Chimeric antigen receptor T-cell therapy for T-cell acute lymphoblastic leukemia.

Chimeric antigen receptor (CAR) T-cell therapy is a new and effective treatment for patients with hematologic malignancies. Clinical responses to CAR T cells in leukemia, lymphoma, and multiple myeloma have provided strong evidence of the antitumor activity of these cells. In patients with refractory or relapsed B-cell acute lymphoblastic leukemia (ALL), the infusion of autologous anti-CD19 CAR T cells is rapidly gaining standard-of-care status and might eventually be incorporated into frontline treatment. In T-ALL, however, leukemic cells generally lack surface molecules recognized by established CAR, such as CD19 and CD22. Such deficiency is particularly important, as outcome is dismal for patients with T-ALL that is refractory to standard chemotherapy and/or hematopoietic stem cell transplant. Recently, CAR T-cell technologies directed against T-cell malignancies have been developed and are beginning to be tested clinically. The main technical obstacles stem from the fact that malignant and normal T cells share most surface antigens. Therefore, CAR T cells directed against T-ALL targets might be susceptible to self-elimination during manufacturing and/or have suboptimal activity after infusion. Moreover, removing leukemic cells that might be present in the cell source used for CAR T-cell manufacturing might be problematic. Finally, reconstitution of T cells and natural killer cells after CAR T-cell infusion might be impaired. In this article, we discuss potential targets for CAR T-cell therapy of T-ALL with an emphasis on CD7, and review CAR configurations as well as early clinical results.

Airway and Systemic Immunoglobulin Profiling and Immune Response in Adult Asthma.

INTRODUCTION: Immunoglobulins play a vital role in host immune response and in the pathogenesis of conditions like asthma. Therapeutic agents such as monoclonal antibodies target specific elements of the asthmatic inflammatory cascade. Decisions to utilize these medications are often based on systemic inflammatory profiling without direct insight into the airway inflammatory profile. We sought to investigate the relationship between immunoglobulin and cytokine profiles in the airway and systemic immune compartments of adult asthmatics. METHODS: Blood sampling and bronchoscopy with bronchoalveolar lavage (BAL) were performed in 76 well-defined adult asthmatics. Antibody and cytokine profiles were measured in both BAL and serum using ELISA and quantibody arrays. RESULTS: There was no relationship between BAL and serum levels of IgE. This is of significance in an asthma population. For some analytes, correlation analysis was significant (P < 0.05) indicating representativeness of our cohort and experimental setup in those cases. Nevertheless, the predictive power (r2) of the BAL-to-serum comparisons was mostly low except for TNF-α (r2 = 0.73) when assuming a simple (linear) relationship. CONCLUSION: This study highlights the importance of sample site when investigating the roles of immunoglobulins and cytokines in disease pathogenesis and suggests that both localized and systemic immune responses are at play. The prescription of asthma monoclonal therapy is generally based on systemic evaluation of cytokine and immunoglobulin levels. Our research suggests that this approach may not fully reflect the pathophysiology of the disease and may provide insight into why some patients respond to these targeted therapies while others do not.

Utilization of an Endobronchial Blocker Through a Double-Lumen Tube as Rescue for Inadequate One-Lung Ventilation.

Failure to provide one-lung ventilation can prohibit minimally invasive thoracic surgeries. Strategies for one-lung ventilation include double-lumen endotracheal tubes or endobronchial blockers, but rarely both. Inability to provide lung isolation after double-lumen endotracheal tube placement requires troubleshooting and sometimes the use of extra equipment. This case describes using a unique Y-shaped endobronchial blocker placed through a left-sided double-lumen endotracheal tube after failure to achieve lung isolation with a double-lumen endotracheal tube alone.

Quality of Life and Real-time Patient Experience During Neoadjuvant Therapy: A Prospective Cohort Study.

