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Abstract Primary lung myoepithelial carcinomas are rare neoplasms arising from the salivary glands of the respiratory epithelium. Given the rare occurrences and reports of these tumors, appropriate recommendations for resection are difficult to formulate. Although classified as low-grade neoplasms, these tumors have a significant rate of recurrence and distant metastasis.

Objective: With robotic technology's rapid growth and integration, an urgent need to bridge the educational gap in thoracic surgical training has emerged. This document, a result of consensus among a group of experts in the practice and training of robotic surgery from The Society of Thoracic Surgeons, aims to provide a framework for a standardized national robotic curriculum for thoracic surgery trainees., Methods: The Society of Thoracic Surgeons Task Force on Robotic Thoracic Surgery and Workforce on E-learning and Educational Innovation assembled an expert group with the input of the Thoracic Surgery Director's Association. A focused literature review was performed, and expert consensus statements were developed using a modified Delphi process to address 3 major themes: (1) program expectations, (2) components of training, and (3) assessment and feedback., Results: A consensus was reached on 12 recommendations. These consensus statements reflect updated insights on developing a standardized robotics curriculum based on the latest literature and current educational experience, focusing on program expectations and educational guidelines to develop an optimal training curriculum., Conclusions: The expert panel provides several key recommendations to provide a framework for developing a standardized national robotic thoracic curriculum, which would improve resident education and abridge any educational disparity that may exist among programs., Competing Interests: Disclosures Samuel Kim reports a relationship with Intuitive Surgical, Inc, that includes: funding grants and speaking and lecture fees. Elliot Servais reports a relationship with Intuitive Surgical, Inc, that includes: speaking and lecture fees. Bernard Park reports a relationship with Becton Dickinson and Company that includes: speaking and lecture fees; with Medtronic, Inc, that includes: consulting or advisory; and with Intuitive Surgical, Inc, that includes: speaking and lecture fees. Desmond D’Souza reports a relationship with Intuitive Surgical, Inc, that includes: speaking and lecture fees. Luis Godoy reports a relationship with Intuitive Surgical, Inc, that includes: speaking and lecture fees. Inderpal Sarkaria reports a relationship with Intuitive Surgical, Inc, that includes: consulting or advisory and speaking and lecture fees; with Oncolys BioPharma, Inc, that includes: consulting or advisory; with Medtronic, Inc, that includes: consulting or advisory; with On Target Laboratories, LLC, that includes: consulting or advisory; with Stryker Corporation that includes: consulting or advisory; and with American Medical Solutions, Inc, that includes: consulting or advisory. The other authors have no conflicts of interest to disclose., (Copyright © 2025 The Authors. Published by Elsevier Inc. All rights reserved.)

Background: Clinical studies have demonstrated that intraoperative molecular imaging (IMI) with pafolacianine identifies occult pulmonary lesions that are not identified by preoperative computed tomography or by intraoperative inspection techniques in ∼20% of patients. This study describes occult lesion clinical data and evaluates characteristics so that surgeons can better incorporate this emerging technology into clinical decision making., Methods: Participants (n = 100) enrolled in a phase 3 trial of IMI with pafolacianine during pulmonary resection (Enabling Lung Cancer Identification Using Folate Receptor Targeting [ELUCIDATE]; NCT04241315) were identified. Participants underwent preoperative computed tomography with 1.25-mm slices. Patient and lesion characteristics were analyzed. Positive predictive value and false positive rates were tabulated for IMI fluorescent lesions, with predictors of malignant vs benign occult lesions described., Results: IMI identified 29 occult lesions in 23 (23%) participants. Seventeen of 29 (58%) lesions were identified within the same lobe as known lesions; 12 of 29 (42%) were identified in a different lobe from the suspicious nodule known by preoperative assessment. Twenty-three of 29 (79%) of occult lesions found by IMI were resected with an additional wedge resection. Ten of 29 (34%) lesions identified by IMI were malignant. There was no additional morbidity in participants with lesions resected. With pafolacianine, 7 participants had a synchronous primary stage I lung cancer identified, and 1 participant had additional metastases identified., Conclusions: IMI with pafolacianine identifies occult malignant lesions during pulmonary resection despite thorough preoperative imaging and intraoperative assessment by experienced surgeons., Competing Interests: Disclosures Linda W. Martin reports a relationship with Bristol Myers Squibb that includes: consulting or advisory. Michael I. Ebright reports a relationship with On Target Laboratories that includes: consulting or advisory; and with Medtronic that includes: consulting or advisory. Tommy Lee reports a relationship with On Target Laboratories LLC that includes: employment and equity or stocks. Jarrod D. Predina reports a relationship with On Target Laboratories LLC that includes: consulting or advisory; and with Olympus that includes: consulting or advisory. All other authors declare that they have no conflicts of interest., (Copyright © 2024. Published by Elsevier Inc.)

