greatest for aortopulmonary nodes (5, 6; {kappa}{sub w} = 0.48-0.55). Amongst experienced reporters in a single centre, there was a very high level of agreement for both mediastinal nodal stage and detection of distant metastases with PET-CT. This supports the use of PET-CT as a robust imaging modality for staging NSCLC. (orig.)

  14. Lung Cancer Workshop XI: Tobacco-Induced Disease: Advances in Policy, Early Detection and Management.

    Science.gov (United States)

    Mulshine, James L; Avila, Rick; Yankelevitz, David; Baer, Thomas M; Estépar, Raul San Jose; Ambrose, Laurie Fenton; Aldigé, Carolyn R

    2015-05-01

    The Prevent Cancer Foundation Lung Cancer Workshop XI: Tobacco-Induced Disease: Advances in Policy, Early Detection and Management was held in New York, NY on May 16 and 17, 2014. The two goals of the Workshop were to define strategies to drive innovation in precompetitive quantitative research on the use of imaging to assess new therapies for management of early lung cancer and to discuss a process to implement a national program to provide high quality computed tomography imaging for lung cancer and other tobacco-induced disease. With the central importance of computed tomography imaging for both early detection and volumetric lung cancer assessment, strategic issues around the development of imaging and ensuring its quality are critical to ensure continued progress against this most lethal cancer.

  15. Prospective study on stereotactic radiotherapy of limited-stage non-small-cell lung cancer

    DEFF Research Database (Denmark)

    Høyer, Morten; Roed, Henrik; Hansen, Anders Traberg

    2006-01-01

    Purpose: To test the effect of stereotactic body radiotherapy (SBRT) in       the treatment of medically inoperable patients with limited-stage       non-small-cell lung cancer (NSCLC) in a Phase II trial. Methods and       Materials: Forty patients with Stage I NSCLC were treated with SBRT...... with a       central dose of 15 Gy x 3 within 5-8 days. Results: Eight patients (20%)       obtained a complete response, 15 (38%) had a partial response, and 12       (30%) had no change or could not be evaluated. Only 3 patients had a local       recurrence, and the local control rate 2 years after SBRT was 85...... resulted in a high       probability of local control and a promising survival rate. The toxicity       after SBRT of lung tumors was moderate. However, deterioration in       performance status, respiratory insufficiency, and other side effects were       observed...

  16. Micrometastasis in non-small-cell lung cancer: Detection and staging

    Directory of Open Access Journals (Sweden)

    Gholamreza Mohajeri

    2012-01-01

    Full Text Available Background: The clinical relevance of bone marrow micrometastasis (BMM in non-small-cell lung cancer is undetermined, and the value of such analyses in advanced stage patients has not been clearly assessed previously. This study was conducted to estimate the accuracy of both polymerase chain reaction (PCR and immunohistochemistry (IHC in micrometastases detection and determine the best site for bone marrow biopsy in order to find micrometastasis. Methods: This prospective cross-sectional study was performed in the Department of Thoracic Surgery, Alzahra University Hospital from September 2008 to June 2009. To evaluate the bone marrow, a 3-cm rib segment and an aspirated specimen from the iliac bone prior to tumor resection were taken. PCR and IHC were performed for each specimen to find micrometastasis. Results: Of 41 patients, 14 (34% were positive for BMM by PCR compared with two positive IHC (4.8%. All BMMs were diagnosed in rib segments, and iliac specimens were all free from metastatic lesion. Our data showed no significant association between variables such as age, sex, histology, tumor location, side of tumor, involved lobe, smoking, or weight loss and presence of BMM. Conclusion: PCR could use as a promising method for BMM detection. BMM in a sanctuary site (rib is not associated with advanced stages of lung cancer. In addition, when predictor variables such as age, sex, histology, tumor location, smoking, or weight loss are analyzed, no correlation can be found between micrometastasis prevalence and any of those variables.

  17. Role of the Endobronchial Landmarks Guiding TBNA and EBUS-TBNA in Lung Cancer Staging

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    S. Arias

    2016-01-01

    Full Text Available Background. Lung cancer is the leading cause of malignancy related mortality in the United States. Accurate staging of NSCLC influences therapeutic decisions. Transbronchial needle aspiration (TBNA and endobronchial ultrasound-guided TBNA (EBUS-TBNA has been accepted as a procedure for the diagnosis and staging of lung cancer. The aim of this study is to evaluate the efficacy and adequacy of TBNA and EBUS-TBNA for sampling of mediastinal adenopathy using the Wang’s eleven lymph node map stations. Methods. We retrospectively reviewed 99 consecutive cases diagnosed with malignancy by EBUS-TBNA and a series 74 patients evaluated for mediastinal adenopathy or a pulmonary lesion using conventional transbronchial needle aspiration. The IASLC lymph node map was correlated with Wang’s map. Results. A total of 182 lymph node stations were sampled using EBUS-TBNA. 96 were positive for nodal metastasis. A total of four cases of samples taken from station 2R showed malignant cells. From the 74 cases series using cTBNA 167 nodes were sampled in 222 passes. Lymphoid or malignant tissue was obtained in 67 (91.8% cases; 55.1% of the nodes were 1 cm or less. Conclusions. The use of the eleven stations described in Wang’s map to guide TBNA of the mediastinal nodes allows sampling of radiologically considered nonpathological nodes. These data suggest that Wang’s map covers the most frequent IASLC nodal stations compromised with metastasis.

  18. Long-term respiratory function recovery in patients with stage I lung cancer receiving video-assisted thoracic surgery versus thoracotomy

    Science.gov (United States)

    Park, Young Sik

    2016-01-01

    Background Video-assisted thoracic surgery (VATS) and thoracotomy are standard treatment methods for early lung cancer. We compared their effects on the long-term recovery of pulmonary function in patients with stage I non-small cell lung cancer (NSCLC). Methods We retrospectively reviewed 203 patients with early NSCLC who underwent VATS or thoracotomy at Seoul University Hospital from January 2005 to December 2010. Two matched groups (VATS and thoracotomy) each consisting of 60 patients were created via propensity score matching according to TNM stage, age, sex, smoking history, lung disease history, and preoperative pulmonary function. Results There were no significant differences in the recovery of forced expiratory volume in 1 second, the forced vital capacity (FVC), or the peak flow rate (PFR), presented as the postoperative value/predicted value, between the VATS and thoracotomy groups during the 12-month follow-up period. The standardized functional loss ratio [(measured postoperative value – predicted postoperative value)/(predicted postoperative value × 100)] did not differ between the two groups at 6 and 12 months. In an intragroup analysis, the postoperative FVC in the thoracotomy group remained below predicted postoperative value during the follow-up period and did not reach the predicted postoperative FVC (6 months/12 months: –6.58%/–2.43%). The analgesic requirements and pain procedures were similar in the VATS and thoracotomy groups during the 12-month follow-up period. Conclusions There were no significant differences in pulmonary function recovery during the late postoperative period in NSCLC patients receiving VATS versus thoracotomy. We suggest that the volume of the resected lung and preoperative lung function are the main determinants of late recovery, rather than postoperative pain. PMID:26904225

  19. Hospitalization costs of lung cancer diagnosis in Turkey: Is there a difference between histological types and stages?

    Science.gov (United States)

    Türk, Murat; Yıldırım, Fatma; Yurdakul, Ahmet Selim; Öztürk, Can

    2016-12-01

    To establish the direct costs of diagnosing lung cancer in hospitalized patients. Hospital data of patients who were hospitalized and diagnosed as lung cancer between September 2013 and August 2014 were retrospectively analyzed. Patients who underwent surgery for diagnosis and who were initiated with cancer treatment during the same hospital stay were excluded from study. Histological types and stages of lung cancer were determined. Expenses were grouped as laboratory costs, pathology costs, diagnostic imaging costs, overnight room charges, medication costs, blood center costs, consumable expenditures' costs and inpatient service charges (including consultants' service, electrocardiogram, follow-up, nursing services, diagnostic interventions). Of the 68 patients, 55 (81%) had non-small cell lung cancer (NSCLC), 13 (19%) had small cell lung cancer (SCLC). 47% of patients with NSCLC had stage 4 disease and 86% of patients with SCLC had extensive stage disease. Median total cost per patient was 910 (95% CI= 832-1291) Euros (€). Of all costs, 37% were due to inpatient service charges and 22% were medication costs. Median total cost per patient was 912 (95% CI= 783-1213) € in NSCLC patients and 908 (95% CI= 456-2203) € in SCLC patients (p> 0.05). In NSCLC group, total cost per patient was 873 (95% CI= 591-1143) € in stage 1-2-3 diseases and 975 (95% CI= 847-1536) € in stage 4 disease (p> 0.05). In SCLC group total cost per patient was 937 € in limited stage and 502 (95% CI= 452-2508) € in extensive stage (p> 0.05). There is no significant difference between costs related to diagnosis of different lung cancer types and stages in patients hospitalized in a university hospital.

  20. Relationship between tumor size and disease stage in non-small cell lung cancer

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    Yang Fu

    2010-09-01

    Full Text Available Abstract Background Whether tumor size and stage distribution are correlated remains controversial. The objective is to assess the relationship between tumor size and disease stage distribution in non-small cell lung cancer (NSCLC. Methods We conducted a retrospective analysis of 917 cases of NSCLC that were resected in the Cancer Hospital of Fudan University and Shanghai Sixth Hospital between January 2000 and February 2009. Tumor sizes were grouped into five categories: ≤20 mm, 21 to 30 mm, 31 to 50 mm, 51 to 70 mm and ≥71 mm. Results Age and tumor size affected stage distribution: patients 60 years or older had a higher percentage of N0M0 disease than patients younger than 60 years (61.67% vs. 44.85%, p Conclusions There is a statistically significant relationship between tumor size and distribution of disease stage of primary NSCLC tumors: the smaller the tumor, the more likely the disease is N0M0 status.

  1. Dream features in the early stages of Parkinson's disease.

    Science.gov (United States)

    Bugalho, Paulo; Paiva, Teresa

    2011-11-01

    Few studies have investigated the relation between dream features and cognition in Parkinson's disease (PD), although vivid dreams, hallucinations and cognitive decline have been proposed as successive steps of a pathological continuum. Our objectives were therefore to characterize the dreams of early stage PD and to study the relation between dream characteristics, cognitive function, motor status, depression, dopaminergic treatment, and the presence of REM sleep behaviour disorder (RBD) and hallucinations. Dreams of 19 male PD patients and 21 matched control subjects were classified according to Hall and van de Castle system. h statistics was used to compare the dream content between patients and controls. We tested the relation between patients' dreams characteristics and cognitive function (Frontal assessment battery (FAB) and Mini-Mental State Examination tests) depression (Beck depression inventory), motor function (UPDRS), dopaminergic treatment, the presence of RBD (according to clinical criteria) and hallucinations, using general linear model statistics. Patients and controls differed only on FAB scores. Relevant differences in the Hall and van de Castle scale were found between patient's dreams and those of the control group, regarding animals, aggression/friendliness, physical aggression, befriender (higher in the patient group) and aggressor and bodily misfortunes (lower in the patient group) features. Cognitive and particularly frontal dysfunction had a significant influence on the frequency of physical aggression and animal related features, while dopaminergic doses, depressive symptoms, hallucinations and RBD did not. We found a pattern of dream alteration characterized by heightened aggressiveness and the presence of animals. These were related to more severe frontal dysfunction, which could be the origin of such changes.

  2. Early Stage of Hypertensive Retinopathy; Is It Really Important?

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    Murat KARAMAN

    2014-09-01

    Full Text Available OBJECTIVE: To investigate the relationship between early stage hypertensive retinopathy (HTRP and endothelial dysfunction (ED in atherogenesis. MATERIAL and METHODS: A total of 99 subjects consisting of 73 patients diagnosed with Essential Hypertension (HT and 26 healthy subjects were included to the study. Flow mediated dilatation (FMD was performed to detect ED. Asymmetric dimethylarginine-ADMA was measured as a marker of ED and the hsCRP and sTWEAK levels were measured for microvascular inflammation. All patients were screened for retinopathy. RESULTS: The mean blood pressure of the hypertensive patients and the control subjects was 140.1±13.7/86.1±10.7 and 107.12±10.0/65.38±10.2 respectively. HTRP was positive in 60.3% (n=44 and negative in 39.7% (n=29 of the patients with hypertension. There was grade 1 retinopathy in 52.1% and grade 2 retinopathy in 8.2% of hypertensive patients. The hsCRP, sTWEAK and ADMA levels were significantly higher in hypertensive patients than in the control group (respectively, p=0,011, p=0,001, p=0,001. FMD levels were lower in the hypertensive group, as expected. FMD levels were lower in the retinopathy group when the hypertensive group with and without retinopathy and the control group compared. hsCRP, sTWEAK and ADMA levels were significantly higher in subjects with retinopathy. hsCRP, sTWEAK and ADMA levels were also significantly higher in subjects with retinopathy (p=0.039, p=0.001, p=0.001. CONCLUSION: ED is thought to play a role in HT etiology and is also important in the development of HT complications. It would be appropriate to evaluate hypertensive patients more carefully and perform the necessary laboratory tests to detect ED so that the proper treatment can be started (ACEI, exercise, lifestyle changes.

  3. Protein dynamics modulated electron transfer kinetics in early stage photosynthesis.

    Science.gov (United States)

    Kundu, Prasanta; Dua, Arti

    2013-01-28

    A recent experiment has probed the electron transfer kinetics in the early stage of photosynthesis in Rhodobacter sphaeroides for the reaction center of wild type and different mutants [Science 316, 747 (2007)]. By monitoring the changes in the transient absorption of the donor-acceptor pair at 280 and 930 nm, both of which show non-exponential temporal decay, the experiment has provided a strong evidence that the initial electron transfer kinetics is modulated by the dynamics of protein backbone. In this work, we present a model where the electron transfer kinetics of the donor-acceptor pair is described along the reaction coordinate associated with the distance fluctuations in a protein backbone. The stochastic evolution of the reaction coordinate is described in terms of a non-Markovian generalized Langevin equation with a memory kernel and Gaussian colored noise, both of which are completely described in terms of the microscopics of the protein normal modes. This model provides excellent fits to the transient absorption signals at 280 and 930 nm associated with protein distance fluctuations and protein dynamics modulated electron transfer reaction, respectively. In contrast to previous models, the present work explains the microscopic origins of the non-exponential decay of the transient absorption curve at 280 nm in terms of multiple time scales of relaxation of the protein normal modes. Dynamic disorder in the reaction pathway due to protein conformational fluctuations which occur on time scales slower than or comparable to the electron transfer kinetics explains the microscopic origin of the non-exponential nature of the transient absorption decay at 930 nm. The theoretical estimates for the relative driving force for five different mutants are in close agreement with the experimental estimates obtained using electrochemical measurements.

