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.
Ex vivo lung perfusion (EVLP) is being increasingly applied as a method to evaluate and treat donor lungs for transplantation. However, with the previous limited worldwide experience, no studies have ...been able to evaluate the impact of indication for EVLP on organ utilization rates and recipient outcomes after lung transplantation (LTx). We examined these outcomes in a large-cohort, single-center series of clinical EVLP cases.
All EVLP procedures performed at our institution between October 2008 and December 2017 were examined. The EVLPs were divided into 4 groups based on the indication for the procedure: group 1, high-risk brain death donors (HR-BDD); group 2, standard-risk donation after cardiac death (S-DCD); group 3, high-risk donation after cardiac death (HR-DCD); and group 4, logistics (LOGISTICS, the need for prolongation of preservation time or organ retrieval by a different transplantation team).
During the study period, a total of 1106 lung transplants were performed in our institution. In this period, 372 EVLPs were performed, 255 (69%) of which were accepted for transplantation, resulting in 262 transplants. Utilization rates were 70% (140 of 198) for group 1, 82% (40 of 49) for group 2, 63% (69 of 109) for group 3, and 81% (13 of 16) for group 4 (P = .42, Fisher's exact test). Recipient age (P = .27) and medical diagnosis (P = .31) were not different across the 4 groups. Kaplan–Meier survival by EVLP indication group demonstrated no differences. Thirty-day mortality was 2.1% in group 1, 5% in group 2, 2.9% in group 3, and 0% in group 4 (P = .87, Fisher's exact test). The median days of mechanical ventilation, intensive care unit stay, and hospital stay were 2, 4, and 21 in group 1; 2, 3, and 21 in group 2; 3, 5, and 28 in group 3; and 2, 4, and 17 in group 4 (P = .29, .17, and .09, respectively, Kruskal–Wallis rank-sum test).
Clinical implementation of EVLP has allowed our program to expand the annual lung transplantation activity by 70% in this time period. It has improved confidence in the utilization of DCD lungs and BDD lungs, with an average 70% utilization of post-EVLP treated donor lungs with excellent outcomes, while addressing significant challenges in donor lung assessment and the logistics of “real-life” clinical lung transplantation.
Sentinel lymph node biopsy for lung cancer Gregor, Alexander; Ujiie, Hideki; Yasufuku, Kazuhiro
General thoracic and cardiovascular surgery,
10/2020, Letnik:
68, Številka:
10
Journal Article
Recenzirano
Sentinel lymph node biopsy is a technique to identify the first lymph node (or nodes) draining a tumor. The underlying principle is that as the first site of cancer spread, evaluation of the sentinel ...node will be most predictive for wider nodal involvement. The introduction of sentinel node biopsy revolutionized the surgical management of cutaneous melanoma and breast cancer, becoming a key component in the management of such patients. For over 20 years, thoracic surgeons have similarly worked to apply this technique to lung cancer but have thus far not had the same impact on lung surgery. In this review, we will summarize the ongoing discussions on the role of sentinel node biopsy in lung cancer, the methods for identifying the sentinel node, and the techniques for evaluating the sentinel node specimen. We will also highlight some of the pressing questions investigators should consider when designing a trial for sentinel node mapping. This will clarify the current status of sentinel node biopsy in lung cancer and thus highlight important future directions for research.
Ex vivo lung perfusion (EVLP) is an effective method to assess and improve the function of otherwise unacceptable lungs, alleviating the shortage of donor lungs. The early results with EVLP have been ...encouraging, but longer-term results, including functional and patient-reported outcomes, are not well characterized.
This retrospective single-center study included all lung transplants performed between September 2008 and December 2012. We investigated whether survival or rate of chronic lung allograft dysfunction (CLAD) differed in recipients of EVLP-treated lungs compared with contemporaneous recipients of conventional donor lungs. We also studied functional (highest forced expiratory volume in 1 second predicted, change in 6-minute walk distance, number of acute rejection episodes) and quality of life outcomes.
Of 403 lung transplants that were performed, 63 patients (15.6%) received EVLP-treated allografts. Allograft survival for EVLP and conventional donor lung recipients was 79% vs 85%, 71% vs 73%, and 58% vs 57% at 1, 3, and 5 years after transplant, respectively (log-rank p = not significant). Freedom from CLAD was also similar (log-rank p = 0.53). There were no significant differences in functional outcomes such as highest forced expiratory volume in 1 second predicted (76.5% ± 23.8% vs 75.8% ± 22.8%, p = 0.85), change in 6-minute walk distance (194 ± 108 meters vs 183 ± 126 meters, p = 0.57), or the number of acute rejection episodes (1.5 ± 1.4 vs 1.3 ± 1.3, p = 0.36). The EVLP and conventional donor groups both reported a significantly improved quality of life after transplantation, but there was no intergroup difference.
EVLP is a safe and effective method of assessing and using high-risk donor lungs before transplantation and leads to acceptable long-term survival, graft function, and improvements of quality of life that are comparable with conventionally selected donor lungs.
During endobronchial ultrasound (EBUS) staging, ultrasonographic features can be used to predict mediastinal lymph node (LN) malignancy. We sought to develop the Canada Lymph Node Score a tool ...capable of predicting LN metastasis at the time of EBUS.
Patients undergoing EBUS staging for lung and esophageal cancer were prospectively enrolled. Features were identified in real time by an endoscopist and video-recorded. Videos were sent to raters. Pathologic specimens from biopsies/surgical resections were used as the gold-standard reference test. Logistic regression, receiver operator characteristic curve, and Gwet's AC1 analyses were used to test the performance, discrimination, and inter-rater reliability, respectively.
