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Objective: Our statewide thoracic quality collaborative has implemented multiple quality improvement initiatives to improve lung cancer nodal staging. We subsequently implemented a value-based reimbursement initiative to further incentivize quality improvement. We compare the impact of these programs to steer future quality improvement initiatives., Methods: Since 2016, our collaborative focused on improving lymph node staging for lung cancer by leveraging unblinded, hospital-level metrics and collaborative feedback. In 2021, a value-based reimbursement initiative was implemented with statewide yearly benchmark rates for (1) preoperative mediastinal staging for ≥T2N0 lung cancer, and (2) sampling ≥5 lymph node stations. Participating surgeons would receive additional reimbursement if either benchmark was met. We reviewed patients from January 2015 to March 2023 at the 21 participating hospitals to determine the differential effects on quality improvement., Results: We analyzed 6228 patients. In 2015, 212 (39%) patients had ≥5 nodal stations sampled, and 99 (51%) patients had appropriate preoperative mediastinal staging. During 2016 to 2020, this increased to 2253 (62%) patients and 739 (56%) patients, respectively. After 2020, 1602 (77%) patients had ≥5 nodal stations sampled, and 403 (73%) patients had appropriate preoperative mediastinal staging. Interrupted time-series analysis demonstrated significant increases in adequate nodal sampling and mediastinal staging before value-based reimbursement. Afterward, preoperative mediastinal staging rates briefly dropped but significantly increased while nodal sampling did not change., Conclusions: Collaborative quality improvement made significant progress before value-based reimbursement, which reinforces the effectiveness of leveraging unblinded data to a collaborative group of thoracic surgeons. Value-based reimbursement may still play a role within a quality collaborative to maintain infrastructure and incentivize participation., Competing Interests: Conflict of Interest Statement R.R. receives consulting fees from Intuitive, Genentech, AtriCure, Medtronic, and On Target Labs. All other authors reported no conflicts of interest. The Journal policy requires editors and reviewers to disclose conflicts of interest and to decline handling or reviewing manuscripts for which they may have a conflict of interest. The editors and reviewers of this article have no conflicts of interest., (Copyright © 2023 The American Association for Thoracic Surgery. Published by Elsevier Inc. All rights reserved.)

Objective: Conversion to thoracotomy continues to be a concern during minimally invasive lobectomy. The aim of this propensity-matched cohort study is to analyze the outcomes and risk factors of intraoperative conversion during video-assisted thoracoscopic surgery (VATS) and robotic lobectomy (RL)., Methods: Data from consecutive lobectomy cases performed for clinical stage IA to IIIA lung cancer was retrospectively collected from the Pulmonary Open, Robotic, and Thoracoscopic Lobectomy study consortium of 21 institutions from 2011 to 2019. The propensity-score method of inverse-probability of treatment weighting was used to balance the baseline characteristics across surgical approaches. Univariate logistic regression models were applied to test risk factors for conversion. Multivariable logistic regression analysis was conducted using a stepwise model selection method., Results: Seven thousand two hundred sixteen patients undergoing lobectomy were identified: RL (n = 2968), VATS (n = 2831), and open lobectomy (n = 1417). RL had lower conversion rate compared with VATS (3.6% vs 12.9%; P < .0001). In the multivariable regression model, tumor size and neoadjuvant therapy were the most significant risk factors for conversion, followed by prior cardiac surgery, congestive heart failure, chronic obstructive pulmonary disease, VATS approach, male gender, body mass index, and forced expiratory volume in 1 minute. Conversions for anatomical reasons were more common in VATS than RL (66.6% vs 45.6%; P = .0002); however, conversions for vascular reasons were more common in RL than VATS (24.8% vs 14%; P = .01). The rate of emergency conversions was comparable between RL and VATS (0.5% vs 0.7%; P = .25) with no intraoperative mortalities., Conclusions: Converted minimally invasive lobectomies were not associated with worse perioperative mortality compared with open lobectomy. Compared with VATS lobectomy, RL is associated with a lower probability of conversion in this propensity-score matched cohort study., (Copyright © 2022 The Authors. Published by Elsevier Inc. All rights reserved.)