Background/aim: There is concern that people who had COVID-19 will develop pulmonary fibrosis. Using mouse models, we compared pulmonary inflammation following injection of the spike protein of SARS-CoV-2 (COVID-19) to radiation-induced inflammation to demonstrate similarities between the two models. SARS-CoV-2 (COVID-19) induces inflammatory cytokines and stress responses, which are also common to ionizing irradiation-induced acute pulmonary damage. Cellular senescence, which is a late effect following exposure to SARS-CoV-2 as well as radiation, was investigated., Materials and Methods: We evaluated the effect of SARS-CoV-2 spike protein compared to ionizing irradiation in K18-hACE2 mouse lung, human lung cell lines, and in freshly explanted human lung. We measured reactive oxygen species, DNA double-strand breaks, stimulation of transforming growth factor-beta pathways, and cellular senescence following exposure to SARS-CoV-2 spike protein, irradiation or SARS-COV-2 and irradiation. We also measured the effects of the antioxidant radiation mitigator MMS350 following irradiation or exposure to SARS-CoV-2., Results: SARS-CoV-2 spike protein induced reactive oxygen species, DNA double-strand breaks, transforming growth factor-β signaling pathways, and senescence, which were exacerbated by prior or subsequent ionizing irradiation. The water-soluble radiation countermeasure, MMS350, reduced spike protein-induced changes., Conclusion: In both the SARS-Co-2 and the irradiation mouse models, similar responses were seen indicating that irradiation or exposure to SARS-CoV-2 virus may lead to similar lung diseases such as pulmonary fibrosis. Combination of irradiation and SARS-CoV-2 may result in a more severe case of pulmonary fibrosis. Cellular senescence may explain some of the late effects of exposure to SARS-CoV-2 spike protein and to ionizing irradiation., (Copyright © 2024, International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved.)

Background: Currently, little is known regarding the optimal technique for the abdominal phase of RAMIE. The aim of this study was to investigate the outcome of robot-assisted minimally invasive esophagectomy (RAMIE) in both the abdominal and thoracic phase (full RAMIE) compared to laparoscopy during the abdominal phase (hybrid laparoscopic RAMIE)., Methods: This retrospective propensity-score matched analysis of the International Upper Gastrointestinal International Robotic Association (UGIRA) database included 807 RAMIE procedures with intrathoracic anastomosis between 2017 and 2021 from 23 centers., Results: After propensity-score matching, 296 hybrid laparoscopic RAMIE patients were compared to 296 full RAMIE patients. Both groups were equal regarding intraoperative blood loss (median 200 ml versus 197 ml, p = 0.6967), operational time (mean 430.3 min versus 417.7 min, p = 0.1032), conversion rate during abdominal phase (2.4% versus 1.7%, p = 0.560), radical resection (R0) rate (95.6% versus 96.3%, p = 0.8526) and total lymph node yield (mean 30.4 versus 29.5, p = 0.3834). The hybrid laparoscopic RAMIE group showed higher rates of anastomotic leakage (28.0% versus 16.6%, p = 0.001) and Clavien Dindo grade 3a or higher (45.3% versus 26.0%, p < 0.001). The length of stay on intensive care unit (median 3 days versus 2 days, p = 0.0005) and in-hospital (median 15 days versus 12 days, p < 0.0001) were longer for the hybrid laparoscopic RAMIE group., Conclusions: Hybrid laparoscopic RAMIE and full RAMIE were oncologically equivalent with a potential decrease of postoperative complications and shorter (intensive care) stay after full RAMIE., (© 2023. The Author(s).)

Background: Minimally invasive esophagectomy (MIE) is increasingly performed in various ways. The lack of international definitions and nomenclature makes accurate comparison of outcomes difficult., Methods: An international, multispecialty consensus-writing committee constructed definitions and nomenclature for MIE. After a PubMed search, vetting, and review with all authors, a consensus was reached., Results: The proposed definition for MIE is an operation "that removes part or all of the esophagus, does not retract, lift, spread or remove any part of the chest or abdominal wall and the surgeon's and assistant's vision of the operative field is via a monitor, the patient's tissue is manipulated only by instruments that are controlled by the operating surgeon or team, except for during the neck portion if used." A flexible nomenclature is proposed that attempts to describe current and future operations and systems., Conclusions: Definitions and nomenclature for MIE are needed to ensure that future studies accurately compare results and outcomes of similar operations. Nomenclatures allow surgeons, researchers, and patients from different cultures to use a common language to facilitate communication and compare. This process is required in order to improve patient outcomes globally to drive adoption of best of practice, yet is lacking for MIE., (Copyright © 2020 The Society of Thoracic Surgeons. Published by Elsevier Inc. All rights reserved.)

