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The objective of this work was to delineate career progression and research productivity of women practicing cardiothoracic surgery in the academic setting.Cardiothoracic surgeons at the 79 accredited US cardiothoracic surgery training programs in 2020 were included in this cross-sectional analysis. Data regarding subspecialization, training, practice history, and publications were gathered from public sources including department websites, CTSNet, and Scopus.A total of 1065 surgeons (51.3% cardiac, 32.1% thoracic, 16.6% congenital) were identified. Women accounted for 10.6% (113) of the population (7.9% of cardiac, 15.5% of thoracic, 9.6% of congenital surgeons). The median number of cardiothoracic surgeons per institution was 12 (interquartile range [IQR], 10-17), with a median of 1 woman (IQR, 0-2). Fifteen of 79 programs (19%) had no women. Among women faculty 5.3% were clinical instructors, 51.3% were assistant professors, 23.0% were associate professors, 16.8% were full professors, and 3.5% had unspecified titles (vs 2.0%, 32.9%, 23.0%, 37.5%, and 4.6% among men, respectively; P.001). Women and men authored a comparable number of first-author (0.4 [IQR, 0.0-1.3] vs 0.5 [IQR, 0.0-1.1], P = .56) publications per year but fewer last-author (0.1 [IQR, 0.0-0.7] vs 0.4 [IQR, 0.0-1.3], P.0001) and total publications per year (2.7 [IQR, 1.0-6.2] vs 3.7 [IQR, 1.3-7.8], P = .05) than men. The H-index was lower for women than for men overall (8.0 [IQR, 3.0-15.0] vs 15.0 [IQR, 7.0-28.0], P.001) but was similar between men and women who had been practicing for 10 to 20 years.Gender disparities persist in academic cardiothoracic surgery. Efforts should be made to support women in achieving senior roles and academic productivity.

A variety of three-dimensional (3D) printing techniques and materials facilitate the creation of customized models that promise to improve surgical procedures and patient outcomes. Three-dimensional-printed models allow patients, trainees, and experienced surgeons to explore anatomy through direct visualization and tactile feedback. Although 3D-printed models serve a range of purposes including preoperative planning, education, skills refinement, patient-specific intraprocedural guides, and implants, much work remains to decrease the turnaround time and cost of printing models, collect long-term effectiveness data, and refine regulatory oversight of 3D printing in medicine.

BACKGROUND Enhanced recovery after surgery pathways in several specialties reduce length of stay, but accelerated discharge after thoracic surgery is not well characterized. This study tested the hypothesis that patients discharged on postoperative day 1 (POD1) after lobectomy for lung cancer have an increased risk of readmission. METHODS Patients who underwent a lobectomy for lung cancer between 2011 and 2019 in the American College of Surgeons National Surgical Quality Improvement Program database were identified. Readmission rates were compared between patients discharged on postoperative day 1 (POD 1) and patients discharged on POD 2 to 6. Early discharge and readmission predictors were evaluated using multivariable logistic regression analysis. RESULTS Only 854 (3.8%) of 22,585 patients who met inclusion criteria were discharged on POD 1, although POD 1 discharge rates increased from 2.3% to 8.1% (P < .001) from 2011 to 2019, respectively. Median hospitalization for patients discharged on POD 2 to 6 was 4 days (interquartile range, 3 to 5 days). Patients' characteristics associated with a lower likelihood of POD 1 discharge were increasing age, smoking, or a history of dyspnea, whereas a minimally invasive approach was the strongest predictor of early discharge (adjusted odds ratio, 5.42; P < .001). Readmission rates were not significantly different for the POD 1 and POD 2 to 6 groups in univariate analysis (6.0% vs 7.0%; P = .269). Further, POD 1 discharge was not a risk factor for readmission in multivariable analysis (adjusted odds ratio, 1.10; P = .537). CONCLUSIONS Select patients can be discharged on POD 1 after lobectomy for lung cancer without an increased readmission risk, a finding supporting this accelerated discharge target inclusion in lobectomy enhanced recovery after surgery protocols.