  4. Survival Analysis of 1,742 Patients with Stage IV Non-small Cell Lung Cancer

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    Hong PENG

    2011-04-01

    Full Text Available Background and objective At present non-small cell lung cancer (NSCLC is still the leading cause of death induced by cancer. The aim of this study is to investigate the prognostic factors of advanced NSCLC. Methods Total 1,742 cases of stage IV NSCLC data from Jan 4, 2000 to Dec 25, 2008 in Shanghai Chest Hospital were collected, confirmed by pathological examinations. Analysis was made to observe the impact of treatment on prognosis in gender, age, smoking history, pathology, classification, clinical TNM stage. Survival rate, survival difference were evaluated by Kaplan-Meire method and Logrank test respectively. The prognosis were analyzed by Cox multivariate regression. Results The median survival time of 1,742 patients was 10.0 months (9.5 months-10.5 months. One, two, three, four, and five-year survival rates were 44%, 22%, 13%, 9%, 6% respectively. The median survivals of single or multiple metastasis were 11 months vs 7 months (P < 0.001. Survival time were different in metastasic organs, with the median survival time as follows: lung for about 12 months (11.0 months-12.9 months, bone for 9 months (8.3 months-9.6 months, brain for 8 months (6.8 months-9.1 months, liver, adrenal gland, distannt lymph node metastasis for 5 months (3.8 months-6.1 months, and subcutaneous for 3 months (1.7 months-4.3 months. The median survival times of adenocarcinoma (n=1,086, 62% and squamous cell carcinoma cases (n=305, 17.5% were 12 months vs 8 months (P < 0.001. The median survival time of chemotherapy and best supportive care were 11 months vs 6 months (P < 0.001; the median survival times of with and without radiotherapy were 11 months vs 9 months (P=0.017. Conclusion Gender, age, gross type, pathological type, clinical T stage, N stage, numbers of metastatic organ, smoking history, treatment of advanced non-small cell lung cancer were independent prognostic factors.

  5. Predictive Parameters of CyberKnife Fiducial-less (XSight Lung) Applicability for Treatment of Early Non-Small Cell Lung Cancer: A Single-Center Experience

    Energy Technology Data Exchange (ETDEWEB)

    Bahig, Houda; Campeau, Marie-Pierre; Vu, Toni; Doucet, Robert; Béliveau Nadeau, Dominic [Radiation Oncology Department, Centre Hospitalier de l' Université de Montréal, Montréal, Quebec (Canada); Fortin, Bernard [Radiation Oncology Department, Maisonneuve-Rosemont Hospital, Montréal, Quebec (Canada); Roberge, David; Lambert, Louise; Carrier, Jean-François [Radiation Oncology Department, Centre Hospitalier de l' Université de Montréal, Montréal, Quebec (Canada); Filion, Edith, E-mail: edith.filion.chum@ssss.gouv.qc.ca [Radiation Oncology Department, Centre Hospitalier de l' Université de Montréal, Montréal, Quebec (Canada)

    2013-11-01

    Purpose: To determine which parameters allow for CyberKnife fiducial-less tumor tracking in stereotactic body radiation therapy (SBRT) for early-stage non-small cell lung cancer. Methods and Materials: A total of 133 lung SBRT patients were preselected for direct soft-tissue tracking based on manufacturer recommendations (peripherally located tumors ≥1.5 cm with a dense appearance) and staff experience. Patients underwent a tumor visualization test to verify adequate detection by the tracking system (orthogonal radiographs). An analysis of potential predictors of successful tumor tracking was conducted looking at: tumor stage, size, histology, tumor projection on the vertebral column or mediastinum, distance to the diaphragm, lung-to-soft tissue ratio, and patient body mass index. Results: Tumor visualization was satisfactory for 88 patients (66%) and unsatisfactory for 45 patients (34%). Median time to treatment start was 6 days in the success group (range, 2-18 days) and 15 days (range, 3-63 days) in the failure group. A stage T2 (P=.04), larger tumor size (volume of 15.3 cm{sup 3} vs 6.5 cm{sup 3} in success and failure group, respectively) (P<.0001), and higher tumor density (0.86 g/cm{sup 3} vs 0.79 g/cm{sup 3}) were predictive of adequate detection. There was a 63% decrease in failure risk with every 1-cm increase in maximum tumor dimension (relative risk for failure = 0.37, CI=0.23-0.60, P=.001). A diameter of 3.6 cm predicted a success probability of 80%. Histology, lung-to-soft tissue ratio, distance to diaphragm, patient's body mass index, and tumor projection on vertebral column and mediastinum were not found to be predictive of success. Conclusions: Tumor size, volume, and density were the most predictive factors of a successful XSight Lung tumor tracking. Tumors >3.5 cm have ≥80% chance of being adequately visualized and therefore should all be considered for direct tumor tracking.

  6. On the interplay effects with proton scanning beams in stage III lung cancer

    Energy Technology Data Exchange (ETDEWEB)

    Li, Yupeng [Department of Radiation Physics, The University of Texas MD Anderson Cancer Center, Houston, Texas 77030 and Applied Research, Varian Medical Systems, Palo Alto, California 94304 (United States); Kardar, Laleh; Liao, Li; Lim, Gino [Department of Industrial Engineering, The University of Houston, Houston, Texas 77204 (United States); Li, Xiaoqiang; Li, Heng; Zhu, Ronald X.; Sahoo, Narayan; Gillin, Michael; Zhang, Xiaodong, E-mail: xizhang@mdanderson.org [Department of Radiation Physics, The University of Texas MD Anderson Cancer Center, Houston, Texas 77030 (United States); Cao, Wenhua [Department of Radiation Physics, The University of Texas MD Anderson Cancer Center, Houston, Texas 77030 and Department of Industrial Engineering, The University of Houston, Houston, Texas 77204 (United States); Chang, Joe Y.; Liao, Zhongxing; Komaki, Ritsuko; Cox, James D. [Department of Radiation Oncology, The University of Texas MD Anderson Cancer Center, Houston, Texas 77030 (United States)

    2014-02-15

    Purpose: To assess the dosimetric impact of interplay between spot-scanning proton beam and respiratory motion in intensity-modulated proton therapy (IMPT) for stage III lung cancer. Methods: Eleven patients were sampled from 112 patients with stage III nonsmall cell lung cancer to well represent the distribution of 112 patients in terms of target size and motion. Clinical target volumes (CTVs) and planning target volumes (PTVs) were defined according to the authors' clinical protocol. Uniform and realistic breathing patterns were considered along with regular- and hypofractionation scenarios. The dose contributed by a spot was fully calculated on the computed tomography (CT) images corresponding to the respiratory phase that the spot is delivered, and then accumulated to the reference phase of the 4DCT to generate the dynamic dose that provides an estimation of what might be delivered under the influence of interplay effect. The dynamic dose distributions at different numbers of fractions were compared with the corresponding 4D composite dose which is the equally weighted average of the doses, respectively, computed on respiratory phases of a 4DCT image set. Results: Under regular fractionation, the average and maximum differences in CTV coverage between the 4D composite and dynamic doses after delivery of all 35 fractions were no more than 0.2% and 0.9%, respectively. The maximum differences between the two dose distributions for the maximum dose to the spinal cord, heart V40, esophagus V55, and lung V20 were 1.2 Gy, 0.1%, 0.8%, and 0.4%, respectively. Although relatively large differences in single fraction, correlated with small CTVs relative to motions, were observed, the authors' biological response calculations suggested that this interfractional dose variation may have limited biological impact. Assuming a hypofractionation scenario, the differences between the 4D composite and dynamic doses were well confined even for single fraction. Conclusions

  7. Impact of Introducing Stereotactic Lung Radiotherapy for Elderly Patients With Stage I Non-Small-Cell Lung Cancer : A Population-Based Time-Trend Analysis

    NARCIS (Netherlands)

    Palma, David; Visser, Otto; Lagerwaard, Frank J.; Belderbos, Jose; Slotman, Ben J.; Senan, Suresh

    2010-01-01

    Purpose Stereotactic body radiotherapy (SBRT) for stage I non-small-cell lung cancer (NSCLC) is associated with high local control rates. The impact of introducing SBRT in patients 75 years of age or older was studied using a population-based cancer registry. Methods The Amsterdam Cancer Registry wa

  8. Effect of ozone oxidative preconditioning in preventing early radiation-induced lung injury in rats

    Directory of Open Access Journals (Sweden)

    B.H. Bakkal

    2013-09-01

    Full Text Available Ionizing radiation causes its biological effects mainly through oxidative damage induced by reactive oxygen species. Previous studies showed that ozone oxidative preconditioning attenuated pathophysiological events mediated by reactive oxygen species. As inhalation of ozone induces lung injury, the aim of this study was to examine whether ozone oxidative preconditioning potentiates or attenuates the effects of irradiation on the lung. Rats were subjected to total body irradiation, with or without treatment with ozone oxidative preconditioning (0.72 mg/kg. Serum proinflammatory cytokine levels, oxidative damage markers, and histopathological analysis were compared at 6 and 72 h after total body irradiation. Irradiation significantly increased lung malondialdehyde levels as an end-product of lipoperoxidation. Irradiation also significantly decreased lung superoxide dismutase activity, which is an indicator of the generation of oxidative stress and an early protective response to oxidative damage. Ozone oxidative preconditioning plus irradiation significantly decreased malondialdehyde levels and increased the activity of superoxide dismutase, which might indicate protection of the lung from radiation-induced lung injury. Serum tumor necrosis factor alpha and interleukin-1 beta levels, which increased significantly following total body irradiation, were decreased with ozone oxidative preconditioning. Moreover, ozone oxidative preconditioning was able to ameliorate radiation-induced lung injury assessed by histopathological evaluation. In conclusion, ozone oxidative preconditioning, repeated low-dose intraperitoneal administration of ozone, did not exacerbate radiation-induced lung injury, and, on the contrary, it provided protection against radiation-induced lung damage.

  9. Effect of ozone oxidative preconditioning in preventing early radiation-induced lung injury in rats

    Energy Technology Data Exchange (ETDEWEB)

    Bakkal, B.H. [Department of Radiation Oncology, School of Medicine, Bulent Ecevit University, Kozlu, Zonguldak (Turkey); Gultekin, F.A. [Department of General Surgery, School of Medicine, Bulent Ecevit University, Kozlu, Zonguldak (Turkey); Guven, B. [Department of Biochemistry, School of Medicine, Bulent Ecevit University, Kozlu, Zonguldak (Turkey); Turkcu, U.O. [Mugla School of Health Sciences, Mugla Sitki Kocman University, Mugla (Turkey); Bektas, S. [Department of Pathology, School of Medicine, Bulent Ecevit University, Kozlu, Zonguldak (Turkey); Can, M. [Department of Biochemistry, School of Medicine, Bulent Ecevit University, Kozlu, Zonguldak (Turkey)

    2013-09-27

    Ionizing radiation causes its biological effects mainly through oxidative damage induced by reactive oxygen species. Previous studies showed that ozone oxidative preconditioning attenuated pathophysiological events mediated by reactive oxygen species. As inhalation of ozone induces lung injury, the aim of this study was to examine whether ozone oxidative preconditioning potentiates or attenuates the effects of irradiation on the lung. Rats were subjected to total body irradiation, with or without treatment with ozone oxidative preconditioning (0.72 mg/kg). Serum proinflammatory cytokine levels, oxidative damage markers, and histopathological analysis were compared at 6 and 72 h after total body irradiation. Irradiation significantly increased lung malondialdehyde levels as an end-product of lipoperoxidation. Irradiation also significantly decreased lung superoxide dismutase activity, which is an indicator of the generation of oxidative stress and an early protective response to oxidative damage. Ozone oxidative preconditioning plus irradiation significantly decreased malondialdehyde levels and increased the activity of superoxide dismutase, which might indicate protection of the lung from radiation-induced lung injury. Serum tumor necrosis factor alpha and interleukin-1 beta levels, which increased significantly following total body irradiation, were decreased with ozone oxidative preconditioning. Moreover, ozone oxidative preconditioning was able to ameliorate radiation-induced lung injury assessed by histopathological evaluation. In conclusion, ozone oxidative preconditioning, repeated low-dose intraperitoneal administration of ozone, did not exacerbate radiation-induced lung injury, and, on the contrary, it provided protection against radiation-induced lung damage.

  10. The diagnostic value of indeterminate lung lesions on staging chest computed tomographies in patients with colorectal cancer

    DEFF Research Database (Denmark)

    Christoffersen, Mette Williaume; Bulut, Orhan; Jess, Per

    2010-01-01

    INTRODUCTION: Selection of pulmonary staging modality in colorectal cancer surgery is controversial. Computed tomography (CT) clearly outperforms x-ray in terms of sensitivity, but findings of indeterminate lung lesions remain a problem. The aim of the present study was to evaluate the significance...... indeterminate lung findings. Four died postoperatively. The remaining 22 were followed for a median period of 26 months. RESULTS: In eight of the 22 patients (36%) lesions progressed. In one patient, the lesion turned out to be a primary lung cancer, in another a lymphoma. In the last six patients (27...... tenth into other lung malignancies, which were most often diagnosed in the second year after surgery. The development of lung metastases was significantly related to positive nodal disease and postoperative CEA elevation....

  11. Should Nonsmokers Be Excluded from Early Lung Cancer Screening with Low-Dose Spiral Computed Tomography? Community-Based Practice in Shanghai

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    Xiaoyang Luo

    2017-08-01

    Full Text Available OBJECTIVE: We investigated the efficacy of early lung cancer screening with low-dose spiral computed tomography(LDCT in both smokers and nonsmokers based on the current situation of community health service, with integration of superior resources of medical institutions at all levels in Shanghai. METHODS: From August 2013 to August 2014, we screened 11,332 (male 7144; female 4188 high-risk individuals in selected communities of Minhang, Shanghai City, for early diagnosis of lung cancer with LDCT combined with multidisciplinary comprehensive treatment pattern including minimally invasive surgery, exploring the medical service network covering prevention, diagnosis, treatment, rehabilitation, and follow-up. RESULTS: Screening resulted in a diagnosis of cancer in 29 participants. Of these participants, 27 had primary lung cancer, 1 had lung metastatic cancer, and 1 had breast cancer. The detection rate of primary lung cancer was 238.26 cases per 100,000 person-years among all the participants. Specifically, the incidence of primary lung cancer was 336.97 cases per 100,000 person-years among the nonsmoking participants, as compared with 159.06 cases per 100,000 person-years among the smoking participants (P = .054. Among the 27 primary lung cancers, 22 (81.48% had stage 0 to I lung cancer. CONCLUSION: Based on community health service, screening with LDCT could improve the early diagnosis rate of lung cancer in both smokers and nonsmokers with feasibility and validity, which could be applicable in qualified eligible medical centers and communities in China. It is not reasonable to exclude nonsmokers from screening with LDCT.

