Search

Background In the era of lung cancer screening with low-dose computed tomography, there is concern that high false-positive rates may lead to an increase in nontherapeutic lung resection. The aim of this study is to determine the current rate of major pulmonary resection for ultimately benign pathology. Materials and Methods A single-institution, retrospective analysis of all patients > 18 y who underwent major pulmonary resection between 2013 and 2018 for suspected malignancy and had benign final pathology was performed. Results Of 394 major pulmonary resections performed for known or presumed malignancy, 10 (2.5%) were benign. Of these 10, the mean age was 61.1 y (SD 14.6). Most were current or former smokers (60%). Ninety percent underwent a fluorodeoxyglucose positron emission tomography scan. Median nodule size was 27 mm (IQR 21-35) and most were in the right middle lobe (50%). Preoperative biopsy was performed in four (40%) but were nondiagnostic. Video-assisted thoracoscopic lobectomy (70%) was the most common surgical approach. Final pathology revealed three (30%) infectious, three (30%) inflammatory, two (20%) fibrotic, and two (20%) benign neoplastic nodules. Two (20%) patients had perioperative complications, both of which were prolonged air leaks, one (10%) patient was readmitted within 30 d, and there was no mortality. Conclusions A small percentage of patients (2.5% in our series) may undergo major pulmonary resection for unexpectedly benign pathology. Knowledge of this rate is useful to inform shared decision-making models between surgeons and patients and evaluation of thoracic surgery program performance.

Transplantation of any organ into a recipient requires a donor. Lung transplant has a long history of an inadequate number of suitable donors to meet demand, leading to deaths on the waiting list annually since national data was collected, and strict listing criteria. Before the Uniform Determination of Death Act (UDDA), passed in 1980, legally defined brain death in the U.S., all donors for lung transplant came from sudden death victims [uncontrolled Donation after Circulatory Death donors (uDCDs)] in the recipient's hospital emergency department. After passage of the UDDA, uDCDs were abandoned to Donation after Brain Death donors (DBDs)-perhaps prematurely. Compared to livers and kidneys, many DBDs have lungs that are unsuitable for transplant, due to aspiration pneumonia, neurogenic pulmonary edema, trauma, and the effects of brain death on lung function. Another group of donors has become available-patients with a devastating irrecoverable brain injury that do not meet criteria for brain death. If a decision is made by next-of-kin (NOK) to withdraw life support and allow death to occur by asphyxiation, with NOK consent, these individuals can have organs recovered if death occurs relatively quickly after cessation of mechanical ventilation and maintenance of their airway. These are known as controlled Donation after Circulatory Death donors (cDCDs). For a variety of reasons, in the U.S., lungs are recovered from cDCDs at a much lower rate than kidneys and livers. Ex-vivo lung perfusion (EVLP) in the last decade has had a modest impact on increasing the number of lungs for transplant from DBDs, but may have had a larger impact on lungs from cDCDs, and may be indispensable for safe transplantation of lungs from uDCDs. In the next decade, DCDs may have a substantial impact on the number of lung transplants performed in the U.S. and around the world.

In 2008, integrated thoracic residency programs (IP) for cardiothoracic (CT) training were created in response to a decline in CT trainees. However, few studies have reported on trends in the CT training pathway since the inception of IPs. This manuscript examines the current trends related to the overall number of surgical trainees entering CT surgery training following the introduction of IPs into the National Resident Match Program (NRMP).Main and specialty match data were gathered from NRMP annual reports between 2008 and 2018. Descriptive statistics were used to analyze program size, applications, and filled and unfilled positions for IPs and traditional CT residency programs. Pearson's correlation coefficient was used to determine associations between program variables.NRMP main and specialty match in 2008 to 2018.Participants of the NRMP main and specialty match in 2008 to 2018.IPs increased from 2 programs offering 3 positions in 2008 to 28 programs offering 36 positions in 2018. However, during the same time period, the number of available traditional CT residency positions have decreased by 29% (130 to 92). As the number of IPs increased, there was a significant decrease in the number of traditional CT residency positions (ρ = -0.95, p0.001). Although, the overall number of CT residency programs (traditional and IP) remained largely unchanged, the proportion of filled CT residency positions increased from 67.7% in 2008 up to 97.7% in 2018.The IP training format has shown success in increasing the number of trainees entering into CT training programs. Consideration should be given to increasing the number of IP positions or increase interest in CT among general surgery residents to increase the number of CT surgery trainees with the goal of increasing the size of the future CT workforce.

Few studies examine outcomes by surgical approach in non-small-cell lung cancer (NSCLC) with N2 disease. We examined time trends in surgical approach and outcomes among patients undergoing minimally invasive (MIS, robotic and video-assisted thoracoscopic surgery [VATS]) vs open lobectomy in this patient population. We performed a retrospective analysis of patients from the National Cancer Database diagnosed with clinical Stage IIIA-N2 NSCLC from 2010 to 2016. We examined the yearly proportion of MIS vs open resections. Multivariable regression was used to assess the association of surgical approach with length of stay, unplanned readmissions, 30-day and 90-day mortality. Multivariable Cox proportional hazards modeling was used to assess the association of surgical approach with 5-year overall mortality. We identified 5741 patients who underwent lobectomy for Stage IIIA-N2 NSCLC (459 robotic, 1403 VATS, 3879 open). From 2010 to 2016, the proportion of minimally invasive procedures increased from 20% to 45%. MIS patients, on average, stayed 1 day less in the hospital (95% confidence interval [CI] 0.7, 1.5) and had lower odds of 90-day (odds ratio [OR] 0.74; 95% CI 0.54, 0.99) and 5-year mortality (OR 0.82; 95% CI 0.75, 0.91), compared to open resections. There was no difference in odds of readmission by surgical approach (OR 0.97; 95% CI 0.71, 1.33). Among MIS procedures, robotic resections had lower odds of 90-day mortality (OR 0.42; 95% CI 0.18, 0.97) than VATS. Among patients undergoing lobectomy for locally advanced N2 NSCLC robotic and VATS techniques appear safe and effective compared to open surgery and may offer short- and long-term advantages.