Tumor genotyping is not routinely performed in localized non–small cell lung cancer (NSCLC) due to lack of associations of mutations with outcome. Here, we analyze 232 consecutive patients with localized NSCLC and demonstrate that KEAP1 and NFE2L2 mutations are predictive of high rates of local recurrence (LR) after radiotherapy but not surgery. Half of LRs occurred in tumors with KEAP1/NFE2L2 mutations, indicating that they are major molecular drivers of clinical radioresistance. Next, we functionally evaluate KEAP1/NFE2L2 mutations in our radiotherapy cohort and demonstrate that only pathogenic mutations are associated with radioresistance. Furthermore, expression of NFE2L2 target genes does not predict LR, underscoring the utility of tumor genotyping. Finally, we show that glutaminase inhibition preferentially radiosensitizes KEAP1-mutant cells via depletion of glutathione and increased radiation-induced DNA damage. Our findings suggest that genotyping for KEAP1/NFE2L2 mutations could facilitate treatment personalization and provide a potential strategy for overcoming radioresistance conferred by these mutations.Significance:This study shows that mutations in KEAP1 and NFE2L2 predict for LR after radiotherapy but not surgery in patients with NSCLC. Approximately half of all LRs are associated with these mutations and glutaminase inhibition may allow personalized radiosensitization of KEAP1/NFE2L2-mutant tumors.This article is highlighted in the In This Issue feature, p. 1775

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Supplementary Figures 1-9

The impact of concomitant lung resection during esophagectomy on short-term outcomes is not well characterized. This study tests the hypothesis that lung resection at the time of esophagectomy is not associated with increased perioperative morbidity or mortality.Perioperative outcomes for esophageal cancer patients who underwent esophagectomy alone (EA) were compared to patients who had concurrent esophagectomy and lung resection (EL) using the NSQIP database between 2006-2017. Predictors of morbidity and mortality, including combined surgery, were evaluated using multivariable logistic regression.Among the 6,225 study patients, 6,068 (97.5%) underwent EA and 157 (2.5%) underwent EL. There were no differences in baseline characteristics between the two groups. Operating time for EL was longer than EA (median 416 versus 371 minutes, P0.01). Median length of stay was 10 d for both groups. Perioperative mortality was not significantly different between EL and EA patients (5.1% versus 2.8%, P = 0.08). EL patients had higher rates of postoperative pneumonia (22.3% versus 16.2%, P = 0.04) and sepsis (11.5% versus 7.1%, P = 0.03), however major complication rates overall were similar (40.8% versus 35.3%, P = 0.16). Combining lung resection with esophagectomy was not independently associated with increased postoperative morbidity (AOR 1.21 [95% CI 0.87-1.69]) or mortality (AOR 1.63 [95% CI 0.74-3.58]).Concurrent lung resection during esophagectomy is not associated with increased mortality or overall morbidity, but is associated with higher rates of pneumonia beyond esophagectomy alone. Surgeons considering combined lung resection with esophagectomy should carefully evaluate the patient's risk for pulmonary complications and pursue interventions preoperatively to optimize respiratory function.

Blurb: This cohort study assesses the number of women who were eligible for and underwent lung cancer screening among those who received mammograms at a single academic medical center.

Diaphragm plication (DP) improves pulmonary function and quality of life for those with diaphragm paralysis or dysfunction. It is unknown whether differing degrees of diaphragm dysfunction as measured by sniff testing affect results after plication.Patients who underwent minimally invasive DP from 2008 to 2019 were dichotomized based on sniff test results: paradoxical motion (PM) versus no paradoxical motion (NPM); the latter included normal, decreased, and no motion. Preoperative and postoperative pulmonary function testing (PFT) after DP was compared between groups. The impact of the diaphragm height index, a measure of diaphragm elevation, was also assessed.A total of 26 patients underwent preoperative sniff testing, DP, and postoperative PFT. Including all patients, DP resulted in a 17.8% ± 5.5% improvement in forced expiratory volume in 1 second (P.001), a 14.4% ± 5.3% improvement in forced vital capacity (P.001), and a 4.7% ± 4.6% improvement in the diffusing capacity of carbon monoxide (P = .539). There were greater improvements in the PM group (n = 16) compared with the NPM group (n = 10) for forced expiratory volume in 1 second (27.2% ± 6.0% versus 3.9% ± 6.2%; P = .017) and forced vital capacity (28.1% ± 5.3% versus -0.5% ± 3.3%; P = .001). There was no difference in the change in the diffusing capacity of carbon monoxide between groups. There were no differences between patients with PM and NPM in the postoperative course or complications. No value for diaphragm height index predicted improvement in PFT after DP.Patients with PM on sniff test have dramatically greater objective improvements in pulmonary function after plication compared with those without PM. Most patients without PM do not demonstrate improvement in standard PFT. Improvements in dyspnea require additional study.