Objective: A recent meta-analysis of 3 randomized controlled trials reported reduced incidence and severity of postesophagectomy anastomotic dehiscence with anastomotic omentoplasty. Unfortunately, these trials excluded neoadjuvant patients who received chemoradiation. We aimed to determine whether anastomotic omentoplasty was associated with differential postesophagectomy anastomotic complications after neoadjuvant chemoradiotherapy., Methods: Data for patients who underwent minimally invasive esophagectomy following neoadjuvant chemoradiotherapy were abstracted (n = 245; 2001-2016; omentoplasty = 147 [60%]). Propensity for omentoplasty was estimated on 21 pretreatment variables, using augmented inverse probability of treatment weights, and used to determine the adjusted proportion of adverse anastomotic outcomes, major morbidity, and 30-day/in-hospital mortality., Results: Overall, anastomotic leak rate was 15%; leak-associated mortality was 13% (n = 5 out of 37). Leak rates (omentoplasty n = 24 [16%] vs no omentoplasty n = 13 [13%]; P = .512) and incidence of any major complications (48% vs 48%; P = .958) were similar. Leaks requiring surgical intervention occurred in 12 patients (5% vs 5%; P = .904). Propensity weighting achieved excellent balance across all 21 pretreatment variables (before weighting, standardized differences ranged from -0.23 to 0.35; postweighting standardized differences ranged from -0.09 to 0.07). In propensity-weighted data, omentoplasty was not associated with differential adjusted risk of anastomotic leak (13.2% vs 14.3%; P = .83), major morbidity (27.9% vs 32.6%; P = .44), or mortality (6.7% vs 4.8%; P = .61)., Conclusions: Within the limits of our sample size and statistical approach, our study failed to find evidence that anastomotic omentoplasty during esophagectomy after neoadjuvant chemoradiation reduced anastomotic leak rate or need for leak-related reoperation., (Copyright © 2020. Published by Elsevier Inc.)

Background and Objectives: Lymph node harvest during esophagectomy has been associated with improved survival for esophageal cancer but the value of enhanced lymph node harvest following complete pathologic response (pCR) is debated. This study investigated if increasing lymph node harvest in esophageal cancer patients with a pCR after neoadjuvant therapy and esophagectomy is associated with improved survival., Methods: We queried the National Cancer Data Base for patients with esophageal cancer between 2004 and 2014 who underwent neoadjuvant chemotherapy or chemoradiation therapy followed by esophagectomy found to have pCR. Multivariable Cox modeling was utilized to evaluate the impact of increasing lymph node counts on overall survival (OS)., Results: A total of 1373 patients met inclusion criteria. A National Comprehensive Cancer Network compliant lymphadenectomy of ≥15 nodes was associated with improved survival (66.7% vs 51.1%; P < .001). Cox modeling showed that the first node cutoff to demonstrate a statistically significant improvement in OS was ≥7 nodes (hazard ratio [HR], 95% confidence interval [CI]: 0.81, 0.68-0.97; 5-year OS: 54.2%) with a trend of decreasing and statistically significant HRs until ≥25 nodes (HR, 95% CI: 0.52, 0.37-0.72; 5-year OS: 68.4%)., Conclusions: High negative node counts after neoadjuvant therapy and esophagectomy are associated with improved survival in patients with pCR., (© 2020 Wiley Periodicals, Inc.)

The surgical approach to giant paraesophageal hernia repair has evolved considerably, from an open approach to minimally invasive approaches. Laparoscopic and robotic-assisted approaches to giant paraesophageal hernia have been considered safe and are associated with less morbidity and mortality. Limited data exist comparing the efficacy between laparoscopic and robotic-assisted giant paraesophageal hernia repairs, but the benefits of robotic surgery include superior optics and freedom of motion, thus allowing surgeons to accomplish the key points in a successful repair without compromising patient outcomes., (Copyright © 2019 Elsevier Inc. All rights reserved.)

