Concomitant Mediastinoscopy Increases the Risk of Postoperative Pneumonia After Pulmonary Lobectomy.

BACKGROUND: Mediastinoscopy is considered the gold standard for preresectional staging of lung cancer. We sought to examine the effect of concomitant mediastinoscopy on postoperative pneumonia (POP) in patients undergoing lobectomy. METHODS: All patients in our institutional database (2008-2015) undergoing lobectomy who did not receive neoadjuvant therapy were included in our study. The relationship between mediastinoscopy and POP was examined using univariate (Chi square) and multivariate analyses (binary logistic regression). In order to validate our institutional findings, lobectomy data in the National Surgical Quality Improvement Program (NSQIP) from 2005 to 2014 were analyzed for these associations. RESULTS: Of 810 patients who underwent a lobectomy at our institution, 741 (91.5%) surgeries were performed by video-assisted thoracic surgery (VATS) and 487 (60.1%) patients underwent concomitant mediastinoscopy. Univariate analysis demonstrated an association between mediastinoscopy and POP in patients undergoing VATS [odds ratio (OR) 1.80; p = 0.003], but not open lobectomy. Multivariate analysis retained mediastinoscopy as a variable, although the relationship showed only a trend (OR 1.64; p = 0.1). In the NSQIP cohort (N = 12,562), concomitant mediastinoscopy was performed in 9.0% of patients, with 44.5% of all the lobectomies performed by VATS. Mediastinoscopy was associated with POP in patients having both open (OR1.69; p < 0.001) and VATS lobectomy (OR 1.72; p = 0.002). This effect remained in multivariate analysis in both the open and VATS lobectomy groups (OR 1.46, p = 0.003; and 1.53, p = 0.02, respectively). CONCLUSIONS: Mediastinoscopy may be associated with an increased risk of POP after pulmonary lobectomy. This observation should be examined in other datasets as it potentially impacts preresectional staging algorithms for patients with lung cancer.

A pilot study of stereotactic body radiation therapy (SBRT) after surgery for stage III non-small cell lung cancer.

BACKGROUND: Standard therapy for stage III non-small cell lung cancer with chemotherapy and conventional radiation has suboptimal outcomes. We hypothesized that a combination of surgery followed by stereotactic body radiation therapy (SBRT) would be a safe alternative. METHODS: Patients with stage IIIA (multistation N2) or IIIB non-small cell lung cancer were enrolled from March 2013 to December 2015. The protocol included transcervical extended mediastinal lymphadenectomy (TEMLA) followed by surgical resection, 10 Gy SBRT directed to the involved mediastinum/hilar stations and/or positive surgical margins, and adjuvant systemic therapy. Patients not suitable for anatomic lung resection were treated with 30 Gy to the primary tumor. The primary efficacy end-point was the proportion of patients with grade 3 or higher adverse events (AE) or toxicities. RESULTS: Of 10 patients, 7 patients underwent neoadjuvant chemotherapy. All patients had TEMLA. Nine of 10 patients underwent surgical resection. The remaining patient had an unresectable tumor and received 30 Gy SBRT to the primary lesion. All patients had post-operative SBRT. Median follow-up was 18 months. There were no perioperative mortalities. Six patients had any grade 3 AEs with no grade 4-5 AEs. Of these, 4 were not attributable to radiation. Pulmonary-related grade 3 AEs were experienced by 2 patients. There were no failures within the 10 Gy volume. Overall survival and progression-free survival rates at 2 years were 68% (90% CI 36-86) and 40% (90% CI 16-63), respectively. CONCLUSIONS: In carefully selected patients with locally advanced non-small cell lung cancer, combining surgery with SBRT was well tolerated with no local failure. TRIAL REGISTRATION: ClinicalTrials.gov identifying number NCT01781741 . Registered February 1, 2013.

Analyzing the impact of minimally invasive surgical approaches on post-operative outcomes of pneumonectomy and sleeve lobectomy patients.

