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Immunohistochemical (IHC) staining is an established technique for visualizing proteins in tissue sections for research studies and clinical applications. IHC is increasingly used as a targeting strategy for procurement of labeled cells via tissue microdissection, including immunodissection, computer-aided laser dissection (CALD), expression microdissection (xMD), and other techniques. The initial antigen retrieval (AR) process increases epitope availability and improves staining characteristics; however, the procedure can damage DNA. To better understand the effects of AR on DNA quality and quantity in immunodissected samples, both clinical specimens ( KRAS gene mutation positive cases) and model system samples (lung cancer patient-derived xenograft tissue) were subjected to commonly employed AR methods (heat induced epitope retrieval [HIER], protease digestion) and the effects on DNA were assessed by Qubit, fragment analysis, quantitative PCR, digital droplet PCR (ddPCR), library preparation, and targeted sequencing. The data showed that HIER resulted in optimal IHC staining characteristics, but induced significant damage to DNA, producing extensive fragmentation and decreased overall yields. However, neither of the AR methods combined with IHC prevented ddPCR amplification of small amplicons and gene mutations were successfully identified from immunodissected clinical samples. The results indicate for the first time that DNA recovered from immunostained slides after standard AR and IHC processing can be successfully employed for genomic mutation analysis via ddPCR and next-generation sequencing (NGS) short-read methods.

Malignancy of the esophagus or mediastinum can present with obstruction. Our focus is to identify the most effective means of managing this population. Data was gathered from a single institution for patients admitted with esophageal obstruction. Patients were categorized based on admission to thoracic surgery or the hospitalist service. Primary end-points were hospital length-of-stay (LOS) and hospital cost. The mean LOS was 4.4 days when admitted to thoracic surgery versus 13.5 days when admitted to a hospitalist ( P = .0005). The mean overall cost was $43,902 less per patient when admitted to thoracic surgery ($75 809 vs $31 907; P = .003).

Background Patients undergoing surgery for oesophageal cancer are at high risk of malnutrition due to pathology and neoadjuvent therapy. This study sought to determine if oesophageal cancer patients undergoing oesophagectomy achieve superior clinical outcomes when preoperative nutritional counselling is performed. Methods Oesophageal cancer patients undergoing oesophagectomy were retrospectively divided into cohorts based on those who received ( n = 48) and did not receive ( n = 58) preoperative nutritional counselling. We compared weight loss, length of stay, 30-day readmission related to nutrition or feeding tube problems, and 90-day mortality. Results Per cent weight loss was less in patients who received preoperative nutritional counselling. There was a trend toward decreased mean length of stay and there were fewer readmissions for feeding tube-related complications in patients who received counselling. Conclusions Nutritional counselling before surgery may lead to decreased weight loss and reduced readmissions for feeding tube-related complications in patients with oesophageal cancer undergoing oesophagectomy.

BACKGROUND: Smoking at the time of surgical treatment for lung cancer increases the risk for perioperative morbidity and mortality. The prevalence of persistent smoking in the postoperative period and its association with long-term oncologic outcomes are poorly described. RESEARCH QUESTION: What is the relationship between persistent smoking and long-term outcomes in early-stage lung cancer after surgical treatment? STUDY DESIGN AND METHODS: We performed a retrospective cohort study using a uniquely compiled Veterans Health Administration dataset of patients with clinical stage I non-small cell lung cancer (NSCLC) undergoing surgical treatment between 2006 and 2016. We defined persistent smoking as individuals who continued smoking 1 year after surgery and characterized the relationship between persistent smoking and disease-free survival and overall survival. RESULTS: This study included 7,489 patients undergoing surgical treatment for clinical stage I NSCLC. Of 4,562 patients (60.9%) who were smoking at the time of surgery, 2,648 patients (58.0%) continued to smoke at 1 year after surgery. Among 2,927 patients (39.1%) who were not smoking at the time of surgical treatment, 573 (19.6%) relapsed and were smoking at 1 year after surgery. Persistent smoking at 1 year after surgery was associated with significantly shorter overall survival (adjusted hazard ration [aHR], 1.291; 95% CI, 1.197-1.392; P < .001). However, persistent smoking was not associated with inferior disease-free survival (aHR, 0.989; 95% CI, 0.884-1.106; P = .84). INTERPRETATION: Persistent smoking after surgery for stage I NSCLC is common and is associated with inferior overall survival. Providers should continue to assess smoking habits in the postoperative period given its disproportionate impact on long-term outcomes after potentially curative treatment for early-stage lung cancer.