Objectives: Although robotic-assisted thoracic surgery (RATS) provides improved dexterity, the effect of RATS on pain compared with video-assisted thoracoscopic surgery (VATS) or open lobectomy is poorly understood. This study evaluated acute and chronic pain following RATS, VATS, and open anatomic pulmonary resection., Methods: A retrospective review of 498 patients (502 procedures) who underwent RATS (74), VATS (227), and open (201) anatomic pulmonary resection including lobectomy and segmentectomy from 2010 to 2014 was performed to identify factors related to acute and chronic pain. Acute pain scores were analyzed over the first 9 postoperative days. Chronic pain was assessed using the validated PainDETECT survey., Results: There were no significant differences in acute or chronic pain between RATS and VATS. There was a significant decrease in acute pain for patients with minimally invasive surgery (P = .0004). Chronic numbness was significantly higher after open resection (25.5% vs 11.6%; P = .0269) but with no difference in other symptoms of chronic pain. Despite no significant difference in pain scores, 69.2% of patients who received RATS felt the approach affected pain versus 44.2% VATS (P = .0330). On multivariable analysis, younger age (P < .0001), female gender (P = .0364), and baseline narcotic use (P = .0142) were associated with acute pain, whereas younger age (P = .0021) and major complications (P = .0003) were associated with chronic numbness in patients who received MIS., Conclusions: Although minimally invasive approaches resulted in less acute pain and chronic numbness, there were no significant differences between RATS and VATS. In contrast, more RATS patients believed the approach affected their pain, suggesting a difference between reality and perception., (Copyright © 2017 The American Association for Thoracic Surgery. Published by Elsevier Inc. All rights reserved.)

Objective: To identify circulating tumor cells (CTCs) in the blood of patients with early-stage lung cancer and to show that sampling pulmonary vein (PV) blood using microfluidic chip technology will yield significantly more CTCs. Improving early detection of lung cancer is critical to improving lung cancer survival. Reproducible detection of CTCs is limited currently in early stage tumors., Methods: Patients undergoing pulmonary resection had PV blood drawn before resection. Peripheral blood was sampled at preoperative, intraoperative, and postoperative times. Samples were analyzed on microfluidic chips using antibody-based capture., Results: A total of 32 patients with primary lung cancer were evaluated. Twenty patients had 1 or more CTCs detected in at least 1 sample (62.5%). The mean number of CTCs from peripheral vein sources at the preoperative, intraoperative, and postoperative time points was 1.3, 1.9, and 0.6 respectively. The average number of CTCs in the PV was 340.0 (range, 0.0-5422.50; P > .01). When PV CTCs were present, the number of CTCs was correlated with pathological tumor size (P = .0236). The number of PV CTCs was not correlated with any other clinical feature (eg, smoking status, preoperative or postoperative stage). Furthermore, the number of PV CTCs was significantly higher when preoperative bronchoscopic biopsy was performed, compared with computed tomography-guided biopsy (P = .0311). Seven patients had evidence of CTC clusters, or microemboli., Conclusions: With a single vein draining the entire tumor basin, lung cancers are unique, allowing the high-yield isolation of CTCs from the PV. This method may facilitate future studies to improve the detection and analysis of early-stage lung CTCs., (Copyright © 2016 The American Association for Thoracic Surgery. Published by Elsevier Inc. All rights reserved.)

Objectives: Esophageal endoscopic ultrasound is now regarded as essential in the staging of esophageal carcinoma. There is an increasing trend toward endoluminal therapies (ie, endoscopic mucosal resection and radiofrequency ablation) for pre-cancer or early-stage cancers because of concerns of high morbidity associated with esophagectomy. This study reviews our institutional experience with preoperative endoscopic ultrasound staging of early esophageal cancers in patients who underwent an esophagectomy to evaluate the accuracy of staging by endoscopic ultrasound and how this affects treatment recommendations., Methods: A prospective esophagectomy database of all patients undergoing an esophagectomy for esophageal cancer at a single high-volume institution was retrospectively reviewed for patients with early-stage esophageal cancer. This study analyzed patients with clinical Tis to T1 disease, as predicted by preoperative endoscopic ultrasound, and correlated this with the pathologic stages after esophagectomy. The surgical outcomes were evaluated to assess the safety of esophagectomy as a treatment modality., Results: From 2005 to 2011, 107 patients (93 male, 14 female) with a mean age of 66 years (range, 39-91 years) were staged by preoperative endoscopic ultrasound to have esophageal high-grade dysplasia, carcinoma in situ, or T1 cancer and underwent an esophagectomy. Tumor depth was correctly staged by endoscopic ultrasound in only 39% (23/59) of pT1a tumors (invading into the lamina propria or muscularis mucosa) and 51% (18/35) of pT1b tumors (submucosal). Of the endoscopic ultrasound-staged cT1a-lpN0 lesions, there were positive lymph nodes in 15% of pathologic specimens (2/13). Patients with pT1a-mm lesions had a 9% rate of pathologic lymph node involvement (1/11), and those with pT1b tumors had a 17% rate of lymph node spread (6/35). Esophagectomy was performed in all 107 patients with a 30-day mortality rate of less than 1% (1/107)., Conclusions: The sensitivity and specificity of endoscopic ultrasound for determining true pathologic staging are poor for early-stage esophageal cancers. Lesions thought to be cT1a-lpN0 by endoscopic ultrasound have at least pN1 disease in 15% of cases. Endoluminal therapy of these lesions based on endoscopic ultrasound undertreats a significant number of patients. Esophagectomy is still the standard therapy for early-stage esophageal cancers in the majority of patients., (Copyright © 2014 The American Association for Thoracic Surgery. Published by Mosby, Inc. All rights reserved.)