Objectives: Sublobar resection (SLR) for early non-small-cell lung carcinoma (NSCLC) has been shown to have a survival rate similar to that of lobectomy. Large-cell neuroendocrine carcinoma (LCNEC) of the lung, although treated like an NSCLC, has a poor prognosis compared to NSCLC. We sought to determine if outcomes are poor in patients with early stage LCNEC treated with SLR versus lobectomy., Methods: We searched for patients with pathological stage I LCNEC ≤3 cm within the National Cancer Database between 2004 and 2014. Propensity score matching was used to compare the 5-year overall survival rate of patients having SLR (wedge or segmentectomy) to that of patients having a lobectomy. Patients were matched for age, node sampling, comorbidity score, tumour size, insurance status and other factors. Patients who received neoadjuvant therapy were excluded. Kaplan-Meier methods were used for analysis., Results: A total of 1011 patients met the inclusion criteria: 263 were treated with SLR (223 wedges and 40 segmentectomies) and 748 patients, with lobectomy. Patients who received SLR were older, had more comorbidities and smaller tumours. On unadjusted Kaplan-Meier analysis, patients who had SLR had decreased 5-year overall survival compared to those who had a lobectomy (37.9% vs 56.6%, P < 0.001). Propensity score matching (1:1) across 12 demographic and tumour variables yielded 185 patients per group with 34 segmentectomies and 151 wedge resections in the SLR cohort. On Kaplan-Meier analysis of the matched cohort, patients who had SLR had a worse 5-year overall survival rate compared to those who had a lobectomy (41.5% vs 60.3%; P = 0.001)., Conclusions: SLR for early stage LCNEC is associated with a lower 5-year overall survival rate compared to lobectomy on unadjusted and propensity matched analyses., (© The Author(s) 2019. Published by Oxford University Press on behalf of the European Association for Cardio-Thoracic Surgery. All rights reserved.)

The diaphragm is an inconspicuous fibromuscular septum, and disorders may result in respiratory impairment and morbidity and mortality when untreated. Radiologists need to accurately diagnose diaphragmatic disorders, understand the surgical approaches to diaphragmatic incisions/repairs, and recognize postoperative changes and complications. Diaphragmatic defects violate the boundary between the chest and abdomen, with the risk of herniation and strangulation of abdominal contents. In our surgical practice, patients with diaphragmatic hernias present acutely with incarceration and/or strangulation. Bochdalek hernias are commonly diagnosed in asymptomatic older adults on computed tomography; however, when viscera or a large amount of fat herniates into the chest, surgical intervention is strongly advocated. Morgagni hernias are rare in adults and typically manifest acutely with bowel obstruction. Patients with traumatic diaphragm injury may have an acute, latent, or delayed presentation, and radiologists should be vigilant in inspecting the diaphragm on the initial and all subsequent thoracoabdominal imaging studies. Almost all traumatic diaphragm injury are surgically repaired. Finally, with porous diaphragm syndrome, fluid, air, and tissue from the abdomen may communicate with the pleural space through diaphragmatic fenestrations and result in a catamenial pneumothorax or large pleural effusion. When the underlying disorder cannot be effectively treated, the goal of surgical intervention is to establish the diagnosis, incite pleural adhesions, and close diaphragmatic defects. Diaphragmatic plication may be helpful in patients with eventration or acquired injuries of the phrenic nerve, as it can stabilize the affected diaphragm. Phrenic nerve pacing may improve respiratory function in select patients with high cervical cord injury or central hypoventilation syndrome.

