Objective The study objective was to compare the outcomes of intraoperative extracorporeal membrane oxygenation versus cardiopulmonary bypass support in lung transplantation. Methods We performed a ...retrospective cohort study from a prospective database of adult lung transplantations performed at the University of Toronto from 2007 to 2013. Among 673 lung transplantations performed in the study period, 267 (39.7%) required cardiopulmonary support. There were 39 cases of extracorporeal membrane oxygenation (2012-2013) and 228 cases of cardiopulmonary bypass (2007-2013). Patients who were bridged with extracorporeal life support, underwent a concomitant cardiac procedure, received a combined liver or heart transplant, were colonized with Burkholderia cenocepacia , or required emergency cannulation for cardiopulmonary support were excluded. Finally, 33 extracorporeal membrane oxygenation cases were matched with 66 cases of cardiopulmonary bypass according to age (±10 years), lung transplantation indication, and procedure type (bilateral vs single lung transplantation). Results Recipient factors such as body mass index and gender were not different between extracorporeal membrane oxygenation and cardiopulmonary bypass groups. Furthermore, donor variables were similar, including age, body mass index, last PaO2/FiO2 ratio, smoking history, positive airway cultures, and donor type (brain death and donation after cardiac death). Early outcomes, such as mechanical ventilation requirement, length of intensive care unit stay, and length of hospital stay, significantly favored extracorporeal membrane oxygenation (median 3 vs 7.5 days, P = .005; 5 vs 9.5 days, P = .026; 19 vs 27 days, P = .029, respectively). Perioperative blood product transfusion requirement was lower in the extracorporeal membrane oxygenation group. The 90-day mortality for the extracorporeal membrane oxygenation group was 6% versus 15% for cardiopulmonary bypass ( P = .32). Conclusions Extracorporeal membrane oxygenation may be considered as the first choice of intraoperative cardiorespiratory support for lung transplantation.
Abstract Objective(s) Localization and resection of non-visible, non-palpable pulmonary nodules during video-assisted thoracoscopic surgery (VATS) is challenging. Our study was to determine the ...feasibility and safety of indocyanine green (ICG) fluorescence localization and resection of small nodules using a near-infrared (NIR) fluorescence thoracoscope. Methods Twenty patients with undiagnosed peripheral nodules smaller than 3cm scheduled for CT-guided microcoil placement followed by VATS wedge resection were enrolled. After microcoil deployment, 100-150 μl of diluted ICG was injected percutaneously near the nodule. The nodule was initially localized solely by using the NIR thoracoscope to visualize ICG fluorescence. Thoracoscopic instruments were used to determine the staple line. Wedge resection was performed after confirmation of the location of the microcoil using fluoroscopy. Results Twenty patients underwent NIR image-guided VATS resection. The median CT tumor size was 1.2 cm. The median depth from the pleural surface was 1.4 cm (range: 0.2-4.8). The median CT-guided intervention time was 35 min and VATS procedural time was 54 min. ICG fluorescence was clearly identified in 18 of 20 cases (90%). The surgical margins were all negative on final pathology without the need of additional resection. The final diagnoses included 18 primary lung cancer, 1 metastatic lung cancer, and 1 benign lung tumor. Conclusions CT-guided percutaneous ICG injection and intraoperative NIR localization of small nodules is safe and feasible. It offers surgeons the ease of localization through direct ICG fluorescence imaging without the use of fluoroscopy and may be a complementary technique to preoperative microcoil placement for non-visible, non-palpable intrapulmonary nodules.
Video-assisted thoracoscopic wedge resection of multiple small, non-visible, and nonpalpable pulmonary nodules is a clinical challenge. We propose an ultra-minimally invasive technique for ...localization of pulmonary nodules using the electromagnetic navigation bronchoscope (ENB)-guided transbronchial indocyanine green (ICG) injection and intraoperative fluorescence detection with a near-infrared (NIR) fluorescence thoracoscope.
Fluorescence properties of ICG topically injected into the lung parenchyma were determined using a resected porcine lung. The combination of ENB-guided ICG injection and NIR fluorescence detection was tested using a live porcine model. An electromagnetic sensor integrated flexible bronchoscope was geometrically registered to the three-dimensional chest computed tomographic image data by way of a real-time electromagnetic tracking system. The ICG mixed with iopamidol was injected into the pulmonary nodules by ENB guidance; ICG fluorescence was visualized by a near-infrared (NIR) thoracoscope.