Postpneumonectomy syndrome is a rare complication in patients who have previously had a pneumonectomy. Over time, the mediastinum may rotate toward the vacant pleural space, which can cause extrinsic airway and esophageal compression. As such, these patients typically present with progressive dyspnea and dysphagia. There is a paucity of reports in the anesthesiology literature regarding the intraoperative anesthetic approach to such rare patients. We present a case of an 18-year-old female found to have postpneumonectomy syndrome requiring thoracotomy with insertion of tissue expanders. Our case report illustrates the complexities involved in the care of these patients with regards to airway management, ventilation concerns, and potential for hemodynamic compromise. This case report underscores the importance of extensive multidisciplinary planning.

264 Background: Postoperative symptom burden is high in surgical oncology patients. Electronic patient-reported outcome (ePRO) remote monitoring systems are rapidly proliferating and have the promise of improving care. However, implementation in diverse practice settings is understudied. More information on ePRO participation may determine addressable barriers. Methods: Patients presenting to the Multidisciplinary Thoracic Oncology Program for surgery were prospectively enrolled. ePROs assessing common postop symptoms and functional impairments were administered via a web-based platform daily for 14 days and then weekly until 3 months post-discharge. Automated reminders were provided by email. Phone calls were made for 2 consecutive missed ePROs. ePRO participation levels were categorized as high (> 80%), medium (50-80%), low (1-49%), and none. Patient characteristics were examined by participation level via Fisher’s exact and Kruskal-Wallis tests. Results: From 2020-2022, 202 patients were recruited to participate, and 113 (56%) agreed. There were no differences in demographics of agreed vs. declined. 99 patients initiated ePROs after discharge. Mean age was 60.5 years (sd 13.4), 37.8% were male, 72.5% were White, and the majority (64%) had lung resection. Patients participated in ePROs for an average of 82 days (sd 24) before discontinuing. Overall, 57.7% (1383/2397) of delivered surveys were completed; response rates were lowest in week 1 (48%) and highest in week 7 (71%). Participation levels are described in Table. Married/partnered patients were significantly more likely to have high levels of participation (p = 0.003), and those who regularly used a computing device almost reached significance (p = 0.057). Age, gender, race, employment, email/internet use, financial status, and quality of life did not vary across ePRO participation levels. Conclusions: Monitoring symptoms with ePROs after discharge from thoracic surgery is feasible in a large academic public hospital. Participation levels in ePROs are lower immediately after discharge, when symptomatic complications drive the highest rates of readmissions. This suggests an opportunity to improve ePRO implementation during the post-acute period when intensive monitoring is desired and in patients who are not partnered or are less frequent device users. As length of stay and readmissions are increasingly targeted for expenditure reduction in academic inpatient settings, it is paramount to design and implement systems to effectively monitor at-risk patients. Clinical trial information: NCT04342260. [Table: see text]

BACKGROUND: Esophagectomies and repair of esophageal perforations are operations used for a variety of clinical indications. Anastomotic leaks are a major post-operative complication after these procedures. At our institution, we routinely use grape juice to detect esophageal leaks in the post-operative setting in addition to other standard imaging modalities. We hypothesize that grape juice can provide similar diagnostic sensitivity and specificity to other modalities for leak detection. METHODS: A retrospective review of all patients who underwent an esophagectomy or repair of esophageal perforations from 2013–2019 by the thoracic surgery service at our institution was performed. All patients underwent a barium swallow study, CT imaging or upper endoscopy, as well as ingesting purple grape juice on post-operative day 5 or greater. Purple grape juice observed in the tube thoracostomy drainage system was identified as a positive esophageal leak. RESULTS: Sixty-four patients were included in the study period (25% female, 88% white, median age 62 years old). Sixty-three patients had both a barium swallow study and grape juice test, while one patient underwent CT imaging and grape juice study. Grape juice test sensitivity and specificity were found to be 80% and 98.3%, respectively. CONCLUSIONS: This pilot study demonstrates the effectiveness of using grape juice in detecting esophageal leaks after esophageal operations in patients with tube thoracostomies. Grape juice may be cheaper and potentially less morbid than other studies performed to detect esophageal leaks. Further research is needed to justify the increased use of grape juice in patients who undergo esophageal operations.

