Industry Sponsorship Bias in Collagenase Clinical Trials for Dupuytren Disease: A Meta-analysis.

BACKGROUND: Collagenase clostridium histolyticum (collagenase) was introduced in 2010 creating a nonoperative treatment option for Dupuytren disease with promising results in sponsored clinical trials. A meta-analysis was performed to investigate industry sponsorship bias. METHODS: A systematic review of collagenase treatment of Dupuytren contracture was conducted. Articles containing mesh terms including "microbial collagenase" and "Dupuytren's contracture" were searched and limited to only clinical trials with similar protocols for inclusion. Meta-analysis of treatment endpoints of correction of contracture to 0-5 degrees after first and last injection was conducted comparing sponsored versus nonsponsored studies. RESULTS: Sixteen of the 29 identified articles met criteria for inclusion. Nonsponsored studies reported a significantly higher rate of meeting the primary treatment endpoint compared to sponsored studies after single injection for all joints (69.6% vs 56% P < 0.01), metacarpophalangeal joint (96% vs 64% P < 0.01), and proximal interphalangeal joint (67% vs 36% P = 0.011). The correction in contracture rates was similar between groups with studies evaluating more than one injection. CONCLUSIONS: Nonsponsored studies published higher success rates in meeting the primary endpoint of full correction after single injection than sponsored studies; however, similar results with multiple injections. This study demonstrated that sponsored studies of collagenase produced highly powered studies that may be reliably depended on for evidence-based clinical application.

Surgical Repair vs Stent for Esophageal Perforation: A Multi-institutional Database Analysis.

BACKGROUND: Endoscopic esophageal stenting is used as an alternative to surgical repair for esophageal perforation. Multi-institutional studies supporting stenting are lacking. The purpose of this study was to compare the outcomes of surgical repair and esophageal stenting in patients with esophageal perforation using a nationally representative database. We hypothesized that mortality between these approaches would not be different. METHODS: The Premier Healthcare Database was used to compare adult inpatients with esophageal perforation receiving either surgical repair or esophageal stenting from 2009 to 2019. Patients receiving intervention ≤7 days of admission were included in the analysis. Patients receiving both stent and repair on the same day were excluded. The composite outcome of interest was death or discharge to hospice. Logistic regression was used to evaluate independent predictors of death or hospice, adjusting for comorbidities. RESULTS: There were 2543 patients with esophageal perforation identified who received repair (1314 [51.7%]) or stenting (1229 [48.3%]). Stenting increased from 7.0% in 2009 to 78.1% in 2019. Patients receiving repair were more likely to be female and White and had fewer Elixhauser comorbidities. Death or discharge to hospice was more common after stent (134/1314 [10.2%] repair vs 199/1229 [16.2%] stent; P < .001); however, after adjustment for comorbidities, logistic regression suggested that death or hospice discharge was similar between approaches (stent vs repair: odds ratio, 1.074; 95% CI, 0.81-1.42; P = .622). Hospital length of stay was shorter after stenting (stent vs repair coefficient, -4.09; P < .001). CONCLUSIONS: In patients with esophageal perforation, the odds for death or discharge to hospice were similar for esophageal stenting compared with surgical repair.

Erratum for Musgrove et al., "Professional Development for Early Career DBER Scholars through In-Person and Virtual Career Panel Workshops".

[This corrects the article DOI: 10.1128/jmbe.00190-21.].

Morphological Phenotyping of Organotropic Brain- and Bone-Seeking Triple Negative Metastatic Breast Tumor Cells.

Triple negative breast cancer (TNBC) follows a non-random pattern of metastasis to the bone and brain tissue. Prior work has found that brain-seeking breast tumor cells display altered proteomic profiles, leading to alterations in pathways related to cell signaling, cell cycle, metabolism, and extracellular matrix remodeling. Given the unique microenvironmental characteristics of brain and bone tissue, we hypothesized that brain- or bone-seeking TNBC cells may have altered morphologic or migratory phenotypes from each other, or from the parental TNBC cells, as a function of the biochemical or mechanical microenvironment. In this study, we utilized TNBC cells (MDA-MB-231) that were conditioned to metastasize solely to brain (MDA-BR) or bone (MDA-BO) tissue. We quantified characteristics such as cell morphology, migration, and stiffness in response to cues that partially mimic their final metastatic niche. We have shown that MDA-BO cells have a distinct protrusive morphology not found in MDA-P or MDA-BR. Further, MDA-BO cells migrate over a larger area when on a collagen I (abundant in bone tissue) substrate when compared to fibronectin (abundant in brain tissue). However, migration in highly confined environments was similar across the cell types. Modest differences were found in the stiffness of MDA-BR and MDA-BO cells plated on collagen I vs. fibronectin-coated surfaces. Lastly, MDA-BO cells were found to have larger focal adhesion area and density in comparison with the other two cell types. These results initiate a quantitative profile of mechanobiological phenotypes in TNBC, with future impacts aiming to help predict metastatic propensities to organ-specific sites in a clinical setting.