The National Lung Screening Trial demonstrated a decrease in both lung cancer mortality and overall mortality in enrollees aged 55–74 with a 30 pack-year smoking history using low-dose computed tomography (LDCT). Lung cancer screening in high-risk groups is supported by the United States Preventive Services Task Force, the National Comprehensive Cancer Network, and multiple other organizations. Inclusion for any lung screening program requires a history of smoking, and many undergoing screening are currently smoking. Screened patients are not only at risk for developing lung cancer, but also carry the risk of developing a host of other smoking related diseases, and cessation at any point is beneficial. Counseling and pharmacotherapy are evidence-based strategies which are well known to help people quit smoking. However, as lung cancer screening is an emerging and evolving field, the integration of cessation resources in screening programs is not uniformly done, and when it is done, there is no standardized approach. The goals of this review are to discuss the rationale for integrating smoking cessation resources in lung cancer screening, review what types of resources may be effective, and discuss different strategies of how integration can be done. Ultimately, the overarching goal of any lung cancer screening program is not merely to find more nodules, or diagnose more cases of cancer, but to help screened patients live longer, better lives. Smoking cessation broadens the impact of any lung cancer screening program well beyond the endpoints of cancer diagnosis and cancer mortality to reduce risk from many other diseases, and can positively impact many more patients than the small percentage that have cancer.

Tobacco use is an etiologic agent for many diseases treated by cardiac, vascular, and thoracic surgeons and contributes to increased perioperative complications and long-term risk. Smoking cessation may be challenging for patients and can be frustrating for clinicians. Lack of familiarity and pessimistic views toward cessation methods lead to underuse by physicians. Evidence-supported measures that increase chances of cessation include direct physician advice, approved pharmacotherapy, structured counseling, and a follow-up plan. Approved pharmacotherapy consists of varenicline, bupropion, or nicotine replacement therapy in the form of long-acting patches and short-acting forms of nicotine such as gum, lozenges, prescription nasal spray, or prescription inhaler. Direct physician advice is critical and strengthened when combined with more in-depth counseling from a specialist who may have more expertise and time. Integrating assessment and referral to counseling services into a clinical workflow can deliver resources in an efficient manner with the goal of providing the best available resources to all patients.

Objectives Hyalinizing clear cell carcinoma (HCCC) is common in head and neck sites but extremely rare in the lung. This case report describes an HCCC in the lung of a 54-year-old female patient. Methods We summarize the histomorphologic, immunophenotypic, and molecular features for our and three previously reported HCCCs of the lung with emphasis on potential diagnostic pitfalls. Results Sections of a well-circumscribed 3.5-cm lung mass were characterized by a bronchocentric tumor growing in sheets, nests, and cords in a background of hyalinized stroma. Tumor cell appearance was clear to eosinophilic, lacking significant pleomorphism or mitotic activity. By immunohistochemistry, the tumor cells were strongly positive with antibodies to pan-keratin, p63, and CK5/6 while negative for CK7, CK20, thyroid transcription factor 1, napsin A, chromogranin, and synaptophysin. Next-generation sequencing demonstrated an EWSR1-ATF1 fusion transcript. Conclusions Awareness of key morphologic features of pulmonary HCCC is crucial for the recognition of this rare entity in the lung. Ancillary studies, including immunohistochemistry and molecular testing, are essential for the distinction from its mimics.