Objective Integrated thoracic surgery residency program (IP) applicants often complete away rotations to stand out from the objective standard criteria. Little is known about the perceptions of these rotations. We aimed to examine the perceptions of value, cost, and expectations of away rotations among IP applicants and program directors. Design Between March and April 2020, anonymous electronic surveys were distributed through e-mails gathered from the Electronic Residency Application Service and the Accreditation Council for Graduate Medical Education IP email list. A follow-up email was sent to all applicants and program directors 1 week after the initial request to improve response rate. Questions assessed the cost, frequency, goals, and objectives for away rotations, as well as the perceived value of these experiences. Setting United States Participants All IP program directors and United States senior medical students who applied to our institution's IP during the 2019-2020 cycle. Results Seventy-eight US medical students participated in the 2020 IP Match with 65 applicants applying to our institution's IP. Thirty-three responses were obtained from applicants who applied to our program (51% response rate). Survey responses were obtained from 8 program directors (31% response rate). Ninety-four percent of applicant respondents completed an IP away rotation (n = 31). Fifty-seven percent of these applicants spent on average $5000 in total for away rotations (n = 19). Overall, applicants felt that away rotations helped refine their perception of program location, educational and operative experience, treatment of medical students, and collegiality. Applicants and program directors acknowledged that creating a good impression and finding a compatible program were central values for participating in away rotations. However, program directors viewed the overall strength of the applicant as the most important factor when evaluating applicants. Fifty-five percent of applicant respondents matched at an IP (n = 17) with 35% matching at an IP where they had completed an away rotation (n = 6). Conclusion Extended interactions that can help create good impressions and establish compatibility are benefits to away rotations. However, given the current application conditions imposed by the pandemic, future studies should examine the impact of no away rotations on the IP Match process so that moving forward applicants and program directors can continue to weigh benefits to the costs and logistics of completing an away rotation.

Background Flail chest and severely displaced rib fractures due to blunt trauma can be associated with intrathoracic injuries. At our institution, two thoracic surgeons perform all surgical stabilization of rib fractures (SSRF): one performs routine uniportal thoracoscopy (R-VATS) at the time of SSRF and the other for only select cases (S-VATS). In this pilot study, we hypothesized that R-VATS at the time of SSRF identifies and addresses intrathoracic injuries not seen on imaging and may impact patient outcomes. Methods A retrospective review of all patients who underwent SSRF from 2013-2019 at our institution was performed for severely displaced rib fractures or flail chest. Data collected included demographics, imaging results, treatment strategy, and operative findings. Results Ninety-nine patients underwent SSRF. Uniportal thoracoscopy was performed on 69% of these patients. When thoracoscopy was performed, 31 additional injuries were identified. R-VATS identified 23 additional intrathoracic findings at time of thoracoscopy not seen on CT scan compared to 8 findings in the S-VATS group (P=0.367). At 3 months follow-up, one empyema and one diaphragmatic hernia required reoperation-neither of which underwent thoracoscopy at time of SSRF. There were no differences in LOS, operative times, and overall mortality between the SSRF/thoracoscopy and SSRF only groups. Conclusions R-VATS at the time of SSRF did not identify a statistically significant greater number of occult intrathoracic injuries compared to S-VATS. R-VATS was not associated with increased operative time, LOS, and mortality. Further study is needed to determine if there is benefit to R-VATS in patients meeting requirements for rib fracture repair.

A term female infant with tracheoesophageal fistula (TEF) and esophageal atresia (EA) underwent primary operative repair that failed with 3 TEF recurrences, which all presented with feeding and respiratory issues. Recurrences were managed with reoperation and an interpositional flap of pleura and a flap of intercostal muscle on 2 separate occasions. The third recurrence was managed with complete dissection of the esophagus prior to the division of the fistula and the interposition of an omental flap between the esophageal and tracheal repair. We present the use of a viable omental flap and complete esophageal mobilization to prevent subsequent TEF recurrences and avoid the additional morbidity of reconstructive surgery.

Unfortunately, the drape dividing the anesthesiologist from the surgeon is far too often a symbol of a greater divide in both communication and culture between the 2 specialties. When anesthesiologists and surgeons spend time rotating on each other's services, they develop a mutual respect for each other's clinical acumen and foster open communication channels for times of both routine clinical care and crisis. There is no better time than in residency, and no better way than cross-training, for anesthesia and surgical residents to hone these skills.

Background Enhanced recovery after surgery (ERAS) is an evidence-based, multidisciplinary perioperative care model shown to reduce complications and hospital length of stay (LOS). While some thoracic ERAS studies were inconclusive, others demonstrated that ERAS improves patient outcomes after lung resections and provides more cost-effective care. We aimed to investigate the effects of preliminary implementation of an ERAS protocol, in comparison with conventional care, on lung resection outcomes at a single academic institution. Methods In this observational study, adult patients undergoing lung resections during the pre-ERAS (April 2014 to September 2015) and post-ERAS (January 2016 to May 2017) periods were identified. Relevant demographic, preoperative, anesthesia, and surgical variables were collected. Pre-ERAS and post-ERAS cohorts were compared in terms of hospital LOS, postoperative complications, and 30-day outcomes. Results We identified 264 patients, half in each cohort. Pre-ERAS and post-ERAS groups were similar with respect to age, race, and comorbidities. There were no significant differences in LOS, complications, 30-day readmission and mortality rates, or patient-reported outcomes. Of the patients with prolonged LOS, 31% had pulmonary complications, almost half of which were prolonged air leaks. ERAS adherence rate was approximately 60%. Conclusions In the first year of implementation, median LOS, complications, and 30-day outcomes did not differ significantly between the pre-ERAS and post-ERAS groups. Prolonged air leaks commonly led to prolonged LOS; therefore, thoracic ERAS protocols could include interventions to reduce air leak and consideration for discharging patients with chest tubes placed to Heimlich valves. Buy-in and adherence to a new protocol are necessary for implementation to be effective.

We have modified the HeartMate 3 (Abbott, Abbott Park, IL) implantation technique to better suit our patient population. This modification optimizes the placement of the HeartMate 3 sewing cuff and allows passage of the suture transmurally from endocardium to epicardium in a "cut then sew" technique. We believe this affords a superior seal and protection from tearing friable myocardium.