OBJECTIVE: To use a customized smartphone application to prospectively measure QOL and the real-time patient experience during neoadjuvant therapy (NT). BACKGROUND: NT is increasingly used for patients with localized gastrointestinal (GI) cancers. There is little data assessing patient experience and quality of life (QOL) during NT for GI cancers. METHODS: Patients with GI cancers receiving NT were instructed on using a customized smartphone application through which the Functional Assessment of Cancer Therapy-General (FACT-G) questionnaire, a validated measure of health-related QOL, was administered at baseline, every 30 days, and at the completion of NT. Participants also tracked their moods and symptoms and used free-text journaling functionalities in the application. Mean overall and subsection health-related QOL scores were calculated during NT. RESULTS: Among 104 enrolled patients, the mean age was 60.5 ± 11.5 years and 55% were males. Common cancer diagnoses were colorectal (40%), pancreatic (37%), and esophageal (15%). Mean overall FACT-G scores did not change during NT ( P = 0.987). While functional well-being scores were consistently the lowest and social well-being scores the highest, FACT subscores similarly did not change during NT (all P > 0.01). The most common symptoms reported during NT were fatigue, insomnia, and anxiety (39.3%, 34.5%, and 28.3% of patient entries, respectively). Qualitative analysis of free-text journaling entries identified anxiety, fear, and frustration as the most common themes, but also the importance of social support systems and confidence in health care providers. CONCLUSIONS: While patient symptom burden remains high, results of this prospective cohort study suggest QOL is maintained during NT for localized GI cancers.

National learning curves among robotic thoracic surgeons in the United States: Quantifying the impact of procedural experience on efficiency and productivity gains.

OBJECTIVE: This study aims to characterize the aggregate learning curves of US surgeons for robotic thoracic procedures and to quantify the impact on productivity. METHODS: National average console times relative to cumulative case number were extracted from the My Intuitive application (Version 1.7.0). Intuitive da Vinci robotic system data for 56,668 lung resections performed by 870 individual surgeons between 2021 and 2022 were reviewed. Console time and hourly productivity (work relative value units/hour) were analyzed using linear regression models. RESULTS: Average console times improved for all robotic procedures with cumulative case experience (P = .003). Segmentectomy and thymectomy had the steepest initial learning curves with a 33% and 34% reduction of the average console time for proficient (51-100 cases) relative to novice surgeons (1-10 cases), respectively. The hourly productivity increase for proficient surgeons ranged from 11.4 work relative value units/hour (+26%) for lobectomy to 17.0 work relative value units/hour (+50%) for segmentectomy. At the expert level (101+ cases), average console times continued to decrease significantly for esophagectomy (-18%) and lobectomy (-23%), but only minimally for wedge resections (-1%) (P = .003). The work relative value units/hour increase at the expert level reached 50% for lobectomy and 40% for esophagectomy. Surgeon experience level, dual console use, system model, and robotic stapler use were factors independently associated with console time for robotic lobectomy. CONCLUSIONS: The aggregate learning curve for robotic thoracic surgeons in the United States varies significantly by procedure type and demonstrate continued improvements in efficiency beyond 100 cases for lobectomy and esophagectomy. Improvements in efficiency with growing experiences translate to substantial productivity gains.

Single Anesthesia Strategy for Definitive Management of Bilateral Ground Glass Opacities Using Robotic Bronchoscopic Localization and Resection.

This case series describes 2 patients who underwent a single anesthesia strategy for definitive management of bilateral ground-glass opacities harboring adenocarcinoma-spectrum lesions using robotic navigational localization paired with robotic thoracoscopic resection.

Thoracic Emergencies for the General Surgeon.

In this review article, we aim to provide an overview of common and uncommon general surgery thoracic emergencies as well as basic thoracic anatomy, common diagnostic tests, and operative positioning and access considerations. We also describe specific thoracic procedures. We hope that this article simplifies some of the challenges associated with the management of thoracic emergencies.

Comparison of Global Evaluative Assessment of Robotic Surgery with objective performance indicators for the assessment of skill during robotic-assisted thoracic surgery.