Objectives: Typical carcinoids (TCs) are rare, slow-growing neoplasms, usually characterized by satisfactory surgical outcomes. Due to the rarity of TCs, international guidelines for the management of particular clinical presentations currently do not exist. In particular, non-anatomical resections (wedges) are sometimes advocated for Stage 1 TCs because of their indolent behaviour. The aim of this paper was to evaluate the most effective type of surgery for Stage 1 TCs, using the European Society of Thoracic Surgeons retrospective database of the Neuroendocrine Tumors of the Lung Working Group., Methods: We analysed the effect of surgical procedure on the survival of patients with Stage 1 TCs. Overall survival (OS) was calculated from the date of intervention. The cumulative incidence of cause-specific death (tumour- and non-tumour-related) was also estimated. The impact of the surgical procedure (i.e. lobectomy vs segmentectomy vs wedge resection) on survival was investigated using the Cox model with shared frailty (for OS, accounting for the within-centre correlation) and the Fine and Gray model (for cause-specific mortality) using the approach based on the multinomial propensity score. Effects were estimated including in the model the logit-transformed propensity scores of segmentectomy and wedge resection as covariates., Results: A total of 876 patients with Stage 1 TCs (569 women, 65%) were included in this study. The median age was 60 years (interquartile range 47-69). At the last follow-up, 66 patients had died: The 5-year OS rate was 94.3% [95% confidence interval (CI) 92.2-95.9]. The 5-year cumulative incidences of tumour- and non-tumour-related deaths were 2.4% (95% CI 1.4-3.9) and 3.9% (95% CI 2.5-5.6%), respectively. The analysis performed using the multinomial propensity score approach confirmed the significantly worse survival of patients treated with a wedge resection compared to those treated with a lobectomy (hazard ratio 2.01, 95% CI 1.09-3.69; P = 0.024). Similar effects of wedge resection are detectable for cause-specific deaths: tumour-related (hazard ratio 2.28, 95% CI 0.86-6.02; P = 0.096) and non-tumour-related (hazard ratio 1.74, 95% CI 0.89-3.40; P = 0.105)., Conclusions: In a large cohort of patients, we were able to demonstrate the superiority of anatomical surgical resection in Stage 1 TCs in terms of OS. This result should therefore be considered for future clinical guidelines for the management of TCs.

Objectives: Large-cell neuroendocrine carcinoma (LCNC) is a rare tumour characterized by aggressive biological behaviour and poor prognosis. Due to its rarity and the lack of randomized clinical trials, the best treatment is still under debate. Some recent reports indicate that adjuvant chemotherapy (CT) may have a beneficial effect on survival. Our goal was to evaluate this finding using a large series of patients with neuroendocrine tumours obtained from the European Society of Thoracic Surgeons database., Methods: Data for 400 patients with LCNC operated on in 14 thoracic surgery institutions worldwide between 1992 and 2014 were collected retrospectively. Overall survival was the primary endpoint; we used a multivariable Cox regression model to evaluate which clinical variables may influence patient outcomes; we also focused on the possible prognostic role of adjuvant CT. A propensity score (PS) analysis using the inverse probability of treatment weighting was also carried out., Results: The 3- and 5-year survival rates were 54.1% and 45%, respectively. With the multivariable model, we found that increasing age, Eastern Cooperative Oncology Group Performance Status ≥2 and advanced TNM stage were indicators of poor prognosis. Weak evidence of a higher overall survival in patients receiving adjuvant CT (adjusted hazard ratio 0.73; 95% confidence interval: 0.56-0.96, P  = 0.022) was observed., Conclusions: A trend towards benefit from adjuvant CT has been observed in patients with LCNC. Although surgical procedures remain the mainstay of curative options, combination with other treatments (e.g. neoadjuvant CT/radiotherapy) should be evaluated by future studies., (© The Author 2017. Published by Oxford University Press on behalf of the European Association for Cardio-Thoracic Surgery. All rights reserved.)

Objective: This study aims to assess the international practice of management of bronchial carcinoids., Materials & Methods: A survey designed by the Neuroendocrine Tumors of the Lung Working Group, was conducted among the members of the European Society of Thoracic Surgeons., Results: A total of 172 centers worldwide replied to the questionnaire. General agreement was observed concerning the use of anatomic resections and parenchyma-sparing surgery, the importance of lymphadenectomy, the adjuvant regimens in N(+) atypical carcinoids and the role of surgery for local recurrences. Controversies emerged in the use of nuclear medicine imaging and measurement of serum markers and on the timing of follow-up., Conclusion: This survey provides the largest international overview of the current practice in the management of bronchial carcinoids and identifies discrepancies that could be the focus of future investigations.

Introduction: Adequate lymphadenectomy is a fundamental aspect of oncologically sound gastrectomies. Robot-assisted laparoscopic gastrectomy is a minimally invasive alternative that allows functional imaging to be easily integrated to the surgical field and may aid in intraoperative identification of lymphovascular bundles., Methods: Indocyanine green application and near-infrared fluorescence imaging were used during robot-assisted laparoscopic gastrectomy as an adjunct for the identification of relevant lymph node basins in real time., Results: A total of 31 patients were included. Twenty-nine gastrectomies were performed for adenocarcinoma and two wedge resections for neuroendocrine tumors. The mean lymph node retrieval was twenty-nine (range 17-61) for adenocarcinoma and five for neuroendocrine tumors. In all cases, at least five lymph nodes were seen along the main nodal basins, which provided real time intraoperative feedback regarding lymph node identification. Average time for indocyanine green application and functional imaging was less than 10 min., Conclusions: Near-infrared fluorescent imaging may provide an improved method to help visualize lymph nodes intraoperatively during robot-assisted laparoscopic gastrectomy, thus adding a potentially valuable adjunct for lymphadenectomy and overall lymph node retrieval. J. Surg. Oncol. 2016;113:768-770. © 2016 Wiley Periodicals, Inc., (© 2016 Wiley Periodicals, Inc.)

