Search

Background Patient-reported outcomes (PROs) for minimally invasive esophagectomy (MIE) have demonstrated benefits compared with open transthoracic or 3-hole esophagectomy. PROs, including quality of life (QoL) and fear of recurrence (FoR), comparing open transhiatal esophagectomy (THE) and transhiatal robotic-assisted MIE (Th-RAMIE) have been limited. Methods At a single, high-volume academic center, patients undergoing THE and Th-RAMIE with gastric conduit for clinical stage I to III esophageal cancer from 2013 to 2018 were evaluated. The European Organization for Research and Treatment of Cancer (EORTC) Quality of Life Questionnaire (QLQ-C30), the EORTC Quality of Life Questionnaire in Esophageal Cancer (QLQ-OES18), and the FoR survey were administered preoperatively and at 1, 6, and 12 months postoperatively. Linear mixed-effects models were used for QoL and FoR score comparisons. Perioperative outcomes were also compared. Results A total of 309 patients (212 in the group and 97 in the Th-RAMIE group) were included. The Th-RAMIE cohort had a significantly higher number of lymph nodes harvested (14 ± 0.8 vs 11.2 ± 0.4; P = .01), a shorter length of stay (days, 10.0 ± 6.7 vs 12.1 ± 7.0; P = .03), lower rates of postoperative ileus (5% vs 15%; P = .02), and fewer opioids prescribed at discharge (71% vs 85%; P = .03). After adjustment, there were no significant differences in QLQ-C30, QLQ-OES18, and FoR scores between the groups out to 1 year postoperatively. Conclusions There were no clear patient-reported benefits of Th-RAMIE over THE for esophageal cancer. However, Th-RAMIE conferred several perioperative benefits.

Supporting information showing CTC enumeration and gene expression profiling data for CTC clusters from early stage lung cancer.

Early detection of metastasis can be aided by circulating tumor cells (CTC), which also show potential to predict early relapse. Because of the limited CTC numbers in peripheral blood in early stages, we investigated CTCs in pulmonary vein blood accessed during surgical resection of tumors. Pulmonary vein (PV) and peripheral vein (Pe) blood specimens from patients with lung cancer were drawn during the perioperative period and assessed for CTC burden using a microfluidic device. From 108 blood samples analyzed from 36 patients, PV had significantly higher number of CTCs compared with preoperative Pe (P < 0.0001) and intraoperative Pe (P < 0.001) blood. CTC clusters with large number of CTCs were observed in 50% of patients, with PV often revealing larger clusters. Long-term surveillance indicated that presence of clusters in preoperative Pe blood predicted a trend toward poor prognosis. Gene expression analysis by RT-qPCR revealed enrichment of p53 signaling and extracellular matrix involvement in PV and Pe samples. Ki67 expression was detected in 62.5% of PV samples and 59.2% of Pe samples, with the majority (72.7%) of patients positive for Ki67 expression in PV having single CTCs as opposed to clusters. Gene ontology analysis revealed enrichment of cell migration and immune-related pathways in CTC clusters, suggesting survival advantage of clusters in circulation. Clusters display characteristics of therapeutic resistance, indicating the aggressive nature of these cells. Thus, CTCs isolated from early stages of lung cancer are predictive of poor prognosis and can be interrogated to determine biomarkers predictive of recurrence. Cancer Res; 77(18); 5194–206. ©2017 AACR.

Esophagectomy is a high-risk operation, regardless of technique. Minimally invasive transthoracic esophagectomy could reduce length of stay and pulmonary complications compared to traditional open approaches, but the benefits of minimally invasive transhiatal esophagectomy are unclear. We performed a retrospective review of prospectively gathered data for open transhiatal esophagectomies (THEs) and transhiatal robot-assisted minimally invasive esophagectomies (TH-RAMIEs) performed at a high-volume academic center between 2013 and 2017. Multivariate logistic regression was used to calculate adjusted odds ratios (aORs) for outcomes. 465 patients met inclusion criteria (378 THE and 87 TH-RAMIE). THE patients more likely had an ASA score of 3 + (89.1% vs 77.0%, p = 0.012), whereas TH-RAMIE patients more likely had a pathologic staging of 3+ (43.7% vs. 31.2%, p = 0.026). TH-RAMIE patients were less likely to receive epidurals (aOR 0.06, 95% confidence interval [CI] 0.03–0.14, p

Subclavian artery aneurysms (SAAs) are rare, and their repair can be technically complex. We have reported the redo repair of a large, expanding, right SAA after primary repair consisting of total aortic arch replacement with bilateral subclavian artery ligation and bypass. The redo repair used claviculectomy to facilitate exposure, ligation of the right deep cervical and internal thoracic arteries from within the aneurysm sac, and revision of the previous axillary artery bypass that had thrombosed owing to the mass effect of the expanding SAA. Claviculectomy can facilitate repair of large SAAs that are poorly suited to more routine exposure approaches, with acceptable risk and functional outcomes.

A laptop-driven, benchtop control system that automatically adjusts carbon dioxide (CO(2)) removal in artificial lungs is described. The proportional-integral-derivative (PID) feedback controller modulates pump-driven air sweep gas flow through an artificial lung to achieve a desired exhaust gas CO(2) partial pressure (EGCO(2)). When EGCO(2) increases, the servoregulator automatically and rapidly increases sweep flow to remove more CO(2). If EGCO(2) decreases, the sweep flow decreases to reduce CO(2) removal. System operation was tested for 6 hr in-vitro using bovine blood and in-vivo in three proof-of-concept sheep experiments. In all studies, the controller automatically adjusted the sweep gas flow to rapidly (

