Mark E. Ginsburg

Functional comparison of unilateral versus bilateral lung volume reduction surgery

BACKGROUND Lung volume reduction surgery (LVRS) has shown early promise as a palliative therapy in severe emphysema. A number of patients, however, are not candidates for a bilateral operation, or exhibit a predominantly unilateral disease distribution. METHODS Over 20 months, we performed LVRS in 92 patients selected on the basis of severe hyperinflation with air trapping, diaphragmatic dysfunction, and disease heterogeneity. Twenty-eight patients underwent unilateral LVRS on the basis of asymmetric disease distribution, prior thoracic operation, or concomitant tumor resection. RESULTS Unilateral LVRS resulted in comparable improvements in exercise capacity and dyspnea as the bilateral procedure, with a similar perioperative mortality and actuarial survival to 24 months. Improvements in spirometric indices of pulmonary function, however, were less in patients undergoing unilateral than bilateral LVRS. CONCLUSIONS In properly selected patients, unilateral LVRS provides functional and subjective benefits of comparable magnitude to those associated with a bilateral operation. Unilateral LVRS is therefore an option in the therapy of end-stage emphysema in patients with asymmetric disease distribution, a prior thoracic operation, or contraindications to sternotomy, and may have a role as a bridge to transplantation in selected cases.

Minimally Invasive Thymectomy and Open Thymectomy: Outcome Analysis of 263 Patients

BACKGROUND 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. METHODS This is an institutional review board-approved, retrospective study of a single centers experience with both open (transsternal) and minimally invasive (video-assisted thoracoscopic surgery) thymectomy. Survival estimates and statistical comparisons were calculated using standard software. RESULTS 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. CONCLUSIONS 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.

Advanced thoracoscopic procedures are facilitated by computer-aided robotic technology

OBJECTIVE 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. METHODS Ten patients underwent advanced thoracoscopic procedures utilizing the Da Vinci robotic surgical system (Intuitive Surgical, Mountain View, CA) at our institution. RESULTS 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. CONCLUSIONS 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.

Lung adenocarcinoma invasion in TGFβRII -deficient cells is mediated by CCL5/RANTES

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-β receptor (TGFβRII), 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-β signaling important for lung adenocarcinoma invasion. We specifically hypothesized that RANTES is required for lung cancer invasion and progression in TGFβRII-repressed cells. We examined invasion in TGFβRII-deficient cells treated with two inhibitors of RANTES activity, Met-RANTES and a CCR5 receptor-blocking antibody. Both treatments blocked invasion induced by TGFβRII 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 TGFβRII-deficient cells and suggest a role for CCR5 inhibition in lung adenocarcinoma prevention and treatment.

Expression of Egr-1 in Late Stage Emphysema

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.

Lysyl oxidase: A lung adenocarcinoma biomarker of invasion and survival

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.

One Hundred Transports on Extracorporeal Support to an Extracorporeal Membrane Oxygenation Center

BACKGROUND Extracorporeal life support technology has gained acceptance as a salvage mode for patients in respiratory or cardiac failure. Patients who are sick enough to require extracorporeal membrane oxygenation (ECMO) support are often too unstable for transfer to a hospital with ECMO capabilities. We highlight the progressive development of an ECMO transport team and the manner in which it provides reliable transport with excellent outcomes. METHODS All data were collected retrospectively from our hospitals electronic medical record. Patient outcomes are reported through April 2, 2014. RESULTS Our institution began an ECMO transport program in 2008, with the initial phase involving transport of highly selected patients for short distances. With experience we refined our intake and evaluation process. We also consolidated care for ECMO patients into two intensive care units and developed a dedicated ECMO intensivist position. As the program has matured, patient selection has become more inclusive and we have extended our capabilities to include interstate and international transport. All 100 patients were successfully placed on ECMO and transported to our center. Seventy-nine patients were placed on venovenous ECMO, 19 on venoarterial ECMO, and 2 on venovenous arterial ECMO. The median transport distance was 16 miles and ranged from 2.5 to 7,084 miles. CONCLUSIONS Extracorporeal membrane oxygenation transport can be performed safely and reliably with excellent outcomes with a dedicated team that maintains stringent adherence to well-designed management protocols.

ACR Appropriateness Criteria Nonsurgical Treatment for Non–Small-Cell Lung Cancer: Poor Performance Status or Palliative Intent

Radiation therapy plays a potential curative role in the treatment of patients with non-small-cell lung cancer with locoregional disease who are not surgical candidates and a palliative role for patients with metastatic disease. Stereotactic body radiation therapy is a relatively new technique in patients with early-stage non-small-cell lung cancer. A trial from RTOG(®) reported >97% local control at 3 years. For patients with locally advanced disease, thoracic radiation to a dose of 60 Gy remains the standard of care. Sequential chemotherapy or radiation alone can be used for patients with poor performance status who cannot tolerate more aggressive approaches. Chemotherapy should be used for patients with metastatic disease. Radiation therapy is useful for palliation of symptomatic tumors, and a dose of approximately 30 Gy is commonly used. Endobronchial brachytherapy is useful for patients with symptomatic endobronchial tumors. The ACR Appropriateness Criteria are evidence-based guidelines for specific clinical conditions that are reviewed every 2 years by a multidisciplinary expert panel. The guideline development and review include an extensive analysis of current medical literature from peer-reviewed journals and the application of a well-established consensus methodology (modified Delphi) to rate the appropriateness of imaging and treatment procedures by the panel. In those instances in which evidence is lacking or not definitive, expert opinion may be used to recommend imaging or treatment.

Histologic assessment of non-small cell lung carcinoma after neoadjuvant therapy.

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.

ACR Appropriateness Criteria® screening for pulmonary metastases.

Screening for pulmonary metastatic disease is an important step for staging a patient with a known or recently discovered malignancy. Here we present our recommendations for screening for metastatic disease based on recommendations from the literature and experiences of pulmonary radiologists. In short, chest computed tomographic (CT) screening is the most appropriate tool for evaluation of pulmonary metastasis in the majority of cases. Chest computed tomographic screening is also recommended for follow-up and to determine response to therapy. Other modalities such as chest radiography, magnetic resonance imaging, and scintigraphy will also be discussed. Please note that this study is a summary of the complete version of this topic, which is available on the ACR website at www.acr.org. Practitioners are encouraged to refer to the complete version.