The ICG existing under 24-mm depth of inflated lung was detectable by the NIR fluorescence thoracoscope. The size of the fluorescence spot made by 0.1 mL of ICG was 10.4 ± 2.2 mm. An ICG or iopamidol spot remained at the injected point of the lung for more than 6 hours in vivo. The ICG fluorescence spot injected into the pulmonary nodule with ENB guidance was identified at the pulmonary nodule with the NIR thoracoscope.
The ENB-guided transbronchial ICG injection and intraoperative NIR thoracoscopic detection is a feasible method to localize multiple pulmonary nodules.
The utility of rapid on-site evaluation (ROSE) during endobronchial ultrasound-guided transbronchial needle aspiration (EBUS-TBNA) for lymph node staging in lung cancer is still controversial. The ...aim of this study was to assess the role of ROSE during EBUS-TBNA and the interpretation of its results.
We performed a retrospective chart review of patients with suspected or diagnosed lung cancer who underwent EBUS-TBNA for lymph node staging. The slides were air-dried and Diff-Quik (American Scientific Products, McGaw Park, IL) staining was used for ROSE. Additional smears were prepared for Papanicolaou staining and any remaining sample was placed in 10% formalin for histologic evaluation. The results of ROSE were compared with the results of the final pathologic diagnosis.
EBUS-TBNA was performed in 438 patients on 965 lymph nodes. Eighty-four lymph nodes (8.7%) were determined insufficient for definitive diagnosis by final cytologic evaluation. However 45 of the 84 lymph nodes were able to be diagnosed by histologic examination. The non-diagnostic sampling rate was 4.0%. There were no false-positive results on ROSE; however 25 cases (5.7%) were falsely evaluated as negative on ROSE. The concordance rate for staging between ROSE and final pathologic diagnosis was 94.3%. The sensitivity, specificity, negative predictive value, and diagnostic accuracy rate of EBUS-TBNA for correct lymph node staging was 96.5%, 100%, 89.8%, and 98.2%, respectively.
ROSE during EBUS-TBNA for material adequacy showed a low rate of non-diagnostic sampling. There was a high agreement between the on-site and final pathologic evaluation during EBUS-TBNA; however immediate diagnosis should be approached with caution.
Background The importance of biomarker analysis in patients with non-small cell lung cancer (NSCLC) is well known. The purpose of this study was to analyze the mutation status of multiple genes in ...metastatic lymph nodes obtained by endobronchial ultrasound-guided transbronchial needle aspiration (EBUS-TBNA) and to examine the correlation between treatments and outcomes. Methods Genetic alterations were analyzed in metastatic hilar or mediastinal lymph nodes diagnosed by EBUS-TBNA in 156 patients with NSCLC. Epidermal growth factor receptor ( EGFR ) was analyzed using the peptide nucleic acid-locked nucleic acid polymerase chain reaction clamp method (n = 156). V-Ki-ras2 Kirsten rat sarcoma viral oncogene homolog ( K-ras ) (exons 2-3) and tumor protein 53 ( p53 ) (exons 4-8) were analyzed by direct sequencing (n = 113). In addition, retrospective chart review was performed for clinical data analysis. Results EGFR gene mutations were detected in 42 cases (26.9%). Twenty-three patients with EGFR mutations received gefitinib, with an overall response rate (partial response PR) of 54.5% and disease control rate (PR + stable disease) of 86.4% (Response Evaluation Criteria in Solid Tumors). K-ras gene mutations were detected in four cases (3.5%), and p53 gene mutations were detected in 47 cases (41.6%). Fifty-two patients underwent conventional chemotherapy (46 patients underwent platinum-based chemotherapy). Patients with p53 gene mutations showed chemoresistance (progressive disease of 42.9%, P = .0339) and a relatively poor prognosis after chemotherapy ( P = .1391). Conclusions Multigene mutation analysis can be performed in EBUS-TBNA samples of metastatic lymph nodes from patients with NSCLC. EBUS-TBNA allows genetic evaluation of tumor cells within the metastatic node, which may allow physicians to better select treatments, particularly EGFR tyrosine kinase inhibitors.
Endobronchial ultrasonography (EBUS)-guided transbronchial needle aspiration allows for sampling of mediastinal lymph nodes. The external diameter, rigidity, and angulation of the convex probe EBUS ...renders limited accessibility. This study compares the accessibility and transbronchial needle aspiration capability of the prototype thin convex probe EBUS against the convex probe EBUS in human ex vivo lungs rejected for transplant.