Study objective Outcomes of extracorporeal cardiopulmonary resuscitation (ECPR) for out-of-hospital cardiac arrest depend on time to therapy initiation. We hypothesize that it would be feasible to select refractory out-of-hospital cardiac arrest patients for expedited transport based on real-time estimates of the 911 call to the emergency department (ED) arrival interval, and for emergency physicians to rapidly initiate ECPR in eligible patients. Methods In a 2-tiered emergency medical service with an ECPR-capable primary destination hospital, adults with refractory shockable or witnessed out-of-hospital cardiac arrest were randomized 4:1 to expedited transport or standard care if the predicted 911 call to ED arrival interval was less than or equal to 30 minutes. The primary outcomes were the proportion of subjects with 911 call to ED arrival less than or equal to 30 minutes and ED arrival to ECPR flow less than or equal to 30 minutes. Results Of 151 out-of-hospital cardiac arrest 911 calls, 15 subjects (10%) were enrolled. Five of 12 subjects randomized to expedited transport had an ED arrival time of less than or equal to 30 minutes (overall mean 32.5 minutes [SD 7.1]), and 5 were eligible for and treated with ECPR. Three of 5 ECPR-treated subjects had flow initiated in less than or equal to 30 minutes of ED arrival (overall mean 32.4 minutes [SD 10.9]). No subject in either group survived with a good neurologic outcome. Conclusion The Extracorporeal Cardiopulmonary Resuscitation for Refractory Out-of-Hospital Cardiac Arrest trial did not meet predefined feasibility outcomes for selecting out-of-hospital cardiac arrest patients for expedited transport and initiating ECPR in the ED. Additional research is needed to improve the accuracy of predicting the 911 call to ED arrival interval, optimize patient selection, and reduce the ED arrival to ECPR flow interval.

Ex vivo lung perfusion (EVLP) allows for a reassessment of lung grafts initially deemed unsuitable for transplantation, increasing the available donor pool; however, this requires a pre- and post-EVLP period of cold ischemic time (CIT). Paucity of data exists on how the sequence of cold normothermic-cold preservations affect outcomes.A total of 110 patients were retrospectively analyzed. Duration of 3 preservation phases was measured: cold pre-EVLP, EVLP, and cold post-EVLP. The donor and recipient clinical data were collected. Primary graft dysfunction (PGD) and survival were monitored. Risk of mortality or PGD was calculated using Cox proportional hazards and logistic regression models to adjust for baseline characteristics.Using the highest quartile, patients were stratified into extended vs non-extended pre-EVLP (264 vs ≥264 minutes) and post-EVLP (287 vs ≥287 minutes) CIT. The rates of 1-year mortality (8.4% vs 29.6%, p = 0.013), PGD 2-3 (20.5% vs 52%, p = 0.002), and PGD 3 (8.4% vs 29.6%, p = 0.005) at 72 hours were increased in the extended post-EVLP CIT group. After adjusting for baseline risk factors, the extended group remained an independent predictor of PGD ≥2 (odd ratio: 6.18, 95% CI: 1.88-20.3, p = 0.003) and PGD 3 (odd ratio: 20.4, 95% CI: 2.56-161.9, p = 0.004) at 72 hours and 1-year mortality (hazard ratio: 17.9, 95% CI: 3.36-95.3, p = 0.001). Cold pre-EVLP was not a significant predictor of primary outcomes.Extended cold post-EVLP preservation is associated with a risk for PGD and 1-year mortality. Pre-EVLP CIT does not increase mortality or high-grade PGD. These findings from a multicenter trial should caution on the implementation of extended cold preservation after EVLP.

Impaired gastric conduit perfusion is a risk factor for anastomotic leak after esophagectomy. Most studies evaluating conduit perfusion have been qualitative with limited impact on post-operative care. The aim of this study is to evaluate the feasibility of intraoperative quantitative assessment of gastric conduit perfusion with indocyanine green (ICG) fluorescence angiography as a predictor for cervical esophagogastric anastomotic (CEGA) leak after esophagectomy. Methods ICG fluorescence angiography using the SPY elite® (Stryker, MI, USA) system was performed in patients who had undergone a transhiatal or McKeown esophagectomy CEGA from July 2015 through December 2020. Fluorescence angiography assessed Ingress (dye uptake) and Egress (dye exit). Ingress Index, Ingress Time, Egress Index, and Egress Time at two anatomic landmarks (tip of the conduit, and 5 cm from tip) were calculated from the measured curve of fluorescence (Figure). The collected data between the leak (L) group and the no-leak (NL) group were compared by both univariate and multivariable analyses to analyze risk factors potentially associated with CEGA leak. Results 304 patients were evaluated. There was no significant difference in patients' demographic and post-operative complications between the groups (L n = 73; NL n = 231), except for anastomotic stricture (42.5 vs 9.1%, p Conclusion This study revealed that gastric conduit perfusion correlates with the incidence of CEGA leak. Intraoperative measurement of gastric conduit perfusion may be predictive for CEGA leak following esophagectomy. These variables can be easily collected intraoperatively with the SPY study and used to make clinical decisions which may avert CEGA leak.

Summary Impaired gastric conduit perfusion is a risk factor for anastomotic leak after esophagectomy. The aim of this study is to evaluate the feasibility of intraoperative quantitative assessment of gastric conduit perfusion with indocyanine green fluorescence angiography as a predictor for cervical esophagogastric anastomotic leak after esophagectomy. Indocyanine green fluorescence angiography using the SPY Elite system was performed in patients undergoing a transhiatal or McKeown esophagectomy from July 2015 through December 2020. Ingress (dye uptake) and Egress (dye exit) at two anatomic landmarks (the tip of a conduit and 5 cm from the tip) were assessed. The collected data in the leak group and no leak group were compared by univariate and multivariable analyses. Of 304 patients who were evaluated, 70 patients developed anastomotic leak (23.0%). There was no significant difference in patients’ demographic between the groups. Ingress Index, which represents a proportion of blood inflow, at both the tip and 5 cm of the conduit was significantly lower in the leak group (17.9 vs. 25.4% [P = 0.011] and 35.9 vs. 44.6% [P = 0.019], respectively). Ingress Time, which represents an estimated time of blood inflow, at 5 cm of the conduit was significantly higher in the leak group (69.9 vs. 57.1 seconds, P = 0.006). Multivariable analysis suggested that these three variables can be used to predict future leak. Variables of gastric conduit perfusion correlated with the incidence of cervical esophagogastric anastomotic leak. Intraoperative measurement of gastric conduit perfusion can be predictive for anastomotic leak following esophagectomy.