Background: Some patients with non-small cell lung cancer (NSCLC) have superior short- and long-term outcomes with sleeve lobectomy rather than pneumonectomy. Originally sleeve lobectomy was reserved for patients with limited pulmonary function, however, the reported superior results allowed sleeve lobectomy to be performed in expanded patient populations. In a further attempt to improve post-operative outcomes surgeons have adopted minimally invasive techniques Minimally invasive approaches have potential benefits to patients such as decreased morbidity and mortality while maintaining the same caliber of oncologic outcomes. Methods: We identified patients at our institution who underwent sleeve lobectomy or pneumonectomy to treat NSCLC from 2007 to 2017. We analyzed these groups in respect to 30- and 90-day mortality, complications, local recurrence, and median survival. We included multivariate analysis to determine the impact of a minimally invasive approach, sex, extent of resection, and histology. Differences in mortality were analyzed using the Kaplan-Meier method using the log-rank test to compare the groups. A two-tailed Z test for difference in proportions was done to analyze complications, local recurrence, 30-day and 90-day mortality. Results: A total of 108 patients underwent sleeve lobectomy (n=34) or pneumonectomy (n=74) for treatment of NSCLC with 18 undergoing open pneumonectomy, 56 undergoing video-assisted thoracoscopic surgery (VATS) pneumonectomy, 29 undergoing open sleeve lobectomy, and 5 undergoing VATS sleeve lobectomy. There was no significant difference in 30-day mortality (P=0.064) but there was a difference in 90-day (P=0.007). There was no difference in complication rates (P=0.234) or local recurrence rates (P=0.779). The pneumonectomy patients had a median survival of 23.6 months (95% CI: 3.8-43.4 months). The sleeve lobectomy group had a median survival of 60.7 months (95% CI: 43.3-78.2 months) (P=0.008). On multivariate analysis extent of resection (P<0.001) and tumor stage (P=0.036) were associated with survival. There was no significant difference between the VATS approach and the open surgical approach (P=0.053). Conclusions: When considering patients undergoing surgery for NSCLC sleeve lobectomy resulted in lower 90-day mortality and better 3-year survival compared to patients undergoing PN. Having a sleeve lobectomy rather than a pneumonectomy and having earlier-stage disease lead to significantly improved survival on multivariate analysis. Having a VATS operation leads to a non-inferior post-operative outcome compared to open surgery.

Impact of a Thoracic Multidisciplinary Conference on Lung Cancer Outcomes.

BACKGROUND: With the complexity of cancer treatment rising, the role of multidisciplinary conferences (MDCs) in making diagnostic and treatment decisions has become critical. This study evaluated the impact of a thoracic MDC (T-MDC) on lung cancer care quality and survival. METHODS: Lung cancer cases over 7 years were identified from the Roswell Park cancer registry system. The survival rates and treatment plans of 300 patients presented at the MDC were compared with 300 matched patients. The National Comprehensive Cancer Network (NCCN) guidelines were used to define the standard of care. The compliance of care plans with NCCN guidelines was summarized using counts and percentages, with comparisons made using the Fisher exact test. Survival outcomes were summarized using Kaplan-Meier methods. RESULTS: There was improvement in median overall survival (36.9 vs 19.3 months; P < .001) and cancer-specific survival (48 vs 28.1 months; P < .001) for lung cancer patients discussed at the T-MDC compared with controls. These differences were statistically significant in patients with stages III/IV disease but not in patients with stages I/II disease. The NCCN guidelines compliance rate of treatment plans improved from 80% to 94% (P < .001) after MDC discussion. MDC recommendations resulted in treatment plan changes in 123 of 300 patients (41%). CONCLUSIONS: Our results suggest that lung cancer patients have a survival benefit from MDC discussion compared with controls. Patients with advanced disease (stages III and IV) benefited the most. Further research is necessary to understand the precise mechanisms that drive these results.

Exceeding Radiation Dose to Volume Parameters for the Proximal Airways with Stereotactic Body Radiation Therapy Is More Likely for Ultracentral Lung Tumors and Associated with Worse Outcome.