We describe a case of a 16-year-old patient who underwent right pneumonectomy for pulmonary vein atresia and developed postpneumonectomy syndrome. She had an 800-cm3 saline-filled silicone tissue expander placed in the right hemithorax with resolution of her postpneumonectomy syndrome. However, 2 years later, she developed fevers, night sweats, and arthralgias. Her medical workup was negative for vasculitis, inflammatory bowel disease, and infectious etiologies. She underwent tissue expander removal, resulting in resolution of her symptoms. This report describes a case of an inflammatory state created by a tissue expander placed for postpneumonectomy syndrome.

The relationship between gastroesophageal reflux disease (GERD) and end-stage lung disease (ESLD) is complex. This relationship remains a challenge to both the clinician and the patients. It is also a target for significant research. The purpose of this chapter is to describe the role of GERD in lung pathology that results in ESLD. This chapter will also review the pathophysiology resulting in chronic lung allograft dysfunction (CLAD) and its relationship to post-lung transplant GERD and the role of early anti-reflux surgery in patients with ESLD and after lung transplant.

Background The purpose of this study was to (1) determine the incidence of postoperative urinary retention (POUR) in patients undergoing lung resection at our institution, (2) identify differences in potential risk factors between patients with and without POUR, and (3) describe patient outcomes across POUR status. Methods The medical records of 225 patients between 2016 and 2017 were reviewed, and 191 met criteria for inclusion. The institution’s catheterization removal protocol was followed in all patients. Recatheterization was defined as requiring in-and-out catheterization or Foley catheter placement. Fisher exact and Wilcoxon tests were used for analysis. Results POUR developed in 35 patients (18%). Patients with POUR were older (P = .01), had increased baseline creatinine (P = .04), and a higher prevalence of benign prostatic hyperplasia (P = .007). POUR patients were also less likely to get a Foley catheter intraoperatively (P = .0002). Other intraoperative factors, such as surgical approach and extent of resection, were not significantly different between patients with and without POUR. Postoperative factors (epidural use or days with chest tube) were similar. Although patients with POUR were more likely to be discharged with a Foley catheter (13% vs 0%, P = .002), no difference in length of stay, incidences of urinary tract infections, or 30-day readmission were observed. Conclusions POUR develops in approximately 1 in 5 patients undergoing lung resection. Patients with POUR were more likely to not have a Foley catheter placed intraoperatively. However, patients who had POUR did not have worsened patient outcomes (urinary tract infections, length of stay, or 30-day readmission).

Background: Approximately twenty percent of lymph node (LN) negative non-small cell lung cancer (NSCLC) patients who undergo curative intent surgery have pan-cytokeratin immunohistochemistry (IHC)-detectable occult micro-metastases (MMs) in resected LNs. The presence of the MMs in NSCLC is associated worsened outcomes. As a substantial proportion of NSCLC LN staging is conducted using endobronchial ultrasound-guided transbronchial needle aspiration (EBUS-TBNA), we sought to determine the frequency of detection of occult MMs in EBUS-TBNA specimens and to evaluate the impact of MMs on progression-free and overall survival. Methods: We performed retrospective IHC staining for pan-cytokeratin of EBUS-TBNA specimens previously deemed negative by a cytopathologist based on conventional hematoxylin and eosin staining. The results were correlated with clinical variables, including survival outcomes. Results: Of 887 patients screened, 44 patients were identified meeting inclusion criteria with sufficient additional tissue for testing. With respect to the time of the EBUS-TBNA procedure, 52% of patients were clinical stage I, 34% clinical stage II, and clinical 14% stage IIIa NSCLC. Three patients (6.8%) were found to have cytokeratin positive MMs. All 3 MMs detected were at N2 LN stations. The presence of MMs was associated with significantly decreased progression-free (median 210 vs . 1,293 days, P=0.0093) and overall survival (median 239 vs . 1,120 days, P=0.0357). Conclusions: Occult LN MMs can be detected in EBUS-TBNA specimens obtained during staging examinations and are associated with poor clinical outcomes. If prospectively confirmed, these results have significant implications for EBUS-TBNA specimen analyses and possibly for the NSCLC staging paradigm.

From the *Department Anesthesiology, and the †Department of Cardiothoracic Surgery, University of North Carolina at Chapel Hill, Chapel Hill, NC. Address reprint requests to Emily G. Teeter, MD, University of North Carolina at Chapel Hill, N2198 UNC Hospitals CB 7010, Chapel Hill, NC 27599-7010. E-mail: eteeter@aims.unc.edu © 2016 Elsevier Inc. All rights reserved. 1053-0770/2602-0033$36.00/0 http://dx.doi.org/10.1053/j.jvca.2016.01.019

Chest tubes are the gold standard for the drainage of the pleural and pericardial spaces. They are an integral part of cardiothoracic surgery, and the well-being of patients depends on their appropriate management. Chest tubes are used to treat a variety of conditions including pneumothorax, pleural effusion, and postoperative evacuation of air and fluid. There are a number of types and sizes of chest tubes available. This chapter will discuss the indications for chest tube placement and removal as well as the best uses for different types of chest tubes. We will address complications associated with chest tube placement and lastly will discuss special situations such as bronchopleural fistula, post-pneumonectomy chest tubes, abrupt changes in chest tube output, and clamping chest tubes.