Esophagectomy is a high-risk operation, regardless of technique. Minimally invasive transthoracic esophagectomy could reduce length of stay and pulmonary complications compared to traditional open approaches, but the benefits of minimally invasive transhiatal esophagectomy are unclear. We performed a retrospective review of prospectively gathered data for open transhiatal esophagectomies (THEs) and transhiatal robot-assisted minimally invasive esophagectomies (TH-RAMIEs) performed at a high-volume academic center between 2013 and 2017. Multivariate logistic regression was used to calculate adjusted odds ratios (aORs) for outcomes. 465 patients met inclusion criteria (378 THE and 87 TH-RAMIE). THE patients more likely had an ASA score of 3 + (89.1% vs 77.0%, p = 0.012), whereas TH-RAMIE patients more likely had a pathologic staging of 3+ (43.7% vs. 31.2%, p = 0.026). TH-RAMIE patients were less likely to receive epidurals (aOR 0.06, 95% confidence interval [CI] 0.03-0.14, p 0.001), but epidural use itself was not associated with differences in outcomes. TH-RAMIE patients experienced higher rates of pulmonary complications (adjusted odds ratio [OR] 1.82, 95% CI 1.03-3.22, p = 0.040), particularly pulmonary embolus (aOR 5.20, 95% CI 1.30-20.82, p = 0.020). There were no statistically significant differences in lymph node harvest, unexpected ICU admission, length of stay, in-hospital mortality, or 30-day readmission or mortality rates. The TH-RAMIE approach had higher rates of pulmonary complications. There were no statistically significant advantages to the TH-RAMIE approach. Further investigation is needed to understand the benefits of a minimally invasive approach to the open transhiatal esophagectomy.

Background: Ex vivo lung perfusion (EVLP) allows re-evaluation of lungs initially deemed not viable for transplantation. However, the mid- and long-term outcomes after transplanting EVLP-screened lungs in a multicenter setting are still unknown. Methods: This was a multicenter, prospective, nonrandomized clinical trial. Donor lungs initially deemed not suitable (n=208) were re-evaluated on EVLP. Lungs that met quality criteria after EVLP were transplanted (n=110). Transplants performed at the same institutions using standard-criteria lungs were enrolled as controls (n=116). Primary outcomes included grade 3 primary graft dysfunction (PGD) 72 hours post-transplant and 1- and 3-year survival. Secondary outcomes included PGD 24 and 48 hours post-transplant, pulmonary function, bronchiolitis obliterans syndrome (BOS) and quality of life. Findings: Half of the lungs placed on EVLP were transplanted (102/208, 49%). The incidence of severe PGD 72 hours post-transplant was not significant different from controls (13·6% vs 6·9%, p=0.09). Moreover, survival was not significantly different 1- and 3-years post-transplant (EVLP, 86%; control, 93%; p=0·09 and EVLP, 68%; control, 77%; p=0·14, respectively). There were also no differences in pulmonary function or the incidence of BOS up to 3 years post-transplant, and no difference in quality-of-life measures 1- and 3-years post-transplant. Interpretation: In this multicenter study, recipients of lungs that were re-evaluated on EVLP and deemed suitable for transplant had similar outcomes as a recipients of a standard lung transplant. EVLP offers the opportunity to screen donated lungs initially considered high risk and can safely increase the availability of transplantable lungs without compromising outcomes. Clinical Trial Registration Details: Registered on ClinicalTrials.gov (NCT 01365429). Funding Information: XVIVO Perfusion, Inc. Declaration of Interests: We declare no competing interests. Ethics Approval Statement: The study was approved by each transplant center’s Institutional Review Board and the FDA. Participants provided written informed consent to participate in this study.

Introduction: Extracorporeal cardiopulmonary resuscitation (ECPR) for out-of-hospital cardiac arrest (OHCA) is promising but is unproven, and outcomes are strongly dependent on time to initiation of therapy. Expedited transport may facilitate opportunities for ECPR in clinical practice and future trials. Hypotheses: We hypothesized that a real-time dispatch-based computer algorithm could select refractory OHCA patients who could be reliably transported to the emergency department (ED) within 30 min of the 911 call, and that Emergency Medicine physicians could initiate ECPR in eligible patients within 30 min of ED arrival. Methods: In a 2-tiered EMS system serving a US city of 100k in 29 square miles with an ECPR capable primary destination hospital, adults with refractory shockable or witnessed OHCA were randomized 4:1 to expedited transport (ET) or standard prehospital care (SC) if the predicted 911 to ED arrival time was Results: Out of 156 cardiac arrest runs, 15 participants (10%) were randomized prior to ending the trial for slow accrual. Five of 12 patients randomized to expedited transport had an ED arrival time of Conclusions: EROCA demonstrated a functional model for selecting patients with refractory OHCA for ET in an ECPR capable system but did not meet predefined time-interval targets. These results provide important insight into the feasibility of ECPR clinical trials and clinical practice based on selected target intervals.