The prototype thin convex probe EBUS (BF-Y0055; Olympus, Tokyo, Japan) with a thinner tip (5.9 mm), greater upward angle (170 degrees), and decreased forward oblique direction of view (20 degrees) was compared with the current convex probe EBUS (6.9-mm tip, 120 degrees, and 35 degrees, respectively). Accessibility and transbronchial needle aspiration capability was assessed in ex vivo human lungs declined for lung transplant. The distance of maximum reach and sustainable endoscopic limit were measured. Transbronchial needle aspiration capability was assessed using the prototype 25G aspiration needle in segmental lymph nodes.
In all evaluated lungs (n = 5), the thin convex probe EBUS demonstrated greater reach and a higher success rate, averaging 22.1 mm greater maximum reach and 10.3 mm further endoscopic visibility range than convex probe EBUS, and could assess selectively almost all segmental bronchi (98% right, 91% left), demonstrating nearly twice the accessibility as the convex probe EBUS (48% right, 47% left). The prototype successfully enabled cytologic assessment of subsegmental lymph nodes with adequate quality using the dedicated 25G aspiration needle.
Thin convex probe EBUS has greater accessibility to peripheral airways in human lungs and is capable of sampling segmental lymph nodes using the aspiration needle. That will allow for more precise assessment of N1 nodes and, possibly, intrapulmonary lesions normally inaccessible to the conventional convex probe EBUS.
The aim of this study was to assess the value of endobronchial ultrasound-guided transbronchial needle aspiration (EBUS-TBNA) for differentiating cN0 versus cN1 non-small cell lung cancer.
A ...retrospective review of EBUS-TBNA results in patients with potentially resectable clinical N0 or N1 non-small cell lung cancer based on computed tomography and positron emission tomography was performed. Systematic mediastinal and hilar lymph node sampling was performed by EBUS-TBNA. Lymph nodes larger than 5 mm in short axis or suspicious nodes were targeted. In the absence of N2 or N3 disease, patients underwent resection with lymph node dissection.
A total of 981 patients underwent EBUS-TBNA during the study period, of which 163 patients met the study criteria. There were 94 cN0 and 69 cN1 patients. A total of 453 lymph nodes (338 mediastinal and 115 N1 lymph nodes, average 2.8 nodes/patient) were sampled. Endobronchial ultrasound upstaged 9 (5.5%) patients to N2 disease, but was falsely negative in the mediastinum in 7 (4.3%) patients. In cN0 patients, EBUS confirmed N0 in 87 (53.4%) and upstaged in 7 (4.3%, N1 in 1, N2 in 6). In cN1 patients, EBUS confirmed N1 in 19 (11.7%), downstaged in 47 (28.8%), and upstaged in 3 (1.8%). The sensitivity, specificity, diagnostic accuracy, and negative predictive value of EBUS-TBNA to accurately differentiate between N0 and N1 disease was 76.2%, 100%, 96.6%, and 96.2%, respectively. The accuracy of mediastinal staging was 95.7%.
Endobronchial ultrasound-guided transbronchial needle aspiration can accurately access the hilar and interlobar lymph nodes in patients with potentially resectable lung cancer. Accurate assessment of cN0 versus cN1 by EBUS-TBNA may be used to guide induction therapy before surgery.
Objective The study objective was to compare endobronchial ultrasound-guided transbronchial needle aspiration (EBUS-TBNA) with mediastinoscopy for mediastinal lymph node staging of potentially ...resectable non–small cell lung cancer. Methods Patients with confirmed or suspected non–small cell lung cancer who required mediastinoscopy to determine suitability for lung cancer resection were entered into the trial. All patients underwent EBUS-TBNA followed by mediastinoscopy under general anesthesia. If both were negative for N2 or N3 disease, the patient underwent pulmonary resection and mediastinal lymphadenectomy. Results Between July 2006 and August 2010, 190 patients were registered in the study, 159 enrolled, and 153 were eligible for analysis. EBUS-TBNA and mediastinoscopy sampled an average of 3 and 4 lymph node stations per patient, respectively. The mean short axis of the lymph node biopsied by EBUS-TBNA was 6.9 ± 2.9 mm. The prevalence of N2/N3 disease was 35% (53/153). There was excellent agreement between EBUS-TBNA and mediastinoscopy for mediastinal staging in 136 patients (91%; Kappa, 0.8; 95% confidence interval, 0.7–0.9). Specificity and positive predictive value for both techniques were 100%. The sensitivity, negative predictive value, and diagnostic accuracy for mediastinal lymph node staging for EBUS-TBNA and mediastinoscopy were 81%, 91%, 93%, and 79%, 90%, 93%, respectively. No significant differences were found between EBUS-TBNA and mediastinoscopy in determining the true pathologic N stage (McNemar’s test, P = .78). There were no complications from EBUS-TBNA. Minor complications from mediastinoscopy were observed in 4 patients (2.6%). Conclusions EBUS-TBNA and mediastinoscopy achieve similar results for the mediastinal staging of lung cancer. As performed in this study, EBUS-TBNA can replace mediastinoscopy in patients with potentially resectable non–small cell lung cancer.