Background Increased use of chest computed tomography and the institution of lung cancer screening have increased the detection of ground-glass and small pulmonary nodules. Intraoperative localization of these lesions via a minimally invasive thoracoscopic approach can be challenging. We present the feasibility of perioperative transthoracic percutaneous nodule localization using a novel electromagnetic navigation platform. Methods This is a multicenter retrospective analysis of a prospectively collected database of patients who underwent perioperative electromagnetic transthoracic nodule localization before attempted minimally invasive resection between July 2016 and March 2018. Localization was performed using methylene blue or a mixture of methylene blue and the patient's blood (1:1 ratio). Patient, nodule, and procedure characteristics were collected and reported. Results Thirty-one nodules were resected from 30 patients. Twenty-nine of 31 nodules (94%) were successfully localized. Minimally invasive resection was successful in 93% of patients (28/30); 7% (2/30) required conversion to thoracotomy. The median nodule size was 13 mm (interquartile range 25%-75%, 9.5-15.5), and the median depth from the surface of the visceral pleura to the nodule was 10 mm (interquartile range 25%-75%, 5.0-15.9). Seventy-one percent (22/31) of nodules were malignant. No complications associated with nodule localization were reported. Conclusions The use of intraoperative electromagnetic transthoracic nodule localization before thoracoscopic resection of small and/or difficult to palpate lung nodules is safe and effective, potentially eliminating the need for direct nodule palpation. Use of this technique aids in minimally invasive localization and resection of small, deep, and/or ground-glass lung nodules.

Background The goal of the present study was to estimate the rate of local/regional failure (LRF) after definitive surgical intervention for early-stage non-small cell lung cancer (NSCLC), without postoperative radiotherapy, in the era of contemporary imaging and minimally invasive surgical techniques. Methods Medical records of patients with early-stage NSCLC (pathologic T1-4, N0-1) who underwent lobectomy, sleeve lobectomy, bilobectomy, or pneumonectomy, with or without adjuvant chemotherapy, between 2007 and 2015, were retrospectively reviewed. LRF was defined as recurrence at the ipsilateral lung, bronchial stump, mediastinum, chest wall, or supraclavicular region. The Kaplan-Meier method was used to estimate time to LRF, with patients censored at death, and log-rank tests were used for comparisons. A two-sided p value of less than 0.05 was considered significant. Results Included were 217 patients (median age, 65 years). Preoperative staging with positron emission tomography/computed tomography was performed in 89% of patients, mediastinoscopy was performed in 42%, and video-assisted thoracoscopic surgery was performed in 51%. At a median follow-up of 36 months (range, 1 to 120 months), the 5-year estimated LRF was 26% (95% confidence interval, 20% to 35%). LRF rates were not significantly different in those with and without staging positron emission tomography/computed tomography (hazard ratio, 1.52; p = 0.43) and those with video-assisted thoracoscopic surgery versus open thoracotomy (hazard ratio, 1.00; p = 0.99). Conclusions Despite contemporary staging procedures and surgical techniques for early-stage NSCLC, LRF occurs in approximately 1 of 4 patients. The observed rates of LRF are similar to those reported more than a decade ago, suggesting that local/regional control remains a persistent problem. The use of additional local treatments, such as radiotherapy, should be reevaluated to further improve outcomes.

Lung transplantation remains a viable option for patients with endstage pulmonary disease. Despite removing the affected organ and replacing both lungs, the risk of lung malignancies still exists. Regardless of the mode of entry, lung cancer affects the prognosis in these patients and diligence is required.

Brain metastases are one of the most malignant complications of lung cancer and constitute a significant cause of cancer related morbidity and mortality worldwide. Recent years of investigation suggested a role of LKB1 in NSCLC development and progression, in synergy with KRAS alteration. In this study, we systematically analyzed how LKB1 and KRAS alteration, measured by mutation, gene expression (GE) and copy number (CN), are associated with brain metastasis in NSCLC.Patients treated at University of North Carolina Hospital from 1990 to 2009 with NSCLC provided frozen, surgically extracted tumors for analysis. GE was measured using Agilent 44,000 custom-designed arrays, CN was assessed by Affymetrix GeneChip Human Mapping 250K Sty Array or the Genome-Wide Human SNP Array 6.0 and gene mutation was detected using ABI sequencing. Integrated analysis was conducted to assess the relationship between these genetic markers and brain metastasis. A model was proposed for brain metastasis prediction using these genetic measurements.17 of the 174 patients developed brain metastasis. LKB1 wild type tumors had significantly higher LKB1 CN (p0.001) and GE (p=0.002) than the LKB1 mutant group. KRAS wild type tumors had significantly lower KRAS GE (p0.001) and lower CN, although the latter failed to be significant (p=0.295). Lower LKB1 CN (p=0.039) and KRAS mutation (p=0.007) were significantly associated with more brain metastasis. The predictive model based on nodal (N) stage, patient age, LKB1 CN and KRAS mutation had a good prediction accuracy, with area under the ROC curve of 0.832 (p0.001).LKB1 CN in combination with KRAS mutation predicted brain metastasis in NSCLC.

Background Endobronchial ultrasonography with transbronchial needle aspiration (EBUS-TBNA) has been shown to be equivalent to mediastinoscopy in lung cancer staging for mediastinal node involvement. Rapid on-site evaluation (ROSE) to determine the adequacy of nodal sampling has been claimed to be beneficial. Methods A retrospective evaluation was performed in 170 patients who underwent EBUS-TBNA from July 2008 to May 2011. The patients were classified as having either high or low pretest probability for mediastinal disease based on history and radiographic imaging. ROSE was compared with the final pathology reports based on slides and cell blocks. Results One hundred thirty-one (77%) patients were classified as being in the high pretest cohort based on clinical staging. Of these, 101 (77%) patients had adequate tissue sampling based on ROSE, with 70 (69%) patients having positive mediastinal disease. In the 30 (23%) patients who had inadequate tissue by ROSE, the final analysis of all the prepared slides and cell blocks allowed for a diagnosis in all but 8 patients. The sensitivity and specificity of ROSE in the high pretest probability cohort were 89.5% and 96.4%, respectively, whereas the overall sensitivity and specificity of EBUS-TBNA was 92.1% and 100%, respectively. Despite having inadequate tissue on ROSE in 30 of 131 patients, sufficient tissue was available on final analysis for diagnosis in 22 of 30 patients. Conclusions ROSE does not impact clinical decision making if a thorough mediastinal staging using EBUS is performed. Despite inadequate tissue sampling assessment by ROSE, a final diagnosis was made in most patients, potentially avoiding an additional surgical procedure to prove mediastinal disease.