Background: This study investigated the rate of contralateral papillary thyroid cancer (PTC) in low-risk PTC patients who had completion thyroidectomy, and were referred for radioactive iodine (RAI) therapy. The study sought predictors of contralateral disease and examined the impact of contralateral disease in RAI-treated patients., Methods: We reviewed 20 years of data from a prospective registry for 150 patients with PTC. These patients had undergone thyroid lobectomy, followed by completion thyroidectomy, and had been referred for RAI., Results: Of the 150 patients, 41% had PTC in the contralateral lobe. There was no difference in the rate of contralateral disease in low-risk patients (age <45 years, T1 tumors, lymph node-negative) compared with the remainder. There were no significant differences between patients with or without contralateral disease with respect to primary tumor size, mean age, time to completion thyroidectomy, or metastatic lymph node disease. Logistic regression analyses showed no histologic parameters that correlated with contralateral disease. There were no recurrence or survival differences in patients with or without contralateral disease after resection and RAI., Conclusions: The prevalence of tumor in the contralateral lobe of low-risk patients with PTC is significant and warrants consideration for completion thyroidectomy and radioiodine treatment. Our results, however, suggest that contralateral disease does not have an impact on recurrence or survival after treatment.

Background: The goal of this study was to evaluate the presence of lymph node metastasis in patients with T1 differentiated thyroid cancer (DTC) and determine prognostic significance for tumor recurrence and cancer-related death., Methods: From a prospective tumor registry, we reviewed data from 551 patients with DTC who underwent total or subtotal thyroidectomy and who had primary tumor size

Objective: Malignant pleural mesothelioma is notoriously refractory to aggressive multimodality therapy. Epidermal growth factor receptor expression has been observed on malignant pleural mesothelioma cells. Epidermal growth factor receptor-mediated signaling promotes tumorigenesis and metastasis of cancer cells. The purpose of this study is to evaluate the ability of the epidermal growth factor receptor tyrosine kinase inhibitor PD153035 to abrogate the expression of prometastasis phenotypes in malignant pleural mesothelioma cells in vitro., Methods: Epidermal growth factor receptor expression of malignant pleural mesothelioma cells and primary normal cells was quantitated by means of flow cytometry. PD153035-mediated growth inhibition was determined by means of 1-(4,5-Dimethylthiazol-2-yl)-3,5-diphenylformazan and clonogenic assays. Cell motility and invasion of extracellular matrix was evaluated with in vitro wound-healing and Matrigel invasion assays, respectively. Vascular epidermal growth factor levels in conditioned media were measured by using enzyme-linked immunosorbent assay., Results: Epidermal growth factor receptor expression was detected on all 6 cultured malignant pleural mesothelioma cells, with 4 of 6 having normal receptor expression and 2 of 6 overexpressing the receptor. PD153035 suppressed cell motility and cell invasion through a Matrigel membrane, regardless of the baseline epidermal growth factor receptor expression. Decreased vascular epidermal growth factor production and significant inhibition of growth only occurred in malignant pleural mesothelioma cells that overexpress epidermal growth factor receptor., Conclusions: Epidermal growth factor receptor tyrosine kinase inhibitor PD153035 significantly inhibited motility and invasion in malignant pleural mesothelioma cells in vitro, regardless of their epidermal growth factor receptor expression levels. Inhibition of epidermal growth factor receptor-dependent signaling might be a useful strategy to diminish malignant pleural mesothelioma recurrence after aggressive cytoreductive surgery.