e15083 Background: Improving patient treatment outcomes based on the application of advanced molecular profiling methodologies applied to pathological specimens is the purview of precision oncology. Optimal utilization of tumor tissue from diagnostic biopsies remains an unmet medical need. This is especially relevant today since precision oncology is a rapidly evolving field where timely tumor genotyping is essential for the indication of many advanced and targeted therapies. National Comprehensive Cancer Network (NCCN) guidelines now mandate molecular testing for clinically actionable targets in certain malignancies. Patients diagnosed with advanced non-small cell lung cancer (NSCLC) are commonly of an older age and have significant co-morbidities. Clinical dilemmas regarding the ability to obtain adequate amounts of tissue for tumor genotyping frequently occur. In these cases, the tumor tissue may have been obtained by an image-guided biopsy, and the diagnosis of NSCLC proper determined via cytology. Adequate tissue for tumor genotyping and/or a more advanced mutational analysis to identify oncogenic drivers may not be available, and the opportunity to explore more optimal therapy options (eg, TKI in lieu of chemotherapy) is lost. Methods: Following a formal pathology review formalin fixed paraffin embedded (FFPE) specimens were examined using advanced immuno-based laser capture microdissection (LCM). In preparation for droplet digital PCR (ddPCR), nucleic acids were extracted from samples and run with a series of positive and negative controls. Results: Utilizing lung cancer as an example, an improved genotyping approach for NSCLC solid tumors was developed and tested. The strategy involves optimization of the microdissection process and analysis of a large number of identical target cells from FFPE specimens sharing similar characteristics, in other words, single-cell subtype analysis. Immunostaining status, cell phenotype, and spatial location within a histological section are examples of shared characteristics that can guide cell procurement. Conclusions: With this approach, tumor molecular analysis is enhanced through the synergy between microdissection and ddPCR. Here we demonstrate a methodology that illustrates genotyping of a solid tumor from a small tissue biopsy sample in a time and cost-efficient manner, using immunohistochemistry-directed LCM along with the detection and absolute quantitation of mutations by ddPCR.

e15571 Background: Improving the utilization of tumor tissue from diagnostic biopsies is an unmet medical need. This is especially relevant today in the rapidly evolving precision oncology field where tumor genotyping is essential for the indication of many advanced and targeted therapies. National Comprehensive Cancer Network (NCCN) guidelines now mandate molecular testing for clinically actionable targets in certain malignancies. Patients diagnosed with advanced non-small cell lung cancer (NSCLC) are commonly of an older age and have significant co-morbidities. This frequently causes clinical dilemmas regarding the ability to obtain adequate amounts of tissue for tumor genotyping. In these cases, the tumor tissue may have been obtained by an image-guided biopsy, and the diagnosis of NSCLC proper determined via cytology. In certain instances, adequate tissue for tumor genotyping and/or a more advanced mutational analysis to identify oncogenic drivers may not be available. Methods: Following pathology review, formalin fixed paraffin embedded (FFPE) specimens were subjected to advanced immuno-based laser capture microdissection (LCM), DNA was extracted and prepped for droplet digital PCR (ddPCR) and run with a series of positive and negative controls. Results: Utilizing advanced stage lung cancer as an example, an improved genotyping approach for solid tumors is possible. The strategy involves optimization of the microdissection process and analysis of a large number of identical target cells from FFPE specimens sharing similar characteristics, in other words, single-cell subtype analysis. The shared characteristics can include immunostaining status, cell phenotype, and/or spatial location within a histological section. Conclusions: Synergy between microdissection and ddPCR enhances the molecular analysis. We demonstrate a methodology that illustrates genotyping of a solid tumor from a small tissue biopsy sample in a time and cost-efficient manner, using immunostain targeting as an example.