The preferred radiotherapeutic approach for central (CLT) and ultracentral (UCLT) lung tumors is unclear. We assessed the toxicity and outcomes of patients with CLT and UCLT who underwent definitive five-fraction stereotactic body radiation therapy (SBRT). We reviewed the charts of patients with either CLT or UCLT managed with SBRT from June 2010-April 2019. CLT were defined as gross tumor volume (GTV) within 2 cm of either the proximal bronchial tree, trachea, mediastinum, aorta, or spinal cord. UCLT were defined as GTV abutting any of these structures. Propensity score matching was performed for gender, performance status, and history of prior lung cancer. Within this cohort of 83 patients, 43 (51.8%) patients had UCLT. The median patient age was 73.1 years with a median follow up of 29.9 months. The two most common dose fractionation schemes were 5000 cGy (44.6%) and 5500 cGy (42.2%) in five fractions. Multivariate analysis revealed UCLT to be associated with worse overall survival (OS) (HR = 1.9, p = 0.02) but not time to progression (TTP). Using propensity score match pairing, UCLT correlated with reduced non-cancer associated survival (p = 0.049) and OS (p = 0.03), but not TTP. Within the matched cohort, dosimetric study found exceeding a D4cc of 18 Gy to either the proximal bronchus (HR = 3.9, p = 0.007) or trachea (HR = 4.0, p = 0.02) was correlated with worse non-cancer associated survival. In patients undergoing five fraction SBRT, UCLT location was associated with worse non-cancer associated survival and OS, which could be secondary to excessive D4cc dose to the proximal airways.

Prior Treatment for Non-small Cell Lung Cancer Is Associated With Improved Survival in Patients who Undergo Definitive Stereotactic Body Radiation Therapy for a Subsequent Lung Malignancy: A Retrospective Multivariate and Matched Pair Analysis.

BACKGROUND: Despite occurring commonly, the prognoses of second early-stage non-small cell lung cancers (NSCLC) are not well known. METHODS: The authors retrospectively reviewed the charts of inoperable patients who underwent thoracic stereotactic body radiation therapy (SBRT) from February 2007 to April 2019. Those with previous small cell lung cancers or SBRT treatments for tumors other than NSCLC were excluded. Multivariate Cox regression and a matched pair cohort analyses evaluated the prognoses of patients undergoing definitive SBRT for a new second primary. RESULTS: Of 438 patients who underwent definitive SBRT for NSCLC, 84 had previously treated NSCLC. Univariate log-rank tests identified gender, Karnofksy performance status (KPS), prior lung cancer, anticoagulation use, and history of heart disease to correlate with overall survival (OS) (P<0.05). These factors were incorporated into a multivariate Cox regression model that demonstrated female sex (P=0.004, hazard ratio [HR]=0.68), KPS (P<0.001, HR=2.0), and prior lung cancer (P=0.049, HR=0.7) to be significantly associated with OS. A similar approach found only gender (P=0.017, HR=0.64) and tumor stage (P=0.02, HR=1.7) to correlate with relapse-free survival. To support the Cox regression analysis, propensity score matching was performed using gender, age, KPS, tumor stage, history of heart disease, and anticoagulation use. Kaplan-Meier survival analysis within the matched pairs found prior lung cancer to be associated with improved OS (P=0.011), but not relapse-free survival (P=0.44). CONCLUSIONS: Compared with initial lung cancer SBRT inoperable cases, ablative radiotherapy for new primaries was associated with improved OS. Physicians should not be dissuaded from offering SBRT to such patients.

Detection of an embolized central venous catheter fragment with endobronchial ultrasound.

An 84-year-old woman underwent Convex-probe Endobronchial Ultrasound (CP-EBUS) for 18 F-fluorodeoxyglucose avid subcarinal lymphadenopathy on Positron Emission Tomogram (PET) scan. Endobronchial ultrasound-guided transbronchial needle aspiration of the subcarinal lymph node revealed squamous cell lung carcinoma. A small hyperechoic rounded density was noted inside the lumen of the azygous vein. Based on chest computed tomography findings and her clinical history, this was felt to be a broken fragment of a peripherally inserted central catheter, which was placed for intravenous antibiotics, a few months prior to this presentation. To the best of our knowledge, this is the first ever CP-EBUS description of a broken fragment of central venous catheter.