BACKGROUND: The Global Evaluative Assessment of Robotic Skills is a popular but ultimately subjective assessment tool in robotic-assisted surgery. An alternative approach is to record system or console events or calculate instrument kinematics to derive objective performance indicators. The aim of this study was to compare these 2 approaches and correlate the Global Evaluative Assessment of Robotic Skills with different types of objective performance indicators during robotic-assisted lobectomy. METHODS: Video, system event, and kinematic data were recorded from the robotic surgical system during left upper lobectomy on a standardized perfused and pulsatile ex vivo porcine heart-lung model. Videos were segmented into steps, and the superior vein dissection was graded independently by 2 blinded expert surgeons with Global Evaluative Assessment of Robotic Skills. Objective performance indicators representing categories for energy use, event data, movement, smoothness, time, and wrist articulation were calculated for the same task and compared to Global Evaluative Assessment of Robotic Skills scores. RESULTS: Video and data from 51 cases were analyzed (44 fellows, 7 attendings). Global Evaluative Assessment of Robotic Skills scores were significantly higher for attendings (P < .05), but there was a significant difference in raters' scores of 31.4% (defined as >20% difference in total score). The interclass correlation was 0.44 for 1 rater and 0.61 for 2 raters. Objective performance indicators correlated with Global Evaluative Assessment of Robotic Skills to varying degrees. The most highly correlated Global Evaluative Assessment of Robotic Skills domain was efficiency. Instrument movement and smoothness were highly correlated among objective performance indicator categories. Of individual objective performance indicators, right-hand median jerk, an objective performance indicator of change of acceleration, had the highest correlation coefficient (0.55). CONCLUSION: There was a relatively poor overall correlation between the Global Evaluative Assessment of Robotic Skills and objective performance indicators. However, both appear strongly correlated for certain metrics such as efficiency and smoothness. Objective performance indicators may be a potentially more quantitative and granular approach to assessing skill, given that they can be calculated mathematically and automatically without subjective interpretation.

Early Human Pathophysiological Responses to Exertional Hypobaric Decompression Stress.

INTRODUCTION: Consistent blood biomarkers of hypobaric (altitude) decompression stress remain elusive. Recent laboratory investigation of decompression sickness risk at 25,000 ft (7620 m) enabled evaluation of early pathophysiological responses to exertional decompression stress.METHODS: In this study, 15 healthy men, aged 20-50 yr, undertook 2 consecutive (same-day) ascents to 25,000 ft (7620 m) for 60 and 90 min, breathing 100% oxygen, each following 1 h of prior denitrogenation. Venous blood was sampled at baseline (T0), immediately after the second ascent (T8), and next morning (T24). Analyses encompassed whole blood hematology, endothelial microparticles, and soluble markers of cytokine response, endothelial function, inflammation, coagulopathy, oxidative stress, and brain insult, plus cortisol and creatine kinase.RESULTS: Acute hematological effects on neutrophils (mean 72% increase), eosinophils (40% decrease), monocytes (37% increase), and platelets (7% increase) normalized by T24. Consistent elevation (mean five-fold) of the cytokine interleukin-6 (IL-6) at T8 was proinflammatory and associated with venous gas emboli (microbubble) load. Levels of C-reactive protein and complement peptide C5a were persistently elevated at T24, the former by 100% over baseline. Additionally, glial fibrillary acidic protein, a sensitive marker of traumatic brain injury, increased by a mean 10% at T24.CONCLUSIONS: This complex composite environmental stress, comprising the triad of hyperoxia, decompression, and moderate exertion at altitude, provoked pathophysiological changes consistent with an IL-6 cytokine-mediated inflammatory response. Multiple persistent biomarker disturbances at T24 imply incomplete recovery the day after exposure. The elevation of glial fibrillary acidic protein similarly implies incomplete resolution following recent neurological insult.Connolly DM, Madden LA, Edwards VC, D'Oyly TJ, Harridge SDR, Smith TG, Lee VM. Early human pathophysiological responses to exertional hypobaric decompression stress. Aerosp Med Hum Perform. 2023; 94(10):738-749.

Decompression Sickness Risk in Parachutist Dispatchers Exposed Repeatedly to High Altitude.