Objective: Histone deacetylase inhibitors mediate a potent growth-inhibitory effect in cancer cells through induction of cell-cycle arrest and apoptosis. Moreover, these agents significantly induce transcriptional activation of nuclear factor kappaB, as well as p21 regulated by protein kinase C, and are thought to negatively influence the ability of histone deacetylase inhibitor to effectively mediate apoptosis. This study aimed to evaluate the effect of calphostin C (a protein kinase C inhibitor) on trichostatin A (a histone deacetylase inhibitor)-mediated upregulation of nuclear factor kappaB and p21 promotor transcriptional activity, as well as induction of apoptosis in lung and esophageal cancer cells., Methods: Cultured lung and esophageal cancer cells were treated with calphostin C and trichostatin A. Nuclear factor kappaB transcriptional activity was quantitated by using the nuclear factor kappaB-luciferase assay. Transcription of p21 gene and p21 protein levels was evaluated by using the p21 promoter-luciferase assay and the p21 enzyme-linked immunoassay, respectively. Apoptosis was evaluated by using the terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling-based ApoBrdU assay. Levels of expression of nuclear factor kappaB-dependent antiapoptotic and proapoptotic proteins were evaluated by means of Western blotting., Results: Exposure of lung or esophageal cancer cells to trichostatin A resulted in a dose- and cell-dependent 2-fold to greater than 20-fold increase of nuclear factor kappaB and p21 transcriptional activity. Treatment with trichostatin A and calphostin C led to a 50% to 90% decrease of trichostatin A- mediated upregulation of nuclear factor kappaB and p21 activation. Inhibition of nuclear factor kappaB activity resulted in significant reduction (30% to >99%) of trichostatin A- mediated activation of not only nuclear factor kappaB transcription but also p21 promotor activity. Importantly, 90% to 96% of thoracic cancer cells under-went apoptosis after exposure to the combination of trichostatin A plus calphostin C., Conclusion: Inhibition of protein kinase C abrogates trichostatin A-mediated upregulation of nuclear factor kappaB transcriptional activity and p21 expression that is associated with profound induction of apoptosis in lung or esophageal cancer cells. Protein kinase C might be a novel target for enhancing the efficacy of histone deacetylase inhibitor in cancer therapy.

Background: Cancer cells frequently exhibit resistance to the cytotoxic effect of tumor necrosis factor-related apoptosis-inducing ligand (TRAIL). Pretreatment of TRAIL-resistant cells with cisplatin sensitizes them to this ligand. Cisplatin also has been shown to enhance adenoviral transgene expression., Objective: This study aims to evaluate the ability of cisplatin to enhance the expression and the cytotoxic effect of the tumor-specific adenoviral vector Ad/gTRAIL, which expresses a green fluorescent protein-TRAIL fusion protein., Methods: Cultured cancer cells and normal human cells were infected with Ad/gTRAIL with or without cisplatin pretreatment. Adenoviral transgene expression was determined by using flow cytometry to measure green fluorescent protein fluorescence. Cytotoxicity was measured by using thiazolyl blue tetrazolium bromide assays and an apoptosis enzyme-linked immunosorbent assay kit., Results: Green fluorescent protein-TRAIL fusion protein expression was significantly enhanced by cisplatin pretreatment in cancer cells. Cisplatin treatment before Ad/gTRAIL infection resulted in a 2- to 12-fold increase in green fluorescent protein fluorescence intensity across cancer lines. Although Ad/gTRAIL induced mild cytotoxicity in all cancer lines (inhibitory concentration of 50% values of >500 pfu/cell), pretreatment with cisplatin resulted in a dose-dependent enhancement of Ad/gTRAIL-mediated cytotoxicity, as indicated by the drastic reduction of inhibitory concentration of 50% values to 4 to 42 pfu/cell in all cell lines. There was no cytotoxicity noted in normal cells treated with both cisplatin and Ad/gTRAIL., Conclusion: Cisplatin pretreatment enhances Ad/gTRAIL cytotoxicity in malignant cells while not affecting normal cells. The mechanisms underlying this effect might include both enhancement of the susceptibility of cisplatin-treated cells to TRAIL and cisplatin-mediated enhancement of TRAIL expression in Ad/gTRAIL infected cells. These findings provide a rationale for development of Ad/gTRAIL-based therapy for thoracic malignancies.