Professional Development for Early Career DBER Scholars through In-Person and Virtual Career Panel Workshops.

In discipline-based education research (DBER), early career scholars, such as graduate students and postdoctoral researchers, observe a slew of possible career pathways. Yet, there is a lack of opportunities to learn about such pathways, particularly when transitioning from traditional science, technology, engineering, or math (STEM) disciplinary training into a DBER position. Thus, the DBER Scholars-in-Training Professional Development subcommittee was created within the Society for the Advancement of Biology Education Research (SABER) community to develop a collection of workshops that would serve the greatest professional development needs of early career scholars entering DBER. Through a series of surveys disseminated over multiple years, early career scholars expressed interest in better navigating their career options, which led to the development of the career panel workshop, held during the 2019 and 2020 SABER Annual National Conferences. In this report, we explore the development, implementation, and results of two career panel workshops and compare and contrast the 2019 in-person workshop with the 2020 virtual workshop. We also offer our insights on the value of the career workshop, discuss the next steps, and explore valuable resources for those planning on organizing similar events.

A programmable encapsulation system improves delivery of therapeutic bacteria in mice.

Living bacteria therapies have been proposed as an alternative approach to treating a broad array of cancers. In this study, we developed a genetically encoded microbial encapsulation system with tunable and dynamic expression of surface capsular polysaccharides that enhances systemic delivery. Based on a small RNA screen of capsular biosynthesis pathways, we constructed inducible synthetic gene circuits that regulate bacterial encapsulation in Escherichia coli Nissle 1917. These bacteria are capable of temporarily evading immune attack, whereas subsequent loss of encapsulation results in effective clearance in vivo. This dynamic delivery strategy enabled a ten-fold increase in maximum tolerated dose of bacteria and improved anti-tumor efficacy in murine models of cancer. Furthermore, in situ encapsulation increased the fraction of microbial translocation among mouse tumors, leading to efficacy in distal tumors. The programmable encapsulation system promises to enhance the therapeutic utility of living engineered bacteria for cancer.

Factors influencing quality of lymphadenectomy in minimally invasive esophagectomy: a US-based analysis.

NCCN guidelines suggest that at least 15 lymph nodes (LN) should be evaluated at the time of esophagectomy to consider the lymphadenectomy 'adequate'. Despite these guidelines, this may not always be achieved in practice. The purpose of this study was to determine factors associated with adequate lymphadenectomy among patients receiving minimally invasive esophagectomy (MIE). Patients receiving MIE in the National Cancer Database from 2010 to 2016 were identified. Patients with metastatic disease were excluded. The primary endpoint was adequate lymphadenectomy, defined as >15 or greater LN evaluated. Factors associated with adequate lymphadenectomy and overall survival were evaluated in univariable and multivariable analyses. Categorical variables were assessed using chi-squared, and continuous variables were assessed with rank-sum test. Survival was evaluated using the Kaplan-Meier method. A total of 6,539 patients underwent MIE between 2010 and 2016 (5,024 thoracoscopic-laparoscopic MIE and 1,515 robotic-assisted MIE). A total of 3,527 patients (53.9%) received adequate lymphadenectomy. Receiving MIE at an academic center (odds ratio [OR] 1.37, 95% confidence interval [CI] 1.15-1.63, P < 0.001), institutional volume of MIE (OR 1.01, 95% CI 1.008-1.011, P < 0.001), and presence of clinical nodal disease (OR 1.17, 95%CI 1.02-1.33, P = 0.025) were associated with adequate lymphadenectomy. Patients with >15 LN removed had increased overall survival (46.6 vs. 41.5 months, P < 0.001). Adequate lymphadenectomy (hazard ratio [HR] 0.77, 95%CI 0.71-0.85, P < 0.001), receiving surgery at an academic center (HR 0.87, 95%CI 0.78-0.96, P = 0.007) and private insurance status (HR 0.88, 95%CI 0.81-0.98, P = 0.02) were independently associated with improved survival. Nearly half of patients receiving MIE do not receive adequate lymphadenectomy as defined by NCCN guidelines. Receiving MIE at an academic center with high procedural volume and the presence of nodal disease were independently associated with adequate lymphadenectomy. Adequate lymphadenectomy was associated with improved survival. These findings suggest that providers performing esophagectomy should follow guideline-based recommendations for lymphadenectomy.