Risk and benefit of neoadjuvant therapy among patients undergoing resection for non-small-cell lung cancer.

OBJECTIVES: Neoadjuvant therapy has emerged as a favoured treatment paradigm for patients with clinical N2 disease undergoing surgical resection for non-small-cell lung cancer. It is unclear whether such a treatment paradigm affects perioperative outcomes. We sought to examine the National Cancer Database (NCDB) to assess the impact of neoadjuvant therapy on perioperative outcomes and long-term survival in these patients. METHODS: All patients with a history of non-small-cell lung cancer undergoing anatomical resection between 2004 and 2014 were included. Thirty-day and 90-day mortality of all patients having neoadjuvant therapy versus those who did not were compared. In addition, the impact of neoadjuvant therapy on the overall survival of patients with clinical N2 disease was examined. RESULTS: Of the 134 428 selected patients, 9896 (7.4%) patients had neoadjuvant chemotherapy. Patients undergoing neoadjuvant therapy had a higher 30-day (3% vs 2.6%; P < 0.01) and 90-day mortality (6.5% vs 4.9%; P < 0.01). This association remained after adjusting for covariates. Among patients with clinical N2 disease (n = 10 139), 42.3%, 35.3% and 22.4% of patients had neoadjuvant, adjuvant and no chemotherapy, respectively. Univariable, multivariable and propensity score-weighted analyses indicated no difference in survival between patients receiving neoadjuvant and adjuvant chemotherapy. CONCLUSIONS: Neoadjuvant therapy may adversely affect perioperative outcomes without providing a survival advantage compared with adjuvant therapy in clinical N2 stage patients. Randomized controlled trials need to be conducted to examine this issue further.

Effect of the number of lymph nodes examined on the survival of patients with stage I non-small cell lung cancer who undergo sublobar resection.

OBJECTIVES: Early stage lung cancer is being detected at a higher frequency with the implementation of screening programs. At the same time, medically complex patients with multiple comorbidities are presenting for surgery, with a concomitant rise in rates of sublobar resection. We sought to examine the effect of sampling lymph nodes on the outcomes of patients who undergo sublobar resection for small (<2 cm) stage I non-small cell lung cancer (NSCLC). METHODS: All patients in the Surveillance, Epidemiology, and End Results database from 2004 to 2013 with small (<2 cm) stage I NSCLC who underwent sublobar resection (wedge/segmentectomy) and no other cancer history were included. The association of the number of lymph nodes examined (LNE; categories none, 1-3, 4-6, 7-9, >9) with the overall survival as well as disease-specific survival were examined using univariate as well as multivariate analyses while controlling for covariates such as age, size (<1 cm, >1 cm), grade, histology (adenocarcinoma vs others), and extent of resection (wedge/segmentectomy). RESULTS: Data from 3916 eligible patients were analyzed. Seven hundred fifteen patients (18.3%) had segmentectomy. No lymph nodes were examined in 49% and 23% of wedge resection and segmentectomy patients, respectively. Among all eligible patients, 1132 (29%), 474 (12%), 228 (6%), and 328 (8%) patients had 1 to 3, 4 to 6, 7 to 9 and >9 LNE, respectively. Univariate analyses showed significant associations between overall and disease-specific survivals with age, grade, histology, sex, extent of surgery, and LNE. The association between the number of LNE and survival remained significant even after adjusting for significant covariates including extent of sublobar resection (hazard ratio for groups with LNE 1-3, 4-6, 7-9, and >9 compared with 0 LNE were 0.79, 0.77, 0.68, and 0.45 for overall survival; P < .001) and 0.85, 0.77, 0.71, and 0.44 for disease-specific survival (P < .05), respectively. In multivariate modeling, LNE was retained as a significant variable and extent of resection was not. In patients in whom at least 1 lymph node was examined, extent of resection was not predictive of outcome. CONCLUSIONS: Many patients having sublobar resection for early stage NSCLC in the United States do not have a single lymph node removed for pathologic examination. The number of LNE is associated with improved survival, presumably due to avoidance of mis-staging. This association seems greater than the association with extent of resection (segmentectomy vs wedge resection). Appropriate lymph node examination remains an important part of resection for lung cancer even if the resection is sublobar.