Slide tracheoplasty is the standard technique to repair congenital long-segment tracheal stenosis. This operation most commonly requires median sternotomy, which has drawbacks in young children. We hypothesized that a transcervical approach without sternotomy would be feasible if done with a single-port robotic system.This proof-of concept study was performed in 2 small adult cadavers using a single-port robotic surgical system via a small neck incision. Relevant information, including operative time and details of operative technique, were recorded.Long-segment slide tracheoplasty was completed successfully in 2 cadavers using a small neck incision and a single-port robotic surgical system. Strengths and pitfalls of the technique were identified, including technical refinements from the first attempt to the second. Operative time for robotic mobilization, incision, and anastomosis of the trachea was comparable to standard open approaches.Small-incision transcervical slide tracheoplasty, assisted by a single-port surgical robotic system, is feasible in a human cadaver. More work is needed to determine safety and applicability in live patients, particularly in children.

Well-differentiated lung neuroendocrine tumors (NETs), also known as typical and atypical carcinoids, have a decreased incidence of lymph node (LN) and distant metastases compared to poorly differentiated lung NETs. We aimed to (i) examine the clinicopathologic features associated with LN involvement in lung carcinoids and (ii) describe the postoperative management of patients with LN metastases.We identified 98 patients who underwent surgical resection and lymph node sampling at Stanford University. We assessed the following and used AJCC staging version 7: clinical features (age, sex, race, prior malignancy, smoking history), tumor features (functional syndrome, histology, size, location, laterality), pre-operative workup performed (imaging and suspicion of LN metastases), surgery (nodes and stations sampled, margin status, surgical approach, and type of surgery), and recurrence outcome. These features were examined between patients with and without LN metastases using the Wilcoxon test (continuous variables) and Fisher's exact test (categorical variables).87 patients (89%) had typical carcinoid and 11 patients (11%) had atypical carcinoid. 17 patients were found to have at least one positive lymph node, with 11 having N1 disease and 6 having N2 disease. In the univariable analysis, patients with lymph node disease were more likely to have recurrence of lung carcinoid (29% vs. 6%, p=0.01). In the multivariable logistic regression, there was a trend towards performance of preoperative SSTR imaging and lymph node involvement (OR = 3.06, p=0.07). No patients received adjuvant therapy.We found a trend for the performance of SSTR imaging and association of lymph node metastases in both univariable and multivariable analysis. A large proportion (41%) of patients with lymph node positive disease had2 cm tumors. This suggests the potential importance of incorporating SSTR imaging into routine practice and not restricting the use of this staging modality in patients with small tumors.

BACKGROUND A Medicare effect has been described to account for increased health care utilization occurring at the age of 65 years. The existence of such an effect in cancer care, where it would be most likely to reduce mortality, has been unclear. METHODS Patients aged 61 to 69 years who were diagnosed with lung, breast, colon, or prostate cancer from 2004 to 2016 were identified with the Surveillance, Epidemiology, and End Results database and were dichotomized on the basis of eligibility for Medicare (61-64 vs 65-69 years). With age-over-age (AoA) percent change calculations, trends in cancer diagnoses and staging were characterized. After matching, uninsured patients who were 61 to 64 years old (pre-Medicare group) were compared with insured patients who were 65 to 69 years old (post-Medicare group) with respect to cancer-specific mortality. RESULTS In all, 134,991 patients were identified with lung cancer, 175,558 were identified with breast cancer, 62,721 were identified with colon cancer, and 238,823 were identified with prostate cancer. The AoA growth in the number of cancer diagnoses was highest at the age of 65 years in comparison with all other ages within the decade for all 4 cancers (P < .01, P < .001, P < .01, and P < .001, respectively). In a comparison of diagnoses at the age of 65 years with those in the 61- to 64-year-old cohort, the greatest difference for all 4 cancers was seen in stage I. In matched analyses, the 5-year cancer-specific mortality was worse for lung (86.3% vs 78.5%; P < .001), breast (32.7% vs 11.0%; P < .001), colon (57.1% vs 35.6%; P < .001), and prostate cancer (16.9% vs 4.8%; P < .001) in the uninsured pre-Medicare group than the insured post-Medicare group. CONCLUSIONS The age threshold of 65 years for Medicare eligibility is associated with more cancer diagnoses (particularly stage I), and this results in lower long-term cancer-specific mortality for all cancers studied. LAY SUMMARY Contributing to the current debate regarding Medicare for all, this study shows that the expansion of Medicare would improve cancer outcomes for the near elderly.