BACKGROUND 18F-fluorodeoxyglucose positron emission tomography is an imaging modality critical to the diagnosis and staging of esophageal cancer. Despite this, the genetic abnormalities associated with increased 18F-fluorodeoxyglucose (FDG)-maximum standardized uptake value (SUVmax) have not been previously explored in esophageal adenocarcinoma. MATERIALS AND METHODS Treatment-naive patients, for whom frozen tissue and 18F-fluorodeoxyglucose positron emission tomography data were available, undergoing esophagectomy from 2003 to 2012, were identified. Primary tumor FDG-uptake (SUVmax) was quantified as low ( 10). Genome-wide expression analyses (e.g., microarray) were used to examine gene expression differences associated with FDG-uptake. RESULTS Eighteen patients with stored positron emission tomography data and tissue were reviewed. Overall survival was similar between patients with high (n = 9) and low (n = 6) FDG-uptake tumors (P = 0.71). Differences in gene expression between tumors with high and low FDG-uptake included enriched expression of various matrix metalloproteinases, extracellular-matrix components, oncogenic signaling members, and PD-L1 (fold-change>2.0, P

Background Anastomotic leak after esophagectomy remains a significant source of morbidity and mortality. The gastrointestinal (GI) microbiome has been found to play a significant role in tumor oncogenesis and postoperative bowel anastomotic leak. We hypothesized that the GI microbiome could differentiate between esophageal cancer histologies and predict postoperative anastomotic leak. Methods A prospective study of esophagectomy patients was performed from May 2013 to August 2014, with the collection of oral saliva, intraoperative esophageal and gastric mucosa, and samples of postoperative infections (neck swab or sputum). The presence and level for each bacterial probe as end points were used to analyze correlations with tumor histology, tumor stage, and presence of postoperative complications by unequal variances t tests for multiple comparisons and principal coordinate analysis. Results Esophagectomy was successful in 55 of 66 patients who were enrolled. Among those, the diagnosis was adenocarcinoma in 44 (80%) squamous cell carcinoma in (13%), and benign disease in 4 (7%). The 30-day mortality was 1.8% (1 of 55). Complications included anastomotic leak requiring local drainage in 18% (10 of 55) and postoperative pneumonia in 2% (1 of 55). No correlation was noted between GI microbiome flora and tumor histology or tumor stage. A significant difference ( p = 0.015) was found when the variance in bacterial composition between the preoperative oral flora was compared with intraoperative gastric flora in patients who had a leak but not in patients with pneumonia. Conclusions Patients with anastomotic leaks had increased variance in their preoperative oral and gastric flora. Microbiome analysis could help identify patients at higher risk for leak after esophagectomy.

Purpose EVLP allows for reassessment of lung grafts initially deemed unsuitable for transplantation, increasing the available donor pool. Standard cold preservation is followed by normothermic EVLP, then lungs undergo a second cold preservation prior to implantation. Paucity of data exist on how the sequence of cold-normothermic-cold preservations affect outcomes. We investigated the effects of preservation times in transplanted EVLP lungs. Methods Data from the NOVEL trial (110pts) was retrospectively analyzed. Duration of the 3 preservation phases was measured: cold pre EVLP; EVLP; cold post EVLP. Donor and recipient clinical data were collected. Primary graft dysfunction (PGD) and survival were monitored. Risk of mortality or PGD were calculated using Cox-proportional hazards and logistic regression models to adjust for baseline characteristics. Results Using the highest quartile, pts were stratified in extended (>287 min, n=27) and non-extended ( Conclusion Extended cold post EVLP preservation (5 hrs or more) associated with risk for PGD and 1-year mortality. These findings from a multicenter trial should caution on the implementation of extended cold preservation post EVLP.

Robotic-assisted thoracic surgery (RATS) lung lobectomy has emerged as an alternative approach to video-assisted thoracoscopic surgery (VATS). Patient-reported outcomes comparing these approaches have been limited.At a single, high-volume academic center, patients undergoing VATS and RATS lobectomies for stage I and II non-small cell lung cancer from 2014 to 2018 were evaluated. The European Organisation for Research and Treatment of Cancer Quality of Life of Cancer Patients Questionnaire (QLQ-C30) and Quality of Life Questionnaire in Lung Cancer (QLQ-LC13), along with the Fear of Recurrence (FoR) survey, were administered preoperatively and at 1, 6, and 12 months postoperatively. Raw scores underwent linear transformation (0-100 scale). Linear mixed-effects models were used for quality of life and FoR score comparisons.The study included 219 patients (139 VATS and 80 RATS). RATS patients had longer (P.05) operative times and a higher incidence (P.05) of postoperative myocardial infarction compared to VATS patients. VATS patients reported higher (P.05) QLQ-C30 summary scores postoperatively and at 12 months, including higher (P.05) Social Functioning and Cognitive scores, and less (P.05) appetite loss. VATS patients reported decreased (P.05) QLQ-LC13 symptom summary scores at 6 months postoperatively, including decreased (P.05) dyspnea, neuropathy, and pain compared with RATS patients. VATS patients also reported lower (P.05) FoR summary scores at 6 months postoperatively.VATS patients report improvement in select quality of life and FoR measures after lobectomy. Further study comparing these 2 approaches is required.

Extracorporeal membrane oxygenation (ECMO) is a lifesaving therapy for severe respiratory and circulatory failure. It is best performed in high-volume centers to optimize resource utilization and outcomes. Regionalization of ECMO might require the implementation of therapy before and during transfer to the high-volume center. The aim of this international survey was to describe the manner in which interhospital ECMO transport care is organized at experienced centers. Fifteen mobile ECMO centers from nine countries participated in this survey. Seven (47%) of them operated under the "Hub-and-Spoke" model. Transport team composition varies from three to nine members, with at least one ECMO specialist (i.e., nurse or perfusionist) participating in all centers, although intensivists and surgeons were present in 69% and 50% of the teams, respectively. All centers responded that the final decision to initiate ECMO is multidisciplinary and made bedside at the referring hospital. Most centers (75%) have a quality control system; all teams practice simulation and water drills. Considering the variability in ECMO transport teams among experienced centers, continuous education, training and quality control within each organization itself are necessary to avoid adverse events and maintain a low mortality rate. A specific international ECMO Transport platform to share data, benchmark outcomes, promote standardization, and provide quality control is required.