Background Locoregional recurrence can occur despite complete anatomic resection of T1N0 non-small cell lung cancer. That may be the result of incomplete resection or inaccurate staging. We assessed the impact of extent of nodal staging on the rate of locoregional failure and patient survival. Methods The records of 742 patients undergoing lobectomy, bilobectomy, or pneumonectomy for non-small cell lung cancer from 1996 to 2006 were reviewed. Operative reports and pathology reports were reviewed for the number of lymph nodes and the anatomic nodal stations examined. The Kaplan-Meier method was applied to analyze recurrence-free survival. Results A total of 119 patients with pathologically staged Ia lung cancer were identified. Histology type included 61% (n = 73) adenocarcinoma, 27% (n = 32) squamous cell cancer, and 12% (n = 14) other. Median age was 65 years (range, 34 to 88). Mean follow-up duration was 40 months (median 47; range, 1 to 121). Locoregional recurrence occurred in 20% (n = 18). The N2 nodal stations were examined in 94% (n = 112). At least one defined N1 nodal station was examined in 70% (n = 83). Station undefined N1 nodes were examined in 27% (n = 32), and no N1 nodes were examined in 3% (n = 4). Median number of N1 lymph nodes analyzed was 5 (range, 0 to 18). The locoregional recurrence rate was 14% (12 of 83) for patients with a defined N1 station node versus 31% (11 of 36) for patients in whom there were undefined N1 nodes ( p = 0.03). Similar differences were seen in disease-free survival, 78.2% versus 62.6%, respectively ( p = 0.06). Conclusions Despite anatomic resection of stage Ia lung cancer and uniform analysis of N2 nodal stations, a high rate of locoregional recurrence occurs. Imprecise staging of N1 lymph nodes may contribute to the understaging and undertreatment of patients with early stage lung cancer.

Identifying strong markers of prognosis is critical to optimize treatment and survival outcomes in patients with nonsmall cell lung cancer (NSCLC). The authors investigated the prognostic significance of preoperative cardiorespiratory fitness (peak oxygen consumption [VO(2peak)]) among operable candidates with NSCLC.By using a prospective design, 398 patients with potentially resectable NSCLC enrolled in Cancer and Leukemia Group B 9238 were recruited between 1993 and 1998. Participants performed a cardiopulmonary exercise test to assess VO(2peak) and were observed until death or June 2008. Cox proportional models were used to estimate the risk of all-cause mortality according to cardiorespiratory fitness category defined by VO(2peak) tertiles (0.96 of 0.96-1.29/1.29 L/min⁻¹) with adjustment for age, sex, and performance status.Median follow-up was 30.8 months; 294 deaths were reported during this period. Compared with patients achieving a VO(2peak)0.96 L/min⁻¹, the adjusted hazard ratio (HR) for all-cause mortality was 0.64 (95% confidence interval [CI], 0.46-0.88) for a VO(2peak) of 0.96 to 1.29 L/min⁻¹, and 0.56 (95% CI, 0.39-0.80) for a VO(2peak) of1.29 L/min⁻¹) (P(trend) = .0037). The corresponding HRs for resected patients were 0.66 (95% CI, 0.46-0.95) and 0.59 (95% CI, 0.40-0.89) relative to the lowest VO(2peak) category (P(trend) = .0247), respectively. For nonresected patients, the HRs were 0.78 (95% CI, 0.34-1.79) and 0.39 (95% CI, 0.16-0.94) relative to the lowest category (P(trend) = .0278).VO(2peak) is a strong independent predictor of survival in NSCLC that may complement traditional markers of prognosis to improve risk stratification and prognostication.

Lung cancer is the leading cause of cancer mortality in the United States. The median age of diagnosis is 69 years and the number of elderly patients with lung cancer is expected to increase as this segment of the population increases. This review article describes surgical resection, rationale for adjuvant therapy, and the role of molecular markers in this growing patient population.