  12. Pre-operative concurrent chemoradiotherapy for stage IIIA (N2) Non-Small cell lung cancer

    Energy Technology Data Exchange (ETDEWEB)

    Lee, Kyu Chan; Ahn, Yong Chan; Park, Keun Chil [College of Medicine, Sungkyunkwan Univ., Seoul (Korea, Republic of)] [and others

    1999-06-01

    This is to evaluate the acute complication, resection rate, and tumor down-staging after pre-operative concurrent chemoradiotherapy for stage IIIA (N2) non-small cell lung cancer. Fifteen patients with non-small cell lung cancer were enrolled in this study from May 1997 to June 1998 in Samsung Medical Center. The median age of the patients was 61 (range, 45-67) years and male to female ratio was 12:3. Pathologic types were squamous cell carcinoma (11) and adenocarcinoma (4). Pre-operative clinical tumor stages were cT1 in 2 patients, cT2 in 12, and cT3 in 1 and all were N2. Ten patients were proved to be N2 with mediastinoscopic biopsy and five had clinically evident mediastinal lymph node metastases on the chest CT scans. Pre-operative radiation therapy field included the primary tumor, the ipsilateral hilum, and the mediastinum. Total radiation dose was 45 Gy over 5 weeks with daily dose of 1.8 Gy. Pre-operative concurrent chemotherapy consisted of two cycles of intraventous cis-Platin (100 mg/m{sup 2}) on day 1 and oral Etoposide (50 mg/m{sup 2}/day) on days 1 through 14 with 4 weeks' interval. Surgery was followed after the pre-operative re-evaluation including chest CT scan in 3 weeks of the completion of the concurrent chemoradiotherapy if there was no evidence of disease progression. Full dose radiation therapy was administered to all the 15 patients. Planned two cycles of chemotherapy was completed in 11 patients and one cycle was given to four. One treatment related death of acute respiratory distress syndrome occurred in 15 days of surgery. Hospital admission was required in three patients including one with radiation pneumonitis and two with neutropenic fever. Hematologic complications and other acute complications including esophagitis were tolerable. Resection rate was 92.3% (12/13) in 13 patients excluding two patients who refused surgery. Pleural seeding was found in one patient after thoracotomy and tumor resection was not feasible. Post

  13. Lung function and bronchial responsiveness after Mycoplasma pneumoniae infection in early childhood

    DEFF Research Database (Denmark)

    Boysen, Birgitte Kjær; Jensen, Jørgen S; Nielsen, Kim G

    2008-01-01

    follow-up examination including lung function testing (28 PCR-positive and 37 PCR-negative). In addition to the PCR-test for M. pneumoniae all respiratory tract specimens were additionally tested for other atypical bacteria and for viruses by PCR. Lung function was measured as specific airway resistance...... by whole-body plethysmography and bronchial hyperresponsiveness was assessed by cold, dry air hyperventilation. Neither baseline lung function nor bronchial response to cold dry air hyperventilation differed between M. pneumoniae-positive and -negative children: mean baseline lung function were 1.17 versus...... 1.21 (kPa sec), P = 0.45; and mean change in specific resistance was 13% versus 9%, P = 0.42. In conclusion, M. pneumoniae infection in early childhood was not associated with long-term effects on lung function and bronchial hyperresponsiveness 2 years after infection....

  14. Quality of Life after Video-assisted Thoracoscopic Surgery or Minimal Incision Thoracotomy for Early Stage Nonsmall Cell Lung Cancer : A Prospective, Randomized Controlled Trial%电视胸腔镜与小切口开胸治疗临床早期非小细胞肺癌患者术后生活质量的前瞻性随机对照研究

    Institute of Scientific and Technical Information of China (English)

    龙浩; 郑燕; 林勇斌; 司徒冬荣; 马国伟; 姜龙

    2012-01-01

    Objective To evaluate video-assisted thoracic surgery (VATS) and minimal incision thoracotomy (MIT) lobectomy for early stage non-small cell lung cancer patients and the impact upon postoperative quality of life (QOL). Methods A prospective randomized controlled trial was conducted. From January 1, 2008 to December 10, 2011, the qualified patients with early stage NSCLC were recruited and randomized to VATS group (57 patients) and MIT group (49 patients), totally 106 patients, 57 males and 49 females, aged 57. 60 years. The quality of life was assessed using Lung Cancer Symptom Scale (LCSS) before operation and at 1,3,6,9,12 months after operation. Results There were no significant differences between the 2 groups in age, sex, the location of tumor, tumor pathologic stage, pathological types, postoperative complications, tumor size, operative time, operative bleeding and air leak days. There were no symptoms after operation at the VATS group worse than the leve before operation. Five major symptoms, including appetite (1.04 ± 0. 71 vs.2.00+0. 83,F=6.357, P=0.021), fatigue(4.55+1.17 vs. 10. 19+2.10,F=A.721, P=0.043),dyspnea(2.18±0.86 vs. 10.26±2.05,F=10.020,P=0.005),normal activity(5.16±1.70 vs. 17.60±3.17,F=12.319.P=0. 002)attheMIT group were deteriorated significantly at 1 month after the operation (P < 0. 05). Conclusion The VATS will lead to better quality of life for the patients with early stage NSCLC after surgery and lead to a smooth postoperative recovery.%目的 比较电视胸腔镜手术(video-assisted thoracoscopic surgery,VATS)与小切口开胸手术(minimal incision thoracotomy,MIT)治疗临床早期非小细胞肺癌(non-small cell lung cancer,NSCLC)及其两种手术方式术后患者生活质量的变化特点.方法 我们的研究为前瞻性随机对照临床研究生活质量的阶段分析.共纳入2008年1月1日至2011年12月10日中山大学肿瘤防治中心收治的106例NSCLC患者(男57例、女49例,平均年龄57,60岁),采

  15. Validation of the Eighth Edition of the TNM Staging System for Lung Cancer in 2043 Surgically Treated Patients With Non-small-cell Lung Cancer.

    Science.gov (United States)

    Chen, Kezhong; Chen, Haiqing; Yang, Fan; Sui, Xizhao; Li, Xiao; Wang, Jun

    2017-04-12

    The International Association for the Study of Lung Cancer has proposed a revision of the Tumor, Node, Metastasis (TNM) classification for lung cancer. The purpose of this study is to evaluate the prognostic value of the eighth edition of the TNM staging system in surgically treated patients with non-small-cell lung cancer. Data from 2043 consecutive patients with non-small-cell lung cancer who underwent surgical treatment in our single center between January 2006 and September 2015 were collected and analyzed retrospectively. Cox proportional hazard models were used to assess the prognostic significance of the T and N descriptors. The reversed overall survival curves of stage IIA and stage IIB in the seventh edition were corrected in the eighth edition. Better prognostic value in predicting overall survival, including a higher log rank test of trend χ(2) statistic (433.6 vs. 414.2), a smaller Akaike Information Criterion value (4759.6 vs. 4768.2), a higher Harrell C-index (0.776 vs. 0.769), and a lower integrated Brier score (0.092 vs. 0.093), was observed for the eighth edition relative to the seventh edition. Recurrence-free survival analysis of subsets of patients stratified by T and N descriptors showed a stepwise deterioration. Significant differences were found between patients of subdivided stage IA (IAI vs. IA2; P = .003 and IA2 vs. IA3; P = .004). The eighth edition of the TNM staging system for lung cancer has prognostic value superior to that of the seventh edition. It was able to predict recurrence-free survival well. Copyright © 2017 Elsevier Inc. All rights reserved.

  16. Exome sequencing identifies early gastric carcinoma as an early stage of advanced gastric cancer.

    Directory of Open Access Journals (Sweden)

    Guhyun Kang

    Full Text Available Gastric carcinoma is one of the major causes of cancer-related mortality worldwide. Early detection and treatment leads to an excellent prognosis in patients with early gastric cancer (EGC, whereas the prognosis of patients with advanced gastric cancer (AGC remains poor. It is unclear whether EGCs and AGCs are distinct entities or whether EGCs are the beginning stages of AGCs. We performed whole exome sequencing of four samples from patients with EGC and compared the results with those from AGCs. In both EGCs and AGCs, a total of 268 genes were commonly mutated and independent mutations were additionally found in EGCs (516 genes and AGCs (3104 genes. A higher frequency of C>G transitions was observed in intestinal-type compared to diffuse-type carcinomas (P = 0.010. The DYRK3, GPR116, MCM10, PCDH17, PCDHB1, RDH5 and UNC5C genes are recurrently mutated in EGCs and may be involved in early carcinogenesis.

  17. Noninvasive staging of lung cancer. Indications and limitations of gallium-67 citrate imaging

    Energy Technology Data Exchange (ETDEWEB)

    Bekerman, C.; Caride, V.J.; Hoffer, P.B.; Boles, C.A. (Univ. of Illinois, Chicago (USA))

    1990-05-01

    The results of evaluation of the hila and mediastinum with 67Ga scans are contradictory, as are the recommendations by different investigators on the use of 67Ga scintigraphy in the clinical evaluation of patients with primary lung carcinoma. Nevertheless, the economy and logistic simplicity of evaluating local and distant metastases with a single imaging procedure are attractive, especially because the symptoms may not enable the physician to make a correct identification of the organ systems affected by metastases. Neumann and Hoffer state that at present conventional Ga-67 scanning techniques cannot be recommended for preoperative staging of mediastinal lymph node metastases in lung cancer patients. According to Waxman, 67Ga scintigraphy, relative to other imaging modalities, is a sensitive indicator of hilar spread of a tumor. However, because of the normally high background activity within the sternum and spine, mediastinal abnormalities may be poorly detected. Since most pulmonary tumors metastasize via regional nodes to the pulmonary hilum and then to the mediastinum, the high sensitivity for the detection of pulmonary hilar abnormalities and the high specificity for detection of mediastinal lesions suggest that gallium scintigraphy is a valuable adjunctive test when used appropriately. The results obtained locally are probably the best guide for individual physicians in the selection of diagnostic tests for their patients. Gallium scans may thus be helpful in the clinical evaluation of patients with lung cancer. Although gallium scans identify mediastinal node involvement, there is considerable controversy over the relationship between the sensitivity and specificity of the method. By detecting distant extrathoracic metastases, the 67Ga scan may identify a small group of patients who can be spared a needless operation. 92 references.

  18. Diagnosis of Late Stage, Early Onset, Small Fiber Polyneuropathy

    Science.gov (United States)

    2016-10-01

    additionally discovered SFPN that affects adolescents and adults [2]. This early-onset SFPN usually begins in adolescence or early adulthood but can...promote early diagnosis. What was the impact on other disciplines? Nothing to report. What was the impact on technology transfer? Nothing to report...What was the impact on society beyond science and technology ? As described above, Veterans’ health and, by extension, public health will be

  19. CYP450 polymorphisms as risk factors for early-onset lung cancer: gender-specific differences.

    Science.gov (United States)

    Timofeeva, Maria N; Kropp, Silke; Sauter, Wiebke; Beckmann, Lars; Rosenberger, Albert; Illig, Thomas; Jäger, Birgit; Mittelstrass, Kirstin; Dienemann, Hendrik; Bartsch, Helmut; Bickeböller, Heike; Chang-Claude, Jenny C; Risch, Angela; Wichmann, Heinz-Erich

    2009-07-01

    Cytochrome P450 (CYP) enzymes, involved in metabolism of tobacco carcinogens, are also involved in estrogen metabolism and many are regulated by estrogens. These genes may thus be of relevance to gender-specific differences in lung cancer risk, particularly in early-onset lung cancer, where a high proportion of women is observed. We conducted a case-control study to investigate genetic polymorphisms in cytochromes that might modify the risk of developing early-onset lung cancer. In total, 638 Caucasian patients under the age of 51 with primary lung cancer and 1300 cancer-free control individuals, matched by age and sex, were included in this analysis. Thirteen polymorphisms in the CYP1A1, CYP1B1, CYP2A13, CYP3A4 and CYP3A5 genes were analyzed. No significant association was found for any of the analyzed polymorphisms and lung cancer risk overall. However, among women, a significantly increased risk of early-onset lung cancer was observed for carriers of the minor allele of CYP1B1 SNP rs1056836 [odds ratio (OR) 1.97; 95% confidence interval (CI) 1.32-2.94; P lung cancer risk was observed in the group of women carriers of the minor allele of CYP2A13 SNP rs1709084 (OR 1.64; 95% CI 1.00-2.70; P = 0.05). The effect of these two polymorphisms was shown to be modified by smoking. Haplotype analysis was performed for CYP1B1 and CYP2A13. No differences between cases and controls were observed for both genes (P = 0.63 and P = 0.42 for CYP1B1 and CYP2A13, respectively). Our results suggest that the CYP1B1 and the CYP2A13 genotypes may contribute to individual susceptibility to early-onset lung cancer in women.

  20. Definition of stereotactic body radiotherapy. Principles and practice for the treatment of stage I non-small cell lung cancer

    Energy Technology Data Exchange (ETDEWEB)

    Guckenberger, M.; Sauer, O. [University of Wuerzburg, Department of Radiation Oncology, Wuerzburg (Germany); Andratschke, N. [University of Rostock, Department of Radiotherapy and Radiation Oncology, Rostock (Germany); Alheit, H. [Distler Radiation Oncology, Bautzen/Pirna (Germany); Holy, R. [RWTH Aachen University, Department of Radiation Oncology, Aachen (Germany); Moustakis, C. [University of Muenster, Department of Radiation Oncology, Muenster (Germany); Nestle, U. [University of Freiburg, Department of Radiation Oncology, Freiburg (Germany)

    2014-01-15

    This report from the Stereotactic Radiotherapy Working Group of the German Society of Radiation Oncology (Deutschen Gesellschaft fuer Radioonkologie, DEGRO) provides a definition of stereotactic body radiotherapy (SBRT) that agrees with that of other international societies. SBRT is defined as a method of external beam radiotherapy (EBRT) that accurately delivers a high irradiation dose to an extracranial target in one or few treatment fractions. Detailed recommendations concerning the principles and practice of SBRT for early stage non-small cell lung cancer (NSCLC) are given. These cover the entire treatment process; from patient selection, staging, treatment planning and delivery to follow-up. SBRT was identified as the method of choice when compared to best supportive care (BSC), conventionally fractionated radiotherapy and radiofrequency ablation. Based on current evidence, SBRT appears to be on a par with sublobar resection and is an effective treatment option in operable patients who refuse lobectomy. (orig.) [German] Die Arbeitsgruppe ''Stereotaktische Radiotherapie'' der Deutschen Gesellschaft fuer Radioonkologie (DEGRO) erarbeitete eine Definition der Koerperstereotaxie (SBRT), die sich an vorhandene internationale Definitionen anlehnt: Die SBRT ist eine Form der perkutanen Strahlentherapie, die mit hoher Praezision eine hohe Bestrahlungsdosis in einer oder wenigen Bestrahlungsfraktionen in einem extrakraniellen Zielvolumen appliziert. Zur Praxis der SBRT beim nichtkleinzelligen Bronchialkarzinom (NSCLC) im fruehen Stadium werden detaillierte Empfehlungen gegeben, die den gesamten Ablauf der Behandlung von der Indikationsstellung, Staging, Behandlungsplanung und Applikation sowie Nachsorge umfassen. Die Koerperstereotaxie wurde als Methode der Wahl im Vergleich zu Best Supportive Care, zur konventionell fraktionierten Strahlentherapie sowie zur Radiofrequenzablation identifiziert. Die Ergebnisse nach SBRT und sublobaerer Resektion

  1. Standard treatment option in stage III non-small-cell lung cancer: case against trimodal therapy and consolidation drug therapy.