Rhinovirus C replication is associated with the endoplasmic reticulum and triggers cytopathic effects in an in vitro model of human airway epithelium.

The clinical impact of rhinovirus C (RV-C) is well-documented; yet, the viral life cycle remains poorly defined. Thus, we characterized RV-C15 replication at the single-cell level and its impact on the human airway epithelium (HAE) using a physiologically-relevant in vitro model. RV-C15 replication was restricted to ciliated cells where viral RNA levels peaked at 12 hours post-infection (hpi), correlating with elevated titers in the apical compartment at 24hpi. Notably, infection was associated with a loss of polarized expression of the RV-C receptor, cadherin-related family member 3. Visualization of double-stranded RNA (dsRNA) during RV-C15 replication revealed two distinct replication complex arrangements within the cell, likely corresponding to different time points in infection. To further define RV-C15 replication sites, we analyzed the expression and colocalization of giantin, phosphatidylinositol-4-phosphate, and calnexin with dsRNA. Despite observing Golgi fragmentation by immunofluorescence during RV-C15 infection as previously reported for other RVs, a high ratio of calnexin-dsRNA colocalization implicated the endoplasmic reticulum as the primary site for RV-C15 replication in HAE. RV-C15 infection was also associated with elevated stimulator of interferon genes (STING) expression and the induction of incomplete autophagy, a mechanism used by other RVs to facilitate non-lytic release of progeny virions. Notably, genetic depletion of STING in HAE attenuated RV-C15 and -A16 (but not -B14) replication, corroborating a previously proposed proviral role for STING in some RV infections. Finally, RV-C15 infection resulted in a temporary loss in epithelial barrier integrity and the translocation of tight junction proteins while a reduction in mucociliary clearance indicated cytopathic effects on epithelial function. Together, our findings identify both shared and unique features of RV-C replication compared to related rhinoviruses and define the impact of RV-C on both epithelial cell organization and tissue functionality-aspects of infection that may contribute to pathogenesis in vivo.

Enhancing the tropism of bacteria via genetically programmed biosensors.

Engineered bacteria for therapeutic applications would benefit from control mechanisms that confine the growth of the bacteria within specific tissues or regions in the body. Here we show that the tropism of engineered bacteria can be enhanced by coupling bacterial growth with genetic circuits that sense oxygen, pH or lactate through the control of the expression of essential genes. Bacteria that were engineered with pH or oxygen sensors showed preferential growth in physiologically relevant acidic or oxygen conditions, and reduced growth outside the permissive environments when orally delivered to mice. In syngeneic mice bearing subcutaneous tumours, bacteria engineered with both hypoxia and lactate biosensors coupled through an AND gate showed increased tumour specificity. The multiplexing of genetic circuits may be more broadly applicable for enhancing the localization of bacteria to specified niches.

Robotic Approach Has Improved Outcomes for Minimally Invasive Resection of Mediastinal Tumors.