Strong for Surgery (S4S) is a public health campaign focused on optimizing patient health prior to surgery by identifying evidence-based modifiable risk factors. The potential impact of S4S bundled risk factors on outcomes after major surgery has not been previously studied. This study tested the hypothesis that a higher number of S4S risk factors is associated with an escalating risk of complications and mortality after major elective surgery in the VA population. The Veterans Affairs Surgical Quality Improvement Program (VASQIP) database was queried for patients who underwent major non-emergent general, thoracic, vascular, urologic, and orthopedic surgeries between the years 2008 and 2015. Patients with complete data pertaining to S4S risk factors, specifically preoperative smoking status, HbA1c level, and serum albumin level, were stratified by number of positive risk factors, and perioperative outcomes were compared. A total of 31,285 patients comprised the study group, with 16,630 (53.2%) patients having no S4S risk factors (S4S0), 12,323 (39.4%) having one (S4S1), 2,186 (7.0%) having two (S4S2), and 146 (0.5%) having three (S4S3). In the S4S1 group, 60.3% were actively smoking, 35.2% had HbA1c > 7, and 4.4% had serum albumin 7, and 27.4% had albumin

OBJECTIVES Sublobar resection is increasingly being utilized for early-stage lung cancers, but optimal management when final pathology shows unsuspected mediastinal nodal disease is unclear. This study tested the hypothesis that lobectomy has improved survival compared to sublobar resection for clinical stage IA tumours with occult N2 disease. METHODS The use of sublobar resection and lobectomy for patients in the National Cancer Database who underwent primary surgical resection for clinical stage IA non-small-cell lung cancer with pathologic N2 disease between 2010 and 2017 was evaluated using logistic regression. Survival was assessed with Kaplan–Meier analysis, log-rank test and Cox proportional hazards model. RESULTS A total of 2419 patients comprised the study cohort, including 320 sublobar resections (13.2%) and 2099 lobectomies (86.8%). Older age, female sex, smaller tumour size and treatment at an academic facility predicted the use of sublobar resection. Patients undergoing lobectomy had larger tumours (2.40 vs 2.05 cm, P CONCLUSIONS Clinical stage IA non-small-cell lung cancer patients with N2 disease on final pathology have similar long-term survival with either sublobar resection or lobectomy. Patients with occult N2 disease after sublobar resection may not require reoperation for completion lobectomy but should instead proceed to adjuvant chemotherapy.

The COVID-19 pandemic has disrupted components of traditional education with shifts toward virtual platforms. This report describes the virtual approach to basic surgical skills training during a high school program in the summers of 2020 and 2021.Two 2-week sessions were held by Zoom (Zoom Video Communications) with 99 students in 2020 and 198 students in 2021. Each student was sent surgical supplies and instruments. Interactive lectures were held each morning, and basic surgical skills instruction was provided each afternoon. After the session, survey links were distributed to students to complete an anonymous 37-item questionnaire regarding surgical skills confidence, simulation kit satisfaction, and technical difficulties.Of the 297 students, 270 (90.9%) completed the questionnaire, including 91 (91.9%) in 2020 and 179 (90.4%) in 2021. On a scale of 1 (fair) to 5 (excellent), students in 2020 and 2021 reported similar confidence in instrument handling (4-5: 90.0% vs 86.3%; P = .38), suturing skin (4-5: 88.9% vs 82.8%; P = .19), and thoracic aorta suturing (4-5: 73.3% vs 73.6%; P = .97). Students reported greater confidence in 2020 in knot tying (4-5: 98.9% vs 87.9%; P = .002), coronary vessel suturing (4-5: 82.2% vs 65.5%; P.001), and valve model suturing (4-5: 68.5% vs 50.3%; P = .005) than students in 2021. Students had similar satisfaction rates with the program (extremely or somewhat satisfied: 92.3% vs 86.0%; p = .51) between 2020 and 2021.Virtual education carries the potential for basic surgical skills training for a more widespread audience with less access to direct surgical education. Further research is needed to optimize teaching finer surgical skills.

