Mark E Ginsburg

Columbia University, New York City, NY, United States

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Publications (30)109.87 Total impact

  • [Show abstract] [Hide abstract]
    ABSTRACT: The purpose of the study was to assess the efficacy of obtaining adequate cytologic specimens by endobronchial ultrasound-guided transbronchial needle aspiration (EBUS-TBNA) for molecular testing of lung adenocarcinomas. This was an institutional review board-approved study of all patients who had undergone EBUS-TBNA from April 2010 through March 2012 for the diagnosis, staging, or both of lung cancer. Patients with a diagnosis of adenocarcinoma were reflexively tested for molecular markers by polymerase chain reaction, sequencing, and fluorescence in situ hybridization (FISH). All procedures were performed with patients under conscious sedation in the bronchoscopy suite. Of 205 patients who underwent EBUS-TBNA, 56 patients (24 male, 32 female) had a diagnosis of adenocarcinoma warranting molecular analysis. Molecular analysis was available for epidermal growth factor receptor (EGFR), Kirsten rat sarcoma (Kras) mutation, and anaplastic lymphoma kinase (ALK) gene rearrangement. The institution's clinical protocol involved initial testing for EGFR mutation with a reflex Kras test if the EGFR test result was negative. ALK FISH molecular testing was completed if both EGFR and Kras test results were negative. A total of 52 of 56 (93%) patients had sufficient cytologic material for complete or partial molecular testing, whereas 46 of 56 (82%) patients had sufficient material for all clinically indicated testing. EGFR, Kras, and ALK analysis yielded positive results in 5 (10%), 10 (25%), and 5 (12%) tested specimens, respectively. No complications were associated with EBUS-TBNA. EBUS-TBNA performed with the patient under moderate sedation can be expected to yield sufficient tissue for sequential molecular analysis in the majority of patients. In an era of targeted therapy for lung adenocarcinomas, EBUS-TBNA is effective in clinical practice for complete diagnosis, staging, and treatment planning in these patients.
    The Annals of thoracic surgery 08/2013; · 3.45 Impact Factor
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    ABSTRACT: Chronotropic incompetence (CI) is a marker of poor prognosis in patients with COPD. Treatments that improve pulmonary function and exercise capacity may affect CI. Objectives are to evaluate CI before and after lung volume reduction surgery (LVRS) and determine if changes in CI are associated with changes in pulmonary function and exercise capacity. We performed a retrospective review of 75 patients who underwent LVRS and who had complete cardiopulmonary exercise testing and concurrent pulmonary function tests two months before and about 6 months after surgery. Additionally we evaluated 28 control patients that were randomized to medical treatment as part of the National Emphysema Treatment Trial at our center. We studied CI using the percent of predicted heart rate reserve=(heart rate peak-heart rate rest)/((208-0.7×age)-heart rate rest)×100, before and after surgery and compared it to the control group. Mean percent of predicted heart rate reserve improved from 41% to 50% (p-value <0.001) after LVRS, while the control group did not change. The mean forced vital capacity and expiratory volume in 1s, peak oxygen consumption, carbon dioxide production, ventilation, tidal volume and maximal workload all improved in the surgery group, while the controls did not improve. CI improves after LVRS in a population of patients with COPD. CI improvements are associated with the increases in pulmonary function and exercise capacity. This improvement is seen in a domain of known cardiopulmonary impairment prior to surgery that improves as a positive response to the therapy of LVRS.