To examine the outcomes of prolonged (≥14 days) extracorporeal membrane oxygenation (P-ECMO) for adult severe respiratory failure and to assess characteristics associated with survival.The use of ECMO for treatment of severe respiratory adult patients is associated with overall survival rates of 50% to 70% with median ECMO duration of 10 days. No prior multi-institutional studies have examined outcomes of P-ECMO for severe respiratory failure.Data on all adult (≥18 years) patients who required P-ECMO for severe respiratory failure from 1989 to 2013 were extracted from the Extracorporeal Life Support Organization international multi-institutional registry. We examined outcomes over 23 years and compared the 2 more recent time periods of 1989 to 2006 versus 2007 to 2013.Up to 974 patients, mean age 40.2 (18-83) years, had ECMO duration of mean 25.2 days/median 21.0 days (range: 14-208 days). Venovenous ECMO support was most common (venovenous: 79.5%, venoarterial: 9.9%). Reason for ECMO discontinuation included native lung recovery (54%), organ failure (23.7%), family request (6.7%), hemorrhage (2.7%), and diagnosis incompatible with life (5.6%). Forty patients (4.1%) underwent lung transplant with 50% postoperative in-hospital mortality. Increased prevalence of P-ECMO was noted with 72% (701/974) of all cases reported since 2008. Survival to hospital discharge was 45.4% (443/974) and did not vary with ECMO duration. Multivariate logistic regression analysis confirmed that P-ECMO patients 2007 to 2013 had a lower risk of death [odds ratio (OR): 0.650; 95% confidence interval (CI), 0.454-0.929; P = 0.010] compared with 1989 to 2006. Factors independently associated with survival were younger age (OR: 0.983; 95% CI, 0.974-0.993; P0.001) and lower PaCO2 (OR, 0.991; 95% CI, 0.986-0.996; P0.001).Prolonged ECMO use for adult respiratory failure was associated with a lower (45.4%) hospital survival rate, compared with prior reported survival rates of short duration ECMO. Prolonged ECMO survival significantly increased in recent years, and increasing ECMO duration did not alter the survival fraction in the 1989 to 2013 study cohort. Although P-ECMO survival rates are less than short ECMO runs, P-ECMO support is justified.

We employed next generation RNA sequencing analysis to reveal dysregulated long non-coding RNAs (lncRNAs) in lung cancer utilizing 461 lung adenocarcinomas (LUAD) and 156 normal lung tissues from 3 separate institutions. We identified 281 lncRNAs with significant differential-expression between LUAD and normal lung tissue. LINC00857, a top deregulated lncRNAs, was overexpressed in tumors and significantly associated with poor survival in LUAD. knockdown of LINC00857 with siRNAs decreased tumor cell proliferation, colony formation, migration and invasion in vitro, as well as tumor growth in vivo. Overexpression of LINC00857 increased cancer cell proliferation, colony formation and invasion. Mechanistic analyses indicated that LINC00857 mediates tumor progression via cell cycle regulation. Our study highlights the diagnostic/prognostic potential of LINC00857 in LUAD besides delineating the functional and mechanistic aspects of its aberrant disease specific expression and potentially using as a new therapeutic target.

Purpose lung transplantation continues to be a life saving therapy for patients with end stage lung disease. In a donor restrictive environment and with only 22% of donor lungs currently being transplanted ex vivo lung perfusion can increase donor use and transplantation preserving safety and good outcomes Methods the NOVEL study is a prospective, multi-center, controlled clinical trial. Seventeen US lung transplant centers evaluated the safety of screening donors initially considered unacceptable for transplant with normothermic ex vivo lung perfusion (EVLP). Results from 2011 to 2017 seventeen lung transplant centers evaluated 216 donors with EVLP. 110 were transplanted for a 50.9% conversion rate. Early and long-term outcomes were compared to 116 control patients that underwent transplantation using standard criteria lungs. The primary endpoints for this study were Primary Graft Dysfunction (PGD) grade 3 at 72 hours and 1-year survival. The rate of PGD grade 3 at 72 hrs. was non-inferior between the ELVP and Control group (8.9% vs 9.5%, p 0.12). The 1-year survival for the EVLP group was 93.2% vs. 96.5% for the Control group, p 0.84. Secondary endpoints such as ICU length of stay, 9.9 vs 9.8 days, hospital length of stay, 23.9 vs 28.5 days, duration of mechanical ventilation, 7.0 vs 5.7 days, were also not significantly different between the EVLP and Control groups. Median FEV 1 was also no different between the EVLP and Control groups 12 months post transplant 65 vs 70 %. Conclusion data from this multi-center, controlled clinical trial demonstrates that the use of ex vivo lung perfusion to screen for viable grafts within the unused donor pool is safe and provides equal short and long therm outcomes to standard criteria donor lungs.

Gender disparities exist in cancer care. Malignant pleural effusions (MPEs) carry a poor prognosis and are managed by different physicians. This study sought to evaluate referral patterns and gender differences for definitive treatment and outcomes of MPE patients.Patients diagnosed with MPE from 1999 to 2015 at a quaternary care hospital were retrospectively reviewed to obtain patient history, referral to thoracic surgery for definitive management, and outcomes. Analysis was performed using chi-squared/Fisher's exact test, logistic regression models, and multivariate analysis.224/686 patients (32.7%) were referred to thoracic surgery. No survival difference existed between referral and nonreferral groups or referred patients who received or did not receive pleurodesis. 405 patients (59.0%) were women. Women were statistically significantly less likely to be referred than men (27.9% versus 39.5%, P = 0.0014). This disparity persisted when comorbidities were controlled for (P = 0.0004) and when gynecologic cancers (e.g., uterine, ovarian, but not including breast; 55 female patients) were excluded from analysis (28.9% versus 39.5%, P = 0.0049). Women had statistically significantly more thoracenteses (3.34 versus 2.19, P 0.0001) and improved survival compared with males (median survival = 136 d versus 54; P = 0.0004).Gender disparity exists in referral patterns for definitive management of MPE; women are less likely to be referred than men. Women have longer survival and a greater number of thoracenteses performed, despite a lower referral rate for definitive care. Further research is needed to understand the differences in referral rates and outcomes between men and women.