    Science.gov (United States)

    Jeremić, Branislav

    2015-03-01

    Prospective randomized trials and meta-analyses established concurrent radiochemotherapy (RT-CHT) as standard treatment approach in patients with inoperable, locally advanced (stage IIIA and B) non-small-cell lung cancer (NSCLC). In patients with either clinically (c) or pathologically (p) staged disease (stage IIIA), including those with pN2 disease, trimodal therapy was also frequently practiced in the past and is currently still advocated by large cooperative groups and organizations. Similarly, consolidation CHT provided after concurrent RT-CHT was suggested to be feasible and effective in inoperable stage III NSCLC. Contrasting these practices and suggestions, there is no evidence that trimodal therapy in stage IIIA (clinically or pathologically staged) or consolidation CHT in inoperable stage III NSCLC plays any role in its treatment. In both cases, evidence clearly demonstrates that concurrent RT-CHT is of similar efficacy and less toxic, and it should be considered a standard treatment option for all patients with stage III NSCLC.

  2. Peripheral blood stem cell harvest in patients with limited stage small-cell lung cancer

    Energy Technology Data Exchange (ETDEWEB)

    Katakami, Nobuyuki; Takakura, Shunji; Fujii, Hiroshi; Nishimura, Takashi; Umeda, Bunichi [Kobe City General Hospital (Japan)

    2000-06-01

    Chemotherapy plus granulocyte colony-stimulating factor (G-CSF) induced mobilization of peripheral blood stem cells (PBSC) was performed in patients with limited stage small-cell lung cancer. Chemotherapy consisted of cisplatin/etoposide or cisplatin/adriamycin/etoposide. The amounts of CD34 positive cells and granulocyte-macrophage colony forming units (CFU-GM) collected during 2-3 courses of apheresis were 3.1{+-}2.9 x 10{sup 6}/kg (n=10) and 3.1{+-}1.5 x 10{sup 5}/kg (n=8) , respectively. Adequate amounts of PBSC were also harvested even in patients treated with concurrent chemoradiotherapy. Eight patients were successfully treated with high-dose chemotherapy consisting of ifosfamide, carboplatin and etoposide with PBSC transfusion. The patients'-bone marrow reconstruction was rapid and no treatment-related death was observed. (author)

  3. Novel treatment options in stage I non-small-cell lung cancer.

    Science.gov (United States)

    Tarasevych, Svitlana; Lauwers, Patrick; Vandaele, Frederik; van Meerbeeck, Jan P

    2014-09-01

    In the last 5 years, the current management of stage I non-small-cell lung cancer has been challenged due to novel surgical approaches and advances in radiation technology. The outcome after a sublobar resection is promising, especially for tumors less than 2 cm. Other treatment opportunities are available for high risk patients with comorbidity and impaired pulmonary function. Stereotactic ablative body radiotherapy is a good alternative treatment to surgery, especially in elderly and comorbid patients. However, randomized evidence comparing sublobar resection and stereotactic radiotherapy is presently lacking. The most recent development in radiotherapy is hadron therapy with a presumed reduced toxicity because of its peculiar physical and biological effects. Promising thermal and microwave ablative techniques are in development and have specific niche indications.

  4. Comparative study of the anatomic segmentectomy versus lobectomy for clinical stage I A peripheral lung cancer by video assistant thoracoscopic surgery

    Directory of Open Access Journals (Sweden)

    Lin Zhang

    2013-01-01

    Conclusions: For stage I A peripheral lung cancer, the thoracoscopic anatomic segmentectomy was safe and effective just as thoracoscopic lobectomy, and furthermore with faster post-operative recovery.

  5. Early administration of IL-6RA does not prevent radiation-induced lung injury in mice

    Directory of Open Access Journals (Sweden)

    Inoue Takehiro

    2010-04-01

    Full Text Available Abstract Background Radiation pneumonia and subsequent radiation lung fibrosis are major dose-limiting complications for patients undergoing thoracic radiotherapy. Interleukin-6 (IL-6 is a pleiotropic cytokine and plays important roles in the regulation of immune response and inflammation. The purpose of this study was to investigate whether anti-IL-6 monoclonal receptor antibody (IL-6RA could ameliorate radiation-induced lung injury in mice. Methods BALB/cAnNCrj mice having received thoracic irradiation of 21 Gy were injected intraperitoneally with IL-6RA (MR16-1 or control rat IgG twice, immediately and seven days after irradiation. Enzyme-linked immunosorbent assay was used to examine the plasma level of IL-6 and serum amyloid A (SAA. Lung injury was assessed by histological staining with haematoxylin and eosin or Azan, measuring lung weight, and hydroxyproline. Results The mice treated with IL-6RA did not survive significantly longer than the rat IgG control. We observed marked up-regulation of IL-6 in mice treated with IL-6RA 150 days after irradiation, whereas IL-6RA temporarily suppressed early radiation-induced increase in the IL-6 release level. Histopathologic assessment showed no differences in lung section or lung weight between mice treated with IL-6RA and control. Conclusions Our findings suggest that early treatment with IL-6RA after irradiation alone does not protect against radiation-induced lung injury.

  6. Early administration of IL-6RA does not prevent radiation-induced lung injury in mice.

    Science.gov (United States)

    Ogata, Toshiyuki; Yamazaki, Hideya; Teshima, Teruki; Kihara, Ayaka; Suzumoto, Yuko; Inoue, Takehiro; Nishimoto, Norihiro; Matsuura, Nariaki

    2010-04-07

    Radiation pneumonia and subsequent radiation lung fibrosis are major dose-limiting complications for patients undergoing thoracic radiotherapy. Interleukin-6 (IL-6) is a pleiotropic cytokine and plays important roles in the regulation of immune response and inflammation. The purpose of this study was to investigate whether anti-IL-6 monoclonal receptor antibody (IL-6RA) could ameliorate radiation-induced lung injury in mice. BALB/cAnNCrj mice having received thoracic irradiation of 21 Gy were injected intraperitoneally with IL-6RA (MR16-1) or control rat IgG twice, immediately and seven days after irradiation. Enzyme-linked immunosorbent assay was used to examine the plasma level of IL-6 and serum amyloid A (SAA). Lung injury was assessed by histological staining with haematoxylin and eosin or Azan, measuring lung weight, and hydroxyproline. The mice treated with IL-6RA did not survive significantly longer than the rat IgG control. We observed marked up-regulation of IL-6 in mice treated with IL-6RA 150 days after irradiation, whereas IL-6RA temporarily suppressed early radiation-induced increase in the IL-6 release level. Histopathologic assessment showed no differences in lung section or lung weight between mice treated with IL-6RA and control. Our findings suggest that early treatment with IL-6RA after irradiation alone does not protect against radiation-induced lung injury.

  7. Approaches to the Treatment of Early Stage of Gallstone Disease in Children

    Directory of Open Access Journals (Sweden)

    O.G. Shadrin

    2013-11-01

    Conclusions. Diagnosis and treatment of GSD at the early stage make it possible to increase the efficacy of therapy in whole. It was noted that ursodeoxycholic acid (Ukrliv suspension possesses high efficiency and safety in the treatment of early GSD stage in children.

  8. Targeted labeling of early-​stage tumor spheroid in chorioallantoic membrane model with upconversion nanoparticles

    NARCIS (Netherlands)

    K. Liu; J.A. Holz; Y. Ding; X. Liu; Y. Zhang; L. Tu; X. Kong; B. Priem; A. Nadort; S.A.G. Lambrechts; M.C.G. Aalders; W.J. Buma; Y. Liu; H. Zhang

    2015-01-01

    In vivo detection of cancer at early-​stage, i.e. smaller than 2 mm, is a challenge in biomedicine. In this work target labeling of early-​stage tumor spheroid (∼500 μm) is realized for the first time in chick embryo chorioallantoic membrane (CAM) model with monoclonal antibody functionalized upconv

  9. 76 FR 76907 - Small Business Investment Companies-Early Stage SBICs

    Science.gov (United States)

    2011-12-09

    ... comments, identified by RIN 3245-AG32, by any of the following methods: Federal eRulemaking Portal: http..., particularly those without the necessary assets or cash flow for traditional bank funding. Although the venture... the ``Early Stage SBIC'' definition. Third, an Early Stage SBIC must invest at least 50 percent of its...

  10. A Pilot Study of Circulating Tumor Cells in Stage IV Non-Small Cell Lung Carcinoma

    Directory of Open Access Journals (Sweden)

    Max Haid

    2016-08-01

    Full Text Available Purpose: Measurement of the number of circulating tumor cells (CTCs in the bloodstream has been shown to have prognostic significance in treating breast carcinoma. This pilot study was formulated to determine if stage IV non-small cell lung carcinomas similarly shed malignant cells into the circulation and if their presence has prognostic significance. Methods: Patients with stage IV non-small cell lung carcinomas were tested once for CTCs in 7.5 ml of their blood prior to receiving any treatments. A proprietary blood collection kit produced by Veridex LLC (Raritan, NJ, which manufactures the instrument that performs the immunomagnetic CELLSEARCH® CTC assay, was used. Tumor measurements were determined in three dimensions by the same radiologist using computerized axial tomography. The three-dimensional sum was used to represent tumor size. Survival from the date of the pretreatment CTC assay was monitored and recorded. Data were analyzed statistically using NCSS8 statistical software (NCSS LLC, Kaysville, UT. Results: Of 19 evaluable patients, 10 had no detectable CTCs. There was no relation between intrapulmonary primary tumor size and the number of CTCs, nor between tumor size and survival. Survival was not affected by gender or age at entry into the trial. The mean survival of those with no detectable CTCs was 536 ± 91.1 days versus 239 ± 96.0 days for those with 1 or more detectable CTCs, a statistically significant advantage (P=0.034 favoring those without CTCs. Conclusions: Patients with a CTC score of 0 survived significantly longer than those with a CTC score of ≥ 1. Survival was not correlated with gender, age or primary tumor size. Recovery of CTCs potentially provides a noninvasive source of tumor cells for genomic profiling, which may enable development of a custom treatment plan for the individual patient. Further investigations are warranted and needed.

  11. Oxidative stress tolerance of early stage diabetic endothelial progenitor cell

    Directory of Open Access Journals (Sweden)

    Dewi Sukmawati

    2015-06-01

    Conclusions: Primitive BM-EPCs showed vasculogenic dysfunction in early diabetes. However the oxidative stress is not denoted as the major initiating factor of its cause. Our results suggest that primitive BM-KSL cell has the ability to compensate oxidative stress levels in early diabetes by increasing the expression of anti-oxidative enzymes.

  12. Neutrophils as early immunologic effectors in hemorrhage- or endotoxemia-induced acute lung injury.

    Science.gov (United States)

    Abraham, E; Carmody, A; Shenkar, R; Arcaroli, J

    2000-12-01

    Acute lung injury is characterized by accumulation of neutrophils in the lungs, accompanied by the development of interstitial edema and an intense inflammatory response. To assess the role of neutrophils as early immune effectors in hemorrhage- or endotoxemia-induced lung injury, mice were made neutropenic with cyclophosphamide or anti-neutrophil antibodies. Endotoxemia- or hemorrhage-induced lung edema was significantly reduced in neutropenic animals. Activation of the transcriptional regulatory factor nuclear factor-kappaB after hemorrhage or endotoxemia was diminished in the lungs of neutropenic mice compared with nonneutropenic controls. Hemorrhage or endotoxemia was followed by increases in pulmonary mRNA and protein levels for interleukin-1beta (IL-1beta), macrophage inflammatory protein-2 (MIP-2), and tumor necrosis factor-alpha (TNF-alpha). Endotoxin-induced increases in proinflammatory cytokine expression were greater than those found after hemorrhage. The amounts of mRNA or protein for IL-1beta, MIP-2, and TNF-alpha were significantly lower after hemorrhage in the lungs of neutropenic versus nonneutropenic mice. Neutropenia was associated with significant reductions in IL-1beta and MIP-2 but not in TNF-alpha expression in the lungs after endotoxemia. These experiments show that neutrophils play a central role in initiating acute inflammatory responses and causing injury in the lungs after hemorrhage or endotoxemia.

  13. Donor age and early graft failure after lung transplantation: a cohort study

    Science.gov (United States)

    Baldwin, Matthew R; Peterson, Eric R; Easthausen, Imaani; Quintanilla, Isaac; Colago, Eric; Sonett, Joshua R.; D’Ovidio, Frank; Costa, Joseph; Diamond, Joshua M; Christie, Jason D; Arcasoy, Selim M; Lederer, David J

    2014-01-01

    Lungs from older adult organ donors are often unused because of concerns for increased mortality. We examined associations between donor age and transplant outcomes among 8,860 adult lung transplant recipients using Organ Procurement and Transplantation Network and Lung Transplant Outcomes Group data. We used stratified Cox proportional hazard models and generalized linear mixed models to examine associations between donor age and both 1-year graft failure and primary graft dysfunction. The rate of 1-year graft failure was similar among recipients of lungs from donors age 18–64 years, but severely ill recipients (LAS > 47.7 or use of mechanical ventilation) of lungs from donors age 56–64 years had increased rates of 1-year graft failure (p-values for interaction = 0.04 and 0.02, respectively). Recipients of lungs from donors <18 and ≥65 years had increased rates of 1-year graft failure (adjusted hazard ratio 1.23, 95% CI 1.01–1.50 and adjusted hazard ratio 2.15, 95% CI 1.47–3.15, respectively). Donor age was not associated with the risk of primary graft dysfunction. In summary, the use of lungs from donors age 56–64 years may be safe for adult candidates without a high LAS, and the use of lungs from pediatric donors is associated with a small increase in early graft failure. PMID:24034167

  14. Mechanisms for split localization of Fgf10 expression in early lung development.

    Science.gov (United States)

    Hirashima, Tsuyoshi; Iwasa, Yoh; Morishita, Yoshihiro

    2009-11-01

    In early lung development, epithelial tubes (lung buds) intrude into mesenchyme covered with pleural cells (lung border), and form tree-like networks, by means of repeated use of morphogenetic processes: "elongation," "terminal bifurcation," and "lateral budding." When a bud is elongating, a peak of Fgf10 expression is formed in the mesenchyme near the tip; whereas when terminal bifurcation and lateral budding occur, two separate peaks are formed instead. To explain the spatial pattern of Fgf10 expression, we developed a mathematical model for the regulation of Fgf10 expression with geometrical conditions including shapes of the lung buds and the lung border. Different localization patterns of Fgf10 expression can be explained by the geometrical conditions. Fgf10 expression has a single peak when a length between the tip of lung bud and the lung border is large. When the length is small, Fgf10 expression has two peaks, whose location depends on the curvature of lung border. Copyright 2009 Wiley-Liss, Inc.