Objectives: Typical carcinoids (TCs) are uncommon, slow-growing neoplasms, usually with high 5-year survival rates. As these are rare tumours, their management is still based on small clinical observations and no international guidelines exist. Based on the European Society of Thoracic Surgeon Neuroendocrine Tumours Working Group (NET-WG) Database, we evaluated factors that may influence TCs mortality., Methods: Using the NET-WG database, an analysis on TC survival was performed. Overall survival (OS) was calculated starting from the date of intervention. Predictors of OS were investigated using the Cox model with shared frailty (accounting for the within-centre correlation). Candidate predictors were: gender, age, smoking habit, tumour location, previous malignancy, Eastern Cooperative Oncology Group (ECOG) performance status (PS), pT, pN, TNM stage and tumour vascular invasion. The final model included predictors with P ≤ 0.15 after a backward selection. Missing data in the evaluated predictors were multiple-imputed and combined estimates were obtained from five imputed data sets., Results: For 58 of 1167 TC patients vital status was unavailable and analyses were therefore performed on 1109 patients from 17 institutions worldwide. During a median follow-up of 50 months, 87 patients died, with a 5-year OS rate of 93.7% (95% confidence interval: 91.7-95.3). Backward selection resulted in a prediction model for mortality containing age, gender, previous malignancies, peripheral tumour, TNM stage and ECOG PS. The final model showed a good discrimination ability with a C-statistic equal to 0.836 (bootstrap optimism-corrected 0.806)., Conclusions: We presented and validated a promising prognostic model for TC survival, showing good calibration and discrimination ability. Further analyses are needed and could be focused on an external validation of this model., (© The Author 2015. Published by Oxford University Press on behalf of the European Association for Cardio-Thoracic Surgery. All rights reserved.)

Background: The current guidelines for follow-up care after treatment of non-small cell lung cancer recommend continued surveillance for detection of recurrent or metachronous disease. However, carcinoid tumors, especially those with a typical histologic profile, tend to be less aggressive. Our goal was to determine the patterns of relapse and the manner of detection of recurrences, to guide follow-up care after resection., Methods: Patients who underwent operations for pulmonary carcinoids at our institution were identified from a prospectively maintained database, and their medical records were reviewed for relapse patterns, detection methods, and outcomes., Results: A total of 337 patients who underwent resection between 1993 and 2010 were included, with a median follow-up time of 3.5 years. Typical and atypical carcinoids were present in 291 (86%) and 46 (14%) patients, respectively. Recurrences occurred in 21 patients (6%), with distant metastases in 20 patients (95%) and locoregional recurrence in only 1 patient. Most recurrences (15 [76%]) were not detected through scheduled surveillance imaging but after the presentation of symptoms (7 [33%]) or incidentally by studies performed for unrelated reasons (8 [38%]). The risk of recurrence increased with positive lymph nodes and atypical histologic type. Only 9 of 291 patients (3%) with typical carcinoids experienced recurrences, with a median time to recurrence of 4 years (range, 0.8-12 years). Conversely, 12 of 46 patients (26%) with atypical carcinoids experienced recurrences, with a median time to recurrence of 1.8 years (range, 0.2-7 years)., Conclusions: After complete resection, scheduled surveillance imaging failed to detect most recurrences. Recurrence was rare in patients with node-negative typical carcinoids. Given the low risk of recurrence and the unclear efficacy of surveillance imaging, routine surveillance imaging may not be warranted in this cohort., (Copyright © 2013 The Society of Thoracic Surgeons. Published by Elsevier Inc. All rights reserved.)