INTRODUCTION: Occurrences of severe decompression sickness (DCS) in military parachutist dispatchers at 25,000 ft (7620 m) prompted revision of exposure guidelines for high altitude parachuting. This study investigated residual risks to dispatchers and explored the potential for safely conducting repeat exposures in a single duty period.METHODS: In this study, 15 healthy men, ages 20-50 yr, undertook 2 profiles of repeated hypobaric chamber decompression conducting activities representative of dispatcher duties. Phase 1 comprised two ascents to 25,000 ft (7620 m) for 60 and then 90 min. Phase 2 included three ascents first to 25,000 ft for 60 min, followed by two ascents to 22,000 ft (6706 m) for 90 min. Denitrogenation was undertaken at 15,000 ft (4572 m) with successive ascents separated by 1-h air breaks at ground level.RESULTS: At 25,000 ft (7620 m), five cases of limb (knee) pain DCS developed, the earliest at 29 min. Additionally, multiple minor knee "niggles" occurred with activity but disappeared when seated at rest. No DCS and few niggles occurred at 22,000 ft (6706 m). Early, heavy, and sustained bubble loads were common at 25,000 ft, particularly in older subjects, but lighter and later loads followed repeat exposure, especially at 22,000 ft.DISCUSSION: Parachutist dispatchers are at high risk of DCS at 25,000 ft (7620 m) commensurate with their heavy level of exertion. However, the potential exists for repeated safe ascents to 22,000 ft (6706 m), in the same duty period, if turn-around times breathing air at ground level are brief. Older dispatchers (>40 yr) with functional right-to-left (intracardiac or pulmonary) vascular shunts will be at risk of arterialization of microbubbles.Connolly DM, D'Oyly TJ, Harridge SDR, Smith TG, Lee VM. Decompression sickness risk in parachutist dispatchers exposed repeatedly to high altitude. Aerosp Med Hum Perform. 2023; 94(9):666-677.

Pulsed stimulated Brillouin microscopy.

Stimulated Brillouin scattering is an emerging technique for probing the mechanical properties of biological samples. However, the nonlinear process requires high optical intensities to generate sufficient signal-to-noise ratio (SNR). Here, we show that the SNR of stimulated Brillouin scattering can exceed that of spontaneous Brillouin scattering with the same average power levels suitable for biological samples. We verify the theoretical prediction by developing a novel scheme using low duty cycle, nanosecond pulses for the pump and probe. A shot noise-limited SNR over 1000 was measured with a total average power of 10 mW for 2 ms or 50 mW for 200 µs integration on water samples. High-resolution maps of Brillouin frequency shift, linewidth, and gain amplitude from cells in vitro are obtained with a spectral acquisition time of 20 ms. Our results demonstrate the superior SNR of pulsed stimulated Brillouin over spontaneous Brillouin microscopy.

ROCK STUDY in CF: sustained anti-inflammatory effects of lumacaftor-ivacaftor in sputum and peripheral blood samples of adult patients with cystic fibrosis-an observational study.

BACKGROUND: Previous studies showed that the combination of Cystic Fibrosis Transmembrane Conductance Regulator (CFTR) corrector and potentiator, lumacaftor-ivacaftor (LUMA-IVA) provides meaningful clinical benefits in patients with cystic fibrosis who are homozygous for the Phe508del CFTR mutation. However, little is known about the effect of LUMA-IVA on Proinflammatory Cytokines (PICs). OBJECTIVES: To investigate the impact of LUMA-IVA CFTR modulation on circulatory and airway cytokines before and after 12 months of LUMA-IVA treatment in a real-world setting. METHODS: We assessed both plasma and sputum PICs, as well as standard clinical outcomes including Forced Expiratory Volume in one second (FEV1) %predicted, Body Mass Index (BMI), sweat chloride and pulmonary exacerbations at baseline and prospectively for one year post commencement of LUMA-IVA in 44 patients with cystic fibrosis aged 16 years and older homozygous for the Phe508del CFTR mutation. RESULTS: Significant reduction in plasma cytokines including interleukin (IL)-8 (p<0.05), tumour necrosis factor (TNF)-α (p<0.001), IL-1ß (p<0.001) levels were observed while plasma IL-6 showed no significant change (p=0.599) post-LUMA-IVA therapy. Significant reduction in sputum IL-6 (p<0.05), IL-8 (p<0.01), IL-1ß (p<0.001) and TNF-α (p<0.001) levels were observed after LUMA-IVA therapy. No significant change was noted in anti-inflammatory cytokine IL-10 levels in both plasma and sputum (p=0.305) and (p=0.585) respectively. Clinically significant improvements in FEV1 %predicted (mean+3.38%, p=0.002), BMI (mean+0.8 kg/m2, p<0.001), sweat chloride (mean -19 mmol/L, p<0.001), as well as reduction in intravenous antibiotics usage (mean -0.73, p<0.001) and hospitalisation (mean -0.38, p=0.002) were observed after initiation of LUMA-IVA therapy. CONCLUSION: This real-world study demonstrates that LUMA-IVA has significant and sustained beneficial effects on both circulatory and airway inflammation. Our findings suggest that LUMA-IVA may improve inflammatory responses, which could potentially contribute to improved standard clinical outcomes.