Intracardiac paragangliomas most commonly arise from the left atrium and are often infiltrative and densely adherent to surrounding structures. Given their rarity, only scattered reports exist in the literature and standardized perioperative and surgical management is not well established. We describe a case of a 60-year-old woman with a mildly functioning intracardiac paraganglioma in which division of the superior vena cava improved exposure and enabled a complex limited resection. Further, we provide an overview of the diagnostic workup, perioperative medical management, surgical approach, and surveillance strategy in patients with these challenging tumors.

PURPOSE: The development of molecularly targeted tracers is likely to improve the accuracy of diagnostic, screening, and therapeutic tools. Despite the many therapeutic antibodies that are FDA-approved with known toxicity, only a limited number of antibody-dye conjugates have been introduced to the clinic. Thorough evaluation of the safety, stability and pharmacokinetics of antibody conjugates in the clinical setting compared to their parental components could accelerate the clinical approval of antibodies as agents for molecular imaging. Here we investigate the safety and stability of a near-infrared fluorescent dye (IRDye800CW) conjugated panitumumab, an approved therapeutic antibody, and report on the product stability, pharmacokinetics, adverse events, and QTc interval changes in patients. PROCEDURES: Panitumumab-IRDye800CW was made under good manufacturing practice (GMP) conditions in a single batch on March 26, 2014 and then evaluated over 4.5 years at 0, 3, and 6 months, and then at 6-month intervals thereafter. We conducted early phase trials in head and neck, lung, pancreas and brain cancers with panitumumab-IRDye800CW. Eighty-one patients scheduled to undergo standard of care surgery were infused with doses between 0.06mg/kg to 2.83mg/kg of antibody. Patient ECGs, blood samples, and adverse events were collected over 30-days post-infusion for analysis. RESULTS: 81 patients underwent infusion of the study drug at a range of doses. Six patients (7.4%) experienced an adverse event that was considered potentially related to the drug. The most common event was a prolonged QTc interval which occurred in three patients (3.7%). Panitumumab-IRDye800CW had two OOS results at 42 and 54 months, while meeting all other stability testing criteria. CONCLUSIONS: Panitumumab-IRDye800CW was safe and stable to administer over a 54-month window with a low rate of adverse events (7.4%) which is consistent with the rate associated with panitumumab alone. This data supports re-purposing therapeutic antibodies as diagnostic imaging agents with limited preclinical toxicology studies.

The extraordinary demands of managing the COVID-19 pandemic has disrupted the world's ability to care for patients with thoracic malignancies. As a hospital's COVID-19 population increases and hospital resources are depleted, the ability to provide surgical care is progressively restricted, forcing surgeons to prioritize among their cancer populations. Representatives from multiple cancer, surgical, and research organizations have come together to provide a guide for triaging patients with thoracic malignancies as the impact of COVID-19 evolves as each hospital.

Extended thymectomy has been proven to improve the course of myasthenia gravis. Retrospective studies demonstrate that several techniques for thymectomy achieve overlapping remission rates. We therefore compared perioperative outcomes and costs among 3 approaches to thymectomy: sternotomy, video and/or robot assisted, and transcervical.To ensure similar study groups, we excluded patients with4 cm or invasive tumors and those who underwent less than an extended thymectomy or concurrent procedures. Hospital costs were collected and analyzed by blinded finance personnel.The final study group consisted of 25 transcervical, 23 video/robot-assisted, and 14 sternotomy subjects. There was a higher incidence of myasthenia gravis in the transcervical and sternotomy groups (P0.001) and of thymoma in the video/robot-assisted and sternotomy groups (P = .002). Mean modified Charlson comorbidity score was higher for sternotomy (2.7 ± 2.1, mean ± SD) than transcervical (1.00 ± 0.58; P.001) and video/robot-assisted (1.13 ± 0.97; P = .001) procedures. There was no difference in complication rates between approaches (P = 0.828). The cost of transcervical thymectomy was 45% of the cost of sternotomy (P.001), and was 58% of the cost of video/robot-assisted (P = .018) approaches; these differences remained highly significant on multivariate analysis. Transcervical thymectomy had a shorter mean length of stay (1.2 ± 0.5 days) than median sternotomy (4.4 ± 3.5; P.001), and video/robot-assisted thymectomy (2.4 ± 0.95; P = .045) and "bed cost" were major contributors to the cost difference between the groups.Transcervical thymectomy, which provides overlapping myasthenia gravis remission rates versus more invasive approaches, is equally safe and far less costly than sternotomy and video/robot-assisted approaches.