    Respiratory medicine 07/2012; 106(10):1389-95. · 2.33 Impact Factor
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    ABSTRACT: An open thymectomy is a morbid procedure. If a minimally invasive thymectomy is performed without compromising the tenets of thymic surgery, it has the potential for decreasing morbidity and may offer similar clinical and oncologic results. This is an institutional review board-approved, retrospective study of a single center's experience with both open (transsternal) and minimally invasive (video-assisted thoracoscopic surgery) thymectomy. Survival estimates and statistical comparisons were calculated using standard software. From 2000 to 2011, 263 patients (93 men; median age, 49 years; interquartile range, 37 to 60 years) underwent thymectomy for indications including myasthenia gravis (n=139) and mediastinal mass (n=108). Seventy-seven thymectomies were performed by minimally invasive approach. Both groups were equally stratified by sex, body mass index, World Health Organization and Masaoka-Koga staging, incidence of myasthenia gravis, and comorbidities except hyperlipidemia and diabetes. The minimally invasive thymectomy cohort had significantly shorter hospital (p<0.01) and intensive care unit lengths of stay (p<0.01) and a lower estimated blood loss (p<0.01). There was an insignificant difference in postoperative cardiac and respiratory complication rates as well as vocal cord paralysis (p=0.60). There was no difference in terms of operative room times (p=0.88) or volume of blood products transfused (p=0.16) between the two groups. Higher estimated blood loss was associated with higher intensive care unit admission rates (p<0.01). All minimally invasive thymoma resections were complete, with negative margins. Minimally invasive thymectomy is safe and achieves a comparable resection and postoperative complication profile when used selectively for all indications, including myasthenia gravis and small thymomas without vascular invasion.
    The Annals of thoracic surgery 06/2012; 94(3):974-81; discussion 981-2. · 3.45 Impact Factor
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    ABSTRACT: Uncertainty exists among surgeons as to whether minimally invasive esophagectomy (MIE) is a comparable operation to open esophagectomy (OE). The surgical technique and oncologic dissection should not be degraded when using a minimally invasive approach. We reviewed a single hospital's experience with both OE and MIE. From 2000 to 2010, 257 patients underwent esophagectomy by 1 of 3 surgical techniques: transhiatal, Ivor Lewis, or 3-hole. Of the 257 patients (median age, 67 years; range, 58-74), 92 underwent MIE. Both groups were comparable in terms of gender, age, comorbidities, surgical technique, and induction chemotherapy and radiotherapy. The overall median follow-up was 29.5 months (range, 9.9-61.5). The MIE group had a significantly shorter operative time (MIE vs OE, 330 vs 365 minutes, P = .04), length of stay (MIE vs OE, 9 vs 12 days, P < .01), intensive care unit admission rate (MIE vs OE, 55% vs 81%, P < .01), intensive care unit length of stay (MIE vs OE, 1 vs 2 days, P < .01), and estimated blood loss (MIE vs OE, 100 vs 400 mL, P < .01). More lymph nodes were harvested in the MIE group than in the OE group (17 vs 11 nodes, P < .01). There were insignificant differences in 30-day mortality (MIE vs OE, 2.2% vs 3.0%; P = .93) and overall survival (P = .19), as well as in the rates of all complications, except pneumonia (MIE vs OE, 2% vs 13%; P = .01). A thoracic surgeon can safely tailor the MIE to a patient's anatomy and oncologic demands while maintaining equivalent survival.
    The Journal of thoracic and cardiovascular surgery 05/2012; 143(5):1125-9. · 3.41 Impact Factor
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    ABSTRACT: Lung adenocarcinoma invasion and metastasis arises from autocrine and paracrine signaling events between tumor epithelial cells and the stromal microenvironment that is mediated in part by transforming growth factor-β (TGF-β) signaling. The copper-dependent amine oxidase lysyl oxidase (LOX) plays a role in extracellular matrix structure and is up-regulated in invasive type II TGF-β receptor-deficient cells. The authors hypothesized that LOX expression is associated with extent of invasion and survival in patients with lung adenocarcinoma. LOX immunohistochemical staining was examined in 166 surgically resected lung adenocarcinomas and results were correlated with clinicopathological features and survival. High-intensity LOX staining was found to be associated with the linear extent of invasion (Spearman correlation coefficient = 0.2; P = .01). There was an association between high LOX staining and decreased 5-year survival observed within the entire cohort (log-rank P < .001) and among the patients with stage I disease (n = 119; P < .001). Cox proportional hazards regression analysis confirmed that LOX was a significant prognostic indicator of increased risk of 5-year mortality for all patients (hazard ratio [HR], 2.55; 95% confidence interval [95% CI], 1.51-4.30 [P < .001]) and for patients with Stage I disease (HR, 3.51; 95% CI, 1.77-6.99 [P < .001]). LOX expression was found to be independently associated with risk of death after adjustment for relevant covariates (HR, 2.29; 95% CI, 1.33-3.94 [P = .003]). Higher expression of LOX is associated with invasion and is an independent predictor of poor prognosis in patients with early stage lung adenocarcinoma.