Objective: Large case series have demonstrated that video-assisted thoracoscopic surgery (VATS) lobectomy is feasible and safe. However, catastrophic intraoperative complications during VATS lobectomy requiring thoracotomy can be overlooked and are not reported in the current literature. We reviewed our experience to determine the frequency, management, and outcome of these complications., Methods: A systematic review of a prospective database was performed after institutional review board approval. All patients who underwent VATS lobectomy or a combination of any VATS procedure plus a thoracotomy were identified. A catastrophic complication was defined as an event that resulted in an additional unplanned major surgical procedure other than the planned lobectomy., Results: From 2002 to 2010, a total of 633 VATS lobectomies were performed and 610 patients had any VATS procedure plus a thoracotomy. Thirteen catastrophic complications were identified in 12 (1%) patients. We included all cases in which a VATS was performed as well as a thoractomy since this would include conversions as well. These cases included 3 main pulmonary arterial and 1 main pulmonary venous transection requiring reanastomosis, 3 unplanned pneumonectomies, 1 unplanned bilobectomy, 1 tracheoesophageal fistula, 1 membranous airway injury to the bronchus intermedius, 1 complete staple line disruption of the inferior pulmonary vein injury to the azygos/superior vena cava junction, and 1 splenectomy. There were no intraoperative deaths., Conclusions: Catastrophic intraoperative complications of VATS lobectomy are uncommon. However, awareness of the possibility of such injuries is critical to avoid them, and development of specific management strategies is necessary to limit morbidity should they occur., (Copyright © 2011 The American Association for Thoracic Surgery. Published by Mosby, Inc. All rights reserved.)

Objective: Reports have questioned the oncologic efficacy of video-assisted thoracoscopic surgery when compared with thoracotomy despite similar survival results. In response, we investigated the pattern of recurrent disease and the incidence of second primary tumors after lobectomy by means of video-assisted thoracoscopic surgery and thoracotomy., Methods: All patients who underwent lobectomy for clinical stage IA lung cancer determined by means of computed tomographic and positron emission tomographic analysis were identified from a prospective database at a single institution. All patients were selected for video-assisted thoracoscopic surgery or thoracotomy by an individual surgeon. Patients' characteristics, perioperative results, recurrences, and second primary tumors were recorded. Variables were compared by using Student's t test, the Pearson χ(2) test, and Fisher's exact test. A logistic regression model was constructed to identify variables influencing the development of recurrent disease or metachronous tumors., Results: From 2002 to 2009, 520 patients underwent lobectomy by means of video-assisted thoracoscopic surgery, and 652 underwent lobectomy by means of thoracotomy. Final pathological stage was similar in the video-assisted thoracoscopic surgery and thoracotomy groups. Logistic regression demonstrated a lower risk (odds ratio, 0.65; P = .01) of recurrent disease in patients undergoing video-assisted thoracoscopic surgery after adjusting for age, stage, sex, histology, tumor location, and synchronous primary tumors., Conclusions: Recurrence rates for video-assisted thoracoscopic surgery appear to be at least equivalent to those for thoracotomy. This study supports lobectomy by means of video-assisted thoracoscopic surgery as an oncologically sound technique., (Copyright © 2011 The American Association for Thoracic Surgery. Published by Mosby, Inc. All rights reserved.)

Purpose: Ectopic expression of squamous cell carcinoma-related oncogene (SCCRO or DCUN1D1) in NIH-3T3 cells induces invasion in vitro and produces highly invasive xenografts in nude mice with a propensity for regional lymphatical metastasis. The aim of this study was to identify the molecular mechanism underlying SCCRO-induced invasion and metastasis., Experimental Design: The molecular mechanism of SCCRO-mediated effects on matrix metalloproteinase-2 (MMP2) levels and activity were assessed using a combination of cell biological and molecular methods, including real-time PCR, reporter assay, RNA interference, and chromatin immunoprecipitation assay. Tumor specimens from primary upper aerodigestive tract carcinomas (n = 89) were examined for levels of SCCRO, MMP2, MMP9, MT1-MMP, TIMP1, and TIMP2 mRNA by real-time PCR., Results: Overexpression of SCCRO increases MMP2 levels and activity, which is required for SCCRO-induced invasion. Modified McKay assays reveal that SCCRO does not bind to the MMP2 promoter, suggesting that its transcriptional effects are indirect. Deletion or mutation of the activator protein-2 (AP2) and p53 binding element within the MMP2 promoter abrogates SCCRO-driven activation. Ectopic expression of SCCRO increases AP2 levels and promotes the binding of p53 to the MMP2 promoter. Consistent with these findings, SCCRO and MMP2 are coexpressed (P<0.0001; r(2)=0.58; 95% confidence interval, 0.46-0.69) in primary (upper aerodigestive tract) carcinomas (n=89), and this coexpression is associated with an increased prevalence of regional nodal metastasis (P=0.04; relative risk, 1.53)., Conclusions: SCCRO-induced invasion involves activation of MMP2 transcription in an AP2- and p53-dependent manner. SCCRO is a potential marker for metastatic progression in affected cancers.