BACKGROUND: The optimal minimally invasive surgical approach to mediastinal tumors is unknown. There are limited reports comparing the outcomes of resection with robotic-assisted thoracoscopic surgery (RATS) and video-assisted thoracoscopic surgery (VATS) surgery. We hypothesized that patients who underwent RATS would have improved outcomes. METHODS: The National Cancer Database was queried for all patients who underwent a minimally invasive surgical approach for any mediastinal tumor from 2010 to 2016. Patients were determined to have an adverse composite outcome if they had any of the adverse perioperative outcomes: conversion to open procedure, 90-day mortality, 30-day readmission, and positive pathologic margins. Secondary outcomes of interest were length of stay and overall survival. Multivariable logistic regression was used to assess likelihood of having a composite adverse outcome based on surgical approach. RESULTS: The study included 856 patients: 402 (47%) underwent VATS and 454 (53%) underwent RATS. RATS resections were associated with fewer conversions (4.9% vs 14.7%, P < .001), fewer positive margins (24.3% vs 31.6%, P = .02), shorter length of stay (3.8 days vs 4.3 days, P = .01), and fewer composite adverse events (36.7% vs 51.3%, P < .001). Multivariate analysis showed RATS (odds ratio, 0.44; P < .001) was independently associated with a decreased likelihood of a composite adverse outcome, even among tumors exceeding 4 cm (odds ratio, 0.45; P = .001). Overall survival was similar between the 2 groups. CONCLUSIONS: Among patients who underwent a minimally invasive surgical approach for a mediastinal tumor, RATS had fewer adverse outcomes than VATS, even for tumors 4 cm or larger. These data suggests that RATS may be the preferred technique for patients who are candidates for minimally invasive resection of mediastinal tumors.

Wedge Resection Offers Similar Survival to Segmentectomy for Typical Carcinoid Tumors.

Current guidelines recommend anatomic lung resection of typical bronchopulmonary carcinoids. Typical carcinoid tumors have excellent prognosis and sublobar resection has been associated with noninferior long-term survival. It's unclear whether wedge resection is acceptable for small typical carcinoid tumors. We hypothesize there is no difference in survival between wedge resection and segmentectomy for Stage I typical bronchopulmonary carcinoid tumors. Using the National Cancer Database from 2010 to 2016, we identified clinical T1N0M0 typical bronchopulmonary carcinoid tumors by wedge resection or segmentectomy. Short-term outcomes included length of stay, lymph nodes evaluated, pathologic node status, positive margin status, and 90-day mortality. Primary outcome was overall survival and estimated using Kaplan-Meier survival analysis. 821 patients were identified: 677 receiving wedge resection, 144 receiving segmentectomy. Segmentectomy was more commonly performed in an academic setting (70.0% vs 57.3%, P = 0.005). The mean tumor size for segmentectomy was 1.7 cm versus 1.4 cm for wedge resection (P < 0.001). There was no difference in LOS, positive margin status, and 90-day mortality between groups. There were significantly more lymph nodes evaluated in segmentectomy patients (median 4 vs 0, P < 0.001), but there was no difference in positive lymph node status (5.3% vs 2.6%, P = 0.165). The OS was similar between wedge and segmental resection (P = 0.613): 3-year survival (93.5% vs 92.8%) and 5-year survival (83.8% vs 84.9%). Wedge resection and segmentectomy have similar survival for Stage I typical bronchopulmonary carcinoids in a large national database. This analysis suggests nonanatomic, parenchymal-sparing resection should be considered an appropriate alternative for Stage I typical bronchopulmonary carcinoids.

Facilitating Constructive Discussions of Difficult Socio-Scientific Issues.

Discussion can be an important and powerful tool in efforts to build a more diverse, equitable, and inclusive future for STEM (i.e., science, technology, engineering, and mathematics). However, facilitating discussions on difficult, complex, and often uncomfortable issues, like racism and sexism, can feel daunting. We outline a series of steps that can be used by educators to facilitate productive discussions that empower everyone to listen, contribute, learn, and ultimately act to transform STEM.

Non-bacterial thrombotic endocarditis and coronary thrombectomy in a patient with metastatic small cell lung carcinoma.

A 66-year-old Caucasian man was initially admitted with a metastatic small cell lung carcinoma, hyponatraemia and obstructive pneumonia. His transthoracic echocardiogram (TTE) was normal. Ten days after admission, he was diagnosed with a non-ST segment elevation myocardial infarction (MI). Both a repeated TTE and a transoesophageal echocardiogram identified thickened, myxomatous mitral valve leaflet tips with small, mobile masses identified as vegetations, and new, eccentric, severe mitral regurgitation. Subsequent cardiac catheterisation recorded thrombotic occlusion of the right coronary artery. Successful coronary thrombectomy was carried out, but the patient died. A diagnosis of non-bacterial thrombotic endocarditis leading to coronary embolisation and MI was made. The clinical course and treatment choices are discussed.