Pleural metastases and malignant pleural effusion may occur with metastatic breast cancer. Presentation can vary widely from an incidental finding on imaging to a large effusion with severe dyspnea. Any pleural effusion in a breast cancer patient can be suspected to be a malignant effusion until proven otherwise. The focus of the clinician should be to provide the most efficient, accurate diagnosis with the least risk of complication and pain for the patient. This chapter reviews diagnosis and management of malignant pleural and pericardial effusions.

Tobacco is the single greatest contributor to development of lung cancer. Nearly all societies across the globe are afflicted with the tobacco epidemic, and smoking rates are rising for certain populations. Successful tobacco control is typically implemented not as a single measure but as part of a comprehensive, multifaceted approach using several concepts; the impact of one measure on smoking rates can be difficult to distill when several are implemented in combination. However, a concerted multifaceted effort using evidence-based strategies can alter the future course of the tobacco epidemic, with the potential to save millions of lives. The World Health Organization Framework Convention on Tobacco Control provides a global tobacco-control strategy, including monitor tobacco use and prevention policies; protect people from tobacco smoke; offer to help quit tobacco use; warn about the dangers of tobacco; enforce bans on tobacco advertising; and, raise taxes as a tobacco control measure.

Hyalinizing clear cell carcinoma (HCCC) is common in head and neck sites but extremely rare in the lung. This case report describes an HCCC in the lung of a 54-year-old female patient.We summarize the histomorphologic, immunophenotypic, and molecular features for our and three previously reported HCCCs of the lung with emphasis on potential diagnostic pitfalls.Sections of a well-circumscribed 3.5-cm lung mass were characterized by a bronchocentric tumor growing in sheets, nests, and cords in a background of hyalinized stroma. Tumor cell appearance was clear to eosinophilic, lacking significant pleomorphism or mitotic activity. By immunohistochemistry, the tumor cells were strongly positive with antibodies to pan-keratin, p63, and CK5/6 while negative for CK7, CK20, thyroid transcription factor 1, napsin A, chromogranin, and synaptophysin. Next-generation sequencing demonstrated an EWSR1-ATF1 fusion transcript.Awareness of key morphologic features of pulmonary HCCC is crucial for the recognition of this rare entity in the lung. Ancillary studies, including immunohistochemistry and molecular testing, are essential for the distinction from its mimics.

Esophageal necrosis after descending aortic dissection has been described but with no reports of successful treatment. A 66-year-old man with aortic dissection extending from the left subclavian artery through the common iliac arteries subsequently experienced esophageal necrosis. He underwent thoracic esophagectomy, cervical end esophagostomy, and open gastrostomy tube placement. Gastrointestinal continuity was established with a gastric tube conduit in the substernal plane. An oral diet was tolerated after reconstruction. Treatment of esophageal necrosis after aortic dissection may require esophageal diversion and esophagectomy. Esophageal continuity can later be restored while avoiding the posterior mediastinum.

The link between smoking and development of lung cancer has been demonstrated, not only for smokers but also for those exposed to secondhand smoke. Despite the obvious carcinogenic effects of tobacco smoking, not all smokers develop lung cancer, and conversely some nonsmokers can develop lung cancer in the absence of other environmental risk factors. A multitude of genetic factors are beginning to be explored that interact with environmental exposure to alter the risk of developing this deadly disease. By more fully appreciating the complex interrelationship between genetics and other risks the development of lung cancer can be more completely understood.

We present a useful technique for the surgical management of long-segment cervicothoracic tracheobronchial injury using a double-wide intercostal muscle flap. This flap is a modification of a previously endorsed technique extending the ability to reinforce repairs of tracheobronchial injuries not adequately covered by a single intercostal muscle flap.