    Cancer 05/2011; 117(10):2186-91. · 5.20 Impact Factor
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    ABSTRACT: The National Emphysema Treatment Trial (NETT) proved that lung volume reduction surgery (LVRS) was safe and effective in patients with certain clinical characteristics and using defined inclusion-exclusion criteria. Based on the selection criteria developed in that trial, we performed bilateral LVRS on 49 patients during the period of February 2004 until May 2009. Forty-nine patients underwent lung volume reduction by either median sternotomy (10) or video-assisted thoracoscopic surgery (39) selected according to NETT described parameters. Preoperative characteristics were the following: mean (±SD) age 62.5±6.6 years, preoperative FEV1 (forced expiratory volume in the first second of expiration) 691 cc (±159), % of predicted FEV1 25.3 (±6.2), preoperative Dlco (diffusing capacity of lung for carbon monoxide) 7.6 (±2.7), and % of predicted DLCO 27% (±7.3). All patients had upper lobe predominant disease and either low exercise capacity (n=23) or high exercise capacity (n=26) as defined by the NETT. There was no operative or 90-day mortality. Median length of stay was 8 days (interquartile range=6 to 10). Two patients required reintubation and tracheostomy but were decannulated prior to discharge. The BODE index (body mass index, airflow obstruction, dyspnea, and exercise capacity), a multidimensional predictor of survival in chronic obstructive pulmonary disease, improved -2.3 (±1.5, p<0.0001) (missing data: 5 of 42, 11.9%) and the FEV1 improved 286 cc (±221, p<0.0001), both 1 year after surgery. Probability of survival was 0.98 (95% CI [confidence interval]=0.94 to 1) at 1 year, and 0.95 (95% CI=0.88 to 1) at 3 years. Surgical lung volume reduction for emphysema can be performed in patients using selection criteria developed by the NETT with very low surgical risk and excellent midterm results. Surgical LVRS is the standard against which other nonsurgical treatments for advanced emphysema should be judged.
    The Annals of thoracic surgery 04/2011; 91(5):1556-60; discussion 1561. · 3.45 Impact Factor
  • American Thoracic Society 2009 International Conference, May 15-20, 2009 • San Diego, California; 04/2009
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    ABSTRACT: Current classification of pulmonary adenocarcinoma includes noninvasive bronchioloalveolar carcinoma, mixed subtype adenocarcinoma, and several patterns of invasive carcinoma. The extent of invasion in mixed subtype adenocarcinoma is variable, and prior studies suggest that estimates of extent of desmoplasia or invasion and gross tumor size are predictors of survival. Pathologic review of 178 consecutive primary lung adenocarcinoma resections from 1997 to 2000 was performed blinded to outcome. Lymph node metastases were not present in adenocarcinomas with less then 0.6 cm of invasion. In multivariate analysis and in strata adjusted for stage, measurement of linear extent of invasion was significantly associated with survival whereas gross size measurement alone was not. Significant differences in median survival were observed when patients were divided into noninvasive, microinvasive (<0.6 cm invasion), and invasive subcategories. In conclusion, among lung adenocarcinomas, histologic assessment of invasive growth may provide valuable prognostic information, and tumors with invasion under 0.6 cm have a more indolent clinical course after resection.