Sarcopenia is a predictor of outcomes after lobectomy.

BACKGROUND: As screening for lung cancer rises, an increase in the diagnosis of early stage lung cancers is expected. Lobectomy remains the standard treatment, but there are alternatives, consideration of which requires an estimation of the risk of surgery. Sarcopenia, irrespective of body mass index, confers a worse prognosis in many groups of patients including those undergoing surgery. Here we examine the association of muscle mass with outcomes for patients undergoing lobectomy. METHODS: Consecutive patients undergoing lobectomy were retrospectively reviewed. Preoperative computed tomography scans were reviewed, and cross-sectional area of the erector spinae muscles and pectoralis muscles was determined and normalized for height. Univariate and multivariate analyses were then done to examine for an association of muscle mass with morbidity and short- and long-term mortality. RESULTS: During the study period, there were 299 lobectomies, 278 of which were done by video assisted thoracoscopic surgery. The average age of the patients was 67.5±10.6 years. Overall complication rate was 52.2%, pneumonia rate was 8.7%, and the 30-day mortality rate was 1.3%. Mean height adjusted-erector spinae muscle cross-sectional area was 10.6±2.6 cm2/m2, and mean height adjusted-pectoralis muscle cross sectional area was 13.3±3.8 cm2/m2. The height adjusted cross sectional areas of the erector spinae and pectoralis muscles were not associated with overall complication rate, rate of pneumonia, readmission, or intensive care unit length of stay. The height adjusted-erector spinae muscle cross sectional area was inversely correlated with 30-day mortality risk, odds ratio 0.77 (95% CI, 0.60-0.98, P=0.036). Mean length of stay was 7.0 days (95% CI, 5.5-8.4 days). Multivariate analysis demonstrated a significant inverse association of the height adjusted-erector spinae muscle cross sectional area with length of stay (P=0.019). CONCLUSIONS: The height adjusted-erector spinae muscle cross sectional area was significantly associated with 30-day mortality and length of stay in the hospital. Measurement of muscle mass on preoperative computed tomography imaging may have a role to help predict risk of morbidity and mortality prior to lobectomy.

Transcervical Extended Mediastinal Lymphadenectomy: Experience From a North American Cancer Center.

BACKGROUND: Accurate staging of the mediastinum is a critical element of therapeutic decision making in non-small cell lung cancer. We sought to determine the utility of transcervical extended mediastinal lymphadenectomy (TEMLA) in staging non-small cell lung cancer for large central tumors and after induction therapy. METHODS: A retrospective record review was performed of all patients who underwent TEMLA at our institution from 2010 to 2015. Clinical stage as assessed by positron emission tomography integrated with computed tomography (PET-CT), stage as assessed by TEMLA, final pathologic stage, lymph node yield, and clinical characteristics of tumors were assessed along with TEMLA-related perioperative morbidity. Accuracy of staging by TEMLA for restaging the mediastinum after neoadjuvant therapy was compared with that of PET-CT. RESULTS: Of 164 patients who underwent TEMLA, 157 (95.7%) were completed successfully. Combined surgical resection along with TEMLA was performed in 138 of these patients, with 131 (94.2%) undergoing a video-assisted thoracoscopic resection. The recurrent laryngeal nerve injury rate was 6.7%. TEMLA was performed in 118 of 164 patients for restaging after neoadjuvant therapy, and 101 of these patients were also restaged by PET-CT. Based on TEMLA, 7 patients did not go on to have resection. Of the 101 patients who did have a resection, TEMLA was more accurate than PET-CT in staging the mediastinum (95% vs 73%, p < 0.0001). However, the pneumonia rate in this subgroup of patients was 13%. CONCLUSIONS: TEMLA is a safe procedure and superior to PET-CT for restaging of the mediastinum after neoadjuvant therapy for non-small cell lung cancer. However, this increased accuracy comes with a high postoperative pneumonia rate.