Photodynamic Priming Modulates Endothelial Cell-Cell Junction Phenotype for Light-activated Remote Control of Drug Delivery.

The blood-brain barrier (BBB) remains a major obstacle for drug delivery to the central nervous system. In particular, the tight and adherens junctions that join the brain capillary endothelial cells limit the diffusion of various molecules from the bloodstream into the brain. Photodynamic priming (PDP) is a non-cytotoxic modality that involves light activation of photosensitizers to photochemically modulate nearby molecules without killing the cells. Here we investigate the effects of sub-lethal photochemistry on junction phenotype (i.e., continuous, punctate, or perpendicular), as well as the BBB permeability in a transwell model of human brain microvascular endothelial cells (HBMECs). We showed that PDP decreases the continuous junction architecture by ~20%, increases the perpendicular junction architecture by ~40%, and has minimal impact on cell morphology in HBMECs. Furthermore, transwell permeability assay revealed that PDP improves the HBMEC permeability to dextran or nanoliposomes by up to 30-fold for 6-9 days. These results suggest that PDP could safely reverse the mature brain endothelial junctions without killing the HBMECs. This study not only emphasizes the critical roles of PDP in the modulation junction phenotype, but also highlights the opportunity to further develop PDP-based combinations that opens the cerebrum endothelium for enhanced drug transporter across the BBB.

Outcomes of robotic esophagectomies for esophageal cancer by hospital volume: an analysis of the national cancer database.

BACKGROUND: Robotic minimally invasive esophagectomies (RMIE) have been associated with superior outcomes; however, it is unclear if these are specific to robotic technique or are present only at high-volume institutions. We hypothesize that low-volume RMIE centers would have inferior outcomes. METHODS: The National Cancer Database (NCDB) identified patients receiving RMIE from 2010 to 2016. Based on the total number of RMIE performed by each hospital system, the lowest quartile performed ≤ 9 RMIE over the study period. Ninety-day mortality, number of lymph nodes evaluated, margins status, unplanned readmissions, length of stay (LOS), and overall survival were compared. Regression models were used to account for confounding. RESULTS: 1565 robotic esophagectomies were performed by 212 institutions. 173 hospitals performed ≤ 9 RMIE (totaling 478 operations over the study period, 30.5% of RMIE) and 39 hospitals performed > 9 RMIE (1087 operations, 69.5%). Hospitals performing > 9 RMIE were more likely to be academic centers (90.4% vs 66.2%, p < 0.001), have patients with advanced tumor stage (65.3% vs 59.8%, p = 0.049), andadministered preoperative radiation (72.8% vs 66.3%, p = 0.010). There were no differences based on demographics, nodal stage, or usage of preoperative chemotherapy. On multivariable regressions, hospitals performing ≤ 9 RMIE were associated with a greater likelihood of experiencing a 90-day mortality, a reduced number of lymph nodes evaluated, and a longer LOS; however, there was no association with rates of positive margins or unplanned readmissions. Median overall survival was decreased at institutions performing ≤ 9 RMIE (37.3 vs 51.5 months, p < 0.001). Multivariable Cox regression demonstrated an association with poor survival comparing hospitals performing ≤ 9 to > 9 RMIE (HR 1.327, p = 0.018). CONCLUSION: Many robotic esophagectomies occur at institutions which performed relatively few RMIE and were associated with inferior short- and long-term outcomes. These data argue for regionalization of robotic esophagectomies or enhanced training in lower volume hospitals.

Surgery following neoadjuvant chemoradiation therapy in clinical N3 esophageal cancer results in improved survival: a propensity-matched analysis.