Individualized approach to elexacaftor/tezacaftor/ivacaftor dosing in cystic fibrosis, in response to self-reported anxiety and neurocognitive adverse events: A case series.

The prevalence of mental health disorders is high among people with Cystic Fibrosis. The psychological symptoms in CF are associated with poor adherence, worse treatment outcomes, and greater health utilization/cost. Mental health and neurocognitive Adverse Events (AEs) have been reported with all available Cystic Fibrosis Transmembrane conductance Regulator (CFTR) modulators in small groups of patients. We report our experience with a dose reduction strategy in 10 of our patients on elexacaftor/tezacaftor/ivacaftor (7.9% of total number of patients) who self-reported developing intense anxiety, irritability, sleep disturbance and/or mental slowness after initiation of full dose treatment. Standard dose elexacaftor/tezacaftor/ivacaftor resulted in 14.3 points improvement in mean Percent Predicted Forced Expiratory Volume in 1 s (ppFEV1), and a mean difference in sweat chloride of -39.3 mmol/L. We initially discontinued and/or reduced therapy according to the AEs severity, with a subsequent planned dose escalation every 4-6 weeks guided by sustainability of clinical effectiveness, absence of AEs recurrence, and patients' preferences. Clinical parameters including lung function and sweat chloride were monitored for up to 12 weeks to assess ongoing clinical response to the reduced dose regimen. Dose reduction resulted in resolution of self-reported mental/psychological AEs, without loss of clinical effectiveness (ppFEV1 was 80.7% on standard dose, and 83.4% at 12 weeks on reduced dose; sweat chloride was 33.4 and 34 mmol/L on standard and reduced dose, respectively). Furthermore, in a subgroup of patients who completed 24 weeks of the reduced dose regimen, repeat low dose Computed Tomography imaging showed a significant response when compared to pre-initiation of elexacaftor/tezacaftor/ivacaftor.

Impact of Airway Virus in Severe Asthmatic Patients: A Pilot Study.

The lungs have their own microbiota which seems to be altered in disease processes such as asthma. Viral infection accounts for many asthma exacerbations. Little is known about the lung virome, and the role that viruses play in non-exacerbating asthmatics. We aimed to assess if detection of virus in bronchoscopy samples of asthmatic patients in a non-exacerbating state influences their asthma control and modulates airway cytokine composition. Patients were recruited from a specialist asthma clinic and underwent bronchoscopy with standardised bronchoalveolar lavage (BAL). Viral analysis was performed; cell differential and cytokine levels were measured. Forty-six samples were obtained of which 10.8% demonstrated evidence of airway virus, and 91.3% of patients in the cohort were classed as severe asthmatics. Oral steroid use was significantly higher in severe asthmatic patients with virus detected, and the forced expiratory volume in one second tended to be lower in the virus-detected group. It was also found that BAL interleukin-13 and tumor necrosis factor-α levels were significantly higher in severe asthmatic patients with virus detected. Our results suggest that in severe asthmatics in a non-exacerbating state, the presence of virus resulted in overall poorer asthma control. The pattern of cytokine elevation seen in asthmatic patients with virus detected may provide insight to the pathophysiology involved.

Use of digital measurement of medication adherence and lung function to guide the management of uncontrolled asthma (INCA Sun): a multicentre, single-blinded, randomised clinical trial.