Whole blood cardioplegia (minicardioplegia) reduces myocardial edema after ischemic injury and cardiopulmonary bypass.

While blood:crystalloid cardioplegia is the clinical standard for patients undergoing cardiopulmonary bypass (CPB), it has been postulated that whole blood minicardioplegia may benefit the severely injured heart by reducing cardioplegic volume, thereby reducing myocardial edema. To test this hypothesis, we compared the cardioprotection of a popular 4:1 blood:crystalloid cardioplegia to whole blood minicardioplegia (WB) in a porcine model of acute myocardial ischemia. Yorkshire pigs (n = 20) were placed on atriofemoral bypass and subjected to 30 minutes of global normothermic ischemia. Animals were randomized to receive either 4:1 cold cardioplegia (n = 10) or WB cold cardioplegia (n = 10) delivered antegrade continuously for 90 minutes. Baseline (BL) echocardiographic determination of left ventricular mass (LVM) was compared within groups for cardiac edema (%) measured by histologic morphometrics. All (100%) animals receiving WB were successfully weaned off CPB, whereas only 40% of animals receiving 4:1 were successfully weaned off CPB. Cardiac edema percentage (p < .004) and LVM (p < .05) were significantly decreased in the WB group compared with 4:1. WB cardioplegia increases the number of hearts successfully weaned from CPB and decreases cardiac edema in our porcine model of acute myocardial ischemia. This finding implies whole blood cardioplegia may be more protective in a select group of patients undergoing extended CPB time by decreasing myocardial edema.

Evidence of systemic cytokine release in patients undergoing cardiopulmonary bypass.

Cardiopulmonary bypass (CPB) causes a systemic inflammatory response syndrome (SIRS), which can progress to an acute lung inflammation known as postperfusion syndrome. We developed a two-phase hypothesis: first, that SIRS, as indicated by elevated cytokines post-CPB, would be correlated with postoperative pulmonary dysfunction (Phase I), and second, that the cytokine interleukin-6 (IL-6) is predominantly released from the heart in CPB patients (Phase II). Blood samples were collected from patients undergoing CPB for elective cardiac surgery. In seven patients (Phase I), arterial samples were drawn before, during (5 minutes and 60 minutes), and after CPB. In 14 patients (Phase II), samples were collected from the coronary sinus, superior vena cava, and a systemic artery at the times indicated previously. Samples were analyzed with enzyme-linked immunosorbent assay: IL-1, IL-6, IL-8, IL-10, and tumor necrosis factor-alpha were assessed in Phase I and IL-6 assessed in Phase II. In Phase I, IL-6, IL-8, and IL-10 were elevated after CPB, but only IL-6 concentrations correlated with lung function. In summary, Phase I data demonstrate that increased IL-6 levels at the end of CPB correlate with reduced lung function postoperatively. In Phase II, IL-6 elevation was similar at all sample sites suggesting that the heart is not the major source of IL-6 production. We suggest that IL-6 be implemented as a prognostic measure in patient care, and that patients with elevated IL-6 after CPB be targeted for more aggressive anti-inflammatory therapy to protect lung function.

Does Thoracoscopic Surgery Decrease the Morbidity of Combined Lung and Chest Wall Resection?

BACKGROUND: Because the traditional open lung approach with en bloc chest wall resection carries substantial risk for complications and death, we studied our thoracoscopic approach for this operation. METHODS: From 2007 to 2013, all consecutive video-assisted thoracoscopic (VATS) and open chest wall resections at a comprehensive cancer center were tabulated retrospectively. Data were analyzed by approach, type, and cause of early major morbidity and mortality. Lung cancer cases (the largest subset, T3) were analyzed separately. Statistical tests included the Kruskal-Wallis test for continuous variables and the χ(2) for categoric variables. Survival data were analyzed by the Kaplan-Meier method and log-rank tests. RESULTS: Of 47 chest wall resections performed, 17 (36%) were performed by VATS with no conversions. Resections were performed for primary non-small cell lung cancer (15 VATS and 16 thoracotomy), sarcoma (11), metastatic disease from a separate primary (2), and benign conditions (3). Patients undergoing a VATS approach were older (76 vs 56 years, p = 0.003), and the operative times, blood loss, and ribs resected were similar between groups. Patients undergoing VATS had shorter intensive care unit and hospital lengths of stay, but both groups had high hospital morbidity and mortality, largely resulting from postoperative pneumonia or respiratory systemic inflammatory response syndrome (n = 5), stroke (n = 2), and postoperative colon ischemia (n = 1). Groups had a 90-day mortality of 26.7% and 25% respectively. Stage-matched survival curves for both approaches were superimposable (p=0.88). CONCLUSIONS: Thoracoscopic chest wall resection was feasible, expanded our case selection, and reduced prosthetic reconstruction. It did not, however, protect frail, elderly patients reliably. Briefer, less traumatic operations may be needed for this cohort.