    The American journal of surgical pathology 12/2008; 33(3):462-9. · 4.06 Impact Factor
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    ABSTRACT: Recently, we identified a lung adenocarcinoma signature that segregated tumors into three clades distinguished by histological invasiveness. Among the genes differentially expressed was the type II transforming growth factor-beta receptor (TGFbetaRII), which was lower in adenocarcinoma mixed subtype and solid invasive subtype tumors compared with bronchioloalveolar carcinoma. We used a tumor cell invasion system to identify the chemokine CCL5 (RANTES, regulated on activation, normal T-cell expressed and presumably secreted) as a potential downstream mediator of TGF-beta signaling important for lung adenocarcinoma invasion. We specifically hypothesized that RANTES is required for lung cancer invasion and progression in TGFbetaRII-repressed cells. We examined invasion in TGFbetaRII-deficient cells treated with two inhibitors of RANTES activity, Met-RANTES and a CCR5 receptor-blocking antibody. Both treatments blocked invasion induced by TGFbetaRII knockdown. In addition, we examined the clinical relevance of the RANTES-CCR5 pathway by establishing an association of RANTES and CCR5 immunostaining with invasion and outcome in human lung adenocarcinoma specimens. Moderate or high expression of both RANTES and CCR5 was associated with an increased risk for death, P=0.014 and 0.002, respectively. In conclusion, our studies indicate RANTES signaling is required for invasion in TGFbetaRII-deficient cells and suggest a role for CCR5 inhibition in lung adenocarcinoma prevention and treatment.
    Oncogene 02/2008; 27(4):557-64. · 8.56 Impact Factor
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    ABSTRACT: We hypothesized that lung-volume reduction surgery for pulmonary emphysema would improve body mass index, airflow obstruction, dyspnea, and exercise capacity (BODE) index, a multidimensional predictor of survival in chronic obstructive pulmonary disease. We also aimed to identify preoperative predictors of improvement in the BODE index. In a prospective cohort study of patients undergoing lung-volume reduction surgery at our center, with the methodology of the National Emphysema Treatment Trial, we compared clinical characteristics before and 1 year after surgery with the Wilcoxon signed rank test. Changes in the BODE index were correlated with preoperative variables with the Spearman correlation coefficient. Twenty-three patients with predominantly upper-lobe pulmonary emphysema underwent lung-volume reduction surgery (14 by video-assisted thoracoscopic surgery, 9 by median sternotomy). There were no postoperative or follow-up deaths. The BODE index improved from a median of 5 (interquartile range 4-5) before surgery to 3 (interquartile range 2-4) 1 year after surgery (P < .0001). Improvements were seen in the lung function and dyspnea components of the BODE index. Lower preoperative 6-minute walk distance and lower postwalk Borg fatigue scores were each associated with greater improvement in the BODE index after 1 year. Lung-volume reduction surgery for pulmonary emphysema improved the BODE index in patients with predominantly upper-lobe disease. Lower preoperative 6-minute walk distance correlated with greater improvement in the BODE index.
    The Journal of thoracic and cardiovascular surgery 06/2007; 133(6):1434-8. · 3.41 Impact Factor
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    ABSTRACT: We sought to identify predictors of operative mortality, pulmonary morbidity, and cardiovascular morbidity after lung volume reduction surgery. Univariate and multivariate logistic regression analyses were performed. Candidate predictors included demographic characteristics, physical condition characteristics, pulmonary function measures, measures of the distribution of emphysema as determined by radiologists and by means of computerized analysis of chest computed tomographic scans, and measures of exercise capacity, dyspnea, and quality of life. End points analyzed were operative mortality (death within 90 days of the operation), major pulmonary morbidities (tracheostomy, failure to wean, reintubation, pneumonia, and ventilator for > or =3 days), and cardiovascular morbidities (infarction, pulmonary embolus, or arrhythmia requiring treatment). Five hundred eleven patients in the non-high-risk group of the National Emphysema Treatment Trial underwent lung volume reduction. The incidence of operative mortality was 5.5%, major pulmonary morbidity occurred in 29.8% of patients, and cardiovascular morbidity occurred in 20.0% of patients. Predictors for these end points are as follows: [table: see text]. Although lung volume reduction can be performed in selected patients with acceptable mortality, the incidence of major cardiopulmonary morbidity remains high. The lone predictor for operative mortality of lung volume reduction was the presence of non-upper-lobe-predominant emphysema, as assessed by the radiologist. Pulmonary morbidity can be expected in elderly patients who have a low diffusing capacity for carbon monoxide and forced expiratory volume in 1 second. When assessing morbidity, the computer-assisted chest computed tomographic analysis proved useful only in predicting cardiovascular complications.