BACKGROUND: The clinical value of using digital tools to assess adherence and lung function in uncontrolled asthma is not known. We aimed to compare treatment decisions guided by digitally acquired data on adherence, inhaler technique, and peak flow with existing methods. METHODS: A 32-week prospective, multicentre, single-blinded, parallel, randomly controlled trial was done in ten severe asthma clinics across Ireland, Northern Ireland, and England. Participants were 18 years or older, had uncontrolled asthma, asthma control test (ACT) score of 19 or less, despite treatment with high-dose inhaled corticosteroids, and had at least one severe exacerbation in the past year despite high-dose inhaled corticosteroids. Patients were randomly assigned in a 1:1 ratio to the active group or the control group, by means of a computer-generated randomisation sequence of permuted blocks of varying sizes (2, 4, and 6) stratified by fractional exhaled nitric oxide (FeNO) concentration and recruitment site. In the control group, participants were masked to their adherence and errors in inhaler technique data. A statistician masked to study allocation did the statistical analysis. After a 1-week run-in period, both groups attended three nurse-led education visits over 8 weeks (day 7, week 4, and week 8) and three physician-led treatment adjustment visits at weeks 8, 20, and 32. In the active group, treatment adjustments during the physician visits were informed by digital data on inhaler adherence, twice daily digital peak expiratory flow (ePEF), patient-reported asthma control, and exacerbation history. Treatment was adjusted in the control group on the basis of pharmacy refill rates (a measure of adherence), asthma control by ACT questionnaire, and history of exacerbations and visual management of inhaler technique. Both groups used a digitally enabled Inhaler Compliance Assessment (INCA) and PEF. The primary outcomes were asthma medication burden measured as proportion of patients who required a net increase in treatment at the end of 32 weeks and adherence rate measured in the last 12 weeks by area under the curve in the intention-to-treat population. The safety analyses included all patients who consented for the trial. The trial is registered with ClinicalTrials.gov, NCT02307669 and is complete. FINDINGS: Between Oct 25, 2015, and Jan 26, 2020, of 425 patients assessed for eligibility, 220 consented to participate in the study, 213 were randomly assigned (n=108 in the active group; n=105 in the control group) and 200 completed the study (n=102 in the active group; n=98 in the control group). In the intention-to-treat analysis at week 32, 14 (14%) active and 31 (32%) control patients had a net increase in treatment compared with baseline (odds ratio [OR] 0·31 [95% CI 0·15-0·64], p=0·0015) and 11 (11%) active and 21 (21%) controls required add-on biological therapy (0·42 [0·19-0·95], p=0·038) adjusted for study site, age, sex, and baseline FeNO. Three (16%) of 19 active and 11 (44%) of 25 control patients increased their medication from fluticasone propionate 500 µg daily to 1000 µg daily (500 µg twice a day; adjusted OR 0·23 [0·06-0·87], p=0·026). 26 (31%) of 83 active and 13 (18%) of 73 controls reduced their medication from fluticasone propionate 1000 µg once daily to 500 µg once daily (adjusted OR 2·43 [1·13-5·20], p=0·022. Week 20-32 actual mean adherence was 64·9% (SD 23·5) in the active group and 55·5% (26·8) in the control group (between-group difference 11·1% [95% CI 4·4-17·9], p=0·0012). A total of 29 serious adverse events were recorded (16 [55%] in the active group, and 13 [45%] in the control group), 11 of which were confirmed as respiratory. None of the adverse events reported were causally linked to the study intervention, to the use of salmeterol-fluticasone inhalers, or the use of the digital PEF or INCA. INTERPRETATION: Evidence-based care informed by digital data led to a modest improvement in medication adherence and a significantly lower treatment burden. FUNDING: Health Research Board of Ireland, Medical Research Council, INTEREG Europe, and an investigator-initiated project grant from GlaxoSmithKline.

Prevalence and Predictability of Occult Satellite Nodules in Clinical Stage Ia Non-small Cell Lung Cancer following Lobectomy.

INTRODUCTION: We sought to assess the prevalence and clinical predictors of satellite nodules in patients undergoing lobectomy for clinical stage Ia disease. PATIENTS AND METHODS: The National Cancer Database was queried for patients who underwent lobectomy for clinical stage cT1N0 NSCLC. Collaborative staging information was used to identify patients who were pathologically upstaged based on having separate tumor nodules in the same lobe as the primary tumor. Multivariable logistic regression was used to assess the association of clinical factors with the detection of separate nodules. RESULTS: A separate tumor nodule was recorded in 2.8% (n = 1284) of 45,842 clinical stage Ia patients treated with lobectomy or bilobectomy. Female gender (3.1% vs. male 2.5%; P = .002) and non-squamous histology (adenocarcinoma 3.2% and large cell neuroendocrine 3.0% vs. squamous cell 1.9% tumors; P < .001) were associated with the presence of separate nodules. The frequency increased for tumors larger than 3 cm (≤ 3cm, 2.7% vs. > 3cm, 3.8%; P < .001). Other factors associated with separate nodules were upper lobe location, pleural and/or lymphovascular invasion and occult lymph node disease. The best predictive model for separate nodules based on the available clinical variables resulted in an area under the curve of 0.645 (95% CI 0.629-0.660). CONCLUSION: Separate tumor nodules may be detected with a low but relatively consistent frequency across the spectrum of patients with clinical stage Ia NSCLC. The predictive ability using basic clinical factors in the database is limited.