  15. Objective malignancy grading of squamous cell carcinoma of the lung. Stereologic estimates of mean nuclear size are of prognostic value, independent of clinical stage of disease

    DEFF Research Database (Denmark)

    Ladekarl, M; Bæk-Hansen, T; Henrik-Nielsen, R

    1995-01-01

    BACKGROUND: The prognostic value of quantitative histopathologic parameters was evaluated in 55 consecutively treated patients with operable lung carcinoma of squamous (N = 39) and mixed, adenosquamous (N = 16) cell type. Patients alive were followed for at least 12 years. METHODS: Using a projec......BACKGROUND: The prognostic value of quantitative histopathologic parameters was evaluated in 55 consecutively treated patients with operable lung carcinoma of squamous (N = 39) and mixed, adenosquamous (N = 16) cell type. Patients alive were followed for at least 12 years. METHODS: Using...... of nuclei to tissue, and the number of mitotic profiles per 10(3) nuclear profiles. For each patient, information was recorded regarding sex, age at diagnosis, and clinical stage of disease. RESULTS: Single-factor analyses showed that a favorable prognosis was associated with early clinical stages (Stages I...... volume were found to be parameters of significant, independent prognostic value. CONCLUSIONS: The present feasibility study indicates that estimates of the mean nuclear volume are of prognostic value, independent of the clinical stage of disease. This quantitative histopathologic variable is highly...

  16. Shape self-regulation in early lung morphogenesis.

    Directory of Open Access Journals (Sweden)

    Raphaël Clément

    Full Text Available The arborescent architecture of mammalian conductive airways results from the repeated branching of lung endoderm into surrounding mesoderm. Subsequent lung's striking geometrical features have long raised the question of developmental mechanisms involved in morphogenesis. Many molecular actors have been identified, and several studies demonstrated the central role of Fgf10 and Shh in growth and branching. However, the actual branching mechanism and the way branching events are organized at the organ scale to achieve a self-avoiding tree remain to be understood through a model compatible with evidenced signaling. In this paper we show that the mere diffusion of FGF10 from distal mesenchyme involves differential epithelial proliferation that spontaneously leads to branching. Modeling FGF10 diffusion from sub-mesothelial mesenchyme where Fgf10 is known to be expressed and computing epithelial and mesenchymal growth in a coupled manner, we found that the resulting laplacian dynamics precisely accounts for the patterning of FGF10-induced genes, and that it spontaneously involves differential proliferation leading to a self-avoiding and space-filling tree, through mechanisms that we detail. The tree's fine morphological features depend on the epithelial growth response to FGF10, underlain by the lung's complex regulatory network. Notably, our results suggest that no branching information has to be encoded and that no master routine is required to organize branching events at the organ scale. Despite its simplicity, this model identifies key mechanisms of lung development, from branching to organ-scale organization, and could prove relevant to the development of other branched organs relying on similar pathways.

  17. Survival after recurrence of stage I-III breast, colorectal, or lung cancer.

    Science.gov (United States)

    Hassett, Michael J; Uno, Hajime; Cronin, Angel M; Carroll, Nikki M; Hornbrook, Mark C; Fishman, Paul; Ritzwoller, Debra P

    2017-08-01

    The experiences of patients with recurrent cancer are assumed to reflect those of patients with de novo stage IV disease; yet, little is truly known because most registries lack recurrence status. Using two databases with excellent recurrence and death information, we examined determinants of survival duration after recurrence of breast (BC), colorectal (CRC), and lung cancers (LC). Recurrence status was abstracted from the medical records of patients who participated in the Cancer Care Outcomes Research and Surveillance study and who received care at two Cancer Research Network sites-the Colorado and Northwest regions of Kaiser Permanente. The analysis included 1653 patients who developed recurrence after completing definitive therapy for stages I-III cancer. Multivariable modeling identified independent determinants of survival duration after recurrence, controlling for other factors. Through 60 months' average follow-up, survival after recurrence for BC, CRC, and LC were 28.4, 23.1 and 16.1 months, respectively. Several factors were independently associated with shorter survival for all three cancers, including higher initial stage (III vs. I: BC -9.9 months; CRC -6.9 months; LC -7.4 months; P≤0.01). Factors associated with shorter survival for selected cancers included: distant/regional recurrence for BC and CRC; current/former smoker for LC; high grade for CRC; and recurrence for BC. Initial stage predicts survival duration after recurrence, whereas time-to-recurrence usually does not. The impact of biologic characteristics (e.g., grade, hormone-receptor status) on survival duration after recurrence needs further study. Predictors of survival duration after recurrence may help facilitate patient decision-making. Copyright © 2017 Elsevier Ltd. All rights reserved.

  18. Efficient and rapid isolation of early-stage embryos from Arabidopsis thaliana seeds

    OpenAIRE

    Raissig, Michael T; Gagliardini, Valeria; Jaenisch, Johan; Grossniklaus, Ueli; Baroux, Célia

    2013-01-01

    In flowering plants, the embryo develops within a nourishing tissue - the endosperm - surrounded by the maternal seed integuments (or seed coat). As a consequence, the isolation of plant embryos at early stages (1 cell to globular stage) is technically challenging due to their relative inaccessibility. Efficient manual dissection at early stages is strongly impaired by the small size of young Arabidopsis seeds and the adhesiveness of the embryo to the surrounding tissues. Here, we describe a ...

  19. Smoking history and lung carcinoma: KRAS mutation is an early hit in lung adenocarcinoma development.

    NARCIS (Netherlands)

    Thunnissen, F.B.J.M.; Prinsen, C.; Hol, B.; Drift, M.A. van der; Vesin, A.; Brambilla, C.; Montuenga, L.; Field, J.K.

    2012-01-01

    BACKGROUND: In a European multicenter prospective study patients with lung cancer were interviewed for smoking history and biological samples centrally collected. The aim of this study was to compare KRAS mutation analysis with smoking status at the time of diagnosis. METHODS: A nested case-study wa

  20. The effect on esophagus after different radiotherapy techniques for early stage Hodgkin's lymphoma

    DEFF Research Database (Denmark)

    Jørgensen, Anni; Maraldo, M.; Brodin, Nils Patrik

    2013-01-01

    The cure rate of early stage Hodgkin's lymphoma (HL) is excellent; investigating the late effects of treatment is thus important. Esophageal toxicity is a known side effect in patients receiving radiotherapy (RT) to the mediastinum, although little is known of this in HL survivors. This study inv...... investigates the dose to the esophagus in the treatment of early stage HL using different RT techniques. Estimated risks of early esophagitis, esophageal stricture and cancer are compared between treatments....

  1. A prospective study of tumor suppressor gene methylation as a prognostic biomarker in surgically-resected stage I-IIIA non-small cell lung cancers

    Science.gov (United States)

    Drilon, Alexander; Sugita, Hirofumi; Sima, Camelia S.; Zauderer, Marjorie; Rudin, Charles M.; Kris, Mark G.; Rusch, Valerie W.; Azzoli, Christopher G.

    2014-01-01

    Introduction While retrospective analyses support an association between early tumor recurrence and tumor suppressor gene (TSG) promoter methylation in early-stage non-small cell lung cancers (NSCLCs), few studies have investigated this question prospectively. Methods Primary tumor tissue from patients with resected pathologic stage I-IIIA NSCLCs was collected at the time of surgery and analyzed for promoter methylation via methylation-specific reverse-transcriptase polymerase chain reaction (MethyLight). The primary objective was to determine an association between promoter methylation of 10 individual TSGs (CDKN2A, CDH13, RASSF1, APC, MGMT, GSTP1, DAPK1, WIF1, SOCS3, and ADAMTS8) and recurrence-free survival (RFS), with the secondary objectives of determining association with overall survival (OS), and relation to clinical or pathologic features. Results 107 patients had sufficient tumor tissue for successful promoter methylation analysis. Majority of patients were former/current smokers (88%) with lung adenocarcinoma (78%) and pathologic stage I disease (66%). Median follow-up was 4 years. When controlled for pathologic stage, promoter methylation of the individual genes CDKN2A, CDH13, RASSF1, APC, MGMT, GSTP1, DAPK1, WIF1, and ADAMTS8 was not associated with RFS. Promoter methylation of the same genes was not associated with OS except for DAPK1 which was associated with improved OS (p=0.03). The total number of genes with methylated promoters did not correlate with RFS (p=0.89) or OS (p=0.55). Conclusions Contrary to data established by previous retrospective series, TSG promoter methylation (CDKN2A, CDH13, RASSF1,APC, MGMT, GSTP1, DAPK1, WIF1, and ADAMTS8) was not prognostic for early tumor recurrence in this prospective study of resected NSCLCs. PMID:25122424

  2. Macrophage Inhibitory Cytokine-1 (MIC-1 as A Biomarker for Diagnosis 
and Prognosis of Stage I-II Non-small Cell Lung Cancer

    Directory of Open Access Journals (Sweden)

    Yuning LIU

    2016-04-01

    Full Text Available Background and objective Increased macrophage inhibitory cytokine-1 (MIC-1, member of transforming growth factor-β (TGF-β superfamily, was found in patients serum with epithelial tumors. Therefore, our aim was to delineate the diagnostic and prognostic value of serum MIC-1 in patients with stage I-II non-small cell lung cancer (NSCLC. Methods A total of 152 consecutive patients with stage I–II NSCLC were prospectively enrolled and underwent follow up after total resection of tumor. Serum MIC-1 level was detected in lung cancer patients by ELISA, 48 benign pulmonary disease patients and 105 healthy controls, and was correlated with clinical features and prognosis of patients. Results The level of MIC-1 of NSCLC patients was significantly higher than that of controls (P<0.001 and benign pulmonary disease patients (P<0.001. A threshold of 1,000 pg/mL could be used to diagnose early-stage NSCLC with 70.4% sensitivity and 99.0% specificity. The level of MIC-1 was associated with elder age (P=0.001, female (P=0.03 and T2 (P=0.022. A threshold of 1,465 pg/mL could identify patients with early poor outcome with 72.2% sensitivity and 66.1% specificity. The overall 3-year survival rate in patients with high level of MIC-1 (≥1,465 pg/mL was significantly lower than that of patients with low MIC-1 level (77.6% vs 94.8%. Multivariable Cox regression revealed that a high level of MIC-1 was an independent risk factor for compromised overall survival (HR=3.37, 95%CI: 1.09-10.42, P=0.035. Conclusion High level of serum MIC-1 could be served as a potential biomarker for diagnosis and poorer outcome in patients with early-stage NSCLC.

  3. Original Paper Early stage leucocytosis in Nigerian pigs ...

    African Journals Online (AJOL)

    Sequential leukocyte changes associated with early phase of Trypanosoma brucei infection were investigated in ... members of the T. brucei sub group, human infective, T. brucei ..... trypanosome antigens to the bone marrow and generation of ...

  4. Efficacy of short-term nivolumab treatment in a Chinese patient with relapsed advanced-stage lung squamous cell carcinoma

    Science.gov (United States)

    Pi, Guoliang; He, Hanping; Bi, Jianping; Li, Ying; Li, Yanping; Zhang, Yong; Wang, Mingwei; Han, Guang; Lin, Chi

    2016-01-01

    Abstract Introduction: Currently, the options are limited for the treatment of patients who have failed 2 lines of chemotherapy for advanced lung squamous cell carcinoma (SCC). Recently, nivolumab, a fully human IgG4 programmed death 1 immune checkpoint inhibitor antibody, was approved to treat patients with advanced stage, relapsed/refractory lung SCC. Although nivolumab has demonstrated antitumor activity with survival benefit in Caucasian patients, its efficacy in Asian patients is unknown. Case Report: In this report, we describe a Chinese patient with relapsed advanced stage lung SCC who had an excellent response to nivolumab after only 2 doses without any adverse effects. Immunohistochemical analysis indicated the tumor was stained positive for programmed death-ligand 1. Conclusion: To our knowledge, this is the first report of satisfactory efficacy of short-term nivolumab treatment in a Chinese patient with relapsed advanced-stage lung SCC. Further clinical trials in Asian countries are needed to test whether nivolumab immunotherapy is a safe and effective treatment for Asian patients with lung SCC. PMID:27749580

  5. Early experience with lung transplantation using donors after cardiac death.

    Science.gov (United States)

    Mason, David P; Murthy, Sudish C; Gonzalez-Stawinski, Gonzalo V; Budev, Marie M; Mehta, Atul C; McNeill, Ann M; Pettersson, Gösta B

    2008-05-01

    Lung transplantations that utilize donor organs after cardiac death (DCD) can substantially increase the number of available allografts for waiting recipients. Unfortunately, reported clinical outcomes are limited and widespread acceptance is slow. To further examine the potential of this modality, the results of 4 patients transplanted with DCD organs, implementing a protocol of controlled organ retrieval (Maastricht Classification III), were reviewed. There were no operative deaths; extracorporeal membrane oxygenation was required in 1 patient secondary to severe primary graft dysfunction. Three patients are alive and well at 4, 15 and 21 months; 1 patient died at 34 months with bronchiolitis obliterans syndrome, in part attributable to medication non-compliance.

  6. Using Motivational Interviewing within the Early Stages of Group Development

    Science.gov (United States)

    Young, Tabitha L.

    2013-01-01

    This article presents developmentally appropriate applications of Motivational Interviewing (MI; Miller & Rollnick, 2002) for use in preparing group members for the working stages of group. Practical strategies are offered for using MI to facilitate an atmosphere of trust, recognize member readiness for change, identify and resolve members'…

  7. FDG-PET/CT Limited to the Thorax and Upper Abdomen for Staging and Management of Lung Cancer

    NARCIS (Netherlands)

    Arens, A.I.; Postema, J.W.; Schreurs, W.M.; Lafeber, A.; Hendrickx, B.W.; Oyen, W.J.G.; Vogel, W.V.

    2016-01-01

    PURPOSE: This study evaluates the diagnostic accuracy of [F-18]-fluorodeoxyglucose-positron emission tomography/computed tomography (FDG-PET/CT) of the chest/upper abdomen compared to the generally performed scan from head to upper thighs, for staging and management of (suspected) lung cancer in

  8. Perception of affective prosody in patients at an early stage of relapsing-remitting multiple sclerosis.

    Science.gov (United States)

    Kraemer, Markus; Herold, Michele; Uekermann, Jennifer; Kis, Bernhard; Daum, Irene; Wiltfang, Jens; Berlit, Peter; Diehl, Rolf R; Abdel-Hamid, Mona

    2013-03-01

    Cognitive dysfunction is well known in patients suffering from multiple sclerosis (MS) and has been described for many years. Cognitive impairment, memory, and attention deficits seem to be features of advanced MS stages, whereas depression and emotional instability already occur in early stages of the disease. However, little is known about processing of affective prosody in patients in early stages of relapsing-remitting MS (RRMS). In this study, tests assessing attention, memory, and processing of affective prosody were administered to 25 adult patients with a diagnosis of RRMS at an early stage and to 25 healthy controls (HC). Early stages of the disease were defined as being diagnosed with RRMS in the last 2 years and having an Expanded Disability Status Scale (EDSS) of 2 or lower. Patients and HC were comparable in intelligence quotient (IQ), educational level, age, handedness, and gender. Patients with early stages of RRMS performed below the control group with respect to the subtests 'discrimination of affective prosody' and 'matching of affective prosody to facial expression' for the emotion 'angry' of the 'Tübingen Affect Battery'. These deficits were not related to executive performance. Our findings suggest that emotional prosody comprehension is deficient in young patients with early stages of RRMS. Deficits in discriminating affective prosody early in the disease may make misunderstandings and poor communication more likely. This might negatively influence interpersonal relationships and quality of life in patients with RRMS.