Radical surgery for malignant pleural mesothelioma does not improve survival in patients with nodal metastases. Imaging is poor at predicting nodal involvement and mediastinoscopy, though frequently used, is of low sensitivity. As endobronchial ultrasound (EBUS) and esophageal endoscopic ultrasound (EUS) are accurate for nodal staging of lung cancer, we hypothesized that they would be at least as sensitive as cervical video-mediastinoscopy for nodal staging of mesothelioma.Eighty-five patients with mesothelioma who were potential candidates for radical surgery underwent preoperative staging with mediastinoscopy (n = 50) or EBUS (n = 38). Eleven patients also underwent EUS.Diagnostic yield (specimens containing lymphocytes or tumor cells) was 100% for mediastinoscopy and 84% for EBUS (p0.001). Mediastinoscopy identified 7 of 50 (14%) patients with nodal metastases. Thirty-eight (76%) mediastinoscopy-negative patients underwent surgery with nodal sampling and there were 18 false negatives. Endobronchial ultrasound identified 13 of 38 (34%) patients with nodal metastases. Twenty-two (58%) EBUS-negative patients underwent surgery with nodal sampling and there were 10 false negatives. Sensitivity and negative predictive value for mediastinoscopy were 28% and 49%, and 59% and 57% for EBUS. Eleven patients had EUS preoperatively, which revealed infradiaphragmatic nodal metastases in 5 patients.Although this study is retrospective, EBUS had higher sensitivity than either mediastinoscopy or imaging studies for detection of nodal metastases. Nevertheless, the ability to accurately identify nodal involvement preoperatively in patients with mesothelioma remains suboptimal. Esophageal ultrasound may complement EBUS particularly in cases where infradiaphragmatic nodal metastases are suspected.

Myxoid mesenchymal tumours are a heterogeneous group of neoplasms characterised histologically by their abundant mucoid and myxoid extracellular matrix (ECM). Encompassing a broad spectrum of clinical behaviour ranging from benign to malignant, there are more than 60 reactive and neoplastic entities currently classified under its domain. Its varied clinical and histopathologic features continue to pose a diagnostic challenge to clinicians and pathologists. Here, we describe a rare case of myxoid mesenchymal tumour presenting as oedema of the upper extremity with pleural metastasis and partial response to chemotherapy, which to the best of our knowledge has not yet been described in the literature.

While there is a great deal to celebrate, there is still a great amount of death, disability, and cost associated with the ongoing tobacco epidemic in our nation and throughout the world.

Management of advanced non-small cell lung cancer patients is dependent on the histologic diagnosis for both testing and treatment. This study was designed to determine the ability of fine needle aspiration and core biopsies to correctly determine histologic diagnosis in non-small cell lung cancer. Our institutional cardiothoracic surgery database was reviewed for cases of non-small cell lung cancer treated with lobectomy after a preoperative biopsy by CT guidance or bronchoscopy over a 10-year period from 2002 to 2011. The histologic diagnosis of the final lobectomy specimen was compared to the histologic diagnosis from the preoperative biopsy, and the concordance rate was calculated. 119 biopsy specimens from 117 patients were reviewed. Eighty of the 119 biopsies had the same histologic diagnosis as the lobectomy specimen, yielding an overall concordance rate of 67.2 %. Patients with poorly differentiated tumors were at the highest risk of an incorrect histologic diagnosis on preoperative biopsy. Reliance on fine needle aspiration and core biopsies to determine histologic diagnosis in non-small cell lung cancer may put some patients at risk for suboptimal treatment.

Tracheobronchial injuries are rare but life threatening sequel of blunt chest trauma. Due to the difficult nature of these injuries and the demanding attributes of the involved surgery, the anesthesiologist faces tough challenges while securing the airway, controlling oxygenation, undertaking one-lung ventilation, maintaining anesthesia during tracheal reconstruction, and gaining adequate postoperative pain control. Amongst the few techniques that can be used with tracheobronchial injuries, cross field ventilation is a remotely described and rarely used technique, especially in injuries around the carina. We effectively applied cross field ventilation in both our cases and the outcome was excellent.