PurposeThe cause of the coagulopathy seen with supraceliac aortic cross-clamping (SC AXC) is unclear. SC AXC for 30 minutes results in both clotting factor consumption and activation of fibrinolytic pathways. This study was undertaken to define the hemostatic alterations that occur with longer intervals of SC AXC.MethodsSeven pigs underwent SC AXC for 60 minutes. Five pigs that underwent infrarenal aortic cross-clamping (IR AXC) for 60 minutes and 11 pigs that underwent SC AXC for 30 minutes served as controls. No heparin was used. Blood samples were drawn at baseline, 5 minutes before release of the aortic clamp, and 5, 30, and 60 minutes after unclamping. Prothrombin time, partial thromboplastin time, platelet count, and fibrinogen concentration were measured as basic tests of hemostatic function. Thrombin-antithrombin complexes were used to detect the presence of intravascular thrombosis. Fibrinolytic pathway activation was assessed with levels of tissue plasminogen activator antigen and tissue plasminogen activator activity, plasminogen activator inhibitor-1 activity, and α2-antiplasmin activity. Statistical analysis was performed with the Student t test and repeated measures of analysis of variance.ResultsProthrombin time, partial thromboplastin time, and platelet count did not differ between groups at any time. Fibrinogen concentration decreased 5 minutes (P = .005) and 30 minutes (P = .006) after unclamping in both SC AXC groups, but did not change in the IR AXC group. Thrombin-antithrombin complexes increased in both SC AXC groups, but were not significantly greater than in the IR AXC group. SC AXC for both 30 and 60 minutes produced a significant increase in tissue plasminogen activator antigen during clamping and 5 minutes after clamping. This increase persisted for 30 and 60 minutes after clamp release in the 60-minute SC AXC group. Tissue plasminogen activator activity, however, increased only in the 60-min SC AXC group during clamping (P = .02), and 5 minutes (P = .05) and 30 minutes (P = .06) after unclamping, compared with both control groups.ConclusionsThirty and 60 minutes of SC AXC results in similar degrees of intravascular thrombosis and fibrinogen depletion. Although SC AXC for both 30 and 60 minutes leads to activation of fibrinolytic pathways, only 60 minutes of SC AXC actually induces a fibrinolytic state. Fibrinolysis appears to be an important component of the coagulopathy associated with SC AXC, and is related to the duration of aortic clamping.AbstractClinical relevanceThe coagulopathy frequently associated with thoracoabdominal aortic aneurysm repair is thought to revolt visceral ischemia-reperfusion. The nature of this coagulopathy is controversial. The current study demonstrates that the major hemostatic alteration associated with supraceliac aortic cross-clamping is activation of fibrinolytic pathways. The magnitude of this fibrinolytic response is directly related to the duration of supraceliac aortic occlusion. Future efforts to treat this coagulopathy may well include judicious use of autofibrinolytic agents.

To address the lung donor shortage, we obtained institutional review board and US Food and Drug Administration approval to transplant lungs recovered from uncontrolled donation after circulatory determination of death donors (uDCDDs).To compare outcomes of recipients of lungs recovered from uDCDDs vs. brain-dead donors.After consent and screening, lungs recovered from uDCDDs were assessed by 4 hours ex vivo lung perfusion (EVLP) and computed tomography (CT) scan.Over the course of 29 months, 502 potential uDCDDs younger than 66 years were identified in a single county, with death declaration by emergency medical services and four emergency departments in this and two other countries. We determined reasons that lungs from these uDCDDs were not able to be transplanted: uDCDDs could not have lungs recovered (224), next-of-kin could not be found or refused to discuss (67), next-of-kin refused (48), medical examiner case (39), logistics/missed (35), and miscellaneous (35). There were 247 medical contraindications: 141 pulmonary and 106 nonpulmonary. Lungs were recovered from 31 uDCDDs. Thirteen lungs did not have EVLP: 5 injured lungs (one pulmonary embolism [PE] with perforated infarct, two motor vehicle crash with severe injuries, one adhesion, and one lightning strike), two large PE, two prolonged ischemic time, two obvious chronic obstructive pulmonary disease, one technical, and one consent withdrawn. Eighteen lungs had EVLP: 10 with immediate edema (three PE, three unknown down time, three long ischemic time, and one ruptured aneurysm into L pleural space, making long cardiopulmonary resuscitation ineffective), and one myocarditis, possible lung involvement. In three lungs, CT showed edema after EVLP: one poor flush and poor EVLP performance, one edema after myocardial infarction (MI) with 10-year history of chronic heart failure, and one edema with MI, resuscitated, arrested again. One concurrent pneumonia was diagnosed by bronchoscopy, CT, and cultures; one patient had chronic obstructive pulmonary disease with small subpleural blebs and poor collapse, confirmed by CT. Two uDCDDs with MIs were suitable but not transplanted: no consented recipient from one large blood type B uDCDD, and the senior surgeon was unavailable to transplant suitable lungs from a uDCDD and did not allow the transplant.The objective was not met: no lungs from uDCDDs were transplanted. uDCDDs can be a source of lungs for transplant. Resolving logistical challenges and better use of first-person authorization, allowing organ recovery without next-of-kin consent or knowledge of death, could increase yield. Donor medical problems were higher than expected and may limit the effect of uDCDDs on the lung donor pool.NCT01615484.

Table I. Patient demographics resents a graft enteric fistula (GEF) and is the more common type of SAEF. A breakdown of the enteric wall overlying the graft resulting in bathing of the graft by enteric contents and chronic graft infection without direct involvement of a suture line represents the less common graft enteric erosion (GEE). The rare SAEFs occurring between the bowel lumen and an aortic suture line in the absence of a prosthetic graft (such as after aortic repair for trauma, aortic endarterectomy or aortic stump closure after removal of a previously placed aortic graft) are considered separately in this report, but

Malignant pleural mesothelioma is a rare disease. Ninety percent of cases are attributed to asbestos exposure. Surgical options include extrapleural pneumonectomy or pleurectomy and decortication. The role of chemotherapy and radiation in resectable disease is controversial. For unresectable or metastatic disease, the standard treatment is the combination of a platinum drug and an antifolate drug. Thymoma is the most common mediastinal tumor. Fifty percent of patients are symptomatic at diagnosis, and thymomas can be associated with paraneoplastic syndromes such as myasthenia gravis. Surgical resection is the standard of care. Postoperative radiation therapy should be considered for patients with stage IIB disease, close surgical margins, World Health Organization (WHO) grade B type, and tumor adherent to the pericardium. Chemotherapy may be helpful for patients with unresectable or metastatic disease. Sunitinib and PD-1/PD-L1 agents are being studied for thymoma and thymic carcinoma. Thymic carcinoids exhibit a spectrum of pathologic and clinical aggressiveness. When possible, the primary treatment is surgical resection. Radiation therapy can palliate symptomatic local and distant metastases. More aggressive atypical carcinoid tumors can be sensitive to the same chemotherapy used for other neuroendocrine cancers. When they bear octreotide receptors, somatostatin analogues or radiolabeled somatostatin analogues may be considered. Mammalian target of rapamycin (mTOR) inhibitors are promising. The most common causes of malignant pleural effusions are lung cancer, breast cancer, lymphoma, pleural mesothelioma, and cancer of unknown primary. Common symptoms include shortness of breath and cough. Management strategies include thoracentesis, indwelling pleural catheters, and pleurodesis.