  9. 大鼠肝缺血再灌注肺损伤早期肺组织差异表达基因的筛选%Selection of the early stage differentially expressed genes in rat lung tissue by eDNA microarray after total hepatic ischemia reperfusion injury

    Institute of Scientific and Technical Information of China (English)

    赵东; 杨拔贤

    2009-01-01

    Objective To examine the early changes in gene expression levels in lung tissues by cDNA microarray using a rat model of total hepatic ischemia reperfusion and to analysis function of the changes. Methods Twelve adult male SD rats weighting 220-250 g were divided randomly into two groups (6 in each group). The rats were sacrificed at end point of the operation and lung tissues were divided into several parts for either microarray analysis or RT-PCR of several genes selected from microarray data. Common change genes were selected from three chips and the final results of microarray analysis were identified by RT-PCR. At last, differentially expressed genes were classified according to their biological functions by cluster analysis. Results Analysis of the results showed those 48 genes up-regulated and 32 genes down-regalated after hepatic ischemia reperfusion lung injury. Only parts of them had we known about the function. Genes significantly up-regnlated were IL-1α, IL-1β, SLPI, MMP9, MMP14, MMP15, TIMP1, PIK3 RL, MAPK, NF-kB, JN K and others. Genes significantly down-regulated were CYP1A1, NQO1, GSTA3, RETNLA and others. Differentially expressed genes were mainly classified into inflammatory reaction, transcription factors, cell metabolism, signals transduction, ion or receptors, cytoskeleton, etc. Conclusions cDNA microarray technique provides a new method for detecting differentially expressed genes in rat lung tissues. Further study may reveal the molecular pathologic mechanism of hepatic ischemia reperfusion lung injury and discern new targets for therapeutic interventions.%目的 筛选肝缺血再灌注肺损伤大鼠早期肺组织差异表达的基因并作初步功能分析.方法 在大鼠全肝缺血再灌注肺损伤模型基础上,将12只雄性成熟SD大鼠随机分为2组,采用含22 012个基因的大鼠全基因组寡核苷酸基因芯片,检测损伤组大鼠肺组织差异表达的基因并进行初步功能分析.差异基因又通过RT

  10. Silica Induced Early Fibrogenic Reaction in Lung of Mice Ameliorated by Nyctanthes arbortristis Extract

    Institute of Scientific and Technical Information of China (English)

    2002-01-01

    Objective To investigate the pharmacological effect of Nyctanthes arbortristis (NAT) leaf extract in the prevention of lung injury induced by silica particles. Method Lung injury was induced in Swiss mice through inhalation exposure to silica particles (<5μ) using a Flow Past Nose Only Inhalation Chamber at the rate of -10 mg/m3 respirable mass for 5 h. Lung bronchoalveolar lavage (BAL) fluid collected between 48 and 72 h was subjected to protein profiling by electrophoresis and cytokine evaluation by solid phase sandwich ELISA. Lung histopathology was performed to evaluate lung injury. Results Inhalation of silica increased the level of tumor necrosis factor-α(TNF-α), and of the 66 and 63 kDa peptides in the BAL fluid in comparison to sham-treated control. Pre-treatment of silica exposed mice with NAT leaf extract significantly prevented the accumulation of TNF-α in the BAL fluid, but the 66 and 63 kDa peptides remained unchanged. The extract was also effective in the prevention of silica-induced early fibrogenic reactions like congestion, edema and infiltration of nucleated cells in the interstitial alveolar spaces, and thickening of alveolar septa in mouse lung. Conclusion NAT leaf extract helps in bypassing silica induced initial lung injury in mice.

  11. Swimming speed alteration in the early developmental stages of Paracentrotus lividus sea urchin as ecotoxicological endpoint.

    Science.gov (United States)

    Morgana, Silvia; Gambardella, Chiara; Falugi, Carla; Pronzato, Roberto; Garaventa, Francesca; Faimali, Marco

    2016-04-01

    Behavioral endpoints have been used for decades to assess chemical impacts at concentrations unlikely to cause mortality. With recently developed techniques, it is possible to investigate the swimming behavior of several organisms under laboratory conditions. The aims of this study were: i) assessing for the first time the feasibility of swimming speed analysis of the early developmental stage sea urchin Paracentrotus lividus by an automatic recording system ii) investigating any Swimming Speed Alteration (SSA) on P. lividus early stages exposed to a chemical reference; iii) identifying the most suitable stage for SSA test. Results show that the swimming speed of all the developmental stages was easily recorded. The swimming speed was inhibited as a function of toxicant concentration. Pluteus were the most appropriate stage for evaluating SSA in P. lividus as ecotoxicological endpoint. Finally, swimming of sea urchin early stages represents a sensitive endpoint to be considered in ecotoxicological investigations. Copyright © 2016 Elsevier Ltd. All rights reserved.

  12. A meta-analysis of the Timing of Chest Radiotherapy in Patients with Limited-stage Small Cell Lung Cancer

    Directory of Open Access Journals (Sweden)

    Hui ZHAO

    2010-09-01

    Full Text Available Background and objective Although evidence for a significant survival benefit of chest radiotherapy has been proven, no conclusion could be drawn regarding the optimal timing of chest radiation. The aim of this study is to explore whether the timing of chest radiation may influence the survival of the patients with limited-stage small-cell lung cancer (LSSCLC by performing a literature-based meta-analysis. Methods By searching Medline, CENTRAL (the Cochrane central register of controlled trials, CBM, and CNKI, et al, we collected both domestic and overseas published documents about randomized trials comparing different timing chest radiotherapy in patients with LS-SCLC. Early chest radiation was regarded as beginning within 30 days after the start of chemotherapy. Random or fixed effect models were applied to conduct meta-analysis on the trials. The combined odds ratio (OR and the 95% confidence interval (CI were calculated to estimate the mortality in 2 or 3 years and toxicity of the two treatments. The statistical heterogeneity was determined by cochran’s Chi-square test (Q test. The Begg’ test was used to determine the publication bias. Results Six trials that included a total of 1 189 patients were analyzed in the meta-analysis 587 patients were in the early radiation group and 602 patients were in the late radiation group. Considering all 6 eligible trials, the overall survival at 2/3 years was not significantly different between early and late chest radiation (OR=0.78, 95%CI: 0.55-1.05, Z=1.68, P=0.093. For the toxicity, no obvious difference was observed for early chest radiotherapy compared with late irradiation in pneumonitis (OR=1.93, 95%CI: 0.97-3.86, P=0.797, esophagitis (OR=1.43, 95%CI: 0.95-2.13, P=0.572 and thrombocytopenia (OR=1.23, 95%CI: 0.88-1.77, P=0.746, respectively. Conclusion No statistical difference was observed in 2/3 years survival and toxicity, including pneumonitis, esophagitis and thrombocytopenia, between

  13. Utility of SPECT Lung Perfusion Scans in Assessing the Early Changes in Pulmonary Function after Radiotherapy for Patients with Lung Cancer

    Institute of Scientific and Technical Information of China (English)

    Wenjie Zhang; Rong Zheng; Luiun Zhao; Luhua Wang; Shengzu Chen

    2005-01-01

    OBJECTIVE Radiation-induced lung injury commonly follows radiotherapy (RT) fortumors within and near the thorax. Lung function is usually measured by pulmonary function tests (PFTs). But RT-induced regional changes of pulmonary function cannot be accurately evaluated by PFTs. Lung perfusion scintigraphy compared with other radiographic methods can assess well regional pulmonary physiological function, and a 3-dimensional conformal radiotherapy planning system can quantitatively calculate irradiation dosage. The purpose of this study is to assess, by lung perfusion scintigraphy, early changes in the pulmonary function of patients with lung cancer when receiving thoracic 3-dimensional conformal radiotherapy (3D-CRT).METHODS Nineteen patients receiving thoracic 3D-CRT for lung cancer were studied. A single photon emission computed tomography (SPECT)lung perfusion scan, X-ray or CT scan before RT and after 40~50Gy radiation were performed. Pre-RT SPECT lung perfusion images were classified by comparing lung perfusion defects with radiological abnormalities before RT. Grade 0: There was no lung perfusion defect in the area of radiological abnormality. Grade 1: The size of the radiological abnormality was similar to the area of the lung perfusion defect. Grade 2: The area of the lung perfusion defect was bigger than the size of the radiological abnormality and extended to one lobe of the lung. Grade 3: The area of lung perfusion defect exceeded one lobe of the lung. The radiation field with more than 20 Gy was drawn as a region of interest (ROI). The proportion of radioactive dose within this ROI relative to total lung dose in one slice was calculated.RESULTS All patients had lung perfusion defects, nine patients with grade 1,five patients with grade 2 and five patients with grade 3 damage,respectively. All tumors in the 19 patients were reduced in CT or X-ray images to various degrees after 40~50 Gy radiation. The mean proportion of ROI in 19 patients was 53.7±29

  14. The prognostic value ofserum C-reactive protein-bound serum amyloid A inearly-stage lung cancer

    Institute of Scientific and Technical Information of China (English)

    XueYanZhang; GeZhang; YingJiang; DanLiu; ManZhiLi; QianZhong; ShanQiZeng; WanLiLiu; MuShengZeng

    2015-01-01

    Background:Elevated levels of serum C‑reactive protein (CRP) have been reported to have prognostic signiifcance in lung cancer patients. This study aimed to further identify CRP‑bound components as prognostic markers for lung cancer and validate their prognostic value. Methods:CRP‑bound components obtained from the serum samples from lung cancer patients or healthy controls were analyzed by differential proteomics analysis. CRP‑bound serum amyloid A (CRP‑SAA) was evaluated by co‑immunoprecipitation (IP). Serum samples from two independent cohorts with lung cancer (retrospective cohort, 242 patients; prospective cohort, 222 patients) and healthy controls (159 subjects) were used to evaluate the prognostic value of CRP‑SAA by enzyme‑linked immunosorbent assay. Results:CRP‑SAA was identiifed speciifcally in serum samples from lung cancer patients by proteomic analysis. CRP binding to SAA was conifrmed by co‑IP in serum samples from lung cancer patients and cell culture media. The level of CRP‑SAA was signiifcantly higher in patients than in healthy controls (0.37±0.58 vs. 0.03±0.04,P<0.001). Elevated CRP‑SAA levels were signiifcantly associated with severe clinical features of lung cancer. The elevation of CRP‑SAA was associated with lower survival rates for both the retrospective (hazard ration [HR]=2.181, 95% conifdence interval [CI]=1.641–2.897,P<0.001) and the prospective cohorts (HR=2.744, 95% CI=1.810–4.161,P<0.001). Multivariate Cox analysis showed that CRP‑SAA was an independent prognostic marker for lung cancer. Remarkably, in stages I–II patients, only CRP‑SAA, not total SAA or CRP, showed signiifcant association with overall survival in two cohorts. Moreover, univariate and multivariate Cox analyses also showed that only CRP‑SAA could be used as an inde‑pendent prognostic marker for early‑stage lung cancer patients. Conclusion:CRP‑SAA could be a better prognostic marker for lung cancer than total SAA or CRP

  15. Systemic immune markers characterizing early stages of rheumatoid arthritis

    NARCIS (Netherlands)

    Chalan, Paulina Luiza

    2016-01-01

    Rheumatoid arthritis is a chronic autoimmune disease occurring in ~1% of the world population. The main feature of the disease is ongoing joint inflammation, caused by immune cells and their soluble factors, leading to irreversible bone erosions and cartilage damage. Early treatment can halt progres

  16. Early death during chemotherapy in patients with small-cell lung cancer

    DEFF Research Database (Denmark)

    Lassen, U N; Osterlind, K; Hirsch, F R

    1999-01-01

    Based on an increased frequency of early death (death within the first treatment cycle) in our two latest randomized trials of combination chemotherapy in small-cell lung cancer (SCLC), we wanted to identify patients at risk of early non-toxic death (ENTD) and early toxic death (ETD). Data were...... stored in a database and logistic regression analyses were performed to identify predictive factors for early death. During the first cycle, 118 out of 937 patients (12.6%) died. In 38 patients (4%), the cause of death was sepsis. Significant risk factors were age, performance status (PS), lactate...

  17. Detection of gene expression pattern in the early stage after spinal cord injury by gene chip

    Institute of Scientific and Technical Information of China (English)

    刘成龙; 靳安民; 童斌辉

    2003-01-01

    Objective: To study the changes of the gene expression pattern of spinal cord tissues in the early stage after injury by DNA microarray (gene chip). Methods: The contusion model of rat spinal cord was established according to Allen's falling strike method and the gene expression patterns of normal and injured spinal cord tissues were studied by gene chip. Results: The expression of 45 genes was significantly changed in the early stage after spinal cord injury, in which 22 genes up-regulated and 23 genes down-regulated. Conclusions: The expression of some genes changes significantly in the early stage after spinal cord injury, which indicates the complexity of secondary spinal cord injury.

  18. Analysis thrombolysis with anticoagulation treatment for early stage of deep vein thrombosis in the lower extremities

    Institute of Scientific and Technical Information of China (English)

    刘心; 张梅; 刘陕西; 祈光裕; 刘亚民

    2003-01-01

    Objective: To explore the effect of thrombolysis with anticoagulation treatment for early stage of deep vein thrombosis of lower extremity. Methods: The clinical data of 106 patients at the early stage of deep vein thrombosis (DVT) in the lower extremities treated by thrombolysis with anticoagulation and dispersion drugs were analyzed retrospectively. Results: The thrombolytic effect was significant. After treatment, the deep veins were recanalized without regurgitation in 75.3% of the patients. The total effective rate was 100%. Only three patients had hemorrhagic complication, but none of the patients died. Conclusion: Thrombolysis with anticoagulation treatment is an effective and safe method for DVT at the early stage.

  19. Laser-Induced Fluorescence Bronchoscopy for Detection and Localization of Early Lung Cancer

    Institute of Scientific and Technical Information of China (English)

    XIE Shusen; LI Buhong; LI Hui; ZHENG Wei; LU Zukang

    2001-01-01

    Experimenatal results on the development of a Laser-Induced Fluorescence Bronchoscopy(LIFB) for the detection and localization of early lung cancer are reported in this paper. The system utilizes fluorescence of photosensitizer drug to provide real time video imaging for the examined lung tissue. Color filters are used to differentiate signal from background and a computer image processing technique is also applied to subtract the background. Moreover, a pseudocolor contrast enhancement method was developed to enhance the fluorescence image displayed on the vidio monitor. Suspicious areas are identified by pseudocolor image to guide biopsy, and several clinical trials show that sensitivity and contrast capability of the system should permit the detection and localization of early lung cancer.