The incidence of lung cancer cases among HIV-infected individuals is increasing with time. It is unclear whether HIV-infected individuals receive the same care for lung cancer as immunocompetent patients because of comorbidities, the potential for interaction between antiretroviral agents and cancer chemotherapy, and concerns regarding complications related to treatment or infection.The objective of this study was to assess the effect of HIV infection on receipt of guidance-concordant care, and its impact on overall survival among non-small cell lung cancer Medicare beneficiaries.The study design was a matched case-control design where each HIV patient was matched by age group, sex, race, and lung cancer stage at diagnosis with 20 controls randomly selected among those who were not HIV infected.The patients included in this study were Medicare beneficiaries diagnosed with non-small cell lung cancer between 1998 and 2007, who qualified for Medicare on the basis of age and were 65 years of age or older at the time of lung cancer diagnosis. HIV infection status was based on Medicare claims data. A total of 174 HIV cases and 3480 controls were included in the analysis.Odds ratios for receiving guidance-concordant care and hazard ratios for overall survival were estimated.HIV infection was not independently associated with the receipt of guidance-concordant care. Among stage I/II patients, median survival times were 26 and 43 months, respectively, for those with and without HIV infection (odds ratio=1.48, P=0.021).HIV infection was not associated with receipt of guidance-concordant care but reduced survival in early-stage patients.

Objective One of the General Surgery milestones focuses on effective handoffs between residents as they change shifts. Although the content of handoffs is crucial, we recognized that the culture of handoffs was equally important. After the reorganization of the trauma service at our institution, there were difficulties in maintaining the standardized handoff culture. We analyzed the culture of handoffs on the trauma service to create an environment more conducive to effective handoffs. Design All trauma activations from 2012 to 2013 were evaluated from our institution's trauma data registry. Data on timing of activations and disposition of the patient were analyzed to understand service work flow. A survey was developed and administered to the residents to assess the culture of trauma handoffs. Setting This work occurred at an academic, state-designated level 1 trauma center. Participants All current residents in the general surgery residency who rotated on the trauma service in the last 5 years. Results There were 1654 admissions to the trauma service from June 2012 to July 2013. The single busiest hour for trauma admissions (7% of admissions) was the same time the residents were designated to handoff. Interruptions occurred often; 83% of residents indicated that a handoff interruption occurred daily, and 73% indicated a new activation interrupted handoffs weekly. A large majority, 61%, felt patient care was frequently compromised by an ineffective handoff. Similarly, as a direct result of inadequate handoffs, 50% felt uncomfortable answering nurses' pages at night. Conclusions The unique situation of the trauma service impaired the handoff culture for residents. Assessment of our trauma activation flow indicates the timing of handoffs was adversely affecting our resident's ability to handoff effectively, requiring interventions to improve the efficacy and safety of handoffs.

Pulmonary vein stenosis, a recognized complication of transcatheter radiofrequency ablation in the left atrium, is often asymptomatic. Significant stenosis is commonly treated with percutaneous balloon dilation with or without stenting. We encountered a case of complete pulmonary vein occlusion that caused lobar thrombosis, pleuritic pain, and persistent cough. Imaging studies revealed virtually no perfusion to the affected lobe. A lobectomy was performed, resolving the persistent cough and pain. Pulmonary vein occlusion should be suspected in patients who present with pulmonary symptoms after having undergone ablative procedures for atrial fibrillation. This condition may necessitate surgical intervention if interventions such as balloon dilation or stenting are not possible or are ineffective.

Osteosarcoma is the most common primary bone malignancy in the United States, comprising approximately 56% of the primary bone tumors.1,2 Most patients present with local disease; their treatment is outlined in greater detail elsewhere in this book. However, 10–20% of patients diagnosed with osteosarcoma will have radiographic evidence of synchronous isolated pulmonary metastases at the time of initial presentation. Of the patients without synchronous pulmonary metastases, 40–55% will develop metachronous pulmonary metastases.3–5