    The Journal of thoracic and cardiovascular surgery 01/2006; 131(1):43-53. · 3.41 Impact Factor
  • Lung Cancer. 01/2006; 54.
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    ABSTRACT: Recently, the authors identified molecular signatures and pathways associated with nonsmall cell lung carcinoma histology and lung development. They hypothesized that genetic classifiers of histology would provide insight into lung tumorigenesis and would be associated with clinical outcome when evaluated in a broader set of specimens. Associations between patient survival and immunostaining for 11 representative histologic classifiers (epidermal growth factor receptor [EGFR], CDK4, syndecan-1, singed-like, TTF-1, keratin 5, HDAC2, docking protein 1, integrin alpha3, P63, and cyclin D1) were examined using a tissue microarray constructed from nonsmall cell lung carcinoma specimens. Sixty-three tumors were examined, including 43 adenocarcinomas, 11 large cell carcinomas, and 9 squamous cell carcinomas. Sixty-three percent of tumors were clinical Stage I lesions, and 37% were Stage II-III lesions. In a multivariate analysis that controlled for age, gender, and race, syndecan-1 expression was found to be associated with a significant reduction in the risk of death (hazard ratio, 0.31 [95% confidence interval, 0.18-0.87]; P < 0.05). Multivariate analysis also indicated that EGFR expression was associated with a significant reduced risk of death. The authors demonstrated that expression of either of the nonsmall cell lung carcinoma subtype classifiers syndecan-1 and EGFR was associated with a 30% reduction in the risk of death, with this reduction being independent of histology and other confounders. The results of the current study suggest that loss of expression of these histologic classifiers is associated with biologic aggressiveness in lung tumors and with poor outcome for patients with such tumors. If their significance can be validated prospectively, these biomarkers may be used to guide therapeutic planning for patients with nonsmall cell lung carcinoma.
    Cancer 11/2004; 101(7):1632-8. · 5.20 Impact Factor
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    ABSTRACT: Chemotherapy or chemoradiation is often used in Stage IIIA non-small cell lung carcinoma before surgical resection (neoadjuvant therapy). In reviewing the histopathology of such tumors after resection, the recognition that the pathologic changes are related to prior therapy and the assessment of tumor regression are both of importance. To refine histologic parameters for tumor regression and describe patterns of tumor reaction to therapy, we identified 30 lobectomy or pneumonectomy specimens from 1996-2000 in which neoadjuvant therapy was received before surgical resection. Histologic patterns of treatment-induced tumor regression were analyzed semiquantitatively and included necrosis, fibrosis, mixed inflammatory infiltrate, foamy macrophages, and giant cells. To identify clinical and histologic parameters that correlate with treatment response, the 30 specimens were graded for tumor regression. No correlation was found between tumor regression and age, gender, or type of therapy (chemoradiation versus chemotherapy alone). Squamous cell carcinoma showed a significantly higher rate of response than adenocarcinoma (P =.04), with a significant number of adenocarcinomas in the nonresponder subgroup (P =.05). Tumor size reduction by radiologic assessment, when compared with histologic regression, did not reveal a statistically significant association. However, a positive correlation was found between extent of fibrosis and radiologic estimate of size reduction.
    Modern Pathology 12/2003; 16(11):1102-8. · 5.25 Impact Factor
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    Journal of Thoracic and Cardiovascular Surgery 09/2003; 126(2):582-3. · 3.53 Impact Factor
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    ABSTRACT: Computer (robotic) enhancement has been used to facilitate simple thoracoscopic procedures such as internal mammary artery (IMA) mobilization. This report describes the use of robotic technology in advanced thoracoscopic procedures. Ten patients underwent advanced thoracoscopic procedures utilizing the Da Vinci robotic surgical system (Intuitive Surgical, Mountain View, CA) at our institution. Patients 1-6 underwent endoscopic phrenic nerve mobilization with insertion of phrenic nerve pacemakers. The indications were quadriplegia (n=2), central hypoventilation syndrome (n=2), and intractable hiccups (n=2). Three 1-cm incisions were made to access each hemithorax. Patients 7 and 8 underwent robotically assisted resection of posterior mediastinal masses. Patient 9 underwent robotically assisted thoracoscopic left lower lobectomy for a lung mass. Patient 10 underwent robotically assisted left ventricular lead placement for biventricular pacing for heart failure. Robotic technology can be used to perform advanced intrathoracic maneuvers thoracoscopically. The increased visualization and instrument dexterity afforded by this technology may facilitate the development of minimally invasive thoracic approaches that were previously not feasible.