Chromosomal amplification at 3q is common to multiple human cancers, but has a specific predilection for squamous cell carcinomas (SCC) of mucosal origin. We identified and characterized a novel oncogene, SCC-related oncogene (SCCRO), which is amplified along the 3q26.3 region in human SCC. Amplification and overexpression of SCCRO in these tumors correlate with poor clinical outcome. The importance of SCCRO amplification in malignant transformation is established by the apoptotic response to short hairpin RNA against SCCRO, exclusively in cancer cell lines carrying SCCRO amplification. The oncogenic potential of SCCRO is underscored by its ability to transform fibroblasts (NIH-3T3 cells) in vitro and in vivo. We show that SCCRO regulates Gli1--a key regulator of the hedgehog (HH) pathway. Collectively, these data suggest that SCCRO is a novel component of the HH signaling pathway involved in the malignant transformation of squamous cell lineage.

Somatic mutations in the tyrosine kinase (TK) domain of the epidermal growth factor receptor (EGFR) gene are reportedly associated with sensitivity of lung cancers to gefitinib (Iressa), kinase inhibitor. In-frame deletions occur in exon 19, whereas point mutations occur frequently in codon 858 (exon 21). We found from sequencing the EGFR TK domain that 7 of 10 gefitinib-sensitive tumors had similar types of alterations; no mutations were found in eight gefitinib-refractory tumors (P = 0.004). Five of seven tumors sensitive to erlotinib (Tarceva), a related kinase inhibitor for which the clinically relevant target is undocumented, had analogous somatic mutations, as opposed to none of 10 erlotinib-refractory tumors (P = 0.003). Because most mutation-positive tumors were adenocarcinomas from patients who smoked <100 cigarettes in a lifetime ("never smokers"), we screened EGFR exons 2-28 in 15 adenocarcinomas resected from untreated never smokers. Seven tumors had TK domain mutations, in contrast to 4 of 81 non-small cell lung cancers resected from untreated former or current smokers (P = 0.0001). Immunoblotting of lysates from cells transiently transfected with various EGFR constructs demonstrated that, compared to wild-type protein, an exon 19 deletion mutant induced diminished levels of phosphotyrosine, whereas the phosphorylation at tyrosine 1092 of an exon 21 point mutant was inhibited at 10-fold lower concentrations of drug. Collectively, these data show that adenocarcinomas from never smokers comprise a distinct subset of lung cancers, frequently containing mutations within the TK domain of EGFR that are associated with gefitinib and erlotinib sensitivity.

Purpose: Gene expression profiling has been shown to be a valuable tool for prognostication and identification of cancer-associated genes in human malignancies. We aimed to identify potential prognostic marker(s) in non-small cell lung cancers using global gene expression profiles., Experimental Design: Twenty-one previously untreated patients with non-small cell lung cancer were analyzed using the Affymetrix GeneChip high-density oligonucleotide array and comparative genomic hybridization. Identified candidate genes were validated in an independent cohort of 45 patients using quantitative real-time reverse transcription-PCR and Western blot analyses. Follow-up data for these patients was collected and used to assess outcome correlations., Results: Hierarchical clustering analysis yielded three distinct subgroups based on gene expression profiling. Cluster I consisted of 4 patients with adenocarcinoma and 1 with squamous cell carcinoma (squamous cell carcinoma); clusters II and III consisted of 6 and 10 patients with squamous cell carcinoma, respectively. Outcome analysis was performed on the cluster groups containing solely squamous cell carcinoma, revealing significant differences in disease-specific survival rates. Moreover, patients having a combination of advanced Tumor-Node-Metastasis stage and assigned to the poor prognosis cluster group (cluster II) had significantly poorer outcomes. Comparative genomic hybridization analysis showed recurrent chromosomal losses at 1p, 3p, 17, 19, and 22 and gains/amplifications at 3q, 5p, and 8q, which did not vary significantly between the cluster groups. We internally and externally validated a subset of 11 cluster II (poor prognosis)-specific genes having corresponding chromosomal aberrations identified by comparative genomic hybridization as prognostic markers in an independent cohort of patients with lung squamous cell carcinoma identifying CSNK2A1 and C1-Inh as independent predictors of outcome., Conclusion: CSNK2A1 and C1-Inh are independent predictors of survival in lung squamous cell carcinoma patients and may be useful as prognostic markers.