Esophageal cancer patients with extensive nodal metastases have poor survival, and benefit of surgery in this population is unclear. The aim of this study is to determine if surgery after neoadjuvant chemoradiotherapy (nCRT) improves overall survival (OS) in patients with clinical N3 (cN3) esophageal cancer relative to chemoradiation therapy (CRT) alone. The National Cancer Database was queried for all patients with cN3 esophageal cancer between 2010 and 2016. Patients who met inclusion criteria (received multiagent chemotherapy and radiation dose ≥30 Gy) were divided into two cohorts: CRT alone and nCRT + surgery. 769 patients met inclusion criteria, including 560 patients who received CRT alone, and 209 patients who received nCRT + surgery. The overall 5-year survival was significantly lower in the CRT alone group compared to the nCRT + surgery group (11.8% vs 18.0%, P < 0.001). A 1:1 propensity matched cohort of CRT alone and nCRT + surgery patients also demonstrated improved survival associated with surgery (13.11 mo vs 23.1 mo, P < 0.001). Predictors of survival were analyzed in the surgery cohort, and demonstrated that lymphovascular invasion was associated with worse survival (HR 2.07, P = 0.004). Despite poor outcomes of patients with advanced nodal metastases, nCRT + surgery is associated with improved OS. Of those with cN3 disease, only 27% underwent esophagectomy. Given the improved OS, patients with advanced nodal disease should be considered for surgery. Further investigation is warranted to determine which patients with cN3 disease would benefit most from esophagectomy, as 5-year survival remains low (18.0%).

Does Timing of Robotic Esophagectomy Adoption Impact Short-Term Postoperative Outcomes?

BACKGROUND: Robotic esophagectomies are increasingly common and are reported to have superior outcomes compared with an open approach; however, it is unclear if all institutions can achieve such outcomes. We hypothesize that early adopters of robotic technique would have improved short-term outcomes. METHODS: The National Cancer Database (2010-2016) was used to identify robotic esophagectomies. Early adopters were defined as programs which performed robotic esophagectomies in 2010-2011, late adopters in 2012-2013. Outcomes of esophagectomies performed between 2014 and 2016 were compared and included length of stay, number of lymph nodes evaluated, readmission, conversion rate, and 90-day mortality. Multivariable regressions, accounting for robotic esophagectomy volume, were used to control for confounding factors. RESULTS: There were 37 early adopters and 35 late adopters. Between 2014 and 2016, 683 robotic esophagectomies were performed: 446 (65.3%) by early adopters and 237 (34.7%) by late adopters. Early adopters were more likely to be academic programs (96.2 versus 72.8%, P < 0.01). Other clinical and demographic variables were similar. Late adopters were found to have decreased a number of lymph nodes evaluated (coefficient -2.407, P = 0.004) compared with early adopters. There were no significant differences in length of stay, readmissions, rate of positive margins, conversion from robotic to open, or 90-day mortality. CONCLUSIONS: When accounting for robotic esophagectomy volume, late adoption of robotic esophagectomy was associated with a reduced lymph node harvest, but other postoperative outcomes were similar. These data suggest that programs can safely start new robotic esophagectomy programs, but must ensure an adequate case load.

Vascularized Composite Allotransplantation in Burn Reconstruction: Systematic Review and Meta-analysis.

Vascularized composite allotransplantation has been successfully employed for burn reconstruction since 2003. However, its safety in this population has been questioned due to high levels of alloimmunization from burn care-related tissue exposures. To investigate this, a systematic review of vascularized composite allotransplantation employed for burn reconstruction was conducted, evaluating literature from January 2000 to September 2019. Articles containing vascularized composite allotransplantation, composite tissue allotransplantation, and burn reconstructive surgery were included; articles without published outcomes were excluded. Observational meta-analysis of pooled mortality and acute rejection episodes relative to allograft type (face vs extremity) and reconstruction type (burn vs non-burn) was performed. Twenty-four of the 63 identified articles met the criteria for inclusion, with 5 more articles added after secondary review. To date, 152 allotransplantations have been performed in 117 patients: 45 face transplants and 107 extremity transplants. Of these, 34 (22%) were performed for burn reconstruction in 25 patients (21%) with an overall higher 1-year mortality rate (12.0% vs 1.1%, P = .030). Of these deaths, 75% received three or more simultaneous allografts. Additionally, more episodes of acute rejection occurred compared to non-burn patients (4.4 vs 2.4, P = .035). Vascularized composite allotransplantation performed for burn reconstruction was found to be associated with a greater risk of 1-year mortality and nearly twice the number of episodes of acute rejection. Future studies should seek to identify unique risk factors of burn patients undergoing this operation and evaluate the relationship between antigenic burden and surgical outcomes.

Robotic minimally invasive esophagectomy provides superior surgical resection.