High-volume, zero balanced ultrafiltration improves pulmonary function in a model of post-pump syndrome.

The systemic inflammatory response syndrome (SIRS), which may develop following cardiopulmonary bypass (CPB), can cause postoperative complications that contribute to the morbidity and mortality associated with open-heart surgery. Inflammatory mediators such as cytokines, are thought to play an important role in SIRS. Zero Balance Ultrafiltration (Z-BUF) is thought to reduce the quantity of inflammatory mediators associated with CPB and may attenuate the adverse effects of bypass. Following ethics committee approval, both an unfiltered experimental group and Z-BUF treatment group consisting of Yorkshire pigs (41 +/- 19 kg) were anesthetized, ventilated, instrumented, cannulated and placed on CPB for 60 minutes. Following CPB, an infusion of low-dose endotoxin (1 microg/kg) was administered I.V. and the animals were monitored for 3.5 hours. The Z-BUF treatment group (n = 5) received high-volume Z-BUF (122 ml/kg +/- 41) and the unfiltered experimental group (n = 5) did not. Hemodynamics, blood gases, and pulmonary functions were measured before, during, and after CPB. Following euthanasia, the middle lobe of the lung was prepared for histological analysis. Necropsy of the lung sample was weighed before and after dehydration to evaluate lung water content. During the experimental time course, plasma samples were evaluated for Interleukin-8 (IL-8) concentrations. Arterial PO2's (mmHg) in the unfiltered experimental group showed a significant reduction at 3.5 hours post CPB when compared to baseline while the Z-BUF treatment group PaO2 did not significantly change. There was a significant difference in the PaO2 between the unfiltered experimental and Z-BUF group at the final 3.5 hour time point (78 +/- 32 vs. 188 +/- 92 mmHg respectively). Pulmonary compliance (ml/cmH2O) was significantly reduced in both the unfiltered experimental and Z-BUF treatment groups with the unfiltered experimental group being the most significant. Lung wet/dry ratios were established and results found the unfiltered experimental group ratio significantly greater than that of the Z-BUF treatment group. Morphometric analysis of histologic lung sections confirmed pulmonary injury in the unfiltered experimental group and protection in the Z-BUF treatment group. This study suggests that Z-BUF provides higher arterial PO2's and lung compliances while reducing pulmonary edema and lung injury in a porcine model of PPS.

Thoracoscopic pneumonectomy: an 11-year experience.