In total, 300 LNs from 140 patients were analyzed by 12 endoscopists (raters) across 7 Canadian centers. Beta-coefficients from a multivariate regression model were used to create a 4-point score: short-axis diameter, margins, central hilar structure, and necrosis. The model showed good discriminatory power (c-statistic = 0.72 ± 0.04, 95% confidence interval CI, 0.64-0.80; bias-corrected c-statistic: 0.66, 95% CI, 0.55-0.76). LNs scoring 3/4 or 4/4 had odds ratios of 15.17 (P < .0001) and 50.56 (P = .001) for predicting malignancy, respectively. Inter-rater reliability for a score ≥3 was 0.81 ± 0.02 (95% CI, 0.77-0.85).
The Canada Lymph Node Score is a 4-point score demonstrating excellent performance in identifying malignant LNs during EBUS. A cut-off of ≥3 may inform decision-making regarding biopsy, repeat biopsy, or mediastinoscopy if the initial results are inconclusive.
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Background 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. ...Methods 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. Results 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%. Conclusions 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 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.
Lung sentinel lymph node mapping, where peritumorally injected material is tracked through the lymphatics, aims to find the first potential sites of nodal metastasis. We sought to evaluate the ...preclinical feasibility of bronchoscopic fluorescence-guided sentinel lymph node mapping.
Healthy Yorkshire pigs were used; sentinel lymph node mapping was performed with indocyanine green. The primary fluorescence imaging method was an ultrathin composite fiberscope placed in the bronchoscope working channel. Secondary methods used a fluorescence thoracoscope placed in the trachea (rigid bronchoscopy) and pretracheal fascial plane (mediastinoscopy) to validate ultrathin composite fiberscope settings for sentinel lymph node detection. A tracheostomy was created, and the pig was placed in a lateral decubitus position. Transbronchial intraparenchymal indocyanine green injection was performed primarily in the right lower lobe. Ultrathin composite fiberscope and rigid bronchoscopy were performed with (n = 6) or without (n = 2) mediastinoscopy, with the former group guiding dose and ultrathin composite fiberscope optimization. Fluorescent targets were interrogated by endobronchial ultrasound before ultrathin composite fiberscope–guided transbronchial needle aspiration. Specimen fluorescence was documented before creating cytological smears. Pigs were killed postprocedure for nodal dissection.
A total of 100 μL of 10 mg/mL indocyanine green generated strong transbronchial fluorescence with low risk of indocyanine green contamination. Fluorescence was detectable by 10 minutes postinjection. There was concordance among ultrathin composite fiberscope, rigid bronchoscopy, and mediastinoscopy. Except for 1 pig with airway contamination, ultrathin composite fiberscope–guided endobronchial ultrasound transbronchial needle aspiration obtained fluorescent material in all pigs. Specimen fluorescence was associated with specimen adequacy.
Bronchoscopic fluorescence-guided sentinel lymph node mapping was feasible, with specimen fluorescence providing real-time feedback on sentinel lymph node biopsy success. If translated to clinical practice, attention must be paid to minimizing indocyanine green leakage.
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Highlights • The high level of KIF23 expression was observed in majority of metastatic lung cancer tissue compared with normal lung control. • KIF23 is crucial for the growth and survival of lung ...cancer cells. • A high level of the KIF23 is strongly associated with poor survival in patients with lung adenocarcinoma. • KIF23 can be valuable for developing new therapeutic targets for advanced lung cancers.
Acceptance of lungs from donation after circulatory determination of death has been generally restricted to donors who have cardiac arrest within 60 minutes after withdrawal of life-sustaining ...therapies. We aimed to determine the effect of the interval between withdrawal of life-sustaining therapies to arrest and recipient outcomes. Second, we aimed to compare outcomes between donation after circulatory determination of death transplants and donation after neurologic determination of death transplants.
A single-center, retrospective review was performed analyzing the clinical outcomes of transplant recipients who received donation after circulatory determination of death lungs and those who received donation after neurologic determination of death lungs. Donation after circulatory determination of death cases were then grouped on the basis of the interval between withdrawal of life-sustaining therapies and asystole: 0 to 19 minutes (rapid), 20 to 59 minutes (intermediate), and more than 60 minutes (long). Recipient outcomes from each of these groups were compared.
A total of 180 cases of donation after circulatory determination of death and 1088 cases of donation after neurologic determination of death were reviewed between 2007 and 2017. There were no significant differences in the 2 groups in terms of age, gender, recipient diagnosis, and type of transplant (bilateral vs single). Ex vivo lung perfusion was used in 118 of 180 (65.6%) donation after circulatory determination of death cases and 149 of 1088 (13.7%) donation after neurologic determination of death cases before transplantation. The median survivals of recipients who received donation after circulatory determination of death lungs versus donation after neurologic determination of death lungs were 8.0 and 6.9 years, respectively. Time between withdrawal of life-sustaining therapies and asystole was available for 148 of 180 donors (82.2%) from the donation after circulatory determination of death group. Mean and median time from withdrawal of life-sustaining therapies to asystole were 28.6 minutes and 16 minutes, respectively. Twenty donors required more than 60 minutes to experience cardiac arrest, with the longest duration being 154 minutes before asystole was recorded. Recipients of donation after circulatory determination of death lungs who had cardiac arrest at 0 to 19 minutes (90 donors), 20 to 59 minutes (38 donors), and more than 60 minutes (20 donors) did not demonstrate any significant differences in terms of short- and long-term survivals, primary graft dysfunction 2 and 3, intensive care unit stay, mechanical ventilation days, or total hospital stay.
Short- and long-term outcomes in recipients who received donation after neurologic determination of death versus donation after circulatory determination of death lungs are similar. Different withdrawals of life-sustaining therapies to arrest intervals were not associated with recipient outcomes. The maximum acceptable duration of this interval has yet to be established.