  20. DYNAMICS OF HEAT SHOCK PROTEIN-70 SYNTHESIS IN LUNGS DEPENDS ON THE STAGE OF EXPERIMENTAL RESPIRATORY DISTRESS SYNDROME

    Directory of Open Access Journals (Sweden)

    E. V. Prutkina

    2013-01-01

    Full Text Available Abstract. Acute respiratory distress syndrome (ARDS was reproduced in a rat model, by means of intratracheal instillation of granulocyte lysates (a method protected by Russian patent. Expression of HSP-70 in lung cells was determined by immunohistochemical technique at each ARDS stage. A significant increase of HSP-70 expression by all cell types was revealed during exudative stage, being more intensive in alveolocytes type 1, and less expressed in endothelium. During proliferative stage of the disorder, a decreased HSP-70 expression was noted in all cell populations. At these terms, it proved to be high in neutrophils and alveveolocytes type 1, whereas lower expression was registered in endothelium. At fibrotic stage, HSP-70 synthesis remained at high levels in neutrophils, macrophages, fibroblasts and alveolocytes type 1. Endothelium and alveolocytes type 2 exhibited a recurrent increase at fibrotic stage of ARDS, however it did not reach the values typical to the initial stage of the syndrome.

  1. Clinical studies in Non-Small Cell Lung Cancer stage III

    NARCIS (Netherlands)

    Hofman-Maas, K.W.

    2013-01-01

    Primary lung cancer was first recognized as a distinct disease in 1761, long before the advent of cigarette smoking.1 Although it was a rare disease at the start of the 20th century,2,3,4,5 at the end, lung cancer had become one of the leading causes of preventable death. Since the 1930s, lung

  2. Budget impact from the incorporation of positron emission tomography – computed tomography for staging lung cancers

    Directory of Open Access Journals (Sweden)

    Aline Navega Biz

    2015-01-01

    Full Text Available OBJECTIVE To estimate the budget impact from the incorporation of positron emission tomography (PET in mediastinal and distant staging of non-small cell lung cancer.METHODS The estimates were calculated by the epidemiological method for years 2014 to 2018. Nation-wide data were used about the incidence; data on distribution of the disease´s prevalence and on the technologies’ accuracy were from the literature; data regarding involved costs were taken from a micro-costing study and from Brazilian Unified Health System (SUS database. Two strategies for using PET were analyzed: the offer to all newly-diagnosed patients, and the restricted offer to the ones who had negative results in previous computed tomography (CT exams. Univariate and extreme scenarios sensitivity analyses were conducted to evaluate the influence from sources of uncertainties in the parameters used.RESULTS The incorporation of PET-CT in SUS would imply the need for additional resources of 158.1 BRL (98.2 USD million for the restricted offer and 202.7 BRL (125.9 USD million for the inclusive offer in five years, with a difference of 44.6 BRL (27.7 USD million between the two offer strategies within that period. In absolute terms, the total budget impact from its incorporation in SUS, in five years, would be 555 BRL (345 USD and 600 BRL (372.8 USD million, respectively. The costs from the PET-CT procedure were the most influential parameter in the results. In the most optimistic scenario, the additional budget impact would be reduced to 86.9 BRL (54 USD and 103.8 BRL (64.5 USD million, considering PET-CT for negative CT and PET-CT for all, respectively.CONCLUSIONS The incorporation of PET in the clinical staging of non-small cell lung cancer seems to be financially feasible considering the high budget of the Brazilian Ministry of Health. The potential reduction in the number of unnecessary surgeries may cause the available resources to be more efficiently allocated.

  3. Early preventive treatment for severe acute pancreatitis combined with lung injury

    Institute of Scientific and Technical Information of China (English)

    刘学民; 刘青光; 潘承恩

    2002-01-01

    @@ Severe acute pancreatitis (SAP) can cause systematic inflammatory response syndrome (SIRS),which leads to injury or failure of the internal organs and systems.1 Among them,acute respiratory distress syndrome(ARDS)is a severe or fatal complication.In this article,the early preventive treatment for SAP combined with lung injure is studied.

  4. [Anxiety-phobic disorders in the early childhood stage].

    Science.gov (United States)

    Volkova, O M; Kozlovskaia, G V; Proselkova, M O

    2012-01-01

    The complex of such phenomena as anxiety and fear in children of the early age and their relationship with risk factors for psychic pathology were investigated. Eighty cases of anxiety-phobic disorders in children of the first five years of life were studied. The types of behavioral and somatic reactions that allowed to reveal not only the clinically expressed phenomena of anxiety and fear but the higher readiness to them were described. The first anxiety-phobic reactions appeared at the age when emotional functions were not completely formed and might be considered as the presentations of emotional dysontogenesis. The authors assume that characteristics of fear expression in the early age allow to suspect a mental disease which might be timely diagnosed in case of its manifestation. The conclusions made in the paper may be useful for clinical practice of pediatricians, children neurologists, psychologists and psychiatrists.

  5. Signs of Early-stage Disk Growth Revealed with ALMA

    Science.gov (United States)

    Yen, Hsi-Wei; Koch, Patrick M.; Takakuwa, Shigehisa; Krasnopolsky, Ruben; Ohashi, Nagayoshi; Aso, Yusuke

    2017-01-01

    We present ALMA 1.3 mm continuum, 12CO, C18O, and SO data for the Class 0 protostars Lupus 3 MMS, IRAS 15398‑3559, and IRAS 16253‑2429 at resolutions of ∼100 au. By measuring a rotational profile in C18O, a 100 au Keplerian disk around a 0.3 M⊙ protostar is observed in Lupus 3 MMS. No 100 au Keplerian disks are observed in IRAS 15398‑3559 and IRAS 16253‑2429. Nevertheless, embedded compact (<30 au) continuum components are detected. The C18O emission in IRAS 15398‑3559 shows signatures of infall with a constant angular momentum. IRAS 16253‑2429 exhibits signatures of infall and rotation, but its rotational profile is unresolved. By fitting the C18O data with our kinematic models, the protostellar masses and the disk radii are inferred to be 0.01 M⊙ and 20 au in IRAS 15398‑3559, and 0.03 M⊙ and 6 au in IRAS 16253‑2429. By comparing the specific angular momentum profiles from 10,000 au to 100 au in eight Class 0 and I protostars, we find that the evolution of envelope rotation can be described with conventional inside-out collapse models. In comparison with a sample of 18 protostars with known disk radii, our results reveal signs of disk growth, with the disk radius increasing as {{M}* }0.8+/- 0.14 or {t}1.09+/- 0.37 in the Class 0 stage, where M* is the protostellar mass and t is the age. The disk growth rate slows down in the Class I stage. In addition, we find a hint that the mass accretion rate declines as {t}-0.26+/- 0.04 from the Class 0 to the Class I stages.

  6. [The organizational characteristics of the APUD system in mammalian lungs at different stages of ontogeny].

    Science.gov (United States)

    Blinova, S A

    1991-02-01

    The organization peculiarities of APUD-system in the lungs of rabbits, rats and guinea pigs has been studied. The endocrine system in the lungs of rabbits in pre- and postnatal ontogenesis is presented by the adipocytes and neuroepithelial bodies (NEB) containing a considerable number of monoamines. The number of argyrophil adipocytes and NEBs in the lungs of 21 and more day-old adult rats seem to be less than in fetuses and newborns. Monoamines are not revealed in the endocrine rat lung structures by means of the glyoxylic acid. In the lungs of guinea pigs the single argyrophil adipocytes and NEBs are determined in the gestation period.

  7. Altered Synapse Stability in the Early Stages of Tauopathy

    Directory of Open Access Journals (Sweden)

    Johanna S. Jackson

    2017-03-01

    Full Text Available Synapse loss is a key feature of dementia, but it is unclear whether synaptic dysfunction precedes degenerative phases of the disease. Here, we show that even before any decrease in synapse density, there is abnormal turnover of cortical axonal boutons and dendritic spines in a mouse model of tauopathy-associated dementia. Strikingly, tauopathy drives a mismatch in synapse turnover; postsynaptic spines turn over more rapidly, whereas presynaptic boutons are stabilized. This imbalance between pre- and post-synaptic stability coincides with reduced synaptically driven neuronal activity in pre-degenerative stages of the disease.

  8. Estramustine phosphate reversibly inhibits an early stage during adenovirus replication.

    Science.gov (United States)

    Everitt, E; Ekstrand, H; Boberg, B; Hartley-Asp, B

    1990-01-01

    Estramustine phosphate, an estradiol-mustard conjugate, was shown to reversibly inhibit a stage during the first hour of productive adenovirus 2 infection of HeLa cells. This drug, employed in the therapy of advanced prostatic cancer, specifically interacts with microtubule-associated proteins (MAPs) of the cytoskeleton. The results obtained under physiological conditions in vivo suggest a MAPs-interference with the microtubule-mediated vectorial migration of the virus inoculum to the nucleus. Virus attachment, uncoating kinetics and the appearance of established uncoating intermediates were not affected.

  9. [Prognostic value of AJCC TNM Staging 7th edition in limited-stage small cell lung cancer: validation in 437 patients].

    Science.gov (United States)

    Zhang, Wenjue; Zhu, Hui; Zhou, Zongmei; Feng, Qinfu; Chen, Dongfu; Zhang, Hongxing; Xiao, Zefen; Wang, Lühua

    2015-12-01

    To explore the impact of AJCC TNM Staging 7th edition on survival outcome of limited stage small cell lung cancer (SCLC). Four hundred and thirty-seven SCLC patients with completed diagnosis and treatment data treated in our department between January 1996 and December 2006 were reclassified according to the AJCC TNM Staging 7th edition. The patients of stages IA, IB, IIA, IIB, IIIA, IIIB were 8, 44, 7, 64, 192 cases, respectively. Kaplan-Meier method was used for survival analysis and log-rank test was used to identify the prognostic factors. The survival rate was determined using chi-square test. The median follow-up time was 64 months. The median survival time was 26.2 months and median progression free survival time was 13.7 months. The 1-, 2- and 5-year overall survival rates were 86.0%, 52.7%, and 29.7%, respectively. The log-rank test showed that TNM stage is a statistically significant prognostic factor for OS in LS-SCLC (PTNM staging system generally allowed a good separation in pairwise comparison for OS between successive stages except there was no significant difference between stages I and II (P=0.061). The 5-year progression free survival rates of patients of stage I, II, IIIA and IIIB were 53.2%, 43.2%, 16.8%, and 10.9%, respectively. TNM stage also was a statistically significant prognostic factor for PFS in LS-SCLC (P0.05 for all). The T staging confirmed significant influence on OS (P0.05 for all), while T stage was not a significant prognostic factor for PFS in the LS-SCLC patients (P=0.194). N stage also had a significant influence on OS (P0.05) except that between the 5-year survival rates of N2 and N3 cases (P=0.013). The cumulative brain metastasis rates of stages I, II, IIIA, and stage IIIB were 17.3%, 28.6%, 33.3%, and 35.8%, respectively(P=0.072), and were 12.8% and 30.8% for pathological stage I and clinical stage I (P=0.203). AJCC TNM Staging 7th edition criteria for LS-SCLC patients have a high prognostic impact and therefore are

  10. MSH2/BRCA1 expression as a DNA-repair signature predicting survival in early–stage lung cancer patients from the IFCT-0002 Phase 3 Trial

    Science.gov (United States)

    Levallet, Guénaëlle; Dubois, Fatéméh; Fouret, Pierre; Antoine, Martine; Brosseau, Solenn; Bergot, Emmanuel; Beau-Faller, Michèle; Gounant, Valérie; Brambilla, Elisabeth; Debieuvre, Didier; Molinier, Olivier; Galateau-Sallé, Françoise; Mazieres, Julien; Quoix, Elisabeth; Pujol, Jean-Louis; Moro-Sibilot, Denis; Langlais, Alexandra; Morin, Franck; Westeel, Virginie; Zalcman, Gérard

    2017-01-01

    Introduction DNA repair is a double-edged sword in lung carcinogenesis. When defective, it promotes genetic instability and accumulated genetic alterations. Conversely these defects could sensitize cancer cells to therapeutic agents inducing DNA breaks. Methods We used immunohistochemistry (IHC) to assess MSH2, XRCC5, and BRCA1 expression in 443 post-chemotherapy specimens from patients randomized in a Phase 3 trial, comparing two neoadjuvant regimens in 528 Stage I-II non-small cell lung cancer (NSCLC) patients (IFCT-0002). O6MGMT promoter gene methylation was analyzed in a subset of 208 patients of the same trial with available snap-frozen specimens. Results Median follow-up was from 90 months onwards. Only high BRCA1 (n = 221, hazard ratio [HR] = 1.58, 95% confidence interval [CI] [1.07-2.34], p = 0.02) and low MSH2 expression (n = 356, HR = 1.52, 95% CI [1.11-2.08], p = 0.008) significantly predicted better overall survival (OS) in univariate and multivariate analysis. A bootstrap re-sampling strategy distinguished three patient groups at high (n = 55, low BRCA1 and high MSH2, median OS >96 months, HR = 2.5, 95% CI [1.45-4.33], p = 0.001), intermediate (n = 82, median OS = 73.4 p = 0.0596), and low (high BRCA1 and low MSH2, n = 67, median OS = ND, HR = 0.51, 95% CI [0.31-0.83], p = 0.006) risk of death. Interpretation DNA repair protein expression assessment identified three different groups of risk of death in early-stage lung cancer patients, according to their tumor MSH2 and BRCA1 expression levels. These results deserve prospective evaluation of MSH2/BRCA1 theranostic value in lung cancer patients treated with combinations of DNA-damaging chemotherapy and drugs targeting DNA repair, such as Poly(ADP-ribose) polymerase (PARP) inhibitors. PMID:28008145

  11. MicroRNA profiling and prediction of recurrence/relapse-free survival in stage I lung cancer.

    Science.gov (United States)

    Lu, Yan; Govindan, Ramaswamy; Wang, Liang; Liu, Peng-yuan; Goodgame, Boone; Wen, Weidong; Sezhiyan, Ananth; Pfeifer, John; Li, Ya-fei; Hua, Xing; Wang, Yian; Yang, Ping; You, Ming

    2012-05-01

    About 30% stage I non-small cell lung cancer (NSCLC) patients undergoing resection will recur. Robust prognostic markers are required to better manage therapy options. MicroRNAs (miRNAs) are a class of small non-coding RNAs of 19-25 nt and play important roles in gene regulation in human cancers. The purpose of this study is to identify miRNA expression profiles that would better predict prognosis of stage I NSCLC. MiRNAs extracted from 527 stage I NSCLC patients were profiled on the human miRNA expression profiling v2 panel (Illumina). The expression profiles were analyzed for their association with cancer subtypes, lung cancer brain metastasis and recurrence/relapse free survival (RFS). MiRNA expression patterns between lung adenocarcinoma and squamous cell carcinoma differed significantly with 171 miRNAs, including Let-7 family members and miR-205. Ten miRNAs associated with brain metastasis were identified including miR-145*, which inhibit cell invasion and metastasis. Two miRNA signatures that are highly predictive of RFS were identified. The first contained 34 miRNAs derived from 357 stage I NSCLC patients independent of cancer subtype, whereas the second containing 27 miRNAs was adenocarcinoma specific. Both signatures were validated using formalin-fixed paraffin embedded and/or fresh frozen tissues in independent data set with 170 stage I patients. Our findings have important prognostic or therapeutic implications for the management of stage I lung cancer patients. The identified miRNAs hold great potential as targets for histology-specific treatment or prevention and treatment of recurrent disease.