BACKGROUND: Tumor size of 8 cm or greater is a risk factor for recurrence after thymoma resection, but the role of induction therapy for large thymomas is not well defined. This study tested the hypothesis that induction therapy for thymomas 8 cm and larger improves survival. METHODS: The use of induction therapy for patients treated with surgical resection for Masaoka stage I–III thymomas in the National Cancer Database between 2006–2013 was evaluated using logistic regression, Kaplan-Meier analysis, and Cox-proportional hazards methods. RESULTS: Of the 1,849 patients who met inclusion criteria, 582 (31.5%) had tumors ≥8 cm. Five-year survival was worse in patients with tumors ≥8 cm compared to smaller tumors [84.6% (95% CI: 81.2–88.1%) vs. 89.4% (95% CI: 87.2–91.7%), P=0.003]. Induction therapy was used in 166 (9.0%) patients overall and was more likely in patients with tumors ≥8 cm [adjusted odds ratio (AOR) 3.257, P

Radiologic screening of high-risk adults reduces lung-cancer-related mortality1,2; however, a small minority of eligible individuals undergo such screening in the United States3,4. The availability of blood-based tests could increase screening uptake. Here we introduce improvements to cancer personalized profiling by deep sequencing (CAPP-Seq)5, a method for the analysis of circulating tumour DNA (ctDNA), to better facilitate screening applications. We show that, although levels are very low in early-stage lung cancers, ctDNA is present prior to treatment in most patients and its presence is strongly prognostic. We also find that the majority of somatic mutations in the cell-free DNA (cfDNA) of patients with lung cancer and of risk-matched controls reflect clonal haematopoiesis and are non-recurrent. Compared with tumour-derived mutations, clonal haematopoiesis mutations occur on longer cfDNA fragments and lack mutational signatures that are associated with tobacco smoking. Integrating these findings with other molecular features, we develop and prospectively validate a machine-learning method termed 'lung cancer likelihood in plasma' (Lung-CLiP), which can robustly discriminate early-stage lung cancer patients from risk-matched controls. This approach achieves performance similar to that of tumour-informed ctDNA detection and enables tuning of assay specificity in order to facilitate distinct clinical applications. Our findings establish the potential of cfDNA for lung cancer screening and highlight the importance of risk-matching cases and controls in cfDNA-based screening studies.

Diffuse idiopathic pulmonary neuroendocrine cell hyperplasia (DIPNECH) is considered a preinvasive lesion that may progress to carcinoid tumour [1]. Histologically, it is marked by a proliferation of neuroendocrine cells that is confined to the basement membrane (neuroendocrine cell hyperplasia; NECH), and/or has invaded past the basement membrane (carcinoid tumourlet) [2]. Tumourlets equal to or larger than 5 mm are classified as carcinoid tumours. Per the World Health Organization 2021 criteria, DIPNECH can be pathological (based solely on characteristic histological features) or clinical (diagnosed per characteristic symptoms and imaging findings, e.g. respiratory symptoms, bilateral pulmonary nodules, mosaic attenuation on computed tomography (CT)) [2]. In contrast to some lung diseases or neoplasms that can cause secondary, reactive NECH/tumourlets to form, DIPNECH is marked by such hyperplasia without an identifiable cause., DIPNECH is a rare disease that is often misdiagnosed. In this study, it primarily affected elderly white women who were non-smokers. Lung nodules could slowly progress over years to carcinoid tumours. Average growth rate per nodule was 0.8 mm per year. https://bit.ly/3q1HD1k