Objective Normothermic ex vivo lung perfusion is a novel method to evaluate and improve the function of injured donor lungs. We reviewed our experience with 50 consecutive transplants after ex vivo ...lung perfusion. Methods A retrospective study using prospectively collected data was performed. High-risk brain death donor lungs (defined as Pa o2 /F io2 <300 mm Hg or lungs with radiographic or clinical findings of pulmonary edema) and lungs from cardiac death donors were subjected to 4 to 6 hours of ex vivo lung perfusion. Lungs that achieved stable airway and vascular pressures and Pa o2 /F io2 greater than 400 mm Hg during ex vivo lung perfusion were transplanted. The primary end point was the incidence of primary graft dysfunction grade 3 at 72 hours after transplantation. End points were compared with lung transplants not treated with ex vivo lung perfusion (controls). Results A total of 317 lung transplants were performed during the study period (39 months). Fifty-eight ex vivo lung perfusion procedures were performed, resulting in 50 transplants (86% use). Of these, 22 were from cardiac death donors and 28 were from brain death donors. The mean donor Pa o2 /F io2 was 334 mm Hg in the ex vivo lung perfusion group and 452 mm Hg in the control group ( P = .0001). The incidence of primary graft dysfunction grade 3 at 72 hours was 2% in the ex vivo lung perfusion group and 8.5% in the control group ( P = .14). One patient (2%) in the ex vivo lung perfusion group and 7 patients (2.7%) in the control group required extracorporeal lung support for primary graft dysfunction ( P = 1.00). The median time to extubation, intensive care unit stay, and hospital length of stay were 2, 4, and 20 days, respectively, in the ex vivo lung perfusion group and 2, 4, and 23 days, respectively, in the control group ( P > .05). Thirty-day mortality (4% in the ex vivo lung perfusion group and 3.5% in the control group, P = 1.00) and 1-year survival (87% in the ex vivo lung perfusion group and 86% in the control group, P = 1.00) were similar in both groups. Conclusions Transplantation of high-risk donor lungs after 4 to 6 hours of ex vivo lung perfusion is safe, and outcomes are similar to those of conventional transplants. Ex vivo lung perfusion improved our center use of donor lungs, accounting for 20% of our current lung transplant activity.
Localization of small, nonvisible and nonpalpable nodules is challenging during video-assisted thoracoscopic surgery. We evaluated the feasibility of using a new ultrasound thoracoscope to localize ...nodules in resected ex vivo human lungs.
The tumor was localized and measured in its greatest dimension with a prototype ultrasound thoracoscope (XLTF-UC180; Olympus Corporation, Tokyo, Japan) at different frequencies (5.0 to 12.0 MHz) and different lung specimen states (deflated, semiinflated). Measured tumor size and depth from lung surface were compared and correlated to the true diameter and depth from lung surface acquired from pathologic morphology.
Ex vivo evaluation was performed on 16 solid nodules and nine part solid ground-glass nodules. All tumors were successfully localized in the deflated lung specimens (average size, 13.7 ± 5.2 mm). The tumor boundaries were best evaluated with an ultrasound frequency of 10 MHz. Solid nodules were more easily visualized than ground-glass nodules. Part solid ground-glass nodules were not easily detected in the semiinflated specimen owing to peritumoral air surrounding the tumor. Tumor boundaries were also difficult to identify in deeply situated tumors and in lungs with underlying disease. A strong positive correlation existed between the ultrasound measurement and true measurement of tumor size (R
= 0.89, p < 0.001).
The ultrasound thoracoscope can be used to localize nodules in resected human lungs. The clarity of the tumor boundaries is influenced by the tumor type and depth and the underlying pulmonary disease. Complete lung deflation and the use of 10 MHz ultrasound frequency optimize the visualization of target tumors.
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