  12. Use of PET/CT for staging and radiation therapy planning in patients with non-small cell lung cancer.

    Science.gov (United States)

    Mac Manus, M P

    2010-10-01

    Positron emission tomography (PET) and more recently PET/computed tomography (CT) scanning represent major advances in the imaging of lung cancer and have an especially high impact on the management of patients who are candidates for potentially curative or "radical" radiotherapy (RT). This article reviews the current status of PET and PET/CT for staging patients before RT and considers the use of PET and PET/CT images for target volume definition. The relevant literature on the use of PET for staging lung cancer is reviewed and placed in the context of patients who are candidates for RT. Research that specifically considers the use of PET for RT planning is considered critically and some promising areas for future research are discussed. The available literature is almost exclusively devoted to non small cell lung cancer (NSCLC) with few relevant studies of small cell lung cancer (SCLC). The primary PET radiopharmaceutical shown to have value for staging and RT planning is 18F-fluorodeoxyglucose (FDG). In prospective studies where PET imaging was used to stage radical RT candidates, 25-30% of patients were excluded from radical therapy because of PET detected advanced disease. In all studies where "PET-assisted" and conventional target or treatment volumes were compared, there were major differences between PET and conventional volumes. Because PET-assisted staging is proven to be significantly more accurate than conventional staging and because all studies show major differences between PET-assisted and conventional treatment volumes in NSCLC, routine use of PET/CT for RT planning is recommended.

  13. The utility of abbreviated patient-reported outcomes for predicting survival in early stage colorectal cancer.

    Science.gov (United States)

    Hsu, Tina; Speers, Caroline H; Kennecke, Hagen F; Cheung, Winson Y

    2017-05-15

    Patient-reported outcomes (PROs) are increasingly used in clinical settings. Prior research suggests that PROs collected at baseline may be associated with cancer survival, but most of those studies were conducted in patients with breast or lung cancer. The objective of this study was to determine the correlation between prospectively collected PROs and cancer-specific outcomes in patients with early stage colorectal cancer. Patients who had newly diagnosed stage II or III colorectal cancer from 2009 to 2010 and had a consultation at the British Columbia Cancer Agency completed the brief Psychosocial Screen for Cancer (PSSCAN) questionnaire, which collects data on patients' perceived social supports, quality of life (QOL), anxiety and depression, and general health. PROs from the PSSCAN were linked with the Gastrointestinal Cancers Outcomes Database, which contains information on patient and tumor characteristics, treatment details, and cancer outcomes. Cox regression models were constructed for overall survival (OS), and Fine and Gray regression models were developed for disease-specific survival (DSS). In total, 692 patients were included. The median patient age was 67 years (range, 26-95 years), and the majority had colon cancer (61%), were diagnosed with stage III disease (54%), and received chemotherapy (58%). In general, patients felt well supported and reported good overall health and QOL. On multivariate analysis, increased fatigue was associated with worse OS (hazard ratio [HR], 1.99; P = .00007) and DSS (HR, 1.63; P = .03), as was lack of emotional support (OS: HR, 4.36; P = .0003; DSS: HR, 1.92; P = .02). Although most patients described good overall health and QOL and indicated that they were generally well supported, patients who experienced more pronounced fatigue or lacked emotional support had a higher likelihood of worse OS and DSS. These findings suggest that abbreviated PROs can inform and assist clinicians to identify patients who have a worse

  14. DISTINCT PHENOTYPES OF INFILTRATING CELLS DURING ACUTE AND CHRONIC LUNG REJECTION IN HUMAN HEART-LUNG TRANSPLANTS

    NARCIS (Netherlands)

    WINTER, JB; CLELLAND, C; GOUW, ASH; PROP, J

    1995-01-01

    To differentiate between acute and chronic lung rejection in an early stage, phenotypes of infiltrating inflammatory cells were analyzed in 34 transbronchial biopsies (TBBs) of 24 patients after heart-lung transplantation. TBBs were taken during during acute lung rejection and chronic lung rejection

  15. The use of lung biopsy to determine early lung pathology and its association with health and production outcomes in feedlot steers.

    Science.gov (United States)

    Burgess, Brandy A; Hendrick, Steve H; Pollock, Colleen M; Hannon, Sherry J; Abutarbush, Sameeh M; Vogstad, Amanda; Jim, G Kee; Booker, Calvin W

    2013-10-01

    The objectives of this study were to determine if percutaneous lung biopsy can be used to characterize early pathologic changes in bovine lung associated with bovine respiratory disease (BRD), to determine if specific infectious respiratory pathogens can be identified in association with these changes, and to determine whether pulmonary pathology at arrival and at the time of initial diagnosis are associated with health and production outcomes. One hundred auction-market derived crossbred steer calves from a commercial feedlot in southern Alberta were included in this study. A percutaneous lung biopsy technique was used to obtain lung samples from the right middle lung. Steers were sampled 295 times yielding 283 samples with 210 (74%) containing lung tissue. Overall, histopathological changes were observed in 20 (9.5%) of lung biopsy samples. There were too few samples with pathology to reveal an association between lung pathology and subsequent health events. In general, percutaneous lung biopsy can be done safely on feedlot steers in a commercial feedlot setting with few clinical side effects. This technique did not prove useful as a diagnostic tool or prognostic indicator for early BRD. However, it may be useful for the diagnosis of BRD in targeted populations of commercial feedlot steers.

  16. Dual-energy snap-shot perfusion CT in suspect pulmonary nodules and masses and for lung cancer staging.

    Science.gov (United States)

    Sudarski, Sonja; Hagelstein, Claudia; Weis, Meike; Schoenberg, Stefan O; Apfaltrer, Paul

    2015-12-01

    Dual energy computed tomography (DECT) has proven its clinical usefulness for improved tissue characterization within the past years. In thoracic oncology, DECT can be used to differentiate between benign and malignant pulmonary nodules and masses. In patients with known lung cancer, DECT can add incremental functional information to staging scans, therapeutic response evaluation, as well as to the assessment of lung function. This review aims to give an overview on the current clinical utilities of DECT of the chest, its multiple post-processing applications and dose saving options. Furthermore, this review highlights promising applications of DECT that merit implementation in future clinical routine.

  17. Screening of early antigen genes of adult-stage Trichinella spiralis using pig serum from different stages of early infection

    Science.gov (United States)

    The goal of this work was to identify novel, early antigens present in Trichinella spiralis. To this end, a cDNA library generated from 3-day old adult worms (Ad3) was immunologically screened using serum from a pig infected with 20,000 muscle larvae. The serum was obtained from multiple, time cours...

  18. New NIA Booklet By and For People With Early-Stage Alzheimer's Disease

    Science.gov (United States)

    ... Booklet By and For People With Early-Stage Alzheimer's Disease Past Issues / Fall 2007 Table of Contents For ... you have a family member or friends with Alzheimer's disease? Are you wondering what they're going through ...

  19. Effect of crude oil extracts on early stages of African catfish ...

    African Journals Online (AJOL)

    Effect of crude oil extracts on early stages of African catfish Heterobranchus ... carried out in the Institute of Oceanography Fish Farm, University of Calabar, Nigeria. Petroleum hydrocarbon was extracted from the two oils in separate 30litre ...

  20. Early-stage visual processing abnormalities in high-functioning autism spectrum disorder (ASD).

    Science.gov (United States)

    Baruth, Joshua M; Casanova, Manuel F; Sears, Lonnie; Sokhadze, Estate

    2010-06-01

    It has been reported that individuals with autism spectrum disorder (ASD) have abnormal responses to the sensory environment. For these individuals sensory overload can impair functioning, raise physiological stress, and adversely affect social interaction. Early-stage (i.e. within 200ms of stimulus onset) auditory processing abnormalities have been widely examined in ASD using event-related potentials (ERP), while ERP studies investigating early-stage visual processing in ASD are less frequent. We wanted to test the hypothesis of early-stage visual processing abnormalities in ASD by investigating ERPs elicited in a visual oddball task using illusory figures. Our results indicate that individuals with ASD have abnormally large cortical responses to task irrelevant stimuli over both parieto-occipital and frontal regions-of-interest (ROI) during early stages of visual processing compared to the control group. Furthermore, ASD patients showed signs of an overall disruption in stimulus discrimination, and had a significantly higher rate of motor response errors.

  1. Collaboration with Pharma Will Introduce Nanotechnologies in Early Stage Drug Development | Poster

    Science.gov (United States)

    The Frederick National Lab has begun to assist several major pharmaceutical companies in adopting nanotechnologies in early stage drug development, when the approach is most efficient and cost-effective.

  2. Collaboration with Pharma Will Introduce Nanotechnologies in Early Stage Drug Development | Poster

    Science.gov (United States)

    The Frederick National Lab has begun to assist several major pharmaceutical companies in adopting nanotechnologies in early stage drug development, when the approach is most efficient and cost-effective.

  3. Increased red blood cell distribution width associates with cancer stage and prognosis in patients with lung cancer.

    Directory of Open Access Journals (Sweden)

    Yasuko Koma

    Full Text Available BACKGROUND: Red cell distribution width (RDW, one of many routinely examined parameters, shows the heterogeneity in erythrocyte size. We investigated the association of RDW levels with clinical parameters and prognosis of lung cancer patients. METHODS: Clinical and laboratory data from 332 patients with lung cancer in a single institution were retrospectively studied by univariate analysis. Kaplan-Meier survival analysis and Cox proportional hazard models were used to examine the effect of RDW on survival. RESULTS: THE RDW LEVELS WERE DIVIDED INTO TWO GROUPS: high RDW (>=15%, n=73 vs. low RDW, n=259 (<15%. Univariate analysis showed that there were significant associations of high RDW values with cancer stage, performance status, presence of other disease, white blood cell count, hemoglobin, mean corpuscular volume, platelet count, albumin level, C-reactive protein level, and cytokeratin 19 fragment level. Kruskal-Wallis tests revealed an association of RDW values with cancer stage in patients irrespective of comorbidity (patient with/without comorbidity: p<0.0001, patient without comorbidity: p<0.0001. Stages I-IV lung cancer patients with higher RDW values had poorer prognoses than those with lower RDW values (Wilcoxon test: p=0.002. In particular, the survival rates of stage I and II patients (n=141 were lower in the high RDW group (n=19 than in the low RDW group (n=122 (Wilcoxon test: p<0.001. Moreover, multivariate analysis showed higher RDW is a significant prognostic factor (p=0.040. CONCLUSION: RDW is associated with several factors that reflect inflammation and malnutrition in lung cancer patients. Moreover, high levels of RDW are associated with poor survival. RDW might be used as a new and convenient marker to determine a patient's general condition and to predict the mortality risk of lung cancer patients.

  4. Modeling Mycobacterium tuberculosis early granuloma formation in experimental human lung tissue

    Directory of Open Access Journals (Sweden)

    Venkata Ramanarao Parasa

    2014-02-01

    Full Text Available The widely used animal models for tuberculosis (TB display fundamental differences from human TB. Therefore, a validated model that recapitulates human lung TB is attractive for TB research. Here, we describe a unique method for establishment of TB infection in an experimental human lung tissue model. The model is based on cell lines derived from human lungs and primary macrophages from peripheral blood, and displays characteristics of human lung tissue, including evenly integrated macrophages throughout the epithelium, production of extracellular matrix, stratified epithelia and mucus secretion. Establishment of experimental infection in the model tissue with Mycobacterium tuberculosis, the bacterium that causes TB, resulted in clustering of macrophages at the site of infection, reminiscent of early TB granuloma formation. We quantitated the extent of granuloma formation induced by different strains of mycobacteria and validated our model against findings in other TB models. We found that early granuloma formation is dependent on ESAT-6, which is secreted via the type VII secretion machinery of virulent mycobacteria. Our model, which can facilitate the discovery of the interactions between mycobacteria and host cells in a physiological environment, is the first lung tissue model described for TB.

  5. Gene identification for risk of relapse in stage I lung adenocarcinoma patients: a combined methodology of gene expression profiling and computational gene network analysis.

    Science.gov (United States)

    Ludovini, Vienna; Bianconi, Fortunato; Siggillino, Annamaria; Piobbico, Danilo; Vannucci, Jacopo; Metro, Giulio; Chiari, Rita; Bellezza, Guido; Puma, Francesco; Della Fazia, Maria Agnese; Servillo, Giuseppe; Crinò, Lucio

    2016-05-24

    Risk assessment and treatment choice remains a challenge in early non-small-cell lung cancer (NSCLC). The aim of this study was to identify novel genes involved in the risk of early relapse (ER) compared to no relapse (NR) in resected lung adenocarcinoma (AD) patients using a combination of high throughput technology and computational analysis. We identified 18 patients (n.13 NR and n.5 ER) with stage I AD. Frozen samples of patients in ER, NR and corresponding normal lung (NL) were subjected to Microarray technology and quantitative-PCR (Q-PCR). A gene network computational analysis was performed to select predictive genes. An independent set of 79 ADs stage I samples was used to validate selected genes by Q-PCR.From microarray analysis we selected 50 genes, using the fold change ratio of ER versus NR. They were validated both in pool and individually in patient samples (ER and NR) by Q-PCR. Fourteen increased and 25 decreased genes showed a concordance between two methods. They were used to perform a computational gene network analysis that identified 4 increased (HOXA10, CLCA2, AKR1B10, FABP3) and 6 decreased (SCGB1A1, PGC, TFF1, PSCA, SPRR1B and PRSS1) genes. Moreover, in an independent dataset of ADs samples, we showed that both high FABP3 expression and low SCGB1A1 expression was associated with a worse disease-free survival (DFS).Our results indicate that it is possible to define, through gene expression and computational analysis, a characteristic gene profiling of patients with an increased risk of relapse that may become a tool for patient selection for adjuvant therapy.

  6. Human Adipose-derived Mesenchymal Stem Cells Attenuate Early Stage of Bleomycin Induced Pulmonary Fibrosis: Comparison with Pirfenidone

    Science.gov (United States)

    Reddy, Manoj; Fonseca, Lyle; Gowda, Shashank; Chougule, Basavraj; Hari, Aarya; Totey, Satish

    2016-01-01

    Background and Objectives Idiopathic pulmonary fibrosis (IPF) is a progressive, irreversible, invariably fatal fibrotic lung disease with no lasting option for therapy. Mesenchymal stem cells (MSCs) could be a promising modality for the treatment of IPF. Aim of the study was to investigate improvement in survivability and anti-fibrotic efficacy of human adipose-derived mesenchymal stem cells (AD-MSCs) in comparison with pirfenidone in the bleomycin-induced pulmonary fibrosis model. Methods Human AD-MSCs were administered intravenously on day 3, 6 and 9 after an intra-tracheal challenge with bleomycin, whereas, pirfenidone was given orally in drinking water at the rate of 100 mg/kg body weight three times a day daily from day 3 onward. AD-MSCs were labelled with PKH-67 before administration to detect engraftment. Disease severity and improvement was assessed and compared between sham control and vehicle control groups using Kaplan-Meier survival analysis, biochemical and molecular analysis, histopathology and high resolution computed