The sensitivity of fluoroscopic esophagography with oral administration of contrast material to exclude anastomotic leak after esophagectomy is not well documented, and the consequences of missing a leak in this setting have not been previously described.We performed a retrospective cohort study of a prospectively maintained institutional database of patients undergoing esophagectomy with esophagogastric anastomosis from 2008 to 2020. Relevant details of leaks, management, and outcomes were obtained from the database and formal chart review. Statistical analysis was performed to compare patients with and without leaks and those with false-negative vs positive esophagrams.There were 384 patients who underwent esophagectomy with gastric reconstruction; the majority were Ivor-Lewis (82%), and 51% were wholly or partially minimally invasive. By use of a broad definition of leak, 55 patients (16.7%) developed an anastomotic leak. Of the 55 patients, 27 (49%) who ultimately were found to have a leak initially had a normal esophagram result (performed on average on postoperative day 6). Those with a normal initial esophagram result were more likely to have an uncontained leak (81% vs 29%; P.01), to require unplanned readmission (70% vs 39%; P = .02), and to undergo reoperation (44% vs 11%; P.01).Early postoperative esophagrams intended to evaluate anastomotic integrity have a low sensitivity of 51%, and leaks missed on the initial esophagram have greater clinical consequences than those identified on the initial esophagram. These findings suggest that a high index of suspicion must be maintained even after a normal esophagram result and call into question the common practice of using this test to triage patients for diet advancement.

Social disparities in lung cancer diagnosis, treatment, and survival have been studied using national databases, statewide registries, and institution-level data. Some disparities emerge consistently, such as lower adherence to treatment guidelines and worse survival by race and socioeconomic status, whereas other disparities are less well studied. A critical appraisal of current data is essential to increasing equity in lung cancer care.

BackgroundAs receptor-ligand based strategies emerge for surgical imaging, the relative importance of receptor expression in different tumor types is unknown. Near-infrared (NIR) labeled epidermal growth factor receptor (EGFR) antibody, panitumumab-IRDye800, was evaluated across three cancers to demonstrate its clinical utilities and a holistic analysis framework.MethodsThirty-one patients diagnosed with high-grade glioma (HGG, n=5, NCT03510208), head and neck squamous cell carcinoma (HNSCC, n=23, NCT02415881) or lung adenocarcinoma (LAC, n=3, NCT03582124) received systemic administration of 50 mg panitumumab-IRDye800 days prior to surgery. Intraoperative NIR laparoscopic or open-field images of the surgical field were acquired and tissue mimicking phantoms were constructed to identify optimal imaging conditions. Margin distance was correlated to fluorescence on resected specimen surface. Panitumumab-IRDye800 distribution was registered to histology in fixed tissue sections. Immunohistochemistry characterized EGFR expression.ResultsIntraoperative NIR imaging enhanced tumor contrast against surrounding healthy tissue by 5.2-fold, 3.4-fold and 1.4-fold in HGG, HNSCC and LAC, respectively. Imaging quality was optimal at the lowest gain possible under ambient light. Ex vivo NIR fluorescence identified 78 – 97% of at-risk resection margins, with 72 – 92% sensitivity and 67 – 96% specificity for tumor in fixed tissue sections. Intratumoral panitumumab-IRDye800 concentration correlated with total tumoral EGFR expression (HGG > HNSCC > LAC) and delivery barrier. Cellular EGFR expression (80%) and tumor cell density (3000 cells/mm2) was highest in HGG.ConclusionsIn multiple tumor types, EGFR-targeting in fluorescence-guided surgery translated to enhanced macroscopic tumor contrast and successful margin assessment despite disparate tumor cell density and heterogeneous delivery of pantimumab-IRDye800.Translational relevanceAs receptor-ligand based strategies emerge for surgical imaging, the relative importance of receptor expression in different tumor types remains unexamined. Near-infrared labeled epidermal growth factor receptor (EGFR) antibody was evaluated across three cancers to demonstrate its clinical utilities and a holistic analysis framework. Targeted fluorescence imaging was performed in patients infused with a consistent dose of panitumumab-IRDye800 using the same fluorescence imaging devices. In high-grade glioma, head and neck squamous cell carcinoma and lung adenocarcinoma, EGFR-targeting in fluorescence-guided surgery translated to enhanced macroscopic tumor contrast and successful margin assessment. While total EGFR expression and delivery barrier corresponded to overall panitumumab-IRDye800 distribution in tissue, tumor depth and operating room lighting can have greater influence over the intraoperative fluorescence contrast at specific tissue surface locations of a certain patient. These factors can facilitate selecting appropriate molecular target and tumor qualities to streamline translation across institutions and regulatory approval of new imaging probes.