Esophageal perforation is an injury associated with high morbidity and mortality. Initial management ranges from observation to esophagectomy. The aim of this study was to evaluate the relative mortality and safety of emergent esophagectomy for acute esophageal rupture when compared with elective esophagectomies.We performed a retrospective review of a prospective esophagectomy database from a single institution from 1977 to 2013. Patients who were admitted for esophageal perforation and underwent esophagectomy were identified and compared with patients who underwent elective esophagectomy.In all, 3,015 patients received an esophagectomy in elective and emergent settings; 90 esophagectomies were for acute injuries (52 for benign and 38 for malignant causes). A longer median length of stay was associated with emergent esophagectomy compared with elective esophagectomy (13 versus 10 days, p0.0001), and the complication rates were higher in the emergent group (51.1% versus 35.6%, p = 0.003). The survival rates at 30 days, 1 year, and 5 years after surgery were not significantly different between the emergent and nonemergent esophagectomy groups for patients with both benign and malignant underlying conditions. Within the emergent group, there was no difference in 30-day or 6-month survival based on benign or malignant causes, but a significant difference was seen at 1 year (85% for benign versus 65% for malignant, p = 0.025) and 5 years for survival (72% versus 21%, p0.001).Emergent esophagectomy represents a safe option for the treatment of esophageal perforation, with mortality comparable to elective esophagectomy.

Early detection of metastasis can be aided by circulating tumor cells (CTC), which also show potential to predict early relapse. Because of the limited CTC numbers in peripheral blood in early stages, we investigated CTCs in pulmonary vein blood accessed during surgical resection of tumors. Pulmonary vein (PV) and peripheral vein (Pe) blood specimens from patients with lung cancer were drawn during the perioperative period and assessed for CTC burden using a microfluidic device. From 108 blood samples analyzed from 36 patients, PV had significantly higher number of CTCs compared with preoperative Pe (P < 0.0001) and intraoperative Pe (P < 0.001) blood. CTC clusters with large number of CTCs were observed in 50% of patients, with PV often revealing larger clusters. Long-term surveillance indicated that presence of clusters in preoperative Pe blood predicted a trend toward poor prognosis. Gene expression analysis by RT-qPCR revealed enrichment of p53 signaling and extracellular matrix involvement in PV and Pe samples. Ki67 expression was detected in 62.5% of PV samples and 59.2% of Pe samples, with the majority (72.7%) of patients positive for Ki67 expression in PV having single CTCs as opposed to clusters. Gene ontology analysis revealed enrichment of cell migration and immune-related pathways in CTC clusters, suggesting survival advantage of clusters in circulation. Clusters display characteristics of therapeutic resistance, indicating the aggressive nature of these cells. Thus, CTCs isolated from early stages of lung cancer are predictive of poor prognosis and can be interrogated to determine biomarkers predictive of recurrence. Cancer Res; 77(18); 5194–206. ©2017 AACR.

Background 18F-fluorodeoxyglucose positron emission tomography (FDG-PET) is critical for staging non-small-cell lung cancer (NSCLC). While PET intensity carries prognostic significance, the genetic abnormalities associated with increased intensity remain unspecified. Methods NSCLC samples (N = 34) from 1999 to 2011 for which PET data were available were identified from a prospectively collected tumor bank. PET intensity was classified as mild, moderate, or intense based on SUVmax measurement or radiology report. Associations between genome-wide expression (RNAseq) and PET intensity were determined. Associations with overall survival were then validated in two external NSCLC cohorts. Results Overall survival was significantly worse in patients with PET-intense (N = 11) versus mild (N = 10) tumors (p = 0.039). Glycolytic gene expression patterns were markedly similar between intense and mild tumors. Gene ontology analysis demonstrated significant enhancement of cell-cycle and proliferative processes in FDG-intense tumors (p

Whole transcriptome analyses of next generation RNA sequencing (RNA-Seq) data from human cancer samples reveled thousands of uncharacterized non-coding RNAs including long non-coding RNA (lncRNA). Recent studies indicated that lncRNAs are emerging as crucial regulators in cancer processes and potentially useful as biomarkers for cancer diagnosis and prognosis. To delineate dysregulated lncRNAs in lung cancer, we analyzed RNA-Seq data from 461 lung adenocarcinomas (LUAD) and 156 normal lung tissues. FAM83H-AS1, one of the top dysregulated lncRNAs, was found to be overexpressed in tumors relative to normal lung and significantly associated with worse patient survival in LUAD. We verified this diagnostic/prognostic potential in an independent cohort of LUAD by qRT-PCR. Cell proliferation, migration and invasion were decreased after FAM83H-AS1 knockdown using siRNAs in lung cancer cells. Flow cytometry analysis indicated the cell cycle was arrested at the G2 phase after FAM83H-AS1 knockdown. Mechanistically, we found that MET/EGFR signaling was regulated by FAM83H-AS1. Our study indicated that FAM83H-AS1 plays an important role in lung tumor progression and may be potentially used as diagnostic/prognostic marker. Further characterization of this lncRNA may provide a novel therapeutic target impacting MET/EGFR signaling.

The use of extracorporeal membrane oxygenation (ECMO) for severe acute respiratory failure (ARF) in adults is growing rapidly given recent advances in technology, even though there is controversy regarding the evidence justifying its use. Because ECMO is a complex, high-risk, and costly modality, at present it should be conducted in centers with sufficient experience, volume, and expertise to ensure it is used safely. This position paper represents the consensus opinion of an international group of physicians and associated health-care workers who have expertise in therapeutic modalities used in the treatment of patients with severe ARF, with a focus on ECMO. The aim of this paper is to provide physicians, ECMO center directors and coordinators, hospital directors, health-care organizations, and regional, national, and international policy makers a description of the optimal approach to organizing ECMO programs for ARF in adult patients. Importantly, this will help ensure that ECMO is delivered safely and...