BACKGROUND: It is unclear whether thoracoscopic (video-assisted thoracoscopic surgery [VATS]) pneumonectomy improves outcomes compared with open approaches. METHODS: One hundred seven consecutive pneumonectomies performed at an experienced center from January 2002 to December 2012 were studied retrospectively. Forty cases were open, and 50 successful VATS and 17 conversions were combined (intent-to-treat [ITT] analysis). RESULTS: The VATS cohort had more preoperative comorbidities (three vs two, P = .003), women (57% vs 30%, P = .009), and older ages (65 years vs 63 years, P = .07). Although advanced clinical stage was less for VATS (26% vs 50% stage III, P = .035), final pathologic staging was similar (25% vs 38%, P = .77). Pursuing a VATS approach yielded similar complications (two vs two, median, P = .73) with no catastrophic intraoperative events like bleeding. Successful VATS pneumonectomy rates rose from 50%-82% by the second half of the series (P < .001). Completion pneumonectomy cases (13.4% VATS, 7.5% open) had similar outcomes. Having similar initial discomforts as patients undergoing open surgery, more patients undergoing VATS were pain-free at 1 year (53% vs 19%, P = .03). Conversions resulted in longer ICU stays (4 days vs 2 days, P = .01). Advanced clinical stage (III-IV) ITT VATS had longer median overall survival (OS) (42 months vs 13 months, log-rank P = .042). Successful VATS cases with early pathologic stage (0-II) had a median OS of 80 vs 16 months for converted and 28 months for open (log rank = 0.083). CONCLUSIONS: Attempting thoracoscopic pneumonectomy at an experienced center appears safe but does not yield the early pain/complication reductions observed for VATS lobectomy. There may be long-term pain/survival advantages for certain stages that warrant further study and refinement of this approach.

Lung cancer lymph node micrometastasis detection using real-time polymerase chain reaction: correlation with vascular endothelial growth factor expression.

OBJECTIVES: Lymph node staging provides critical information in patients with non-small cell lung cancer (NSCLC). Lymphangiogenesis may be an important contributor to the pathophysiology of lymphatic metastases. We hypothesized that the presence of lymph node micrometastases positively correlates with vascular endothelial growth factors (VEGFs) A, C, and D as well as VEGF-receptor-3 (lymphangiogenic factors) expression in lymph nodes. METHODS: Forty patients with NSCLC underwent preoperative positron emission tomography-computed tomography and mediastinoscopy. Real-time polymerase chain reaction (RT-PCR) assays for messenger RNA expression of epithelial markers (ie, cytokeratin 7; carcinoembryonic antigen-related cell adhesion molecule 5; and palate, lung, and nasal epithelium carcinoma-associated protein) were performed in selected fluorodeoxyglucose-avid lymph nodes. VEGF-A, VEGF-C, VEGF-D, and VEGF receptor-3 expression levels were measured in primary tumors and lymph nodes. Wilcoxon rank sum test was run for the association between the RT-PCR epithelial marker levels and VEGF expression levels in the lymph nodes. RESULTS: RT-PCR for cytokeratin 7; carcinoembryonic antigen-related cell adhesion molecule 5; or palate, lung, and nasal epithelium carcinoma-associated protein indicated lymph node micrometastatic disease in 19 of 35 patients (54%). There was a high correlation between detection of micrometastases and VEGF-A, VEGF-C, VEGF-D, or VEGF receptor-3 expression levels in lymph nodes. Median follow-up was 12.6 months. CONCLUSIONS: RT-PCR analysis of fluorodeoxyglucose-avid lymph nodes results in up-staging a patient's cancer. Micrometastases correlate with the expression of VEGF in lymph nodes in patients with NSCLC. This may reflect the role of lymphangiogenesis in promoting metastases.

Thoracoscopic maneuvers for chest wall resection and reconstruction.

OBJECTIVE: The aim of this report is to describe technical maneuvers used to complete minimally invasive resections of the chest wall successfully. METHODS: Case videos of advanced thoracoscopic chest wall resections performed at a comprehensive cancer center were reviewed, as were published reports. These were analyzed for similarities and also categorized to summarize alternative approaches. RESULTS: Limited chest wall resections en bloc with lobectomy can be accomplished with port placement similar to that used for typical thoracoscopic anatomic resections, particularly when the utility incision is close to the region of excision. Generally, chest wall resection precedes lobectomy. Ribs can be transected with Gigli saws, endoscopic shears, or high-speed drills. Division of bone and overlying soft tissue can be planned precisely using thoracoscopic guidance. Isolated primary chest wall masses may require different port position and selective reconstruction using synthetic materials. Patch anchoring can be accomplished by devices that facilitate laparoscopic port site fascial closure. CONCLUSIONS: Thoracoscopic chest wall resections have been accomplished safely using tools and maneuvers summarized here. Further outcomes research is necessary to identify the benefits of thoracoscopic chest wall resection over an open approach.