The authors review current data on pneumonectomy in patients with non-small cell cancer after induction chemotherapy and radiation therapy and make recommendations for treatment: Evaluation by a multidisciplinary team for all advanced stage non-small cell lung cancer cases; parenchymal-conserving R0 resection for patients undergoing therapy for resectable NSCLC; pneumonectomies after induction therapy, done in experienced centers; right pneumonectomy in an experienced center after neoadjuvant therapy - if not feasible, consider referral or treatment with chemo radiotherapy.

The complete sequence of the caprine beta-mannosidase cDNA coding region has been determined, and a mutation that is associated with caprine beta-mannosidosis has been identified. Reverse transcriptase-polymerase chain reactions were performed using primers based on bovine and, later, goat cDNA sequences to produce an overlapping series of amplicons covering the entire coding region. The composite cDNA codes for an 879-amino-acid peptide that has four potential N-glycosylation sites. Comparison of the caprine and bovine cDNAs reveals that 96.3% of the nucleotides and 95.2% of the deduced amino acids are identical. A single-base deletion at position 1398 of the coding sequence was identified in the cDNA isolated from a goat affected with beta-mannosidosis. This deletion results in a shift in the reading frame and a premature termination of translation, yielding a deduced peptide of 481 amino acids. An assay, developed to determine the presence or absence of this mutation, confirmed that animals affected with beta-mannosidosis were homozygous for the mutation and that obligate carriers in a caprine beta-mannosidosis colony were heterozygous. This assay accurately distinguished between mutation carrier and noncarrier goats and was used for prenatal diagnosis using DNA collected from fetal fluids. The assay also confirmed chimerism in a goat with an atypically mild beta-mannosidosis phenotype. Thus, this application enables assessment of the efficacy of engraftment of hematopoietic stem cells after prenatal transfer from donor sources.

Background Lung adenocarcinoma (LAD) has extreme genetic variation among patients, which is currently not well understood, limiting progress in therapy development and research. LAD intrinsic molecular subtypes are a validated stratification of naturally-occurring gene expression patterns and encompass different functional pathways and patient outcomes. Patients may have incurred different mutations and alterations that led to the different subtypes. We hypothesized that the LAD molecular subtypes co-occur with distinct mutations and alterations in patient tumors. Methodology/Principal Findings The LAD molecular subtypes (Bronchioid, Magnoid, and Squamoid) were tested for association with gene mutations and DNA copy number alterations using statistical methods and published cohorts (n = 504). A novel validation (n = 116) cohort was assayed and interrogated to confirm subtype-alteration associations. Gene mutation rates (EGFR, KRAS, STK11, TP53), chromosomal instability, regional copy number, and genomewide DNA methylation were significantly different among tumors of the molecular subtypes. Secondary analyses compared subtypes by integrated alterations and patient outcomes. Tumors having integrated alterations in the same gene associated with the subtypes, e.g. mutation, deletion and underexpression of STK11 with Magnoid, and mutation, amplification, and overexpression of EGFR with Bronchioid. The subtypes also associated with tumors having concurrent mutant genes, such as KRAS-STK11 with Magnoid. Patient overall survival, cisplatin plus vinorelbine therapy response and predicted gefitinib sensitivity were significantly different among the subtypes. Conclusions/ Significance The lung adenocarcinoma intrinsic molecular subtypes co-occur with grossly distinct genomic alterations and with patient therapy response. These results advance the understanding of lung adenocarcinoma etiology and nominate patient subgroups for future evaluation of treatment response.

Background Applications to cardiothoracic training programs have declined dramatically. Increased effort in recruiting trainees is paramount. In this study, we test our hypothesis that mentored instruction on cardiothoracic simulators will enhance the interest of junior medical students in cardiothoracic surgery. Methods First- and second-year medical students were recruited from a "surgery interest group" to receive mentored instruction on high-fidelity cardiothoracic simulators. Before and after simulation assessment tools were used to assess attitudes toward simulation, general surgery, and cardiothoracic surgery. Results Forty-four medical students participated in the study. Although 80% of the students were interested in pursuing a career in surgery before the course, the majority (64%) indicated they were "neutral" about pursuing a career in cardiothoracic surgery. After participating in the course, 61% of the students agreed or strongly agreed that they were interested in pursuing a career in cardiothoracic surgery ( p = 0.001). When asked to select a surgical subspecialty for their third-year clerkship rotation, 18% of the students selected thoracic surgery before participating in the simulator course versus 39% after completing the course. This increase was most evident among the female participants, of whom only 3 (12%) selected a thoracic rotation before the simulator course versus 9 (35%) after completion of the course ( p Conclusions High-fidelity surgical simulators are an effective way to introduce medical students to cardiothoracic surgery. Participation in moderated simulator sessions improves attitudes toward cardiothoracic surgery as a career choice and correlates with a greater interest in selecting thoracic surgery as a third-year clerkship rotation. The role of surgical simulation as a recruitment tool should be further delineated.