Extracorporeal membrane oxygenation (ECMO) is recommended as a treatment modality for severe acute respiratory distress syndrome (PaO2/FiO2 ≤ 100 mm Hg with positive end-expiratory pressure ≥ 5 cm H2O) as defined by the Berlin definition. The reported usual duration of ECMO in these patients is 7-10 days. However, increasing reports of prolonged duration ECMO (>14 days) for respiratory failure document survival rates of 50-70% with native lung recovery, and ECMO bridge to lung transplantation has been performed at many centers. At present, there are no established national criteria for when to consider futility or lung transplantation in adult patients requiring ECMO for acute respiratory failure. We report a case of prolonged duration venovenous-ECMO (1,347 hours, 56.13 days), with native lung recovery and discuss treatment strategies to optimize native lung recovery in ECMO patients. The lung may have unexpected regenerative capacity with native lung recovery after prolonged mechanical support, similar to acute kidney injury and native renal recovery. We recommend redefining irreversible lung injury and futility in ECMO.

In the past the only option for the treatment of respiratory failure due to acute exacerbation of chronic obstructive pulmonary disease (aeCOPD) was invasive mechanical ventilation. In recent decades, the potential for extracorporeal carbon dioxide (CO2) removal has been realized. We review the various types of extracorporeal CO2 removal, outline the optimal use of these therapies for aeCOPD, and make suggestions for future controlled trials. We also describe the advantages and requirements for an ideal long-term ambulatory CO2 removal system for palliation of COPD.

Background Esophagectomies have high morbidity rates regardless of approach. Minimally invasive approaches have been shown to have lower complication rates compared to open operations for Transthoracic and Three-hole (McKeown type) esophagectomies. We examined the perioperative outcomes of a transhiatal robot-assisted approach compared to concurrent transhiatal esophagectomies at the same institution. Methods A retrospective review was performed of all transhiatal and robot-assisted transhiatal esophagectomies performed for esophageal cancer at a single large academic center between January 2013 and December 2017. Outcomes assessed included postoperative complications, procedure time, length of stay, unexpected ICU admissions, 30-day readmission and 30-day mortality. A multivariate logistic regression model, adjusted for demographics, comorbidities and disease severity, was used to evaluate outcomes. Results 378 transhiatal (THE) and 87 robot-assisted (RTHE) esophagectomies met inclusion criteria. RTHE was associated with higher rates of pleural effusion requiring drainage, pneumothorax, pulmonary embolism and respiratory failure, as well as empyema requiring treatment. RTHE was associated with a higher number of lymph nodes resected. 56.3% of RTHEs used epidurals vs. 92.3% of THEs. Epidural use had no statistical association with the incidence of pulmonary complications. Differences in atrial fibrillation, anastomotic leak, pneumonia, procedure length, length of stay, 30-day survival and readmission rates were not statistically significant. Conclusion Implementation of a new robot-assisted transhiatal esophagectomy program was associated with higher rates of pulmonary complications and empyema, although there were no differences in length of stay. Further investigation is needed to understand the difference in complications. Disclosure All authors have declared no conflicts of interest.

Background Pulmonary nodules are spherical radiographic opacities that measure up to 30 mm in diameter. Nodules are extremely common in clinical practice and challenging to manage, especially small, "subcentimeter" nodules. Identification of malignant nodules is important because they represent a potentially curable form of lung cancer. Methods We developed evidence-based clinical practice guidelines based on a systematic literature review and discussion with a large, multidisciplinary group of clinical experts and other stakeholders. Results We generated a list of 29 recommendations for managing the solitary pulmonary nodule (SPN) that measures at least 8 to 10 mm in diameter; small, subcentimeter nodules that measure Conclusion Patients with pulmonary nodules should be evaluated by estimation of the probability of malignancy, performance of imaging tests to characterize the lesion(s) better, evaluation of the risks associated with various management alternatives, and elicitation of patient preferences for treatment.

MAP3K3 is involved in both the immune response and in tumor progression. Its potential biological role in vitro in lung cancer cell lines and the association of mRNA/protein expression patterns with clinical outcome of primary lung tumors were investigated in this study. Silencing MAP3K3 using siRNA in lung cancer cell lines resulted in decreased cell proliferation, migration and invasion. These effects were associated with down-regulation of the JNK, p38, AKT and GSK3β pathways as determined using phospho-protein and gene expression array analyses. However, MAP3K3 mRNA and protein overexpression in primary lung tumors correlated significantly with favorable patient survival. Gene cluster and pathway analyses of primary tumor datasets indicated that genes positively-correlated with MAP3K3 are significantly involved in immune response rather than the cell cycle regulators observed using in vitro analyses. These results indicate that although MAP3K3 overexpression has an oncogenic role in vitro, in primary lung adenocarcinomas it correlates with an active immune response in the tumor environment that correlates with improved patient survival. MAP3K3 may potentially not only serve as diagnostic/prognostic markers for patients with lung cancer but also provide an indicator for future investigations into immunomodulatory therapies for lung cancer.

Fibrotic diseases display mesenchymal cell (MC) activation with pathologic deposition of matrix proteins such as collagen. Here we investigate the role of mTOR complex 1 (mTORC1) and mTORC2 in regulating MC collagen expression, a hallmark of fibrotic disease. Relative to normal MCs (non-Fib MCs), MCs derived from fibrotic human lung allografts (Fib-MCs) demonstrated increased phosphoinositide-3kinase (PI3K) dependent activation of both mTORC1 and mTORC2, as measured by increased phosphorylation of S6K1 and 4E-BP1 (mTORC1 substrates) and AKT (an mTORC2 substrate). Dual ATP-competitive TORC1/2 inhibitor AZD8055, in contrast to allosteric mTORC1-specific inhibitor rapamycin, strongly inhibited 4E-BP1 phosphorylation and collagen I expression in Fib-MCs. In non-Fib MCs, increased mTORC1 signaling was shown to augment collagen I expression. mTORC1/4E-BP1 pathway was identified as an important driver of collagen I expression in Fib-MCs in experiments utilizing raptor gene silencing and overexpression of dominant-inhibitory 4E-BP1. Furthermore, siRNA-mediated knockdown of rictor, an mTORC2 partner protein, reduced mTORC1 substrate phosphorylation and collagen expression in Fib-, but not non-Fib MCs, revealing a dependence of mTORC1 signaling on mTORC2 function in activated MCs. Together these studies suggest a novel paradigm where fibrotic activation in MCs increases PI3K dependent mTORC1 and mTORC2 signaling and leads to increased collagen I expression via the mTORC1-dependent 4E-BP1/eIF4E pathway. These data provide rationale for targeting specific components of mTORC pathways in fibrotic states and underscore the need to further delineate mTORC2 signaling in activated cell states.