INTRODUCTION: Robotic minimally invasive esophagectomy (RMIE) and "traditional" minimally invasive esophagectomy techniques (tMIE) have reported superior outcomes relative to open techniques. Differences in the outcomes of these two approaches have not been examined. We hypothesized that short-term outcomes of RMIE would be superior to tMIE. METHODS AND PROCEDURES: The National Cancer Database was used to analyze outcomes of patients undergoing RMIE and tMIE from 2010 to 2016. Patients with clinical metastatic disease were excluded. Trends in the number of procedures performed with each approach were described using linear regression testing. Primary outcome of interest was 90-day mortality rate. Secondary outcomes of interest were positive surgical margin rate, number of lymph nodes (LN) removed, adequate lymphadenectomy (> 15 LNs), length of hospitalization (LOS), readmission rate, and conversion to open rate. Outcomes of RMIE and tMIE were compared using Wilcoxon rank sum test and chi square test as appropriate. Multivariable regression was also performed to reduce the impact of differences in the cohorts of patients receiving RMIE and tMIE. RESULTS: 6661 minimally invasive esophagectomies were performed from 2010 to 2016 (1543/6661 (23.2%) RMIE and 5118/6661 (76.8%) tMIE). Over the study period, the proportion of RMIE increased from 10.4% (64/618) in 2010 to 27.2% (331/1216) in 2016 (p < 0.001) (Fig. 1). The primary outcome of 90-day mortality was similar between RMIE and tMIE (92/1170 (7.4%) vs 305/4148 (7.9%), p = 0.558) (Table 2). RMIE and tMIE also had similar readmission rate (6.3 vs 7%, p = 0.380). There was no difference between the cohorts based on sex, age, race, insurance, and tumor size. The cohorts of patients receiving RMIE and tMIE differed in that RMIE patients had lower rates of elevated Charlson scores, were more likely to be treated at an academic institution, had a higher rate of advanced clinical T-stage and clinical nodal involvement, and had received neoadjuvant therapy. In a univariate analysis, RMIE had a lower rate of positive margin (3.9 vs 6.1%, p = 0.001), more mean lymph nodes evaluated (16.6 ± 9.74 vs 16.1 ± 10.08 p = 0.018), lower conversion to open rate (5.4 vs 11.4%, p < 0.001), and a shorter mean length of stay (12.1 ± 10.39 vs 12.8 ± 11.18 days, p < 0.001). In multivariable analysis, RMIE was associated with lower risk of conversion to open (OR 0.51, 95% CI: 0.37-0.70, p < 0.001) and lower rate of positive margin (OR 0.62, 95% CI: 0.41-0.93, p = 0.021).). Additionally, in a multivariable logistic regression, RMIE demonstrated superior adequate lymphadenectomy (> 15 LNs) (OR 1.18, 95% CI 1.02-1.37, p < 0.032). CONCLUSION: In the National Cancer Database, robotic esophagectomy is associated with superior rate of conversion to open and positive surgical margin status. We speculate enhanced dexterity and visualization of RMIE facilitates intraoperative performance leading to improvement in these outcomes.

Conversion from thoracoscopic to open pneumonectomy is not associated with short- or long-term mortality.

BACKGROUND: Thoracoscopic pneumonectomy commonly requires conversion to thoracotomy. We hypothesize that conversion would lead to worse short- and long-term outcomes compared with operations completed thoracoscopically. METHODS: The National Cancer Database identified patients who underwent a pneumonectomy from 2010 to 2016. Trends in conversion were described using linear regression. Multivariable regression of factors associated with conversion was performed. Short-term outcomes included duration of stay, number of lymph nodes harvested, margin status, readmission, and 90-day mortality. Long-term outcome was evaluated as overall survival. RESULTS: A total of 8,037 patients underwent a pneumonectomy. The rate of attempted thoracoscopic pneumonectomies increased from 11% to 22% (P < .001) and the rate of conversion decreased from 39% to 33% (P = .011). On multivariable analysis, a greater patient comorbidity index and pathologic nodal-stage 2 disease were associated with an increased rate of conversion. The mean number of lymph nodes evaluated was greater as was the duration of stay in the conversion group, but conversion to open thoracotomy was not associated with positive surgical margins, readmission rate, 90-day mortality, or survival. CONCLUSION: Thoracoscopic pneumonectomy is performed with increasing frequency and decreasing conversion rate. Conversion is associated with a greater duration of stay but other short- and long-term outcomes are similar. This observation suggests minimal harm in conversion from minimally invasive to open pneumonectomy.