    European Journal of Cardio-Thoracic Surgery 07/2003; 23(6):883-7; discussion 887. · 2.67 Impact Factor
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    ABSTRACT: While robotic technology is gaining popularity in cardiac surgery, it also is being used to facilitate thoracoscopic procedures, such as insertion of phrenic pacemakers and resection of mediastinal masses. This report describes the use of robotic technology in performing thoracoscopic lobectomy. One patient underwent a left lower lobectomy with the da Vinci robotic surgical system (Intuitive Surgical, Mountain View, CA, USA). With 3 1-cm port incisions and a 4-cm minithoracotomy in the left chest, visualization of the pertinent anatomy was excellent. Standard lymph node dissection was performed. The specimen was removed through the 4-cm minithoracotomy incision. Pathologic examination revealed mucinous adenocarcinoma. The margins of the specimen were negative, and there was no vascular or bronchial invasion. The patient's postoperative course was uneventful, and he was discharged to home on postoperative day 5. Robotic technology enhances visualization and instrument dexterity during thoracoscopic intrathoracic procedures. This technology can be used to facilitate development of minimally invasive thoracic approaches.
    Heart Surgery Forum 02/2003; 6(6):E167-9. · 0.63 Impact Factor
  • M. Argenziano, M. E. Ginsburg
    British Journal of Surgery 01/2002; 89(5). · 4.84 Impact Factor
  • F Nurozler, M Argenziano, M E Ginsburg
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    ABSTRACT: Pneumonectomy is rarely required in the surgical management of thoracic traumatic injuries with high mortality rates. Right heart failure due to elevated pulmonary artery pressure and the adult respiratory distress syndrome have been leading causes of mortality reported after posttraumatic pneumonectomy. The beneficial effect of inhaled nitric oxide has been shown in pulmonary hypertension and in adult respiratory distress syndrome. We report the use of inhaled nitric oxide in the perioperative management of a patient undergoing emergent pneumonectomy.
    The Annals of Thoracic Surgery 02/2001; 71(1):364-6. · 3.45 Impact Factor
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    ABSTRACT: The transcription factor early growth response (Egr)-1 is an immediate-early gene product rapidly and transiently expressed after acute tissue injury. In contrast, in this report we demonstrate that lung tissue from patients undergoing lung reduction surgery for advanced emphysema, without clinical or anatomical evidence of acute infection, displays a selective and apparently sustained increase in Egr-1 transcripts and antigen, compared with a broad survey of other genes, including the transcription factor Sp1, whose levels were not significantly altered. Enhanced Egr-1 expression was especially evident in smooth muscle cells of bronchial and vascular walls, in alveolar macrophages, and some vascular endothelium. Gel shift analysis with (32)P-labeled Egr probe showed a band with nuclear extracts from emphysematous lung which was supershifted with antibody to Egr-1. Egr-1 has the capacity to regulate genes relevant to the pathophysiology of emphysema, namely those related to extracellular matrix formation and remodeling, thrombogenesis, and those encoding cytokines/chemokines and growth factors. Thus, we propose that further analysis of Egr-1, which appears to be up-regulated in a sustained fashion in patients with late stage emphysema, may provide insights into the pathogenesis of this destructive pulmonary disease, as well as a new facet in the biology of Egr-1.
    American Journal Of Pathology 11/2000; 157(4):1311-20. · 4.60 Impact Factor

Publication Stats

520 Citations
109.87 Total Impact Points

Institutions

  • 2001–2011
    • Columbia University
      • • Department of Surgery
      • • College of Physicians and Surgeons
      New York City, NY, United States
  • 1997–2008
    • CUNY Graduate Center
      New York City, New York, United States
  • 1998
    • New York Presbyterian Hospital
      • Department of Radiology
      New York City, NY, United States