Objective To identify circulating tumor cells (CTCs) in the blood of patients with early-stage lung cancer and to show that sampling pulmonary vein (PV) blood using microfluidic chip technology will yield significantly more CTCs. Improving early detection of lung cancer is critical to improving lung cancer survival. Reproducible detection of CTCs is limited currently in early stage tumors. Methods Patients undergoing pulmonary resection had PV blood drawn before resection. Peripheral blood was sampled at preoperative, intraoperative, and postoperative times. Samples were analyzed on microfluidic chips using antibody-based capture. Results A total of 32 patients with primary lung cancer were evaluated. Twenty patients had 1 or more CTCs detected in at least 1 sample (62.5%). The mean number of CTCs from peripheral vein sources at the preoperative, intraoperative, and postoperative time points was 1.3, 1.9, and 0.6 respectively. The average number of CTCs in the PV was 340.0 (range, 0.0-5422.50; P > .01). When PV CTCs were present, the number of CTCs was correlated with pathological tumor size ( P = .0236). The number of PV CTCs was not correlated with any other clinical feature (eg, smoking status, preoperative or postoperative stage). Furthermore, the number of PV CTCs was significantly higher when preoperative bronchoscopic biopsy was performed, compared with computed tomography–guided biopsy ( P = .0311). Seven patients had evidence of CTC clusters, or microemboli. Conclusions With a single vein draining the entire tumor basin, lung cancers are unique, allowing the high-yield isolation of CTCs from the PV. This method may facilitate future studies to improve the detection and analysis of early-stage lung CTCs.

Centrifugal pumps are increasingly used for extracorporeal membrane oxygenation (ECMO) rather than roller pumps. However, shear forces induced by these types of continuousflow pumps are associated with acquired von Willebrand factor deficiency and bleeding complications. This study was undertaken to compare adverse bleeding complications with the use of centrifugal and roller pumps in patients on prolonged ECMO support. The records of all adult ECMO patients from June 2002 to 2013 were retrospectively reviewed using the University of Michigan Health System database and the Extracorporeal Life Support Organization registry, focusing on patients supported for at least 5 days. Ninety-five ECMO patients met criteria for inclusion (48 roller vs. 47 centrifugal pump). Indications included pulmonary (79%), cardiac (15%), and extracorporeal cardiopulmonary resuscitation (6%), without significant difference between the two groups. Despite lower heparin anticoagulation (10.9 vs. 13.7 IU/kg/hr) with centrifugal pumps, there was a higher incidence of nonsurgical bleeding (gastrointestinal, pulmonary, and neurological) in centrifugal pump patients (26.1 vs. 9.0 events/1,000 patient-days, p = 0.024). In conclusion, in our historical comparison, despite reduced anticoagulation, ECMO support using centrifugal pumps was associated with a higher incidence of nonsurgical bleeding. The mechanisms behind this are multifactorial and require further investigation.

Extracorporeal membrane oxygenation (ECMO) is a temporary technique for providing life support for cardiac dysfunction, pulmonary dysfunction, or both. The two forms of ECMO, veno-arterial (VA) and veno-venous (VV), are used to support cardiopulmonary and pulmonary dysfunction, respectively. Historically, ECMO was predominantly used in the neonatal and pediatric populations, as early adult studies failed to improve outcomes. ECMO has become far more common in the adult population because of positive results in published case series and clinical trials during the 2009 influenza A(H1N1) pandemic in 2009 to 2010. Advances in technology that make the technique much easier to implement likely fueled the renewed interest. Although exact criteria for ECMO are not available, patients who are good candidates are generally considered to be relatively young and suffering from acute illness that is believed to be reversible or organ dysfunction that is otherwise treatable. With the increase in the use in the adult population, a number of different codes have been generated to better identify the method of support with distinctly different relative value units assigned to each code from a very simple prior coding scheme. To effectively be reimbursed for use of the technique, it is imperative that the clinician understands the new coding scheme and works with payers to determine what is incorporated into each specific code.

Objective: To examine the isolated and combined effects of positive end-expiratory pressure (PEEP) and partial liquid ventilation (PLV) on the development of ventilator-induced lung injury in an ovine model. Design: Prospective controlled animal study. Setting: University-based cardiovascular animal physiology laboratory. Subjects: Thirty-eight anesthetized supine sheep weighing 22.3 ± 2.2 kg. Interventions: Animals were ventilated for 6 hrs (respiratory rate, 15; FIO 2 , 1.0, inspiratory/expiratory ratio, 1:1) with one of five pressure-controlled strategies, expressed as peak inspiratory pressure (PIP)/PEEP: low-PIP, 25/5 cm H 2 O (n = 8); high-PIP, 50/5 cm H 2 O (n = 8); high-PIP-PLV, 50/5 cm H 2 O-PLV (n = 8); high-PEEP, 50/20 cm H 2 O (n = 7); and high-PEEP-PLV, 50/20 cm H 2 O-PLV (n = 7). Measurements and Main Results: Compared with the low-PIP control, high-PIP ventilation increased airleak, shunt, histologic evidence of lung injury, neutrophil infiltrates, and wet lung weight. Maintaining PEEP at 20 cm H 2 O or adding PLV reduced the development of physiologic shunt and dependent histologic injury indexes. Neither higher PEEP nor PLV reduced the high incidence of barotrauma observed in high-PIP animals. Conclusions: We conclude that application of PLV or PEEP at 20 cm H 2 O may improve gas exchange and afford lung protection from ventilator-induced lung injury during high-pressure mechanical ventilation in this model.