Analysis of trends in perioperative outcomes in over 1000 robotic-assisted anatomic lung resections.

Robotic-assisted surgery is gaining popularity as a minimally invasive approach for anatomic lung resection. We investigated the temporal changes in case volume, costs, and postoperative outcomes for robotic-assisted anatomic lung resection in over 1000 cases. We reviewed our institutional STS database for patients who had undergone robotic-assisted lobectomy, bi-lobectomy, or segmentectomy as the primary procedure between years 2009-2021. The patients were divided into two groups: first 500 cases (n = 501) and second 500 cases (n = 500). Temporal trends of case volume, surgical indications, hospital length of stay, costs, and perioperative outcomes were analyzed. A total of 1001 patients were analyzed, of which 968 (96.7%) patients underwent robotic-assisted lobectomy, 21 (2.1%) patients underwent bi-lobectomy, 10 (1.0%) patients underwent segmentectomy, and 3 (0.3%) patients underwent sleeve lobectomy. Primary lung cancer was the most common indication (87.7%), followed by metastatic lung tumors (7.1%), and benign diagnosis (5.2%). The overall postoperative complication rate decreased from 46.1% for the first 500 cases compared to 29.6% for the second 500 cases (p < 0.0001). The median hospital length of stay was down trending, which was 4 days [IQR: 3-7] for the first 500 cases and 3 days [IQR: 3-5] (p = 0.0001) for the second. The inflation-adjusted direct and indirect hospital costs were significantly lower in the second 500 cases (p < 0.0001). The complications rates, hospital costs, and hospital length of stay for robotic-assisted anatomic pulmonary resection decreased significantly over time at a single institution. Continuous improvement in perioperative outcomes may be observed with increasing institutional experience.

Lymph Node Upstaging for Robotic, Thoracoscopic, and Open Lobectomy for Stage T2-3N0 Lung Cancer.

BACKGROUND: There may be equivalent efficacy of the lymph node evaluation for minimally invasive lobectomy compared with open lobectomy for stage I non-small cell lung cancer. We sought to compare the lymph node evaluation for lobectomy by approach for patients with larger tumors who are clinically node negative. METHODS: This retrospective study analyzed 24 257 patients with clinical stage T2-3N0M0 non-small cell lung cancer from the National Cancer Database. Inverse probability of treatment weighting (IPTW) was applied to balance baseline characteristics. The rates of pathologic lymph node upstaging were compared. A Cox multivariable regression model was performed to test the association with overall survival. RESULTS: After IPTW adjustment 20 834 patients were included in the analysis. Of these, 1996 patients underwent robotic lobectomy, 5122 patients underwent thoracoscopic lobectomy, and 13 725 patients underwent open lobectomy from 2010 to 2017. The IPTW-adjusted N1 upstaging rate was similar for robotic (11.79%), thoracoscopic (11.49%), and open (11.85%) lobectomy (P = .274). The adjusted N2 upstaging rates were 5.03%, 5.66%, and 6.15% for robotic, thoracoscopic, and open lobectomy, respectively (P = .274). On IPTW-adjusted multivariable analysis, robotic and thoracoscopic lobectomy were associated with improved survival compared with open lobectomy (P < .001). CONCLUSIONS: There was no significant difference in N1 and N2 lymph node upstaging rates between surgical approaches for patients with clinical stage T2-3N0 non-small cell lung cancer, indicating similarly effective lymph node evaluation. Overall survival after robotic and thoracoscopic lobectomy was significantly better compared with open lobectomy in this patient population with a high propensity for occult nodal disease.